Printed as commentary in the Owosso Argus Press 10/15/07 - five months post BPM
Their title - Cancer prevention too aggressive course for physician.
__________________________
My Title - Proud to be able to make life affirming choices to reduce cancer risk - I like it better.
I had always assumed that I was at high risk for breast cancer. Mom had been diagnosed with it in her 40s. Dad’s sister had breast cancer in her 40’s. I am single and never had any children and am overweight. If you had asked me or my physician, we would have estimated my risk to be around 18%. The average woman has a 12% risk. Because of these risk factors, my doc started me on screening mammograms before age 40, and even mentioned taking tamoxifen as a preventative measure.
Despite studying families with hereditary breast and ovarian cancers in medical school, it never occurred to me that I might be at risk of carrying a “breast cancer” gene until my aunt tested positive for BRCA1 mutation in March of 2006. I am so thankful that my cousin recognized that her mother might be at risk, after having breast cancer in her 40s and then having it return in the same breast after lumpectomy.
BRCA1 and BRCA2 are breast and ovarian cancer prevention genes, which if normal help protect a woman from getting either type of cancer. A mutation of these genes can be inherited from one’s mother or father. If one parent has the faulty gene, then there is a 50 % chance that each child will get it. These mutations are rare, affecting about one in 50 women of Ashkenazi Jewish heritage (Northern European) and about 1 in 500 women of other heritage.
Nine months after my aunt told us about her situation, my father tested and found out that he also carried the mutation.
Once Dad’s test came back, I immediately went to the internet to learn more about this condition, as I suddenly realized I had a 50% chance of inheriting it as well. I was looking for a loophole that meant I did not have to worry. While waiting to test myself, I spent 2 weeks online reading scientific articles and feeling very scared and alone. It was hard to accept having such a high risk of getting cancer, and even harder to imagine having to decide about the various risk reduction strategies, including preventative surgery.
It was during this time that I found FORCE. ( www.facingourrisk.org ) Facing Our Risk of Cancer Empowered is an organization started by Sue Friedman, a veterinarian who learned that her breast cancer at age 33 was the result of a BRCA mutation. This website includes resources and information for other women facing the prospect of hereditary breast or ovarian cancer.
(Most useful to me is the message board, where hundreds of women and a few men have posted stories, questions and discussions about every aspect of this syndrome. I knew I was in the right place after reading about a woman in New Zealand, my age, with my name, who was involved in the process of taking action to minimize her risk of getting cancer. - edited out) Despite the fact that this syndrome is so rare, I was able to get advice from women all over the world, who understood exactly what my hopes and fears were. The site was so comforting. ( These people held my hand, virtually, as I waited for test results and then served as guides, as I wound my way through the array of preventative options available to me. Edited out)
This year, I learned that I had tested positive. I had inherited a breast cancer gene mutation.
Despite the scary news about my condition, I felt blessed and very thankful that my cousin had appropriately assessed the risk of this gene being present in our family, and encouraged my aunt to test. I am also so thankful that my aunt was proactive, got tested, and gained the knowledge that my sisters, cousins and I needed to be aware of our risks.
Most people recommend seeing a certified genetics counselor before testing, but I did things a little backwards. After my test results were received, I looked to this expert regarding this rare condition to help me figure out what my options were to minimize my risk of getting cancer.
My choices included surveillance, medications or surgery.
Surveillance means frequent testing to try to catch cancer at an early and curable stage. (To me, it seems like a reasonable option for managing breast cancer risk, because clinical breast exams( by physician, PA or Nurse Practitioner), mammogram and MRI are pretty good at catching breast cancer at an early stage. I am not comfortable with the idea of surveillance as a strategy for managing ovarian cancer risk in a patient with a BRCA mutation, because there is not any test which can reliably catch ovarian cancer at a treatable stage. Edited out)
Medication treatment would involve using tamoxifen to limit my exposure to estrogen, and therefore decrease the risk of breast cancer. ( benefit is higher in women who start treatment at a younger age. Edited out)
I, however, was determined not to get cancer at all, and opted for risk reduction surgery instead. I did not want to have to worry about whether or when I would have to take 9 months out of my life to fight cancer. I had watched my mother thrive after having bilateral mastectomies to treat and prevent recurrent cancer after her diagnosis. A friend labeled my decisions “life affirming.” I like that term.
The removal of the ovaries was my first priority. Usually it is recommended to do this surgery at age 35 in women with my mutation, because this age seems to balance the risk of getting cancer with the side effects of no longer having the usual hormones that younger women should have (surgical menopause.) (I opted for a laparoscopic surgery and my recovery was quick and nearly painless. I was able to return to work in 10 days and have been lucky that my menopausal symptoms have been minimal. Edited out)
Next up was the BPM. This is short for bilateral prophylactic (preventative) mastectomy, or removal of both breasts. It was tough for me to grasp the notion that this was the “best” option for me to avoid getting breast cancer. (One medical text pointed out that this preventative step is actually more drastic than the treatment for a usual case of early breast cancer. Edited out) Unfortunately, because of the gene mutation, I knew that if I waited to get breast cancer, there was no guarantee that I would catch it early enough to be able to avoid chemotherapy. (There would be a risk that it could spread to lymph nodes or other organs and be incurable. –edited out)
The next decision that I faced was whether to have reconstruction or not. I was pleasantly surprised to learn of my options for surgical reconstruction and to see that the results looked much better than I imagined. I was, however, very interested in getting back to work and life quickly and ultimately decided not to have reconstruction. I did worry about what people would think, who would notice, how I would look, and how I would cope with the whole situation. ( My therapist and I decided that I would be able to handle whatever ensued. Edited out)
The surgery was uneventful. I woke afterward, relieved to be done. I did have some pain for several weeks after surgery. (This was an interesting situation for me, because I frequently prescribe pain medications for patients and had never needed them myself in the past. It was educational to see that I needed higher dosages than average right away, and a relief to see that the new nerve pain medication worked so well. Edited out) For the first 4 weeks after surgery, my assignment was to rest and let my body heal. Then, I was on to the rehab phase where I was allowed to gradually increase my activity and begin to exercise. I was very glad to be back to biking, golfing and yard work 6 weeks after surgery.
I have been pleasantly surprised that strangers don’t seem to notice my, new, flat appearance. Clothes fit well and my diet and exercise program seems to be going well. ( I am very committed to losing ‘the other 60 pounds of excess health risk.’ Edited out)
Last week one of my colleagues asked about the impact of my surgeries on my likelihood of getting cancer. I felt relief and pride as I rattled off the change in my cancer risks. Breast cancer risk decreased from 87% to 2% and ovarian cancer risk from 44% to 2%. (It is very nice to be done. Edited out)
I am glad to be able to share my story, in the hopes that others will become more aware of hereditary breast and ovarian cancer syndrome, of the availability of testing, and of the fact that many women are glad to have the information and the choice of how to manage their risk of cancer if they have a faulty BRCA gene. Certainly it is a scary subject, and it is important to realize that most breast and ovarian cancer is NOT hereditary. Indicators of risk for a BRCA mutation include: breast cancer before the age of 50 or ovarian cancer at any age, mother, grandmothers, sisters or aunts with breast cancer before 50, any relative with ovarian cancer, a male relative with breast cancer, or if 2 or more close relatives had breast cancer. Those who think they might be at risk should ask their doctor about whether genetic counseling would be appropriate for them. Those at high risk should start screening with annual breast MRI's in their 30's.
All women should follow the recommended screening routine to ensure that breast cancer is caught early. Early stage breast cancer is very treatable.
1. All women age 40 and older should have a screening mammogram every year and should continue to do so for as long as they are in good health.
2. All women in their 20s and 30s should have a clinical breast exam (CBE) as part of a periodic (regular) health exam by a health professional preferably every 3 years. After age 40, women should have a breast exam by a health professional every year.
3. Self breast exam is recommended for all women over 20.
____________________________________________
This paragraph belongs in the article, but unfortunately I did not include it. Written for another source
Although ovarian cancer is relatively rare (1 in 67 women will get it), it is difficult to catch early. Most of the warning signs more commonly represent other conditions. There are new recommendations, however that women who have daily symptoms for more than a few weeks should see a gynecologist, particularly if these symptoms represent a change from normal, or become more severe. Symptoms of concern include: bloating, pelvic or abdominal pain, trouble eating or feeling full quickly, or urinary symptoms such as always feeling like you have to go or going more often.
Showing posts with label HBOC. Show all posts
Showing posts with label HBOC. Show all posts
Saturday, October 06, 2007
The rest of the BRCA risk reduction story
Once I had finished the oophorectomy, the BPM loomed ahead. Bilateral prophylactic or preventative mastectomy meant removal of both breasts before cancer was identified. I only had 36 days between the 2 surgeries. BPM is such a hard thing to consider. Definitely disfiguring. Extreme. More drastic than the treatment of most breast cancers. Unfortunately, BRCA breast cancer is not like most breast cancers. It tends to recur if mastectomy is not done. No one could assure me that surveillance could promise catching the cancer early enough to be curable.
Both my Gyn and Family Medicine doc said that the oophorectomy was needed, but that I did not have to have BPM. I suspected that they did not want me to get stuck on whether to have the mastectomies and put off the ooph in the process. The appointment with the genetics counselor had confirmed that my risk of getting breast cancer was very high, and that tamoxifen would reduce my risk by only 1/3 as many BRCA1 cancers are estrogen negative. To gain the full 50% reduction of risk for breast cancer by having an oophorectomy, I would have needed to have the ooph at 35. Unfortunately, I was blissfully ignorant at that time. The GC mentioned some modest benefit from dietary and supplement measures I could take. Then she seemed very relieved to hear that I was planning on BPM.
I played with the statistics. 87% risk x 80% long term survival still came out to 17% chance of being dead, and possibly in my 50s.
I felt that there were many things that made this choice easier for me. Mom did so well after her BPM for lobular carcinoma in situ in 1988. I knew how devastating cancer could be after watching and unrelated uncle die of colon cancer, seeing patients struggle with it, and watching my housemate’s mother fight so hard against metastatic kidney cancer. A patient’s CT scan is indelibly etched in my brain. I saw her 2 days before my test results came back. At 52, she had mastectomy with saline implant on one side, mastectomy with external prosthesis on the other and lung mets, all on the same film.
I wanted my BPM as soon as I could arrange it.
The next step was to decide on reconstruction or not. I explored the FORCE site and took note of the posts about each type of reconstruction. I was very pleasantly surprised at the post op photos on FORCE and elsewhere. I was also pleasantly surprised to see a photo of a topless Dutch woman, swimming on the beach, surrounded by her children with a big smile on her face. The scars were evident, but not bad at all. I participated in a spirited thread about “no recon” options, including discussions of whether it is possible to have a cosmetically appealing surgery, like some male to female transsexuals receive.
Reconstruction seemed like a long process whichever type was chosen. I was very aware of my aunt’s complications after her TRAM procedure. I never did consider traveling for a “One Step” procedure.
I felt that “no recon” fit with my personality and my body image. When younger, I was thin, fit, and small chested. I still tend to think of myself that way, although the body got away from me long ago. I tended to begrudge the D’s that went up and down first with every fluctuation in my weight. I dress androgynously, and usually in men’s clothes, which often don’t fit well or require a larger size because of my large chest. (and wide hips) I thought that reconstruction would result in longer rehab time and more restrictions, as well as a higher risk of complications. In my profession, as a physiatrist, I had seen some serious disabilities result from surgical complications. I wanted to avoid that at all costs.
The morning of the surgery, I felt calm, and was pleased that the anesthesiologist honored my request for no versed. I had been in la-la land for about 5 hours after my previous surgery and did not like that feeling. My friend and my parents were in the waiting room with me. It was nice for me, to be awake in the OR until they gave me the general anesthetic. I awoke in the recovery room, clear, but in pain, and very relieved to be done. I was a bit dismayed by the pink flowered binder around my chest, but took it in stride. The pink binder was a good source of comic relief during the next few weeks. It also made car rides much more manageable. The pain meds were delivered quickly and worked well. I had a long ride to the overnight stay area, and was glad to be awake to reassure my parents that I was fine.
There was a brief struggle with balancing the pain and nausea during my night in the hospital. I was so glad to be in the hospital overnight. The ride home was uneventful. It was very nice to have my parents stay the first few days. It was also nice to feel comfortable managing for myself. I was able to take care of the drains myself and get a quick meal or snack. I slept a lot, and vegged out. I gladly included my mom and my housemate in my photo project to document my look over the first few weeks after surgery. I was very pleased with how well the muscle shirts worked for drain holders. My appearance at the local Relay for Life event 4 days after my surgery was ceremonial only, but there is a photo. My Great Goose photo earned some money for the event.
The next few weeks revolved around pain meds, meals, rest and computer time. My family doctor helped me get a pain regimen that worked. It included Vicodin during the day and MS Contin at night, and low dose lyrica for the nerve pain. I posted on FORCE a lot. At 3 weeks after surgery, I went back to the breast surgeon. She deemed my drain output too large to pull the drains and chided me for typing too much.
One week later, I had my local surgeon pull the second drain, after the Family Medicine physician helped with the first. We decided that we would watch any fluid that remained and take action if needed. I returned to work 4 weeks after surgery. My heart was not really in it. I was thrilled to see that my patients were so supportive and welcoming.
Gradually, I resumed my usual activities, including golf, kayaking, biking, and a little yard work. The pain and ropelike sensation around my chest gradually resolved. The scars have evolved over time. It took about 8 weeks for the fluid to resolve. I had small scares with a stitch granuloma and a case of cellulitis without pain, fever or illness. Those resolved with oral antibiotics.
Now, at 6 months out, the scars are still red and obvious. The chest muscles only occasionally get tight, and there are intermittent weird sensations as the numbness slowly resolves. I am back to full activity, and more engaged at work. I still rely on the FORCE message board and chatroom as a part of my coping process. I was thrilled to be able to meet men and women from the Boston group this weekend. Strangers don’t seem to notice that I don’t have breasts and a few of the FORCE women asked which kind of reconstruction I had.
I am very proud of myself for being able to take action so quickly. I was thrilled last week to be able to respond to a coworker’s question that I had decreased my breast cancer risk from 87% to 2%. I am still not sure what the future will look like, but am happy to be planning instead of worrying.
Both my Gyn and Family Medicine doc said that the oophorectomy was needed, but that I did not have to have BPM. I suspected that they did not want me to get stuck on whether to have the mastectomies and put off the ooph in the process. The appointment with the genetics counselor had confirmed that my risk of getting breast cancer was very high, and that tamoxifen would reduce my risk by only 1/3 as many BRCA1 cancers are estrogen negative. To gain the full 50% reduction of risk for breast cancer by having an oophorectomy, I would have needed to have the ooph at 35. Unfortunately, I was blissfully ignorant at that time. The GC mentioned some modest benefit from dietary and supplement measures I could take. Then she seemed very relieved to hear that I was planning on BPM.
I played with the statistics. 87% risk x 80% long term survival still came out to 17% chance of being dead, and possibly in my 50s.
I felt that there were many things that made this choice easier for me. Mom did so well after her BPM for lobular carcinoma in situ in 1988. I knew how devastating cancer could be after watching and unrelated uncle die of colon cancer, seeing patients struggle with it, and watching my housemate’s mother fight so hard against metastatic kidney cancer. A patient’s CT scan is indelibly etched in my brain. I saw her 2 days before my test results came back. At 52, she had mastectomy with saline implant on one side, mastectomy with external prosthesis on the other and lung mets, all on the same film.
I wanted my BPM as soon as I could arrange it.
The next step was to decide on reconstruction or not. I explored the FORCE site and took note of the posts about each type of reconstruction. I was very pleasantly surprised at the post op photos on FORCE and elsewhere. I was also pleasantly surprised to see a photo of a topless Dutch woman, swimming on the beach, surrounded by her children with a big smile on her face. The scars were evident, but not bad at all. I participated in a spirited thread about “no recon” options, including discussions of whether it is possible to have a cosmetically appealing surgery, like some male to female transsexuals receive.
Reconstruction seemed like a long process whichever type was chosen. I was very aware of my aunt’s complications after her TRAM procedure. I never did consider traveling for a “One Step” procedure.
I felt that “no recon” fit with my personality and my body image. When younger, I was thin, fit, and small chested. I still tend to think of myself that way, although the body got away from me long ago. I tended to begrudge the D’s that went up and down first with every fluctuation in my weight. I dress androgynously, and usually in men’s clothes, which often don’t fit well or require a larger size because of my large chest. (and wide hips) I thought that reconstruction would result in longer rehab time and more restrictions, as well as a higher risk of complications. In my profession, as a physiatrist, I had seen some serious disabilities result from surgical complications. I wanted to avoid that at all costs.
The morning of the surgery, I felt calm, and was pleased that the anesthesiologist honored my request for no versed. I had been in la-la land for about 5 hours after my previous surgery and did not like that feeling. My friend and my parents were in the waiting room with me. It was nice for me, to be awake in the OR until they gave me the general anesthetic. I awoke in the recovery room, clear, but in pain, and very relieved to be done. I was a bit dismayed by the pink flowered binder around my chest, but took it in stride. The pink binder was a good source of comic relief during the next few weeks. It also made car rides much more manageable. The pain meds were delivered quickly and worked well. I had a long ride to the overnight stay area, and was glad to be awake to reassure my parents that I was fine.
There was a brief struggle with balancing the pain and nausea during my night in the hospital. I was so glad to be in the hospital overnight. The ride home was uneventful. It was very nice to have my parents stay the first few days. It was also nice to feel comfortable managing for myself. I was able to take care of the drains myself and get a quick meal or snack. I slept a lot, and vegged out. I gladly included my mom and my housemate in my photo project to document my look over the first few weeks after surgery. I was very pleased with how well the muscle shirts worked for drain holders. My appearance at the local Relay for Life event 4 days after my surgery was ceremonial only, but there is a photo. My Great Goose photo earned some money for the event.
The next few weeks revolved around pain meds, meals, rest and computer time. My family doctor helped me get a pain regimen that worked. It included Vicodin during the day and MS Contin at night, and low dose lyrica for the nerve pain. I posted on FORCE a lot. At 3 weeks after surgery, I went back to the breast surgeon. She deemed my drain output too large to pull the drains and chided me for typing too much.
One week later, I had my local surgeon pull the second drain, after the Family Medicine physician helped with the first. We decided that we would watch any fluid that remained and take action if needed. I returned to work 4 weeks after surgery. My heart was not really in it. I was thrilled to see that my patients were so supportive and welcoming.
Gradually, I resumed my usual activities, including golf, kayaking, biking, and a little yard work. The pain and ropelike sensation around my chest gradually resolved. The scars have evolved over time. It took about 8 weeks for the fluid to resolve. I had small scares with a stitch granuloma and a case of cellulitis without pain, fever or illness. Those resolved with oral antibiotics.
Now, at 6 months out, the scars are still red and obvious. The chest muscles only occasionally get tight, and there are intermittent weird sensations as the numbness slowly resolves. I am back to full activity, and more engaged at work. I still rely on the FORCE message board and chatroom as a part of my coping process. I was thrilled to be able to meet men and women from the Boston group this weekend. Strangers don’t seem to notice that I don’t have breasts and a few of the FORCE women asked which kind of reconstruction I had.
I am very proud of myself for being able to take action so quickly. I was thrilled last week to be able to respond to a coworker’s question that I had decreased my breast cancer risk from 87% to 2%. I am still not sure what the future will look like, but am happy to be planning instead of worrying.
Saturday, March 31, 2007
March 17th FORCE post, Genetics Counselor Appt.
Hello all. Was incredibly nervous heading into the genetics counselor meeting, despite knowing much of what would be said. Genetics counselor was nice, and helpful. A moment of panic, as I was lead into a normal exam room. I think I would have freaked out a little if I had to gown up for the GC (genetics counselor )appt. Definitely did not fit my vision of a consultation in an academic office across her desk.
Oh well. We did still trade articles. Gave me the spiel about all of my "bad" conservative options. I had not been aware of how little use tamoxifen was for BRCA1 bc(breast cancer) prevention. She made it sound like only 1/3 or less reduction in BC risk, as more of the tumors end up being estrogen receptor negative. Agreed that I am probably too old to get much bc prevention benefit by having ovaries out.
All ( GC, oncologist, and resident) seemed relieved that I was opting for surgical risk reduction. Optimistic news about the gyn onc doing supracervical hysterectomy through the laparoscope. They seemed to agree that no recon fits with my goal of being off work as little as possible. No funny looks. PS appt was briefly offered, but not pushed.
The doc was quite interested in my history of already having a colon polyp removed. I am due for repeat colonoscopy in Sept. (great, one more thing to stress over. Stats are ambivalent about BRCA1 and colon cancer. I guess the stats don't matter that much as a gal with a polyp at 40) My gastroenterologist is praying for me.
The packet of info include several FORCE newsletters and the flyer for the conference. Whitney will be going to the FORCE conference.
Good info about having brothers start high risk prostate screening at 40 instead of 50.
So weird being a patient. So nice to walk into the Breast Center without cancer. Very motivating to keep it that way.
So, it does feel more real, having the folks who know confirm that my research and my FP(family practice doc) and my Gyn are all correct. Sucks to be right. (how could I not be with such good info and advice from the FORCE site)
Arrived at work yesterday to find an article from my local Gyn about ovca (ovarian cancer) in BRCA carriers. Not sure what his point is. I guess, a gentle reminder not to take too long to get mine out. I messaged him back about my concerns regarding BRCA pathology protocol and occult ovca found at rr ooph (risk reduction oophorectomy - ovarian resection). No response yet. Got an email last night from my proactive cousin, urging me to get my ooph soon. While waiting for her mom's skin graft, she got to sit next to a different high school acquaintance who at 36 was alone in the waiting room, ready to get her chemo port in for treatment of ovarian ca.
After listening to my biological clock wind down for so many years, who knew that it was the switch for tiny internal time bombs.
Grieving the impending loss of my fertility, even though I have been deciding for 5 years that a child would not fit into the life that I had, and not willing or able to change the situation enough to make it work.
So what else is going on:
1. still struggling with a challenging "presumed" metastatic bc patient electing not to clarify her dx or take chemo.
2. bought my luminaries for the local Relay for Life event. Scheduled May 18-19. I bought 8, but realized that I forgot one for my high school friend in the Ukraine and my uncle who died of throat CA. 2 years ago it was a shock to count up the relatives with cancer. Now it just raises the curiosity level. No ovca thankfully.
3. Enjoying reading and posting obsessively on the FORCE site.
4. PT. felt like my therapist was trying to kill me yesterday. Turns out my round shouldered posture has been hiding how prominent my breasts actually are. Feels very weird to be improving posture, making them more prominent right before I get them cut off. Trying not to feel guilty for indulging myself in the magical PTs services for a sore neck at a time like this. I know it will help in the long run.
5. obsessively watching my email. Surprised at how few responses I got from my first round of mass emailing people. Very appreciative of the ones who have written back. It makes a great distraction for me. Helps me feel connected.
6. Fretting about my youngest brother, who is usually quite communicative, but who has been too busy to finish a phone call, and has not emailed. I hope he is just busy.
7. Enjoying my sister's blog site with new pictures of her daughters. She is perplexed about how the love of princesses and the color pink is transmitted as both mom and dad have worked hard not to encourage it. Her pre-school is the most progressive ever, with rules against comercial toys, policies against passing on gender stereotyping etc. It was painful for Aunt Margaret to have to buy a disney princess Leapfrog book for her. (And some of the messages in it are horrible. Ariel asking her husband if she can ever go back and visit her family. Yuck.) No offense to the princesses on this site.
8. Being interrupted from typing this post by the 4 deer grazing in my back yard. So nice to get absorbed in the moment. They stayed 10 minutes. Fun to indulge my naturalist tendencies.
9. Told my first menopause joke.
10. Found a new way to make my patients cry. One, who is quite well connected to the hospital gossip network asked me straight out what was going on and then broke out in tears and hugged me. (usually I make them cry by being too blunt or by being a mean pain doc)
11. Practicing golf at the indoor range. Focus, being in the moment. Emotions leaking through. Grieving the loss of part of the golf season. Inspired to be back by August to take on one of my nemesis courses for the Mich women's golf assn state tournament. Last time we played there I think I shot 113, with a 20 handicap.
12. Feeling blessed and amazed by the sequence of events that got me here and able to be saving my life. I do hear you ladies, who remind me that there does not have to be a reason for God to bless me with this chance. Hard to not feel some responsibility from it. More on this in a separate post.
13. Gradually feeling more accepting that BRCA1 + and rr(risk reduction) surgeries are my fate for this spring. When speaking with my therapist, I told her that I can't believe this is happening to me, but can't really imagine who else it should happen to.
14. Feeling very chic. Oprah, Self and Cosmo in the same month. Thankfully the cosmo article is online at BeBrightPink so I do not have to undergo the trauma of buying all three magazines for the first time ever.
15. Wondering whether I should be writing a book. Revising my plans for the blog. Wishing that I was able to take advantage of the current climate and have something ready soon.
Oh well. We did still trade articles. Gave me the spiel about all of my "bad" conservative options. I had not been aware of how little use tamoxifen was for BRCA1 bc(breast cancer) prevention. She made it sound like only 1/3 or less reduction in BC risk, as more of the tumors end up being estrogen receptor negative. Agreed that I am probably too old to get much bc prevention benefit by having ovaries out.
All ( GC, oncologist, and resident) seemed relieved that I was opting for surgical risk reduction. Optimistic news about the gyn onc doing supracervical hysterectomy through the laparoscope. They seemed to agree that no recon fits with my goal of being off work as little as possible. No funny looks. PS appt was briefly offered, but not pushed.
The doc was quite interested in my history of already having a colon polyp removed. I am due for repeat colonoscopy in Sept. (great, one more thing to stress over. Stats are ambivalent about BRCA1 and colon cancer. I guess the stats don't matter that much as a gal with a polyp at 40) My gastroenterologist is praying for me.
The packet of info include several FORCE newsletters and the flyer for the conference. Whitney will be going to the FORCE conference.
Good info about having brothers start high risk prostate screening at 40 instead of 50.
So weird being a patient. So nice to walk into the Breast Center without cancer. Very motivating to keep it that way.
So, it does feel more real, having the folks who know confirm that my research and my FP(family practice doc) and my Gyn are all correct. Sucks to be right. (how could I not be with such good info and advice from the FORCE site)
Arrived at work yesterday to find an article from my local Gyn about ovca (ovarian cancer) in BRCA carriers. Not sure what his point is. I guess, a gentle reminder not to take too long to get mine out. I messaged him back about my concerns regarding BRCA pathology protocol and occult ovca found at rr ooph (risk reduction oophorectomy - ovarian resection). No response yet. Got an email last night from my proactive cousin, urging me to get my ooph soon. While waiting for her mom's skin graft, she got to sit next to a different high school acquaintance who at 36 was alone in the waiting room, ready to get her chemo port in for treatment of ovarian ca.
After listening to my biological clock wind down for so many years, who knew that it was the switch for tiny internal time bombs.
Grieving the impending loss of my fertility, even though I have been deciding for 5 years that a child would not fit into the life that I had, and not willing or able to change the situation enough to make it work.
So what else is going on:
1. still struggling with a challenging "presumed" metastatic bc patient electing not to clarify her dx or take chemo.
2. bought my luminaries for the local Relay for Life event. Scheduled May 18-19. I bought 8, but realized that I forgot one for my high school friend in the Ukraine and my uncle who died of throat CA. 2 years ago it was a shock to count up the relatives with cancer. Now it just raises the curiosity level. No ovca thankfully.
3. Enjoying reading and posting obsessively on the FORCE site.
4. PT. felt like my therapist was trying to kill me yesterday. Turns out my round shouldered posture has been hiding how prominent my breasts actually are. Feels very weird to be improving posture, making them more prominent right before I get them cut off. Trying not to feel guilty for indulging myself in the magical PTs services for a sore neck at a time like this. I know it will help in the long run.
5. obsessively watching my email. Surprised at how few responses I got from my first round of mass emailing people. Very appreciative of the ones who have written back. It makes a great distraction for me. Helps me feel connected.
6. Fretting about my youngest brother, who is usually quite communicative, but who has been too busy to finish a phone call, and has not emailed. I hope he is just busy.
7. Enjoying my sister's blog site with new pictures of her daughters. She is perplexed about how the love of princesses and the color pink is transmitted as both mom and dad have worked hard not to encourage it. Her pre-school is the most progressive ever, with rules against comercial toys, policies against passing on gender stereotyping etc. It was painful for Aunt Margaret to have to buy a disney princess Leapfrog book for her. (And some of the messages in it are horrible. Ariel asking her husband if she can ever go back and visit her family. Yuck.) No offense to the princesses on this site.
8. Being interrupted from typing this post by the 4 deer grazing in my back yard. So nice to get absorbed in the moment. They stayed 10 minutes. Fun to indulge my naturalist tendencies.
9. Told my first menopause joke.
10. Found a new way to make my patients cry. One, who is quite well connected to the hospital gossip network asked me straight out what was going on and then broke out in tears and hugged me. (usually I make them cry by being too blunt or by being a mean pain doc)
11. Practicing golf at the indoor range. Focus, being in the moment. Emotions leaking through. Grieving the loss of part of the golf season. Inspired to be back by August to take on one of my nemesis courses for the Mich women's golf assn state tournament. Last time we played there I think I shot 113, with a 20 handicap.
12. Feeling blessed and amazed by the sequence of events that got me here and able to be saving my life. I do hear you ladies, who remind me that there does not have to be a reason for God to bless me with this chance. Hard to not feel some responsibility from it. More on this in a separate post.
13. Gradually feeling more accepting that BRCA1 + and rr(risk reduction) surgeries are my fate for this spring. When speaking with my therapist, I told her that I can't believe this is happening to me, but can't really imagine who else it should happen to.
14. Feeling very chic. Oprah, Self and Cosmo in the same month. Thankfully the cosmo article is online at BeBrightPink so I do not have to undergo the trauma of buying all three magazines for the first time ever.
15. Wondering whether I should be writing a book. Revising my plans for the blog. Wishing that I was able to take advantage of the current climate and have something ready soon.
Tuesday, March 06, 2007
Now What?
The shock of my diagnosis is slowly lifting. I have told family. I have told bosses. Started telling friends and associates. Not yet patients.
I have a genetics counselor appointment on the 15th, more than a week away. 3 surgeon appointments on the 26 through the 28th. Way too far from now.
I have had a few concerned looks and many supportive emails. A few surprised looks from people. I have explained plans to good friends and new coworkers. In general, not as bad as expected.
I have mailed packets of information to brothers, sisters, uncles and attempted to email the same information to 2 of dad's cousins. I cheated and did not use the statistics, sparing me the nausea and the recipients the shock. I have circulated the blog address so all can delve as deeply as they like.
I have been informed that at some point, I actually need to feel what is going on. Not sure I want to do that yet. What feelings I have had so far come in shades and flavors I have not experienced before and am a little reluctant to learn about.
So... I surf the internet, and read the posts on the FORCE site. I have bought silicone bracelets in teal to match my pink one. Procrastinate work and stare into space.
Found an interesting series on my situation through another woman's eyes, on Slate. Passed a good hour doing that. http://www.slate.com/id/2102171/entry/2102173/
Only 188 hours before my meeting with the genetic counselor, who I am afraid will not tell me that I miscalculated somewhere and do not have to worry about this syndrome, or my choices.
I have a genetics counselor appointment on the 15th, more than a week away. 3 surgeon appointments on the 26 through the 28th. Way too far from now.
I have had a few concerned looks and many supportive emails. A few surprised looks from people. I have explained plans to good friends and new coworkers. In general, not as bad as expected.
I have mailed packets of information to brothers, sisters, uncles and attempted to email the same information to 2 of dad's cousins. I cheated and did not use the statistics, sparing me the nausea and the recipients the shock. I have circulated the blog address so all can delve as deeply as they like.
I have been informed that at some point, I actually need to feel what is going on. Not sure I want to do that yet. What feelings I have had so far come in shades and flavors I have not experienced before and am a little reluctant to learn about.
So... I surf the internet, and read the posts on the FORCE site. I have bought silicone bracelets in teal to match my pink one. Procrastinate work and stare into space.
Found an interesting series on my situation through another woman's eyes, on Slate. Passed a good hour doing that. http://www.slate.com/id/2102171/entry/2102173/
Only 188 hours before my meeting with the genetic counselor, who I am afraid will not tell me that I miscalculated somewhere and do not have to worry about this syndrome, or my choices.
Thursday, March 01, 2007
Test is positive - at least the waiting is over
Got my test results today. Even though I had sort of expected them to be positive, was a little stunned by the reading the test.
Have been busy telling people. Partly to get enough people told before the shock of it wore off. So... on to the next steps.
And all of the questions that I have been refraining from entertaining until I knew one way or the other.
Had my mamm and TVU (transvaginal ultrasound )today. No call backs, so that is a good sign. Will get CA-125 (blood test which gets elevated in ovarian cancer) tomorrow. Feeling ok about being cancer free and not too late to be in the risk reduction category. DSO was supportive, despite me telling her by phone. I knew I could not make it all day without telling anyone and did not want her to find out from anyone else. Mom and Dad were also supportive, despite being distant on the subject before. Bosses and co-workers are great so far. I anticipate more shock and disbelief at my risk reduction strategies as I go on. Stumbled on to a very nice GC (genetic counselor) at a hospital about 2 hours away, but near DSO's family. And at the center where our friend is having her surgery in a few weeks. They have a BRCA clinic at Beaumont , and GYN/Onc, and a dedicated breast surgeon. Should pass muster as far as seeking experts. Appointment with Whitney Ducaine, CGC on 3/15 and encouraged to set up appointments with the surgeons before then. Anxious to move on to action.
So, for the questions? To hyst or not to hyst? I have no known uterine problems, no cancer anywhere, I hope? Doubt that I will want to take steroids, or that my FP would give them to me. BPM (Bilateral prophylactic mastectomies )and oophorectomies together or separately? I have never been off work for even 2 weeks the past 11 years. Practice pretty much shuts down when I am not working. Relatively healthy, I think I have a high pain tolerance. (niece has congenital indifference to pain and feels none. )
How long after BPM can I push hard on my golf cleat tool to change DSO golf spikes? How long to golf? How soon to come back to work? Not planning recon. Will I be able to wear those golf shirts that are too small for my 42Ds now. if I go without prostheses? (Mom warns that I will be pear shaped. Also says that people are either too kind to say anything or don't notice. She had BPM 20 years ago for LCIS and estimates that she wears a bra with prosthesis or socks a couple times per year. I generally care less about what people think about how I dress than she does. ) Who to tell and how? I am considering sending out a mass email at work. There are 10 or so nurses, several administrators, and 10 or so docs that I am close enough with to definitely tell, and will be talking about it( maybe once or twice?:J) in front of many others, as my main social interactions with these folks are on the wards during rounds. Knowing that some will consider a mass email weird. Knowing that my absence for 3 weeks will definitely be missed, and after, the absence of my breasts will definitely be noticed.
Also considering letting myself be a news story in the local paper. Has anyone done that? It just seems so random and senseless, that the teacher in me wants to find some meaning. This all makes DSO very nervous.
Good things about the challenge of being BRCA1 positive
1. Way better than having cancer.
2. Life lessons
3. No way for my uncles and cousins to ignore the potential impact of our family genetic issue.
4. Get to be a real live amazon.
5. Don't have to worry of mom's LCIS makes me at higher risk.
6. Good reason to reach out to old friends and make new friends.
7. Excellent reason to re-prioritize my life.
8. Head start on the new weight loss program.
9. Learning what it is like to be a patient.
Bad things about having ghe challenge of being BRCA1 positive
1. Surgeries
2. Funny looks from people who think I am being radical
3. Worry about getting cancer before I am done reducing my risk. (and after, I guess)
4. Stress for me, co-workers, family, DSO etc.
5. Time off work, away from golf, etc.
6. Having to be a patient.
That is enough for now.
Have been busy telling people. Partly to get enough people told before the shock of it wore off. So... on to the next steps.
And all of the questions that I have been refraining from entertaining until I knew one way or the other.
Had my mamm and TVU (transvaginal ultrasound )today. No call backs, so that is a good sign. Will get CA-125 (blood test which gets elevated in ovarian cancer) tomorrow. Feeling ok about being cancer free and not too late to be in the risk reduction category. DSO was supportive, despite me telling her by phone. I knew I could not make it all day without telling anyone and did not want her to find out from anyone else. Mom and Dad were also supportive, despite being distant on the subject before. Bosses and co-workers are great so far. I anticipate more shock and disbelief at my risk reduction strategies as I go on. Stumbled on to a very nice GC (genetic counselor) at a hospital about 2 hours away, but near DSO's family. And at the center where our friend is having her surgery in a few weeks. They have a BRCA clinic at Beaumont , and GYN/Onc, and a dedicated breast surgeon. Should pass muster as far as seeking experts. Appointment with Whitney Ducaine, CGC on 3/15 and encouraged to set up appointments with the surgeons before then. Anxious to move on to action.
So, for the questions? To hyst or not to hyst? I have no known uterine problems, no cancer anywhere, I hope? Doubt that I will want to take steroids, or that my FP would give them to me. BPM (Bilateral prophylactic mastectomies )and oophorectomies together or separately? I have never been off work for even 2 weeks the past 11 years. Practice pretty much shuts down when I am not working. Relatively healthy, I think I have a high pain tolerance. (niece has congenital indifference to pain and feels none. )
How long after BPM can I push hard on my golf cleat tool to change DSO golf spikes? How long to golf? How soon to come back to work? Not planning recon. Will I be able to wear those golf shirts that are too small for my 42Ds now. if I go without prostheses? (Mom warns that I will be pear shaped. Also says that people are either too kind to say anything or don't notice. She had BPM 20 years ago for LCIS and estimates that she wears a bra with prosthesis or socks a couple times per year. I generally care less about what people think about how I dress than she does. ) Who to tell and how? I am considering sending out a mass email at work. There are 10 or so nurses, several administrators, and 10 or so docs that I am close enough with to definitely tell, and will be talking about it( maybe once or twice?:J) in front of many others, as my main social interactions with these folks are on the wards during rounds. Knowing that some will consider a mass email weird. Knowing that my absence for 3 weeks will definitely be missed, and after, the absence of my breasts will definitely be noticed.
Also considering letting myself be a news story in the local paper. Has anyone done that? It just seems so random and senseless, that the teacher in me wants to find some meaning. This all makes DSO very nervous.
Good things about the challenge of being BRCA1 positive
1. Way better than having cancer.
2. Life lessons
3. No way for my uncles and cousins to ignore the potential impact of our family genetic issue.
4. Get to be a real live amazon.
5. Don't have to worry of mom's LCIS makes me at higher risk.
6. Good reason to reach out to old friends and make new friends.
7. Excellent reason to re-prioritize my life.
8. Head start on the new weight loss program.
9. Learning what it is like to be a patient.
Bad things about having ghe challenge of being BRCA1 positive
1. Surgeries
2. Funny looks from people who think I am being radical
3. Worry about getting cancer before I am done reducing my risk. (and after, I guess)
4. Stress for me, co-workers, family, DSO etc.
5. Time off work, away from golf, etc.
6. Having to be a patient.
That is enough for now.
Tuesday, February 27, 2007
BRCA1 and BRCA2 gene mutations - Genetics
****Caveat: I am just a physiatrist,(PMR doctor) not a genetics specialist. But... suddenly very interested in genetics. ****
This is an edited copy of some explanations about BRCA gene mutations from the FORCE site.
BRCA1 is actually a breast and ovarian cancer preventative gene, on the 17th chromosome, which when certain mutations - abnormalities that interfere with proper gene function - occur, then the person carrying it is at high risk of developing one or both cancers.
Each person carries 2 - 17th chromosomes one from their mother's egg and one from their fathers sperm. As a person's body produces each egg and each sperm half receives one or the other chromosome. Usually a person would have one normal and one mutated gene. ( I guess most people not surfing this web site have 2 normal copies. ) So, the 50/50 chance that the offspring will get the defective gene or the normal gene, at the time of conception. The HBOC (hereditary breast and ovarian cancer syndrome) is an autosomal dominant inheritance situation, so having one defective (not sure that sounds any better than mutant) gene is necessary to cause all of the cancer risk associated with the syndrome.
(Autosomal means on a non sex linked chromosome, so you can get it from mom or dad. Dominant means that you only need on copy of the gene to have the effect)
As a carrier of a BRCA1 mutation, your daughter or son has a 50% theoretical chance of getting or not getting the gene, decided at conception, assuming her dad does not also carry a gene mutation(and that you have one normal BRCA1 gene). Nieces are only at risk if their related parent is positive for the BRCA1 gene mutation, 50 % chance, so testing of the related parent is the first step in determining their risk.
As far as manifestation of the gene mutation, this term is called penetrance, and the studies show that there is a very high penetrance, meaning high likelihood that the presence of the mutation will raise risk for causing a cancer. (this is more complicated that in normal genetics, as the mutation only interferes with body’s ability to heal cellular mutations that can cause cancer, so some carriers will never get cancer.
So the only loophole is that statistically only half the offspring should get it. Unfortunately for many of the families listed here, the stats don't always hold. In my family, for instance, I have 2 sisters, with Dad being positive for a BRCA1 mutation. So... I have a 50% chance of testing positive, and each of my sisters have a 50% chance. And that means only a 12.5% chance that all three of us are negative, and a 12.5% chance that all three of us are negative. There are a bunch of different mutations, and appear to act a little differently, so I am not confident that my avoidance of BC or OVCA until age 43, is any indicator of what my results might be.
Everything about applies equally to the BRCA2 mutations, except that it is carried on the 13th chromosome. BRCA2 mutations cause breast cancer in men, and the cancer rates for women are somewhat different.
Response to question about penetrance and risk:
You raise a very good question, and point out interesting issues about BRCA and hereditary breast and ovca(ovarian cancer) statistics. It would be wonderful if your hypothesis(that the same mutation carries lower risk in families without high incidence of cancer) was true, but it is not, as far as my reading indicates. Below is a long winded explanation.
****Keep in mind that this is a very complex syndrome with a lot of variables, so not everything applies to every person finding this message board.****
*****I will be going to a genetics counselor whether or not my test is positive, to have someone professional re-assess my specific situation.*****
What we know about genetics comes initially from observing non - pathologic traits, over several generations, by observation. Mendel studied peas, human geneticists studied eye color, hair color, whether you can roll your tongue, whether you can taste sour things, blood type etc. In these areas, penetrance is very high, and it is easy to see how the genes behave because you can look at them and see that if mom has blue eyes and dad has brown eyes, that if all of the kids have brown eyes, that brown eye genes are dominant over blue eye genes, then in the next generation if the brown eyed kids marry brown eyed kids with the same heritage, that 1/4 will have blue eyes, because all the kids from the first generation got one blue from mom and one brown from dad. (this example assumes that dad is brown/brown - 2 copies the same)
Moving in to medical genetics, there are well studied genes autosomal genes in some diseases where the severity of the symptoms vary. (certain types of muscular dystrophy) This is a low penetrance type genetic flaw, meaning that someone can have the gene mutation, but not get the disease, or a very mild case of the disease. (I like flaw) Other genetic disorders are autosomal dominant like Huntington's disease which has a high penetrance, meaning if your Dad shows symptoms of Huntington's in his 40s and 50s, you have to decide to get tested and if your test is positive you know that you will face the same fate. This is a high penetrance gene, meaning that everyone with the gene gets the disease equally as severe.
(Autosomal means on a non sex linked chromosome, so you can get it from mom or dad.)
The studies on breast cancer heredity and ovarian cancer heredity started by looking at families where many members of many generations had breast or ovarian CA. The statistical studies showed that it acted like a high penetrance autosomal dominant gene. The DNA studies in these families allowed scientists to start finding the BRCA1 and BRCA2 gene mutations. It is a bit harder to make inferences about exactly how the heredity works with regard to penetrance because the mutations don't cause cancer, just impair one's ability to fight the cell level mutations that happen all the time. So there is a baseline rate of breast CA that everyone is at risk for and the heightened rate that gene mutation carriers have. The crux of the penetrance issue is whether everyone with a gene mutation is at the same high risk as everyone else or not.
That gets to penetrance.
This is where I stopped learning about this stuff in school and from my research about my mom. As the gene was identified, the hope was that there was a variable penetrance to the gene mutations, meaning that the folks with the families where lots of people got cancer had the same mutation of unsuspecting people out in the world, but that their mutation caused worse problems for some reason. I was really hanging my hat on this possibility.
So, the scientists went back to the same type of families and studied whether they had mutations, and when they studied other people who had the mutations, but did not have the same family history. Unfortunately, they found that the people in the previously known high risk families where there were known mutations were the ones getting cancer, and the ones who did not, did not have the genes. (50% loophole) They also found that the people without previously known high risk families who had the gene mutations got cancer just like the high risk families(slightly lower percentages 75% BC risk vs. 85% BC risk for the high risk families).
Hence high penetrance and that loophole does not actually exist. The other thing that makes this all so complicated is that not all of the high risk families have BRCA1 or BRCA2 mutations that we know about, so we can assume that there are other genes somewhere that control hereditary breast and ovarian cancer syndromes, in addition to the fact that they are finding different mutations all the time, and that new mutations can crop up spontaneously. This is why a positive gene test is usually considered to make someone high risk, but a negative test is only useful in a known high risk family if the affected members of the previous generations test positive and you test negative. Sorry for the very long winded answer. Very complicated stuff.
Challenge from another site member, stolen verbatim 2/25/2007, 8:15 pm Great explanations, But I would also add, that as it says on this website, there is still debate about the penetrance rates for any individual because there are so many different mutations (literally hundreds) and it is likely that they do not all behave exactly alike. That is why you will find different risk rates quoted - different studies have shown different results. There are also probably other factors and maybe other genes that influence the penetrance in certain families. We really don't know enough yet to give any individual risk rates with great accuracy. Even in what appear to be the highest risk families there are individuals who are known to carry the gene and have never had cancer.
I argued long and hard about some of this with my geneticist (she is a colleague and friend - so that helps) who was trying to convince me that my risk was in fact lower than what I imagined - she was quoting standard BRCA2 risks from the most recent community based studies which are significantly lower than the original risks that were devised from studies on only very high risk (high penetrance) families. I was using my family as a guide (virtually no woman has survived it yet in my family). I agreed with her explanations but could not accept them for me. In the end I decided that really no geneticist was able to accurately tell me my risk at this point in time and whatever my risk is, it is high enough that my decisions would be the same whether my penetrance was 45% or 85%. Understanding these risks is not an easy or straightforward matter. Worth going over again with geneticists or genetic counselors - several times if you need to!
My response 2/25/2007, 10:48 pm
I agree completely. Despite strong motivation, I could not find enough specific to the mutation my family carries to make me feel confident of exactly where my risk lies. Reading the site, I can hear several types of stories, from women with the same classes of mutations. There is much more research to do. Hopefully, as all of the women on the Force web site(and others getting tested and taking action) are taking our futures into our hands, we will change the shape of this syndrome. (unfortunately making it even harder to study.)
This is an edited copy of some explanations about BRCA gene mutations from the FORCE site.
BRCA1 is actually a breast and ovarian cancer preventative gene, on the 17th chromosome, which when certain mutations - abnormalities that interfere with proper gene function - occur, then the person carrying it is at high risk of developing one or both cancers.
Each person carries 2 - 17th chromosomes one from their mother's egg and one from their fathers sperm. As a person's body produces each egg and each sperm half receives one or the other chromosome. Usually a person would have one normal and one mutated gene. ( I guess most people not surfing this web site have 2 normal copies. ) So, the 50/50 chance that the offspring will get the defective gene or the normal gene, at the time of conception. The HBOC (hereditary breast and ovarian cancer syndrome) is an autosomal dominant inheritance situation, so having one defective (not sure that sounds any better than mutant) gene is necessary to cause all of the cancer risk associated with the syndrome.
(Autosomal means on a non sex linked chromosome, so you can get it from mom or dad. Dominant means that you only need on copy of the gene to have the effect)
As a carrier of a BRCA1 mutation, your daughter or son has a 50% theoretical chance of getting or not getting the gene, decided at conception, assuming her dad does not also carry a gene mutation(and that you have one normal BRCA1 gene). Nieces are only at risk if their related parent is positive for the BRCA1 gene mutation, 50 % chance, so testing of the related parent is the first step in determining their risk.
As far as manifestation of the gene mutation, this term is called penetrance, and the studies show that there is a very high penetrance, meaning high likelihood that the presence of the mutation will raise risk for causing a cancer. (this is more complicated that in normal genetics, as the mutation only interferes with body’s ability to heal cellular mutations that can cause cancer, so some carriers will never get cancer.
So the only loophole is that statistically only half the offspring should get it. Unfortunately for many of the families listed here, the stats don't always hold. In my family, for instance, I have 2 sisters, with Dad being positive for a BRCA1 mutation. So... I have a 50% chance of testing positive, and each of my sisters have a 50% chance. And that means only a 12.5% chance that all three of us are negative, and a 12.5% chance that all three of us are negative. There are a bunch of different mutations, and appear to act a little differently, so I am not confident that my avoidance of BC or OVCA until age 43, is any indicator of what my results might be.
Everything about applies equally to the BRCA2 mutations, except that it is carried on the 13th chromosome. BRCA2 mutations cause breast cancer in men, and the cancer rates for women are somewhat different.
Response to question about penetrance and risk:
You raise a very good question, and point out interesting issues about BRCA and hereditary breast and ovca(ovarian cancer) statistics. It would be wonderful if your hypothesis(that the same mutation carries lower risk in families without high incidence of cancer) was true, but it is not, as far as my reading indicates. Below is a long winded explanation.
****Keep in mind that this is a very complex syndrome with a lot of variables, so not everything applies to every person finding this message board.****
*****I will be going to a genetics counselor whether or not my test is positive, to have someone professional re-assess my specific situation.*****
What we know about genetics comes initially from observing non - pathologic traits, over several generations, by observation. Mendel studied peas, human geneticists studied eye color, hair color, whether you can roll your tongue, whether you can taste sour things, blood type etc. In these areas, penetrance is very high, and it is easy to see how the genes behave because you can look at them and see that if mom has blue eyes and dad has brown eyes, that if all of the kids have brown eyes, that brown eye genes are dominant over blue eye genes, then in the next generation if the brown eyed kids marry brown eyed kids with the same heritage, that 1/4 will have blue eyes, because all the kids from the first generation got one blue from mom and one brown from dad. (this example assumes that dad is brown/brown - 2 copies the same)
Moving in to medical genetics, there are well studied genes autosomal genes in some diseases where the severity of the symptoms vary. (certain types of muscular dystrophy) This is a low penetrance type genetic flaw, meaning that someone can have the gene mutation, but not get the disease, or a very mild case of the disease. (I like flaw) Other genetic disorders are autosomal dominant like Huntington's disease which has a high penetrance, meaning if your Dad shows symptoms of Huntington's in his 40s and 50s, you have to decide to get tested and if your test is positive you know that you will face the same fate. This is a high penetrance gene, meaning that everyone with the gene gets the disease equally as severe.
(Autosomal means on a non sex linked chromosome, so you can get it from mom or dad.)
The studies on breast cancer heredity and ovarian cancer heredity started by looking at families where many members of many generations had breast or ovarian CA. The statistical studies showed that it acted like a high penetrance autosomal dominant gene. The DNA studies in these families allowed scientists to start finding the BRCA1 and BRCA2 gene mutations. It is a bit harder to make inferences about exactly how the heredity works with regard to penetrance because the mutations don't cause cancer, just impair one's ability to fight the cell level mutations that happen all the time. So there is a baseline rate of breast CA that everyone is at risk for and the heightened rate that gene mutation carriers have. The crux of the penetrance issue is whether everyone with a gene mutation is at the same high risk as everyone else or not.
That gets to penetrance.
This is where I stopped learning about this stuff in school and from my research about my mom. As the gene was identified, the hope was that there was a variable penetrance to the gene mutations, meaning that the folks with the families where lots of people got cancer had the same mutation of unsuspecting people out in the world, but that their mutation caused worse problems for some reason. I was really hanging my hat on this possibility.
So, the scientists went back to the same type of families and studied whether they had mutations, and when they studied other people who had the mutations, but did not have the same family history. Unfortunately, they found that the people in the previously known high risk families where there were known mutations were the ones getting cancer, and the ones who did not, did not have the genes. (50% loophole) They also found that the people without previously known high risk families who had the gene mutations got cancer just like the high risk families(slightly lower percentages 75% BC risk vs. 85% BC risk for the high risk families).
Hence high penetrance and that loophole does not actually exist. The other thing that makes this all so complicated is that not all of the high risk families have BRCA1 or BRCA2 mutations that we know about, so we can assume that there are other genes somewhere that control hereditary breast and ovarian cancer syndromes, in addition to the fact that they are finding different mutations all the time, and that new mutations can crop up spontaneously. This is why a positive gene test is usually considered to make someone high risk, but a negative test is only useful in a known high risk family if the affected members of the previous generations test positive and you test negative. Sorry for the very long winded answer. Very complicated stuff.
Challenge from another site member, stolen verbatim 2/25/2007, 8:15 pm Great explanations, But I would also add, that as it says on this website, there is still debate about the penetrance rates for any individual because there are so many different mutations (literally hundreds) and it is likely that they do not all behave exactly alike. That is why you will find different risk rates quoted - different studies have shown different results. There are also probably other factors and maybe other genes that influence the penetrance in certain families. We really don't know enough yet to give any individual risk rates with great accuracy. Even in what appear to be the highest risk families there are individuals who are known to carry the gene and have never had cancer.
I argued long and hard about some of this with my geneticist (she is a colleague and friend - so that helps) who was trying to convince me that my risk was in fact lower than what I imagined - she was quoting standard BRCA2 risks from the most recent community based studies which are significantly lower than the original risks that were devised from studies on only very high risk (high penetrance) families. I was using my family as a guide (virtually no woman has survived it yet in my family). I agreed with her explanations but could not accept them for me. In the end I decided that really no geneticist was able to accurately tell me my risk at this point in time and whatever my risk is, it is high enough that my decisions would be the same whether my penetrance was 45% or 85%. Understanding these risks is not an easy or straightforward matter. Worth going over again with geneticists or genetic counselors - several times if you need to!
My response 2/25/2007, 10:48 pm
I agree completely. Despite strong motivation, I could not find enough specific to the mutation my family carries to make me feel confident of exactly where my risk lies. Reading the site, I can hear several types of stories, from women with the same classes of mutations. There is much more research to do. Hopefully, as all of the women on the Force web site(and others getting tested and taking action) are taking our futures into our hands, we will change the shape of this syndrome. (unfortunately making it even harder to study.)
Sunday, February 18, 2007
Force - Facing our Risk
Finally, I found a site devoted to people at risk for hereditary breast or ovarian cancer.
FORCE - Facing Our Risk Cancer Empowered.
http://www.facingourrisk.org/index.php
Women on that site are grappling with choices about what to do if BRCA gene mutation positive and talking about their progress through oophorectomies and prophylactic bilateral mastectomies.
I am trying not to beat myself up too much about being obsessed by the whole subject.
Reasonable for me to be more into this whole subject than I was in December about reading, thinking and quoting Eragon, and The End of the Spear.
Brainstorm as I lay awake at 5 AM. How many families like mine will never get a warning, because we only had one relative with breast cancer at age 40. How to get people thinking about the percentage of susceptible people with early breast or ovarian cancer.
And the link and date of the article from Dr. Len's Cancer Blog about limitations of genetic testing for hereditary breast cancer is: Posted 3/21/06
http://www.cancer.org/aspx/blog/Comments.aspx?id=62
And, I guess I better warn more relatives about this site, as I actually found it on the search blog search engine today.
FORCE - Facing Our Risk Cancer Empowered.
http://www.facingourrisk.org/index.php
Women on that site are grappling with choices about what to do if BRCA gene mutation positive and talking about their progress through oophorectomies and prophylactic bilateral mastectomies.
I am trying not to beat myself up too much about being obsessed by the whole subject.
Reasonable for me to be more into this whole subject than I was in December about reading, thinking and quoting Eragon, and The End of the Spear.
Brainstorm as I lay awake at 5 AM. How many families like mine will never get a warning, because we only had one relative with breast cancer at age 40. How to get people thinking about the percentage of susceptible people with early breast or ovarian cancer.
And the link and date of the article from Dr. Len's Cancer Blog about limitations of genetic testing for hereditary breast cancer is: Posted 3/21/06
http://www.cancer.org/aspx/blog/Comments.aspx?id=62
And, I guess I better warn more relatives about this site, as I actually found it on the search blog search engine today.
Saturday, February 17, 2007
Damn lies and statistics
I am borrowing a quote that Stephen Jay Gould borrowed from Mark Twain, who attributed it to Disraeli.
Thinking about statistics does get rather complicated, especially when medical issues and health are concerned. I am sure that delving into it will reveal me for the geek that I am.
Hereditary statistics - theoretical probability of having a gene or mutation. In actuality, ones genes are set at conception. (Parents do not have any control over which ones they pass on.) The probability indicates the likelihood of finding presence of a specific gene or mutation once we get around to looking. With the BRCA1 mutation in our family, in January of last year, my chances of having a mutation of that gene were 17.4 %. (8.7 x 2 one relative on each side of the family) In March they went up to 25%. (50% chance that Dad would have it x 50% that he would pass it to me if he did) This month, the chances are up to 50% now that we know he carries the gene. In three weeks, the probability will be either 0 pr 100%. And in actuality, I either have the mutation or not, since 1963.
BRCA mutation + carrier statistics - at least these numbers are real. Assuming adequate surveillance to ensure that she does not already have cancer, a female carrier has ~56-87% risk of developing breast cancer by age 70 and a 27-44% (or higher) risk of developing ovarian cancer by age 70. The deleterious mutations interfere with the body's cancer preventing mechanisms and predisposes the carrier to cancer. Of course, the kicker here is that the actual risk conferred by each different mutation differs, and other factors such as actual family history of which type of cancer at which age also change the actual risk of the carrier. BRCA1 gene mutations confer high risk of both breast and ovarian cancer to women. BRCA2 gene mutations confer high risk of breast cancer not as high of risk of ovarian cancer for women, but also carry high risk of breast cancer and some other cancers in men.
Risk reduction statistics - these get a little more amorphous, in light of the wide range of reported risks as above. The question then becomes whether a 40-50 % reduction of a 56-87 %risk is good enough or not for tamoxifen. Probably not.
Cancer survival and treatment statistics are a whole other story. Survival rates are stratified by each subtype of cancer and the stage of the cancer at time of diagnosis. Looking at overall statistics for breast cancer the survival rate is 80% at five years. For ovarian cancer the survival rate is 50% at 5 years.
Below is a copy of Steven Gould's article about using cancer statistics because I think it is important for everyone to have his insight about avoiding despair and planning strategies to keep oneself on the best side of the probabilities for a particular situation.
I ran across this article while researching kidney cancer for my friend, Jo. She has been defying statistics for the past 17 months since her diagnosis of metastatic kidney cancer in September of 2005.
http://cancerguide.org/median_not_msg.html
-----------------------------------------------------------------------------
The Median Isn't the Message
Prefatory Note by Steve Dunn
Stephen Jay Gould was an influential evolutionary biologist who taught at Harvard University. He was the author of at least ten popular books on evolution, and science, including, among others, The Flamingo's Smile, The Mismeasure of Man, Wonderful Life, and Full House.
As far as I'm concerned, Gould's The Median Isn't the Message is the wisest, most humane thing ever written about cancer and statistics. It is the antidote both to those who say that, "the statistics don't matter," and to those who have the unfortunate habit of pronouncing death sentences on patients who face a difficult prognosis. Anyone who researches the medical literature will confront the statistics for their disease. Anyone who reads this will be armed with reason and with hope.
------------------------------------------------------------------
The Median Isn't the Message by Stephen Jay Gould
My life has recently intersected, in a most personal way, two of Mark Twain's famous quips. One I shall defer to the end of this essay. The other (sometimes attributed to Disraeli), identifies three species of mendacity, each worse than the one before - lies, damned lies, and statistics.
Consider the standard example of stretching the truth with numbers - a case quite relevant to my story. Statistics recognizes different measures of an "average," or central tendency. The mean is our usual concept of an overall average - add up the items and divide them by the number of sharers (100 candy bars collected for five kids next Halloween will yield 20 for each in a just world). The median, a different measure of central tendency, is the half-way point. If I line up five kids by height, the median child is shorter than two and taller than the other two (who might have trouble getting their mean share of the candy). A politician in power might say with pride, "The mean income of our citizens is $15,000 per year." The leader of the opposition might retort, "But half our citizens make less than $10,000 per year." Both are right, but neither cites a statistic with impassive objectivity. The first invokes a mean, the second a median. (Means are higher than medians in such cases because one millionaire may outweigh hundreds of poor people in setting a mean; but he can balance only one mendicant in calculating a median).
The larger issue that creates a common distrust or contempt for statistics is more troubling. Many people make an unfortunate and invalid separation between heart and mind, or feeling and intellect. In some contemporary traditions, abetted by attitudes stereotypically centered on Southern California, feelings are exalted as more "real" and the only proper basis for action - if it feels good, do it - while intellect gets short shrift as a hang-up of outmoded elitism. Statistics, in this absurd dichotomy, often become the symbol of the enemy. As Hilaire Belloc wrote, "Statistics are the triumph of the quantitative method, and the quantitative method is the victory of sterility and death."
This is a personal story of statistics, properly interpreted, as profoundly nurturant and life-giving. It declares holy war on the downgrading of intellect by telling a small story about the utility of dry, academic knowledge about science. Heart and head are focal points of one body, one personality.
In July 1982, I learned that I was suffering from abdominal mesothelioma, a rare and serious cancer usually associated with exposure to asbestos. When I revived after surgery, I asked my first question of my doctor and chemotherapist: "What is the best technical literature about mesothelioma?" She replied, with a touch of diplomacy (the only departure she has ever made from direct frankness), that the medical literature contained nothing really worth reading.
Of course, trying to keep an intellectual away from literature works about as well as recommending chastity to Homo sapiens, the sexiest primate of all. As soon as I could walk, I made a beeline for Harvard's Countway medical library and punched mesothelioma into the computer's bibliographic search program. An hour later, surrounded by the latest literature on abdominal mesothelioma, I realized with a gulp why my doctor had offered that humane advice. The literature couldn't have been more brutally clear: mesothelioma is incurable, with a median mortality of only eight months after discovery. I sat stunned for about fifteen minutes, then smiled and said to myself: so that's why they didn't give me anything to read. Then my mind started to work again, thank goodness.
If a little learning could ever be a dangerous thing, I had encountered a classic example. Attitude clearly matters in fighting cancer. We don't know why (from my old-style materialistic perspective, I suspect that mental states feed back upon the immune system). But match people with the same cancer for age, class, health, socioeconomic status, and, in general, those with positive attitudes, with a strong will and purpose for living, with commitment to struggle, with an active response to aiding their own treatment and not just a passive acceptance of anything doctors say, tend to live longer. A few months later I asked Sir Peter Medawar, my personal scientific guru and a Nobelist in immunology, what the best prescription for success against cancer might be. "A sanguine personality," he replied. Fortunately (since one can't reconstruct oneself at short notice and for a definite purpose), I am, if anything, even-tempered and confident in just this manner.
Hence the dilemma for humane doctors: since attitude matters so critically, should such a sombre conclusion be advertised, especially since few people have sufficient understanding of statistics to evaluate what the statements really mean? From years of experience with the small-scale evolution of Bahamian land snails treated quantitatively, I have developed this technical knowledge - and I am convinced that it played a major role in saving my life. Knowledge is indeed power, in Bacon's proverb.
The problem may be briefly stated: What does "median mortality of eight months" signify in our vernacular? I suspect that most people, without training in statistics, would read such a statement as "I will probably be dead in eight months" - the very conclusion that must be avoided, since it isn't so, and since attitude matters so much.
I was not, of course, overjoyed, but I didn't read the statement in this vernacular way either. My technical training enjoined a different perspective on "eight months median mortality." The point is a subtle one, but profound - for it embodies the distinctive way of thinking in my own field of evolutionary biology and natural history.
We still carry the historical baggage of a Platonic heritage that seeks sharp essences and definite boundaries. (Thus we hope to find an unambiguous "beginning of life" or "definition of death," although nature often comes to us as irreducible continua.) This Platonic heritage, with its emphasis in clear distinctions and separated immutable entities, leads us to view statistical measures of central tendency wrongly, indeed opposite to the appropriate interpretation in our actual world of variation, shadings, and continua. In short, we view means and medians as the hard "realities," and the variation that permits their calculation as a set of transient and imperfect measurements of this hidden essence. If the median is the reality and variation around the median just a device for its calculation, the "I will probably be dead in eight months" may pass as a reasonable interpretation.
But all evolutionary biologists know that variation itself is nature's only irreducible essence. Variation is the hard reality, not a set of imperfect measures for a central tendency. Means and medians are the abstractions. Therefore, I looked at the mesothelioma statistics quite differently - and not only because I am an optimist who tends to see the doughnut instead of the hole, but primarily because I know that variation itself is the reality. I had to place myself amidst the variation.
When I learned about the eight-month median, my first intellectual reaction was: fine, half the people will live longer; now what are my chances of being in that half. I read for a furious and nervous hour and concluded, with relief: damned good. I possessed every one of the characteristics conferring a probability of longer life: I was young; my disease had been recognized in a relatively early stage; I would receive the nation's best medical treatment; I had the world to live for; I knew how to read the data properly and not despair.
Another technical point then added even more solace. I immediately recognized that the distribution of variation about the eight-month median would almost surely be what statisticians call "right skewed." (In a symmetrical distribution, the profile of variation to the left of the central tendency is a mirror image of variation to the right. In skewed distributions, variation to one side of the central tendency is more stretched out - left skewed if extended to the left, right skewed if stretched out to the right.) The distribution of variation had to be right skewed, I reasoned. After all, the left of the distribution contains an irrevocable lower boundary of zero (since mesothelioma can only be identified at death or before). Thus, there isn't much room for the distribution's lower (or left) half - it must be scrunched up between zero and eight months. But the upper (or right) half can extend out for years and years, even if nobody ultimately survives. The distribution must be right skewed, and I needed to know how long the extended tail ran - for I had already concluded that my favorable profile made me a good candidate for that part of the curve.
The distribution was indeed, strongly right skewed, with a long tail (however small) that extended for several years above the eight month median. I saw no reason why I shouldn't be in that small tail, and I breathed a very long sigh of relief. My technical knowledge had helped. I had read the graph correctly. I had asked the right question and found the answers. I had obtained, in all probability, the most precious of all possible gifts in the circumstances - substantial time. I didn't have to stop and immediately follow Isaiah's injunction to Hezekiah - set thine house in order for thou shalt die, and not live. I would have time to think, to plan, and to fight.
One final point about statistical distributions. They apply only to a prescribed set of circumstances - in this case to survival with mesothelioma under conventional modes of treatment. If circumstances change, the distribution may alter. I was placed on an experimental protocol of treatment and, if fortune holds, will be in the first cohort of a new distribution with high median and a right tail extending to death by natural causes at advanced old age.
It has become, in my view, a bit too trendy to regard the acceptance of death as something tantamount to intrinsic dignity. Of course I agree with the preacher of Ecclesiastes that there is a time to love and a time to die - and when my skein runs out I hope to face the end calmly and in my own way. For most situations, however, I prefer the more martial view that death is the ultimate enemy - and I find nothing reproachable in those who rage mightily against the dying of the light.
The swords of battle are numerous, and none more effective than humor. My death was announced at a meeting of my colleagues in Scotland, and I almost experienced the delicious pleasure of reading my obituary penned by one of my best friends (the so-and-so got suspicious and checked; he too is a statistician, and didn't expect to find me so far out on the right tail). Still, the incident provided my first good laugh after the diagnosis. Just think, I almost got to repeat Mark Twain's most famous line of all: the reports of my death are greatly exaggerated.
------------------------------------------------------------------------------------------
Postscript By Steve Dunn
Many people have written me to ask what became of Stephen Jay Gould. Sadly, Dr. Gould died in May of 2002 at the age of 60. Dr. Gould lived for 20 very productive years after his diagnosis, thus exceeding his 8 month median survival by a factor of thirty! Although he did die of cancer, it apparently wasn't mesothelioma, but a second and unrelated cancer.
In March 2002, Dr. Gould published his 1342 page "Magnum Opus", The Structure of Evolutionary Theory. It is fitting that Gould, one of the world's most prolific scientists and writers, was able to complete the definitive statement of his scientific work and philosophy just in time. That text is far too long and dense for almost any layman - but the works of Stephen Jay Gould will live on. Especially I hope, The Median Isn't The Message .
Thinking about statistics does get rather complicated, especially when medical issues and health are concerned. I am sure that delving into it will reveal me for the geek that I am.
Hereditary statistics - theoretical probability of having a gene or mutation. In actuality, ones genes are set at conception. (Parents do not have any control over which ones they pass on.) The probability indicates the likelihood of finding presence of a specific gene or mutation once we get around to looking. With the BRCA1 mutation in our family, in January of last year, my chances of having a mutation of that gene were 17.4 %. (8.7 x 2 one relative on each side of the family) In March they went up to 25%. (50% chance that Dad would have it x 50% that he would pass it to me if he did) This month, the chances are up to 50% now that we know he carries the gene. In three weeks, the probability will be either 0 pr 100%. And in actuality, I either have the mutation or not, since 1963.
BRCA mutation + carrier statistics - at least these numbers are real. Assuming adequate surveillance to ensure that she does not already have cancer, a female carrier has ~56-87% risk of developing breast cancer by age 70 and a 27-44% (or higher) risk of developing ovarian cancer by age 70. The deleterious mutations interfere with the body's cancer preventing mechanisms and predisposes the carrier to cancer. Of course, the kicker here is that the actual risk conferred by each different mutation differs, and other factors such as actual family history of which type of cancer at which age also change the actual risk of the carrier. BRCA1 gene mutations confer high risk of both breast and ovarian cancer to women. BRCA2 gene mutations confer high risk of breast cancer not as high of risk of ovarian cancer for women, but also carry high risk of breast cancer and some other cancers in men.
Risk reduction statistics - these get a little more amorphous, in light of the wide range of reported risks as above. The question then becomes whether a 40-50 % reduction of a 56-87 %risk is good enough or not for tamoxifen. Probably not.
Cancer survival and treatment statistics are a whole other story. Survival rates are stratified by each subtype of cancer and the stage of the cancer at time of diagnosis. Looking at overall statistics for breast cancer the survival rate is 80% at five years. For ovarian cancer the survival rate is 50% at 5 years.
Below is a copy of Steven Gould's article about using cancer statistics because I think it is important for everyone to have his insight about avoiding despair and planning strategies to keep oneself on the best side of the probabilities for a particular situation.
I ran across this article while researching kidney cancer for my friend, Jo. She has been defying statistics for the past 17 months since her diagnosis of metastatic kidney cancer in September of 2005.
http://cancerguide.org/median_not_msg.html
-----------------------------------------------------------------------------
The Median Isn't the Message
Prefatory Note by Steve Dunn
Stephen Jay Gould was an influential evolutionary biologist who taught at Harvard University. He was the author of at least ten popular books on evolution, and science, including, among others, The Flamingo's Smile, The Mismeasure of Man, Wonderful Life, and Full House.
As far as I'm concerned, Gould's The Median Isn't the Message is the wisest, most humane thing ever written about cancer and statistics. It is the antidote both to those who say that, "the statistics don't matter," and to those who have the unfortunate habit of pronouncing death sentences on patients who face a difficult prognosis. Anyone who researches the medical literature will confront the statistics for their disease. Anyone who reads this will be armed with reason and with hope.
------------------------------------------------------------------
The Median Isn't the Message by Stephen Jay Gould
My life has recently intersected, in a most personal way, two of Mark Twain's famous quips. One I shall defer to the end of this essay. The other (sometimes attributed to Disraeli), identifies three species of mendacity, each worse than the one before - lies, damned lies, and statistics.
Consider the standard example of stretching the truth with numbers - a case quite relevant to my story. Statistics recognizes different measures of an "average," or central tendency. The mean is our usual concept of an overall average - add up the items and divide them by the number of sharers (100 candy bars collected for five kids next Halloween will yield 20 for each in a just world). The median, a different measure of central tendency, is the half-way point. If I line up five kids by height, the median child is shorter than two and taller than the other two (who might have trouble getting their mean share of the candy). A politician in power might say with pride, "The mean income of our citizens is $15,000 per year." The leader of the opposition might retort, "But half our citizens make less than $10,000 per year." Both are right, but neither cites a statistic with impassive objectivity. The first invokes a mean, the second a median. (Means are higher than medians in such cases because one millionaire may outweigh hundreds of poor people in setting a mean; but he can balance only one mendicant in calculating a median).
The larger issue that creates a common distrust or contempt for statistics is more troubling. Many people make an unfortunate and invalid separation between heart and mind, or feeling and intellect. In some contemporary traditions, abetted by attitudes stereotypically centered on Southern California, feelings are exalted as more "real" and the only proper basis for action - if it feels good, do it - while intellect gets short shrift as a hang-up of outmoded elitism. Statistics, in this absurd dichotomy, often become the symbol of the enemy. As Hilaire Belloc wrote, "Statistics are the triumph of the quantitative method, and the quantitative method is the victory of sterility and death."
This is a personal story of statistics, properly interpreted, as profoundly nurturant and life-giving. It declares holy war on the downgrading of intellect by telling a small story about the utility of dry, academic knowledge about science. Heart and head are focal points of one body, one personality.
In July 1982, I learned that I was suffering from abdominal mesothelioma, a rare and serious cancer usually associated with exposure to asbestos. When I revived after surgery, I asked my first question of my doctor and chemotherapist: "What is the best technical literature about mesothelioma?" She replied, with a touch of diplomacy (the only departure she has ever made from direct frankness), that the medical literature contained nothing really worth reading.
Of course, trying to keep an intellectual away from literature works about as well as recommending chastity to Homo sapiens, the sexiest primate of all. As soon as I could walk, I made a beeline for Harvard's Countway medical library and punched mesothelioma into the computer's bibliographic search program. An hour later, surrounded by the latest literature on abdominal mesothelioma, I realized with a gulp why my doctor had offered that humane advice. The literature couldn't have been more brutally clear: mesothelioma is incurable, with a median mortality of only eight months after discovery. I sat stunned for about fifteen minutes, then smiled and said to myself: so that's why they didn't give me anything to read. Then my mind started to work again, thank goodness.
If a little learning could ever be a dangerous thing, I had encountered a classic example. Attitude clearly matters in fighting cancer. We don't know why (from my old-style materialistic perspective, I suspect that mental states feed back upon the immune system). But match people with the same cancer for age, class, health, socioeconomic status, and, in general, those with positive attitudes, with a strong will and purpose for living, with commitment to struggle, with an active response to aiding their own treatment and not just a passive acceptance of anything doctors say, tend to live longer. A few months later I asked Sir Peter Medawar, my personal scientific guru and a Nobelist in immunology, what the best prescription for success against cancer might be. "A sanguine personality," he replied. Fortunately (since one can't reconstruct oneself at short notice and for a definite purpose), I am, if anything, even-tempered and confident in just this manner.
Hence the dilemma for humane doctors: since attitude matters so critically, should such a sombre conclusion be advertised, especially since few people have sufficient understanding of statistics to evaluate what the statements really mean? From years of experience with the small-scale evolution of Bahamian land snails treated quantitatively, I have developed this technical knowledge - and I am convinced that it played a major role in saving my life. Knowledge is indeed power, in Bacon's proverb.
The problem may be briefly stated: What does "median mortality of eight months" signify in our vernacular? I suspect that most people, without training in statistics, would read such a statement as "I will probably be dead in eight months" - the very conclusion that must be avoided, since it isn't so, and since attitude matters so much.
I was not, of course, overjoyed, but I didn't read the statement in this vernacular way either. My technical training enjoined a different perspective on "eight months median mortality." The point is a subtle one, but profound - for it embodies the distinctive way of thinking in my own field of evolutionary biology and natural history.
We still carry the historical baggage of a Platonic heritage that seeks sharp essences and definite boundaries. (Thus we hope to find an unambiguous "beginning of life" or "definition of death," although nature often comes to us as irreducible continua.) This Platonic heritage, with its emphasis in clear distinctions and separated immutable entities, leads us to view statistical measures of central tendency wrongly, indeed opposite to the appropriate interpretation in our actual world of variation, shadings, and continua. In short, we view means and medians as the hard "realities," and the variation that permits their calculation as a set of transient and imperfect measurements of this hidden essence. If the median is the reality and variation around the median just a device for its calculation, the "I will probably be dead in eight months" may pass as a reasonable interpretation.
But all evolutionary biologists know that variation itself is nature's only irreducible essence. Variation is the hard reality, not a set of imperfect measures for a central tendency. Means and medians are the abstractions. Therefore, I looked at the mesothelioma statistics quite differently - and not only because I am an optimist who tends to see the doughnut instead of the hole, but primarily because I know that variation itself is the reality. I had to place myself amidst the variation.
When I learned about the eight-month median, my first intellectual reaction was: fine, half the people will live longer; now what are my chances of being in that half. I read for a furious and nervous hour and concluded, with relief: damned good. I possessed every one of the characteristics conferring a probability of longer life: I was young; my disease had been recognized in a relatively early stage; I would receive the nation's best medical treatment; I had the world to live for; I knew how to read the data properly and not despair.
Another technical point then added even more solace. I immediately recognized that the distribution of variation about the eight-month median would almost surely be what statisticians call "right skewed." (In a symmetrical distribution, the profile of variation to the left of the central tendency is a mirror image of variation to the right. In skewed distributions, variation to one side of the central tendency is more stretched out - left skewed if extended to the left, right skewed if stretched out to the right.) The distribution of variation had to be right skewed, I reasoned. After all, the left of the distribution contains an irrevocable lower boundary of zero (since mesothelioma can only be identified at death or before). Thus, there isn't much room for the distribution's lower (or left) half - it must be scrunched up between zero and eight months. But the upper (or right) half can extend out for years and years, even if nobody ultimately survives. The distribution must be right skewed, and I needed to know how long the extended tail ran - for I had already concluded that my favorable profile made me a good candidate for that part of the curve.
The distribution was indeed, strongly right skewed, with a long tail (however small) that extended for several years above the eight month median. I saw no reason why I shouldn't be in that small tail, and I breathed a very long sigh of relief. My technical knowledge had helped. I had read the graph correctly. I had asked the right question and found the answers. I had obtained, in all probability, the most precious of all possible gifts in the circumstances - substantial time. I didn't have to stop and immediately follow Isaiah's injunction to Hezekiah - set thine house in order for thou shalt die, and not live. I would have time to think, to plan, and to fight.
One final point about statistical distributions. They apply only to a prescribed set of circumstances - in this case to survival with mesothelioma under conventional modes of treatment. If circumstances change, the distribution may alter. I was placed on an experimental protocol of treatment and, if fortune holds, will be in the first cohort of a new distribution with high median and a right tail extending to death by natural causes at advanced old age.
It has become, in my view, a bit too trendy to regard the acceptance of death as something tantamount to intrinsic dignity. Of course I agree with the preacher of Ecclesiastes that there is a time to love and a time to die - and when my skein runs out I hope to face the end calmly and in my own way. For most situations, however, I prefer the more martial view that death is the ultimate enemy - and I find nothing reproachable in those who rage mightily against the dying of the light.
The swords of battle are numerous, and none more effective than humor. My death was announced at a meeting of my colleagues in Scotland, and I almost experienced the delicious pleasure of reading my obituary penned by one of my best friends (the so-and-so got suspicious and checked; he too is a statistician, and didn't expect to find me so far out on the right tail). Still, the incident provided my first good laugh after the diagnosis. Just think, I almost got to repeat Mark Twain's most famous line of all: the reports of my death are greatly exaggerated.
------------------------------------------------------------------------------------------
Postscript By Steve Dunn
Many people have written me to ask what became of Stephen Jay Gould. Sadly, Dr. Gould died in May of 2002 at the age of 60. Dr. Gould lived for 20 very productive years after his diagnosis, thus exceeding his 8 month median survival by a factor of thirty! Although he did die of cancer, it apparently wasn't mesothelioma, but a second and unrelated cancer.
In March 2002, Dr. Gould published his 1342 page "Magnum Opus", The Structure of Evolutionary Theory. It is fitting that Gould, one of the world's most prolific scientists and writers, was able to complete the definitive statement of his scientific work and philosophy just in time. That text is far too long and dense for almost any layman - but the works of Stephen Jay Gould will live on. Especially I hope, The Median Isn't The Message .
Friday, February 16, 2007
Snow Genes
Well, I found a reason to use this blog. Right now I am passing time and trying not to get too far ahead of myself with concerns about the implications of my dad having one of the breast cancer gene mutations. I am surprised that I have not yet been able to stumble on a lot of personal information about other people going through this situation. Being a physician, I am able to get a good deal of information out of the scientific studies, but really want to read about someone else who is at this stage of life. Guess I will need to talk to my aunt and cousin. Two sisters have the same decisions to make but are busy with other more pressing situations right now.
We found out in March that Aunt Mary Ann has a BRCA 1 mutation. It was a little bit of a surprise, because, she is the only one in her extended family to have ever had breast cancer. She was young, about forty when she had her cancer, and did have a recurrence. Apparently, her daughter, Brenda, convinced her to get tested, out of concern for her three daughters.
It took 9 months to get Dad and Grandma tested, and Dad's test also came back positive.
I had always considered myself at high risk for breast cancer. Dr. Merrill is very diligent about pointing out my reasons each year when she offers me tamoxifen and sends me off to my mammograms.
1. I am a single woman who has never been pregnant and never been on birth control.
2. Mom also had breast cancer when she was 40. She had LCIS (lobular carcinoma in situ) which is not considered an invasive cancer, but carries risk of future cancer in each breast. In 1988, when she was seeking treatment, her options ranged from "do nothing, the cancer is already removed with the excisional biopsy" to "radiation therapy" to " bilateral mastectomies." Mom is a registered nurse, who has worked on an OB/GYN ward for years. She decided that she did not have time for radiation therapy and did not want to worry about having her cancer return. She opted for bilateral mastectomies and seems to have been very satisfied with her decision.
3. Aunt Mary Ann - dad's sister had breast cancer around age 40.
Now, I have found out that I have a 50% risk of having inherited a breast cancer gene mutation from my dad, who apparently inherited if from his father, who probably got it from his father. Aunt Mary Ann is the oldest female relative along this familial line. She has one sister, who is also waiting for her test results and then I am the oldest of 14 cousins, 7 of whom are women still at risk of inheriting the gene mutation. Brenda has already been tested and has not inherited the mutation. She now knows that she and her daughters are not at increased risk because of this mutation.
So, what is the big deal? Turns out that the breast cancer genes are dominant genes that carry a very high risk of the carrier getting breast cancer (up to 85% of getting breast cancer by age 70) and a very high risk of getting ovarian cancer (up to 45% by age 70.)
Here is an outline of the whole testing process.
1. Assess whether you have a high risk of having breast cancer gene.
a. relative with breast cancer before menopause
b. two or more blood relatives having breast cancer
c. relative with ovarian cancer
d. relative with the breast cancer gene mutation
2. Get the right person tested. Best to get the person with breast or ovarian cancer tested.
a. if they test positive for a known breast cancer gene mutation, then the rest of the family can get a more specific, cheaper test for that specific mutation.
b. if they test negative for a known breast cancer gene mutation, then it is possible that there may still be a risk of a hereditary breast cancer not associated with a known gene. Then it is hard to assess risk of other family members.
3. Visit a genetic counselor, to learn more about risks of testing - fear, discrimination etc, and the implications of a positive or negative test. Counselor will assist in getting the proper details from the relative's test results. The lab is very picky about informed consent and proper releases of information.
4. Get tested. Wait 2 - 3 weeks to get results from genetic counselor.
5. If test is negative after a relative's test is positive- breathe a sigh of relief, and then re-assess your risk and plan healthy strategies. Your risk for cancer should be near the baseline 7% unless other characteristics raise your risk, or you have another relative passing on a hereditary risk from another blood line.
6. If test is positive - breathe anyway. There should be plenty of time to figure out what to do.
As a doctor, I deviated from the rules in a number of ways. First, I was recruited to be the one getting Grandma and Dad's tests organized. Insurance hassles and paperwork hassles galore. And then I was in the awkward position of knowing Dad's positive results as his doctor, but not having permission to tell anyone as his daughter. He was on his first cruise ever, with Mom in Hawaii. Ten days later, I got to talk to him about it. Fortunately, the implications for a man are minimal for the BRCA1 gene mutation that runs in our family, other than passing it on to daughters. Grandma's test is negative, and her memory is impaired, so I can't explain much about it to her, but have started disseminating details to her other 2 sons.
Caveat regarding the status of the medical information on this page: I am a physician but my specialty is physical medicine and rehabilitation. I treat patients with back injuries, carpal tunnel syndrome, strokes, chronic pain and amputations. I peripherally deal with people who have had cancer in the past and at times with cancer patients who have also broken a hip or had a stroke. Please do consult a geneticist or breast cancer specialist to get the latest, most correct details.
I did have good intentions of having talking with my doctor, seeing a geneticist etc, but got impatient. Sent in my test after getting my doctor's signature via fax. I did have a telephone conversation with her and set up a gyn appointment with the new doc in town. Spoke to the local genetics counselor, who was quite concerned I was doing things out of order.
I have also been surfing the net considering my strategies if my test comes back positive.
Interesting findings from today's search. Different mutations apparently have different risks of cancer. And found information about why testing is not perfect. Search Dr. Len's Cancer Blog at www.cancer.org
So... Worrying about treatment options for the genetic defect that I might not have:
1. surveillance - extra mammograms, ultrasounds CA127 testing etc.
2. Tamoxifen - anti - estrogen drug that lowers breast cancer risk. May increase uterine cancer risk, and does not protect against ovarian cancer.
3. Oophorectomy - lowers both breast cancer risk by 50% and ovarian cancer risk by 95%
4. Oophorectomy and Mastectomy - lowers both by 90%
This info comes distilled from the Myriad website www.myriadtests.com/provider/hboc.com And appears to match what I have read from other sites and medical studies.
The mutation in our family BRCA1 C61G is apparently a Polish "founder" gene and carries high risk to women but little risk to men.
Good advice from Pam last night and Jo this morning, about trying to think about what is right for me, and trying not to worry too much about what other people will think. Not sure they expected me to respond by publishing my situation on a public blog site.
We found out in March that Aunt Mary Ann has a BRCA 1 mutation. It was a little bit of a surprise, because, she is the only one in her extended family to have ever had breast cancer. She was young, about forty when she had her cancer, and did have a recurrence. Apparently, her daughter, Brenda, convinced her to get tested, out of concern for her three daughters.
It took 9 months to get Dad and Grandma tested, and Dad's test also came back positive.
I had always considered myself at high risk for breast cancer. Dr. Merrill is very diligent about pointing out my reasons each year when she offers me tamoxifen and sends me off to my mammograms.
1. I am a single woman who has never been pregnant and never been on birth control.
2. Mom also had breast cancer when she was 40. She had LCIS (lobular carcinoma in situ) which is not considered an invasive cancer, but carries risk of future cancer in each breast. In 1988, when she was seeking treatment, her options ranged from "do nothing, the cancer is already removed with the excisional biopsy" to "radiation therapy" to " bilateral mastectomies." Mom is a registered nurse, who has worked on an OB/GYN ward for years. She decided that she did not have time for radiation therapy and did not want to worry about having her cancer return. She opted for bilateral mastectomies and seems to have been very satisfied with her decision.
3. Aunt Mary Ann - dad's sister had breast cancer around age 40.
Now, I have found out that I have a 50% risk of having inherited a breast cancer gene mutation from my dad, who apparently inherited if from his father, who probably got it from his father. Aunt Mary Ann is the oldest female relative along this familial line. She has one sister, who is also waiting for her test results and then I am the oldest of 14 cousins, 7 of whom are women still at risk of inheriting the gene mutation. Brenda has already been tested and has not inherited the mutation. She now knows that she and her daughters are not at increased risk because of this mutation.
So, what is the big deal? Turns out that the breast cancer genes are dominant genes that carry a very high risk of the carrier getting breast cancer (up to 85% of getting breast cancer by age 70) and a very high risk of getting ovarian cancer (up to 45% by age 70.)
Here is an outline of the whole testing process.
1. Assess whether you have a high risk of having breast cancer gene.
a. relative with breast cancer before menopause
b. two or more blood relatives having breast cancer
c. relative with ovarian cancer
d. relative with the breast cancer gene mutation
2. Get the right person tested. Best to get the person with breast or ovarian cancer tested.
a. if they test positive for a known breast cancer gene mutation, then the rest of the family can get a more specific, cheaper test for that specific mutation.
b. if they test negative for a known breast cancer gene mutation, then it is possible that there may still be a risk of a hereditary breast cancer not associated with a known gene. Then it is hard to assess risk of other family members.
3. Visit a genetic counselor, to learn more about risks of testing - fear, discrimination etc, and the implications of a positive or negative test. Counselor will assist in getting the proper details from the relative's test results. The lab is very picky about informed consent and proper releases of information.
4. Get tested. Wait 2 - 3 weeks to get results from genetic counselor.
5. If test is negative after a relative's test is positive- breathe a sigh of relief, and then re-assess your risk and plan healthy strategies. Your risk for cancer should be near the baseline 7% unless other characteristics raise your risk, or you have another relative passing on a hereditary risk from another blood line.
6. If test is positive - breathe anyway. There should be plenty of time to figure out what to do.
As a doctor, I deviated from the rules in a number of ways. First, I was recruited to be the one getting Grandma and Dad's tests organized. Insurance hassles and paperwork hassles galore. And then I was in the awkward position of knowing Dad's positive results as his doctor, but not having permission to tell anyone as his daughter. He was on his first cruise ever, with Mom in Hawaii. Ten days later, I got to talk to him about it. Fortunately, the implications for a man are minimal for the BRCA1 gene mutation that runs in our family, other than passing it on to daughters. Grandma's test is negative, and her memory is impaired, so I can't explain much about it to her, but have started disseminating details to her other 2 sons.
Caveat regarding the status of the medical information on this page: I am a physician but my specialty is physical medicine and rehabilitation. I treat patients with back injuries, carpal tunnel syndrome, strokes, chronic pain and amputations. I peripherally deal with people who have had cancer in the past and at times with cancer patients who have also broken a hip or had a stroke. Please do consult a geneticist or breast cancer specialist to get the latest, most correct details.
I did have good intentions of having talking with my doctor, seeing a geneticist etc, but got impatient. Sent in my test after getting my doctor's signature via fax. I did have a telephone conversation with her and set up a gyn appointment with the new doc in town. Spoke to the local genetics counselor, who was quite concerned I was doing things out of order.
I have also been surfing the net considering my strategies if my test comes back positive.
Interesting findings from today's search. Different mutations apparently have different risks of cancer. And found information about why testing is not perfect. Search Dr. Len's Cancer Blog at www.cancer.org
So... Worrying about treatment options for the genetic defect that I might not have:
1. surveillance - extra mammograms, ultrasounds CA127 testing etc.
2. Tamoxifen - anti - estrogen drug that lowers breast cancer risk. May increase uterine cancer risk, and does not protect against ovarian cancer.
3. Oophorectomy - lowers both breast cancer risk by 50% and ovarian cancer risk by 95%
4. Oophorectomy and Mastectomy - lowers both by 90%
This info comes distilled from the Myriad website www.myriadtests.com/provider/hboc.com And appears to match what I have read from other sites and medical studies.
The mutation in our family BRCA1 C61G is apparently a Polish "founder" gene and carries high risk to women but little risk to men.
Good advice from Pam last night and Jo this morning, about trying to think about what is right for me, and trying not to worry too much about what other people will think. Not sure they expected me to respond by publishing my situation on a public blog site.
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