Friday, February 18, 2011

Breast cancer after prophylactic mastectomy?

“You have breast cancer” are the last words any woman wants to hear. But women facing hereditary breast and ovarian cancer risk who opt for prophylactic mastectomies hope never to hear these words. Avoiding breast cancer is why these women take dramatic action to reduce risk. So when a new study comes out that may indicate that residual breast cancer risk is higher than previously thought, alarm bells start sounding in the high-risk community. The journal Clinical Genetics did publish such a study recently. This study, entitled Breast cancer after bilateral risk-reducing mastectomy is based on research out of Denmark involving 307 BRCA-positive women, 96 of whom chose to have prophylactic bilateral mastectomies to reduce their risk.

On one level, the study’s finding are concerning. Three of the 96 women developed breast cancer 2 years, 5 years, and 7 years after prophylactic mastectomy respectively. All of these women were BRCA1 positive and all of the cancers were triple negative. These numbers led the researchers to alarming conclusion that the breast cancer risk after preventive mastectomy for BRCA-positive women is roughly 10 percent, almost the same level of risk as the average risk women.

It is easy to panic when confronted with this conclusion but a closer look at the study, its assumptions, and other studies of breast cancer risk after prophylactic mastectomy are necessary to gain some perspective on the issue. It is dangerous to focus exclusively on any one study, especially when it has a relatively small sample size.

We are in early days for the results of studies that estimate the residual breast cancer risk of BRCA-positive women after prophylactic mastectomies with only a handful of studies having been published thus far. The largest study to date involving 2482 BRCA-positive women analyzed the effect of both prophylactic mastectomy and prophylactic bilateral salpino oophorectomy on future cancer risk.  This study, entitled Association of Risk-Reducing Surgery in BRCA1 and BRCA2 Mutation Carriers With Cancer Risk and Mortality, was published in the Journal of the American Medical association September 1, 2010 and we blogged about it in our post Beyond the headlines: Prophylactic surgery reduces cancer risk and saves lives. Interestingly, in this study 247 women chose to have prophylactic mastectomies and none of them developed breast cancer, which resulted in the conclusion that prophylactic mastectomies are highly effective at reducing breast cancer risk in BRCA1 and BRCA2-positive women. BUT the study made no attempt to statistically quantify the remaining breast cancer risk because such a calculation was not possible given no breast cancer events in the preventive mastectomy group.

A 2004 U.S. study had results more similar to the Danish study. It involved 483 BRCA-positive women 105 of whom chose prophylactic mastectomies. Two women in this study developed breast cancer after preventive mastectomies, one was diagnosed with breast cancer in her lymph nodes less than 2 years after her preventive mastectomies and the other was diagnosed with breast cancer 9 years later in what was described as "significant residual right breast tissue" that had been left after the prophylactic mastectomies.

Statistical analysis of risk reduction in these studies is complex business involving a discipline called biostatistics.  In calculating the final residual risk number the statistical analysis involves a number of assumptions and complex calculations involving the raw data. Changes in any of the assumptions will change the end result and may account for why the Danish study resulted in a seemingly large residual risk analysis.  We leave the statistical analysis to the mathematicians but raise this as one thing to consider when confronted with a study conclusion that seems alarming.

Unfortunately, more years of follow-up and more published studies are needed before the experts will have a good handle on the amount of breast cancer risk that remains after preventive mastectomies.

What lessons can be learned from the research so far?

While the conclusion from this new Danish study should probably be taken with a grain of salt, it nonetheless raises issues that women should discuss with their doctors and one thing is clear: prophylactic mastectomy does not totally eliminate breast cancer risk.

Another thing that comes through from the studies to date is the suggestion that the residual risk is directly affected by the amount of breast tissue left by the breast surgeon performing the surgery. In the 2004 U.S. study, both of the post-mastectomy breast cancers occurred after subcutaneous mastectomies, which generally leave behind a greater amount of breast tissue than does a simple mastectomy. In the Danish study all three of the women who developed cancer had simple mastectomies but the study authors nonetheless placed most of the blame on breast tissue that should have been removed. One of the three breast cancers occurred two years after the mastectomies and was already metastatic with a small tumor in the residual breast tissue that the breast surgeon had not removed in the axilla (under the arm). The study authors speculated that because of the presentation it was likely that the cancer either had been present at the time of the prophylactic mastectomies but was not found by the pathologist or that it subsequently developed in the breast tissue under the arm that had not been removed. The study authors concluded that “inadequate surgery” was the probable cause of the other two post-mastectomy cancers.

On the other hand, the 2010 JAMA study authors noted that their “observation of no prospectively identified breast cancer cases may be due to biases in prior retrospective studies or to improved surgical techniques.” Further studies will hopefully determine whether surgical technique and/or skill of the breast surgeon play a role in residual risk. The studies to date suggest that maximum risk reduction likely comes from high-risk women being treated by highly-skilled specialists who remove the maximum amount of breast tissue. If this proves to be true, women considering prophylactic mastectomies may need to choose their breast surgeon even more carefully than they choose their reconstructive surgeon.

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  1. This is a very interesting post - thanks again for always addressing things that our on our minds. The big question I can't help but wonder, how do we know after our PBM's, is just how much breast tissue was left behind? And just what is the after-care required after PBM? Should a regular breast mri be part of our lives, even after PBM? And are doctors across the board even aware of the answer to this?

  2. Hi Teri,

    Those are all good questions, and ones the experts don't yet have consistent answers for. The point of this post is to not panic at any one study. It took nearly a decade of research before annual MRI became the standard of care for surveillance of high-risk women. And these are harder questions than the efficacy of MRI for surveillance. There is no study that says regular MRI is standard of care post mastectomy and in fact there are studies that say no surveillance whatsover is warranted because the residual risk is so low. It seems to me that the experts first need to nail down the issue of residual risk before they can figure out what after care to recommend.

    I think doctors are fully aware of the uncertainty in this area and they each have their own recommendations for their patients. And of course there is the issue of whether insurance will pay for expensive procedures like MRI or whether they will deem them not medically necessary after a prophylactic mastectomy.

    As always, I think the uncertainty means that we are best served by putting our care in the hands of doctors who are BRCA experts and trusting that they are keeping up on the lastest research and will let us know when and if recommendations change.

  3. And how do we find these "experts"?

  4. Hi Wedding Queen,

    Good question. By asking a lot of questions. First from doctors you trust and then from the doctors to whom you are referred. Another place to ask for referrals is from other BRCA-positive women. For me though, the best referrals came from my geneticist and from my oncologist, both of whom were very familiar will all of the surgeons in my geographic area. They knew which doctors had a lot of experience with BRCA-positive women.

    For example, when I was looking for a breast surgeon, I got referrals from many sources and had consults with several doctors. I asked all of the doctors how many of their patients were BRCA positive and how many preventive mastectomies he had done for women like me. I also asked what percentage of their practice was breast surgery (most general surgeons do different types of surgery). One of the doctors, who came highly recommended by one of my doctors, had treated very few BRCA positive women and less than a quarter of his practice was breast surgery. By contrast, several of the others were primarily breast surgeons and had treated a lot of BRCA-positive women. In the end though, you ask all the right questions then you have to go with your gut.

    As far as gynecologic oncologists go, you can find one near you though the Foundation for Women's Cancer, formerly the Women's Cancer Network, which is on the Resources link of the Positive Results Book website at Although again it pays to ask questions. One woman I met recently was set to proceed with prophylactic surgery with a gynecologic oncologist near her and asked about laparoscopic surgery. It turned out this doctor had never done a laparoscopic preventive bilateral salpingo oophorectomy and my friend decided that she did not want to be his first patient for this procedure.

    None of this is easy, just keep asking questions though and you will go in the right direction.


  5. It is a morbid fear for those who have the heredity and they go on continuous check for fear of breast cancer.Also those who have undergone one surgery have the fear of recurrence.

  6. When faced with the level of risk that women in the high-risk community must live with, it is only natural that it is hard to let go of that fear. But the bottom line is that we need evidence-based medicine to help us understand our residual risk and make informed decisions for going forward with our lives after prophylactic surgery.

  7. How did the women discover they had breast cancer?

  8. Unfortunately the studies don't specify how the cancer was discovered.


  9. yeah, that would be nice to know. How important is it for our breast and Gyn to be well versed in BRCA? Is there a need for us to see an Gyn Onc?

  10. This is very good insight of the prolem that is faced by the cancer patients.It is a very difficult disease to fight and though there i hope with surgery not all could be done well for them.

  11. You put the all great things which makes all people getting interested. but yes that is right, i agree. all you mention is make a sense. Thanks
    I have not any word to appreciate this post.Really i am impressed from this post. Thanks.

  12. Even though you are BRCA positive there are other underlying factors not explored...perhaps other genes that cause cancer etc. I am not sold on the BRCA research. In ten years, it will all change and then new findings will come out. Surveillance will change, treatment will change etc.

  13. Great post!

    I think what is important to remember is the vast amount of lowering the risk of breast cancer, by going through preventative double mastectomy. This is nothing to belittle.
    Yes, unfortunately there is the residual tissues at risk that remain, also after preventative oophorectomy, but the risk is being lowered dramatically.
    Thus, keeping in mind the latter lowered risk, accompanied with still the presence of some risk, a some what follow up might be a sensible matter to consider.And this with a lessen anxiety....after all every woman is at risk of having breast cancer and we can not control all that will happen to each and everyone of us.....

  14. Thanks so much Dorit! It is easy to get sidetracked by alarming headlines and not keep your eye on the ultimate goal, which is as you say the very significant lowering of risk achieved by preventive surgeries.


  15. I am BRCA2 positive and have lost my two sisters, mother, aunt and uncle to breast cancer. In 2003, I underwent preventative surgeries, including a bi-lateral mastectomy. The post-surgery pathology found 4mm of DCIS on the left side. I was told that this didn't constitute cancer and, since I'd had the surgery, I was cancer free with a 2% or less chance of ever getting BC. [I noticed recently that they have changed these statistics so that it is now 2% chance within only 5 years.]

    In November 2011, I was diagnosed with Stage IV breast cancer that had metastasized in my bones with "innumerable lesions" throughout my spine, ribs, sternum, shoulder blades, pelvis, etc. This included multiple spinal compression fractures and a large tumor in my T12 vertebra almost damaging my spine. There was also concern about bone fragments of this fractured vertebra moving into the spinal column.

    This was only caught because, after a couple of months of severe back spasms and pain, my doctor finally ordered some blood tests. The test results showed dangerously high levels of calcium in my blood that turned out to be due to the disintegration of bone by the cancer. I spent 3 weeks in the hospital, had left-side lymph nodes removed and 14 radiation treatments.

    I was totally blindsided by this diagnosis. How could I have Stage IV BC when I had never actually had BC to begin with? I had had follow up monitoring by my physician since my surgeries. I had also had 5 follow up breast area surgeries due to complications with my LD Flap reconstruction. My chest and back had been receiving care for almost all of those 8 years.

    I am one of the rare few that you discussed above. Not only are the assessments of cancer risk after preventative surgeries lacking, but the information for those of us unlucky enough to get such cancer are rare to non-existent. There are no studies on life expectancy, courses of treatment, etc. I have only found a couple of online comments by a few other similarly affected women. In addition, very few oncologists have had experience treating these type of patients since it is so rare.

    On the positive side, after 5 months of anti-hormone treatment with Femara, I am doing well and my cancer markers continue to decline. Who knows how long this will last, but for now it is working. I have read about some women who lived years using just this type of treatment. Hopefully, I'll be one of them.

    1. Lynn,

      First, we are so sorry for what you have been through. You are absolutely right though that women need better assessments of post-surgery risk as well as prognosis and options for treatment. We are glad you are doing well on your current treatment and hope that this brings you many good years.

      In the meantime, would you please send us an email to PositiveResultsTheBook @

  16. To have breast cancer after prophylactic is very tough. You have described it very well

  17. Breast cancer is a silent killer in our Country, thank for your great post.

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