Saturday, January 8, 2011

Is the jury still out?

Prior to my prophylactic oophorectomy, my gynecologic oncologist told me unequivocally that my BRCA status required that my ovaries and fallopian tubes be removed but that I did not need to remove my uterus because my BRCA mutation did not raise my risk of uterine cancer.  We discussed that there are other reasons for removing the uterus at the time of my BSO (bilateral salpingo-oophorectomy), including in my case a desire to simplify hormonal management of surgical menopause by using estrogen alone rather than using estrogen plus progesterone or progestins (synthetic progesterone).

Although my surgeon presented the issue as relatively straightforward, I did not consider it an easy decision.  I didn’t want more surgery than was necessary but I had a few nagging questions: What was the risk posed by residual fallopian tube tissue if I retained my uterus?  What was the risk of uterine cancer should I retain the uterus and how was this affected by my choice of hormone replacement therapy?  What was my risk of cervical cancer given my history of cervical dysplasia (even though more than 10 years in the past) and should this play into my decision to keep or remove my uterus?

We discussed these issues in Chapter 13 of Positive Results and I am lucky that as part of my research I was able to pose these and other questions to a number of experts on this subject.  Consensus at the time was that uterine cancer was not linked to BRCA mutations (despite two small studies that questioned whether it might be linked) and that the portion of the fallopian tube retained at the insertion point of the uterus was unlikely to result in any significant residual fallopian tube cancer risk.

Two studies have come out since the publication of Positive Results that merit some discussion and which may indicate that the jury is still out on whether women opting for risk reducing surgery should consider removing their uterus as well.

The first study, published in the April 2010 issue of Gynecologic Oncology examined the amount of residual fallopian tube tissue left after removing the ovaries and tubes.  The second study, published in the December 2010 issue of the International Journal of Gynecologic Cancer addressed the issue of uterine cancer risk in BRCA-positive women.

The fallopian tube tissue study, entitled “Does risk-reducing salpingo-oophorectomy leave behind residual tube?” was a small study (20 women) done at Cedars-Sinai Medical Center in Los Angeles.  Full disclosure:  Cedars is the medical center where Dr. Gordon works, is the hospital where I had my surgery, and two of the study authors were consultants for the ovarian cancer chapters of Positive Results.

In this study, the doctors examined post-hysterectomy uterus specimens to determine the amount of tubal tissue remaining at the uterine insertion site after surgery to remove the ovaries and tubes.  A strength of this study is that all of the surgeries were performed by gynecologic oncologists and that a single pathologist performed all of the pathology.  Prior studies have shown that the amount of tubal tissue remaining varies widely depending on the skill of the surgeon, which is one of the reasons why many experts recommend that gynecologic oncologists are the best option for women seeking maximum risk reduction from their prophylactic surgery.  The results of this study showed that even with a gynecologic oncologist, most women will end up with some retained tubal tissue near the uterus.  Specifically, this study showed that 73 percent of the tubal sites examined had some residual tubal tissue, although the average amount of residual tissue was small (6mm).  One thing clearly shown by this study is that even when done by highly-skilled surgeons, BSO is likely to leave behind some amount of residual tubal tissue, albeit most likely a very small amount.

What does this residual tissue mean for residual risk?  This question was not answered by this study.  The end of the fallopian tube where it inserts into the uterus is called the proximal end.  Even in the women in this study who had early fallopian tube cancer or early precancerous cellular changes, none of those changes happened in the proximal end of the tube, all were closer to the ovaries.  The same is true for other studies, fallopian tube cancers seem to start in the distal end of the tube (near the ovaries) or the fimbria (part surrounding the ovaries).   Thus, even though BSO is likely to leave a small segment of fallopian tube behind, this alone is not sufficient reason to recommend that women with BRCA mutations also have hysterectomies as this additional procedure is unlikely to improve the risk reduction benefit of the surgery.

The study authors noted that even though improved fallopian tube/ovarian cancer risk reduction is not a reason to remove the uterus in a BRCA carrier, other factors do come into play, including the possibility of uterine cancer being linked to BRCA status; the use of tamoxifen to treat breast cancer because it increases uterine cancer risk; and simplified hormonal management of premenopausal women.  On the other side of the equation are the increased surgical risks that come from the more extensive surgery to remove the uterus.

At the time this study was published, only a couple small studies linked BRCA mutations to uterine cancer.  These were offset by a number of studies that showed no link.  The new study published in December in the International Journal of Gynecological Cancer, entitled “BRCA Germline Mutations in Women With Uterine Serous CarcinomaStill a Debate” raised this question anew.  This study examined the family history and BRCA status of 51 women with uterine cancer and found that a significant number of these women had a family history of breast or ovarian cancer (33 percent) and that approximately 16 percent of these women had BRCA mutations.  This study raises the issue of a potential link between BRCA mutations and uterine cancer without providing any answers whatsoever.  In fact, the study authors note that there is currently insufficient evidence to make any recommendations to BRCA-positive women regarding removing the uterus or, if so, the potential timing of such a surgery. 

In short, the jury is still out on the issue of uterine cancer and BRCA mutations although this most recent study may signal the need for further study of the issue.  For now, BRCA carriers will continue to make this tough decision in consultation with their doctors without a clear answer from the research.

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  1. What's the latest on this study? By the way, HRT has great potential benefits for women, as some studies have already issued by WHI and HERS if I'm not mistaken. It helps decrease discomfort in menopausal stage for women.

  2. Hi Jennifer,

    Most doctors seen to still believe that uterine cancer is not BRCA linked, despite the finding of this small study. And yes, HRT is well known for easing menopausal symptoms, the issue is with the counterbalancing risks of taking these drugs depending on your circumstances, which is a complex issue.

    Thanks for stopping by and chiming in!