Prophylactic Mastectomy Reduces Breast Cancer Risk for Women with BRCA1 or BRCA2 Gene Mutations
San Antonio Breast Cancer Symposium, December 2004, Abstract #10

J.G.M. Klijn et al.

Background and importance of the study: Women with abnormal or mutated BRCA1 or BRCA2 genes have a significantly greater chance of developing breast cancer. In the general population, a woman who lives to age 90 has about a 12% chance of developing breast cancer. But if she has an abnormal BRCA1 or BRCA2 gene, her risk can be as high as 60% to 85%. Researchers continue to look for the best ways for women with one or both of these abnormal genes to reduce their risk of breast cancer.

Surgically removing the breasts before any sign of cancer is one way to lower the risk dramatically. This procedure, called double prophylactic mastectomy, removes nearly all of the breast tissue, so there are fewer breast cells that might develop into a cancer.

Surgical removal of the ovaries, called oophorectomy, is another procedure that can reduce a woman's risk for breast cancer, particularly if she is pre-menopausal. Here's why: Estrogen can make certain types of breast cancers— hormone-receptor-positive cancers—grow. Before menopause, most estrogen is produced in the ovaries. So removing the ovaries lowers the risk of breast cancer in pre-menopausal women by dramatically lowering the amount of estrogen in the body.

Removing the ovaries also reduces the risk of ovarian cancer.

Women with abnormal BRCA1 or BRCA2 genes can reduce their risk of developing breast cancer in non-surgical ways, such as by taking tamoxifen and maintaining a healthy lifestyle.

High-quality early detection with MRI scanning, digital mammography, and ultrasound can help detect breast cancer early, when it's most treatable.

An earlier study tracked 139 women who had a BRCA1 or BRCA2 abnormality with no previous diagnosis of breast cancer. About half of the women chose to have double prophylactic mastectomy, and the others had no surgery and were watched closely. About half of the women who had mastectomy also chose to have oophorectomy. None of the women who had prophylactic mastectomy developed breast cancer. It was hard to know what helped reduce the risk of developing breast cancer the most: prophylactic mastectomy, prophylactic oophorectomy, or both.

Another, more recent study followed 483 women with BRCA1 or BRCA2 abnormalities who did not have breast cancer. In this study, women who had double prophylactic mastectomy but not oophorectomy were compared with women who had neither of these surgeries. The researchers found that double prophylactic mastectomy ALONE could lower the relative risk of breast cancer in women with abnormal BRCA1 or BRCA2 genes by as much as 90%.

In the study reviewed here, researchers compared women with BRCA1 or BRCA2 gene abnormalities who had either:

double prophylactic mastectomy and close monitoring, or
no prophylactic surgery, only close monitoring.
The researchers used statistical analysis to take into account the women who had both ovaries removed with their double mastectomy, as well as women who were post-menopausal. Both of these groups of women would have low levels of estrogen in their bodies.

Study design: The study looked at 286 women who had either a BRCA1 or BRCA2 gene abnormality who did not have breast cancer. The research was done at a clinic in the Netherlands.

• 113 of the women (average age 36) chose to have double prophylactic mastectomy
• 173 women (average age 39) chose to be monitored closely (this included an exam every six months and an annual mammogram; many also had a screening MRI).
  The researchers followed the women for three to five years.

Study results: In the 173 women being closely monitored, 24 developed breast cancer and two women died. In the 113 women who had double prophylactic mastectomy, one woman developed cancer in another part of her body 3.5 years after her double prophylactic mastectomy. When the cancer was detected, there was no cancer in the area where the breast used to be. Breast cancers were found in two of the breasts that were removed in the prophylactic mastectomy group. None of the women who had prophylactic mastectomy developed breast cancer during the follow-up period.

Conclusions: After statistically adjusting for women who also had prophylactic removal of their ovaries or were post-menopausal, the researchers concluded that double prophylactic mastectomy reduced the risk of breast cancer by 93% in women with BRCA1 or BRCA2 gene abnormalities.

Take-home message: This study confirms the results of earlier research that showed a dramatic reduction in breast cancer risk with double prophylactic mastectomy for women with abnormal BRCA1 or BRCA2 genes.

But because of the small numbers of women in this study, it is still hard to say for sure whether double prophylactic mastectomy alone reduces the risk. We don't know how much prophylactic removal of the ovaries (oophorectomy) affects the risk reduction. More studies are needed to look at this question.

If you have an abnormal BRCA1 or BRCA2 gene, you might be considering surgery to lower your risk of developing breast cancer. Deciding to undergo any surgical procedure requires careful consideration and discussion with your doctor. And considering breast or ovary removal can be especially difficult, because these surgeries can affect your body image, sense of self, sexuality, quality of life, and overall health. Keep in mind that there is no rush to make these decisions and get the procedures done. You can take the time you need to make the best decisions for you.

It's also important to remember that removing your breasts does not guarantee that you will never get breast cancer. Although it does lower the risk a great deal, in a small number of cases, cancer can still develop in the little bit of breast tissue that remains after surgery.

Prophylactic surgery is more likely to be chosen by women who want to be as aggressive as possible about their care. If you don't want to have prophylactic surgery, there are other effective options. These include taking tamoxifen, which has been shown to lower the risk of developing breast cancer for women at high risk by about 50%. Maintaining a healthy lifestyle—getting regular exercise, controlling your weight, avoiding supplemental estrogen, limiting alcohol intake, and not smoking—is another effective way to lower your risk.

No matter what steps you choose to take to reduce your risk , if you have a BRCA1 or BRCA2 gene abnormality, you should be followed closely by a breast care specialist. Discuss with your doctor the best screening plan for your situation.