Double Mastectomy Boosts Survival in BRCA Mutation Carriers

Roxanne Nelson

February 12, 2014

A double mastectomy can increase survival in breast cancer patients carrying a BRCA gene mutation, according to a study published online February 11 in BMJ.

Women who underwent this procedure nearly halved their risk of dying from breast cancer, compared with those who had only 1 breast removed.

At 20 years, the survival rate was 88% for those who underwent double mastectomy, compared with 66% for those who had just the affected breast removed.

The researchers, led by Kelly Metcalfe, PhD, adjunct scientist at Women's College Research Institute in Toronto, note that it is "reasonable" to discuss bilateral mastectomy as an initial treatment option for women with early-stage breast cancer who are carriers of a BRCA1 or BRCA2 mutation.

For women who have already undergone s unilateral mastectomy or breast-conserving surgery, the health provider should discuss the possibility of a second surgery, they write. However, given the small number of women in this group, these observations need confirmation in other study populations.

Breasts Are Not Statistics

BRCA mutations hit center stage last year when actress Angelina Jolie publicly announced that she was a carrier and had undergone a prophylactic double mastectomy. Although Jolie did not have cancer, she made her decision to prevent the disease in the first place.

Women with BRCA1/2 mutations who develop breast cancer face a similar decision, notes Karin B. Michels, ScD, PhD, from the Department of Epidemiology at Harvard School of Public Health in Boston, in an accompanying editorial. They want to know if removing their unaffected breast is going to lower their risk of dying from breast cancer, Dr. Michels explains.

This study provides "new data for consideration by affected women and their doctors," she notes, although she agrees that confirmatory results are needed.

Removing all breast tissue should translate into decreased breast-cancer-specific mortality, given the worse prognosis of BRCA-associated breast cancers, she writes. Nevertheless, "larger studies tackling this issue are needed and will undoubtedly be generated in the years to come."

Breasts are not statistics. "They are essential parts of women's identity, sexuality, and self-perception, Dr. Michels points out. "Parting with a breast may result in anxiety, lack of self-esteem, and possibly depression. Parting with a healthy breast (or 2) to prevent a probability is even more difficult."

The decision to undergo bilateral mastectomy is a personal choice a woman needs to make with her physician, and they need to weigh alternative options. "No statistics and no statistician can make this decision for her," she concludes.

Significant Survival Benefit

Dr. Metcalfe and colleagues conducted a retrospective analysis comparing survival rates in women with BRCA-associated breast cancer who did and did not undergo mastectomy of the contralateral breast.

For women without a BRCA gene mutation, the survival benefit for contralateral prophylactic mastectomy is negligible. One study reported that it is less than 1% at 20 years, whereas the 10-year cumulative risk for developing contralateral breast cancer is estimated at 4% to 5%.

The situation is different for carriers. The researchers note that women with a BRCA1/2 mutation face a lifetime risk for breast cancer of about 60% to 70%. Once they are diagnosed with the disease, they face a high risk for a second primary breast cancer.

However, information on the long-term survival of breast cancer patients with a BRCA1 or BRCA2 mutation is limited, Dr. Metcalfe and colleagues point out. Most of the previous studies have involved only a small number of participants or very short follow-up periods. And no previous studies have addressed the question of contralateral breast mastectomy.

The researchers reviewed records at 12 participating genetics clinics, and their final cohort consisted of 390 women with a family history of stage I or II breast cancer who had a BRCA1 or BRCA2 mutation. The women were initially treated with unilateral or bilateral mastectomy.

All the women were diagnosed with cancer from 1977 to 2009 and were followed until June 2012 (mean follow-up, 13 years). Overall, 79 women (20%) died of breast cancer during the follow-up period, and the mean time from diagnosis to death was 7.1 years.

The majority of women underwent a unilateral mastectomy; only 44 initially underwent bilateral mastectomy. Of the 346 initially treated with unilateral mastectomy, 137 subsequently underwent mastectomy of the contralateral breast. The average time from diagnosis to contralateral mastectomy was 2.3 years.

On multivariable analysis, after controlling for age at diagnosis, year of diagnosis, treatment, and other prognostic features, contralateral mastectomy was associated with a 48% reduction in death from breast cancer (hazard ratio, 0.52; P = .03). In a propensity-score-adjusted analysis of 79 matched pairs, the association was not significant (0.60; P = .08).

"Based on these results, we predict that of 100 women treated with contralateral mastectomy, 87 will be alive at 20 years compared with 66 of 100 women treated with unilateral mastectomy," write the authors.

This study was funded by the Canadian Breast Cancer Foundation. The authors and Dr. Michels have disclosed no relevant financial relationships.

BMJ. Published online February 11, 2014. Abstract, Editorial


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