Less Than 1% Absolute Survival Benefit at 20 Years Found for Contralateral Prophylactic Mastectomy

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Theorizing that an exaggerated perceived benefit from contralateral prophylactic mastectomy may have led to the substantial increase in its use in recent years, researchers from the University of Minnesota in Minneapolis used a Markov simulated decision-analytic model to evaluate the magnitude of the survival benefit of contralateral prophylactic mastectomy for women with unilateral breast cancer. The investigators found that the absolute 20-year survival benefit was less than 1%.

Predicted life expectancy gains from contralateral prophylactic mastectomy “ranged from 0.13 to 0.59 years for women with stage I breast cancer and 0.08 to 0.29 years for those with stage II breast cancer. Absolute 20-year survival differences ranged from 0.56% to 0.94% for women with stage I breast cancer and 0.36% to 0.61% for women with stage II breast cancer,” the researchers reported in the Journal of the National Cancer Institute.

Contralateral prophylactic mastectomy was more beneficial among women with stage I and estrogen receptor (ER)-negative breast cancer, and those who were younger. For example, a 60-year-old woman would gain less than 2 months in life expectancy from contralateral prophylactic mastectomy, whereas a 40-year-old woman would gain as much as 7 months, according to the model.

The authors explained that the model simulates long-term prognosis of hypothetical cohorts of women with newly diagnosed unilateral breast cancer under the following two scenarios: (1) contralateral prophylactic mastectomy (ie, double mastectomy) and (2) no contralateral prophylactic mastectomy (assuming that women undergo either lumpectomy with radiation therapy or unilateral mastectomy).

Using this model, they projected the benefit of contralateral prophylactic mastectomy for cohorts of women defined by age at breast cancer diagnosis (40, 50, or 60 years), stage of primary breast cancer (I, II), and ER status. Women with BRCA mutations were excluded. Probabilities for developing contralateral breast cancer, dying from contralateral breast cancer, dying from primary breast cancer, and age-specific mortality rates were estimated from published studies, the authors noted.

“In this analysis, we assumed that the only plausible way that [contralateral prophylactic mastectomy] improves breast cancer survival is by preventing a potentially fatal [contralateral breast cancer],” the investigators stated. In 2011, the 10-year risk of contralateral breast cancer was estimated to be 4% to 5%, and the risk “may be even lower for patients diagnosed today,” the authors added.

Further Considerations

The authors acknowledged that survival “is only one potential benefit of a cancer risk-reduction strategy; effects on cancer-related anxiety, cosmesis, and self-image are also important in decision-making processes. For some women, the negative impact of [contralateral prophylactic mastectomy] on quality of life may outweigh a potential survival benefit. For others who are very anxious about [contralateral breast cancer], [contralateral prophylactic mastectomy] may result in a psychological benefit even if survival benefits are minimal.”

The researchers noted that prospective randomized trials of contralateral prophylactic mastectomy vs no contralateral prophylactic mastectomy are not feasible and retrospective studies evaluating a potential survival benefit with contralateral prophylactic mastectomy “are limited by short follow-up, potential selection bias, and lack of important clinical information.” They concluded, “Survival estimates derived from our model may be useful for physicians and breast cancer patients to arrive at evidence-based informed decisions regarding [contralateral prophylactic mastectomy].”

Although the survival benefit of contralateral prophylactic mastectomy is small, “in a fraction of patients who are very troubled by a 0.7% risk of a second, contralateral cancer, [contralateral prophylactic mastectomy] might still provide an acceptable benefit,” according to an accompanying editorial. “The balance between harm and benefit depends on the patient’s preferences and highlights the importance of capturing the patient’s values and expectations before considering [contralateral prophylactic mastectomy],” wrote Stephen G. Pauker, MD, and Mohamed Alseiari, MD, of the Division of Clinical Decision Making, Department of Medicine, Tufts Medical Center, Boston. ■

Portschy PR, Kuntz KM, Tuttle TM: J Natl Cancer Inst 106(8):dju160, 2014.

Pauker SG, Alseiari M: J Natl Cancer Inst 106(8):dju175, 2014.