For women with stage I and II breast cancer without BRCA mutations, the absolute 20-year survival benefit from contralateral prophylactic mastectomy was less than 1%, regardless of age, estrogen receptor status, and cancer stage, according to a decision analysis study using a Markov model to simulate survival outcomes with or without the procedure. The study, published in the Journal of the National Cancer Institute,¹ also noted that the 10-year cumulative risk of contralateral breast cancer is about 4% to 5% but may be even lower for women diagnosed with breast cancer today.

These figures are at odds with the estimated risks of contralateral breast cancer and expected benefits of contralateral prophylactic mastectomy reported by patients. Todd M. Tuttle, MD, MS, Chief of the Division of Surgical Oncology at the University of Minnesota in Minneapolis and Medical Director of the University of Minnesota Breast Center, and one of three study authors, told The ASCO Post “A few years ago, we conducted a prospective study in our institution of women with unilateral breast cancer who didn’t have a BRCA mutation. We asked them to estimate their 10-year risk of getting a contralateral breast cancer. The mean perceived risk was over 30%, which is about the same as what it is for a BRCA mutation.”

Dr. Tuttle also cited another survey study of women under 40 diagnosed with breast cancer, published in 2013.² “They also substantially overestimated their risk of developing a contralateral breast cancer,” he noted. “In that study, a large proportion of women said the reason that they chose to have a [contralateral prophylactic mastectomy] was to improve their survival; it was one of the most common reasons women cited for having a contralateral prophylactic mastectomy. However, our data clearly show that the vast majority of women will not have a meaningful survival benefit from this operation.”

Complex Modelling, High Sensitivity

Asked if the finding of an overall survival benefit of less than 1% surprised him and his coauthors, Dr. Tuttle replied, “No, it actually didn’t. We had previously performed crude estimations, and this is the number that kept coming up. But this study is a much more rigorous analysis, with sensitivity analysis and complex modeling.” He added that the Markov model “is a well accepted methodology when a randomized clinical trial cannot be performed. We used the highest quality of resources that were available.”

The model simulates the long-term prognosis of hypothetical cohorts of women with newly diagnosed unilateral breast cancer according to two scenarios: (1) contralateral prophylactic mastectomy (ie, double mastectomy) and (2) no contralateral mastectomy (assuming that women undergo either lumpectomy with radiation therapy or unilateral mastectomy), the authors explained in the JNCI article. “We 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 estrogen receptor status (positive, negative).”

Stage-specific breast cancer mortality rates were derived from relative survival curves reported in the Surveillance, Epidemiology, and End Results (SEER) data. Probabilities for developing contralateral breast cancer, dying from contralteral and primary breast cancer, and age-specific mortality rates were estimated from published studies. Those studies included meta-analyses of large numbers of randomized clinical trials, sometimes spanning 10 to 15 years, Dr. Tuttle noted.

Explaining the use of the model, the researchers contended 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.”

In retrospective studies comparing the outcomes of women who have had a contralateral prophylactic mastectomy vs those who have not, the patients who undergo the procedure have better survival rates, primarily because women who undergo contralateral prophylactic mastectomy are younger, healthier, and often have better access to health-care insurance, Dr. Tuttle noted.

Stage and Age Differences

Contralateral prophylactic mastectomy was more beneficial among women with stage I than those with stage II cancer, according to the model. 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 results showed.

“We focused on stage I and II disease because as the stage goes up, your chances of dying from your known cancer go markedly up as well. So if you have a stage III breast cancer, there is going to be no benefit at all, because almost all the survival risk is due to the known cancer,” Dr. Tuttle explained.

Contralateral prophylactic mastectomy was also more beneficial among women with estrogen receptor–negative breast cancer and younger women. For example, a 60-year old woman would gain less than 2 months life expectancy from contralateral prophylactic mastectomy, while a 40-year-old woman would gain as much as 7 months, according to the model.

Dr. Tuttle said that older women frequently opt for contralateral prophylactic mastectomy, but not as often as younger women. “Young age is consistently associated with having a [contralateral prophylactic mastectomy].”

Overall Exaggerated Risk

Women with BRCA mutations were excluded from the study. Women who do not have BRCA mutations have a lower risk of breast cancer and “don’t have contralateral prophylactic mastectomies as frequently as those women who do have a BRCA mutation,” Dr. Tuttle said, but the rate has been rising.

“Numerous studies in the United States have shown that the rates of [contralateral prophylactic mastectomy] use among all women, but also including women who don’t have BRCA mutations, is markedly increased,” he added. Those studies include one that Dr. Tuttle coauthored in 2007 that found the use of contralateral prophylactic mastectomy had doubled in a 6-year period.³

“In the United States, there is an overall exaggerated risk for breast cancer,” Dr. Tuttle said. “For example, women who do not have breast cancer substantially overestimate their chances of getting breast cancer. Women who have early breast cancer, or ductal carcinoma in situ, substantially overestimate their risk of getting a recurrence or dying from that cancer. And, as we found, women who have cancer in one breast substantially overestimate the risk of getting cancer in the opposite breast.”

The reason for the exaggerated risk is unclear, he said. It could be due to the prevalence of breast cancer themes in movies and on television, or races and other fundraising events, “or maybe the unintended consequence of increased breast cancer awareness.” ■

Disclosure: Dr. Tuttle reported no potential conflicts of interest.

References

1. Portschy PR, Kuntz KM, Tuttle TM: Survival outcomes after contralateral prophylactic mastectomy: A decision analysis. J Natl Cancer Inst 106(8):dju160, 2014.

2. Rosenberg SM, Tracy MS, Meyer ME, et al: Perceptions, knowledge, and satisfaction with contralateral prophylactic mastectomy among young women with breast cancer: A cross-sectional survey. Ann Intern Med 159:373-381, 2013.

3. Tuttle TM, Haberman EB, Grund EH, et al: Increasing use of contralateral prophylactic mastectomy for breast cancer patients: A trend toward more aggressive surgical treatment. J Clin Oncol 25:5203-5209, 2007.