Guidelines

Survival benefit from contralateral prophylactic mastectomy small

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Some patients may still benefit from the procedure

The decision of whether or not to undergo a contralateral prophylactic mastectomy after being treated for breast cancer is a difficult one for many women. The goal of such aggressive therapy is to lower the likelihood of a second primary carcinoma. The downsides are operative risk, impairment of the woman’s self-image, and short-term and long-term morbidities.

This is a well done analysis from an experienced group of investigators and is based on the currently available data. Given the JNCI audience, we shall refrain from niggling points about modeling. Rather, we will stick to the big picture and clinical implications. Although the survival benefit from CPM is small as demonstrated in this model, it is greater than zero, which suggests that for some patients even that small gain may be enough to make it a not unreasonable choice.

From a societal perspective, which was not addressed by Portschy et al., the associated costs of CPM, including the procedure, its complications, reconstruction, and perhaps psychotherapy, may outweigh the modest benefit CPM provides. The small denominator of the cost-effectiveness ratio, were one to be calculated, would imply that the ratio would be very high, making CPM a suboptimal use of health care dollars. Further, we suspect that adding quality of life to the analysis would diminish the benefit and well might turn it into a net harm, in particular for patients with high concern for negative impact of CPM on cosmesis, self image, and morbidity. However, in a fraction of patients who are very troubled by a 0.7% risk of a second, contralateral cancer, CPM might provide an acceptable benefit. 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 CPM.

Of course, these conclusions are based on analysis of women who are at average risk for a contralateral second primary. In women at substantially higher risk (based either on family history or genetics), the benefit of CPM might be far greater, and CPM might be a good choice for the patient or for society.

Dr. Stephen G. Pauker and Dr. Mohamed Alseiari are with the division of clinical decision making in the department of medicine at Tufts Medical Center, Boston. They reported no relevant financial conflicts. This was excerpted from an editorial (J. Natl. Cancer Inst. 2014 July 16 [doi:10.1093/jnci/dju175]).


 

FROM THE JOURNAL OF THE NATIONAL CANCER INSTITUTE

References

The absolute 20-year survival benefit from contralateral prophylactic mastectomy stands at less than 1%, regardless of age, estrogen receptor status, and cancer stage, a decision analysis demonstrated.

"Long-term survival in women with unilateral breast cancer treated with or without CPM depends upon several factors, including mortality of the primary breast cancer, risk of CBC [contralateral breast cancer], stage and mortality of the CBC, and the individual patient’s overall life expectancy," wrote Dr. Pamela R. Portschy of the University of Minnesota, Minneapolis.

The report was published July 16 in the Journal of the National Cancer Institute.

"Prospective randomized trials comparing CPM with no CPM are not feasible. Retrospective studies evaluating a potential survival benefit with CPM are limited by short follow-up, potential selection bias, and lack of important clinical information," noted Dr. Portschy and her associates.

They limited their analysis to women with stage I and II breast cancer without BRCA mutations. They developed a Markov model to simulate survival outcomes among those who did and did not have contralateral prophylactic mastectomy (CPM), and they used published studies to estimate probabilities for developing CBC, dying from CBC, dying from primary breast cancer, and age-specific mortality rates. Data were extracted from numerous sources including Surveillance, Epidemiology, and End Results (SEER), the Early Breast Cancer Trialists’ Collaborative Group, and the Oregon State Cancer Registry.

The researchers estimated the 20-year overall survival and life expectancy, but not quality of life or cost, and their analysis considered variation in age, estrogen receptor status, and cancer stage (J. Natl. Cancer Inst. 2014 July 16 [doi:10.1093/jnci/dju160]).

The predicted life expectancy gain from CPM ranged from .13 to .59 years for women with stage I breast cancer, and .08 to .29 years for those with stage II breast cancer. CPM conferred a life expectancy benefit among younger women and among those who had stage I and estrogen receptor–positive disease. "The potential benefit of CPM was consistently lower for patients with stage II breast cancer because of the worse prognosis associated with the primary breast cancer," the researchers wrote. "Similarly, the potential benefits of CPM are more modest for older women because they have relatively fewer years remaining of [life expectancy]."

Dr. Portschy and her associates could not identify any cohort of women that had a greater than 1% absolute survival difference at 20 years. In fact, the predicted 20-year survival differences ranged from .56 to .94% for women with stage I breast cancer and .36 to .61% for those with stage II breast cancer.

The researchers acknowledged limitations of the study, including the fact that the results "do not apply to BRCA gene mutation carriers with unilateral breast cancer who have a cumulative 10-year risk of CBC of approximately 30% to 40%," they wrote. "The outcomes of this analysis were limited to overall and disease-specific survival; we did not evaluate other important outcomes such as surgical complications and quality of life. Also, we assumed the mortality of CBC was the same as the mortality of the index cancer reported by SEER."

They also noted that survival is not the only potential benefit of a cancer risk reduction strategy. "Effects on cancer-related anxiety, cosmesis, and self-image are also important in the decision-making process," they wrote. "For some women, the negative impact of CPM on quality of life may outweigh a potential survival benefit. For others who are very anxious about CBC, CPM may result in a psychological benefit even if survival benefits are minimal."

They concluded that the survival estimates from their Markov model "may be useful for physicians and breast cancer patients to arrive at evidence-based informed decisions regarding CPM. Moreover, the use of accurate and easily understood decision aids may reverse some of the mastectomy trends recently observed in the United States."

The researchers stated that they had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

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