Oncologists need a better understanding of why women choose contralateral prophylactic mastectomies without indication, and they need data to counter their patients’ misperceptions about this treatment choice.
“Many women who choose [contralateral prophylactic mastectomy] are not at increased risk of a contralateral breast cancer,” said Tari A. King, MD, FACS, Deputy Chief and Director of Research, Breast Surgery Service, Memorial Sloan Kettering Cancer Center, New York. “There is a frequent disconnect in the decision-making process that is likely fueled by fear and anxiety.”
On the other hand, a minority of patients, in particular young women with early-stage estrogen receptor (ER)-negative breast cancer may derive a small disease-free survival benefit from contralateral prophylactic mastectomy.
“To simply say there’s no benefit to these younger women—and it’s a very small population—is an oversimplification. While level I evidence would be ideal to confirm these retrospective population based observations, such evidence is not likely to ever be had. Therefore, we need use the emerging data to appropriately counsel our patients,” according to Isabelle Bedrosian, MD, FACS, Associate Professor in the Department of Surgical Oncology at The University of Texas MD Anderson Cancer Center, Houston.
In general, 3% to 5% of early breast cancer patients will develop contralateral breast cancer over 10 years’ time, but patients estimate this risk at greater than 30%. Clinicians and patients alike need data to make informed decisions, said Drs. King and Bedrosian, speaking at the 2014 American College of Surgeons Clinical Congress in San Francisco.
Surgeon’s Opinion Critical
Perhaps nothing is more influential to the patient contemplating contralateral mastectomy than their surgeon, but surgeons say they feel ineffectual. A patient who wants a contralateral mastectomy merely goes where she can get one, the speakers agreed.
Data from the Young Women’s Breast Cancer Study (YWS) reflect the importance of the surgeon in discussing all the risks and benefits of the procedure. Among 132 women under the age of 40, 80% aid their physicians discussed reasons to have a contralateral prophylactic mastectomy, whereas only 51% said their physicians discussed reasons not to have the procedure. Further, when asked about their reasons for choosing contralateral prophylactic mastectomy, “to improve survival” and “to prevent metastatic disease” was rated as extremely important or very important by 94% and 85% of patients, respectively, reflecting a real disconnect between the data and the decision-making process.1
“Surgeons can play a major role in the decision-making process,” said Dr. King, who added that despite the evidence, physicians need to remain sensitive to their patients’ needs, and this is challenging.
“We are trying to practice evidence-based medicine, but we are also trying to do so in the era of patient-centered care—defined by the Institute of Medicine as care that is respective of and responsive to individual patient preferences, needs, and values,” she added.
“This does not mean giving patients what they want,” she emphasized. “Rather, patients want guidance from their care providers, and they expect that guidance to be provided in the context of full and unbiased information about options, benefits, and risks.”
Trend in Younger Patients
The rise in contralateral mastectomy has been widely documented. In one study involving 189,734 patients, bilateral mastectomy rates increased from 2.0% in 1998 to 12.3% in 2011, an annual increase of 14.3%; among women younger than 40 years, the rate increased from 3.6% to 33%.2
“Very recent data show the trend is occurring across all age groups, but especially in younger patients,” Dr. King said. Contralateral prophylactic mastectomy rates are 40% for women under 40, dropping to 20% among women aged 40 to 50 and to 10% among those 50 to 60. Only 5% of the oldest patients undergo contralateral mastectomy.
“In concert, the rate of unilateral mastectomy is decreasing. Women are choosing between the most minimal surgery [ie, lumpectomy] and the maximum,” she said.
Things the Surgeon Can Control
Multiple studies have demonstrated that preoperative magnetic resonance imaging (MRI) is a trigger for contralateral prophylactic mastectomy. In fact, a Memorial Sloan Kettering study of 2,965 women found MRI at diagnosis to be the strongest predictor (odds ratio = 3.2) for having a contralateral prophylactic mastectomy.3 Prior attempt at breast-conserving surgery is another trigger. Rather than undergo reexcision per the surgeon’s desire for a negative margin of a certain distance, many patients opt for contralateral mastectomy.
“Surgeons need to come to a consensus on what is a negative margin so that we avoid unnecessary reoperations,” she offered. This, and routine MRI, are factors that surgeons can potentially impact.
Operating on Anxiety?
“We know there are some patients who may benefit from [contralateral prophylactic mastectomy],” Dr. King acknowledged. They include patients at high risk (eg, those with BRCA mutations), those for whom surveillance is difficult (eg, extremely dense breasts, diffuse indeterminate calcifications, or who are difficult to examine); and those with significant reconstructive issues (eg, to improve symmetry).
“But an increasing number of women choosing [contralateral mastectomy] are not necessarily falling into these groups,” she pointed out. “Instead, surgeons appear to be operating on anxiety.”
In the YWS, 95% listed “peace of mind” as extremely important or very important in the decision for contralateral prophylactic mastectomy. While undergoing prophylactic mastectomy may calm some of these fears, “We have all seen failed reconstructions and women who are still worried after the operation,” Dr. King noted.
Outcomes do not always meet expectations. “[Contralateral prophylactic mastectomy] is not a quick fix. A woman can be trading one problem for another,” she said. “We need to encourage patients to focus on the net benefit, not the total threat.”
What Is the Actual Risk?
While women vastly overestimate their risk of contralateral cancer, the fact is that for women initially diagnosed with an ER-positive breast cancer, the rate of contralateral cancer is only 0.4% per year in the youngest patients, and 0.2% in women over 60, largely because adjuvant hormone therapy reduces risk by 50%. The rate of contralateral breast cancer among women treated for ER-negative breast cancer is 1% per year in the youngest patients. For those treated for HER2 amplified breast cancer, anti-HER2 therapy is also protective.
Risks of contralateral breast cancer associated with family history are also overestimated. Women with a family history of breast cancer, who are younger than age 55 at first diagnosis and not BRCA mutation carriers have less than a 10% risk of contralateral cancer at 10 years. The risk exceeds 10% only when a first-degree relative had a bilateral breast cancer or if the patient is a BRCA mutation carrier.4
Challenges in Estimating Risk of Contralateral Breast Cancer
When predicting the impact of contralateral prophylactic mastectomy on contralateral breast cancer risk, Dr. Bedrosian indicated that “different patients have different degrees of benefit.” While, in general, contralateral prophylactic mastectomy conveys a 90% relative reduction in risk of contralateral breast cancer events, patients with the highest baseline risk of contralateral breast cancer will derive far greater absolute benefit than patients with lower risk.
When determining the risk of contralateral breast cancer for any given individual, it is hard to give a straightforward number, since there are dynamic interactions among factors that influence risk: BRCA status, age at diagnosis, and ER status of the index cancer, as well as family history (number of relatives and relatedness). “Combinations of these are much more informative than any one alone,” Dr. Bedrosian noted.
Even BRCA status is more heterogeneous than first believed, with first diagnosis before age 40 carrying a twofold greater risk of developing a contralateral breast cancer at 10 years compared to first diagnosis after age 50. The analysis of survival benefit in BRCA mutation carriers is also complicated by prophylactic oophorectomy and by the preventive effect of endocrine therapy.
What Is the Actual Survival Benefit?
The determination of survival benefit is also challenging because of the retrospective nature of studies and the bias inherent in statistical modeling. For example, women choosing contralateral prophylactic mastectomy tend to be healthier; hence, they live longer and can undergo more aggressive systemic cancer treatment, which alters outcomes, she pointed out.
Dr. Bedrosian and her colleagues evaluated the Surveillance, Epidemiology, and End Results (SEER) database, stratifying by age (a surrogate for comorbidity), stage of index tumor, and ER status, and concluded that for young women (< age 50) with stage I/II ER-negative breast cancer, contralateral prophylactic mastectomy conveyed approximately a 5% disease-free survival benefit; this was not true for young women with early-stage, ER-positive patients.5
“There is not a straightforward relationship between [contralateral prophylactic mastectomy] and survival,” she emphasized. The model must include a woman’s estimated risk of dying from the index tumor and from a noncancer cause. For women with a relatively high risk for a contralateral breast cancer event, a relatively low risk of death from the index tumor, and low risk of death from something other than cancer, the data suggests an association between contralateral prophylactic mastectomy and improved disease-free survival, she explained.
“But this perfect storm scenario is not common. We saw this in only 6% of women in our series,” Dr. Bedrosian emphasized. “In the majority of patients, we can find no association between a disease-free survival benefit and [contralateral prophylactic mastectomy].”
This was confirmed in her matched propensity analysis of patients at MD Anderson,7 which observed a benefit in the subset of ER-negative matched patients only (HR = 0.48, P = .05) and not in ER-positive pairs (HR = 0.73, P = .19).6 A recent, unrelated study, using a Markov analysis to estimate the effect of contralateral prophylactic mastectomy on survival outcomes, confirms a modest disease-free survival benefit across younger ages and earlier stages of index disease, but the overall survival benefit is less than 1% across all patient groups.7
“Looked at another way, the additional life expectancy gained from [contralateral prophylactic mastectomy] could be measured at best in a matter of months,” Dr. Bedrosian concluded.
“For the majority of breast cancer patients, there are no compelling data to show an improvement in either disease-free or overall survival,” Dr. Bedrosian emphasized. “In a very small subset, [contralateral prophylactic mastectomy] is associated with improved disease-free survival, but if you believe that overall survival is the endpoint of interest, the data are less compelling.”
She said she tells young women who are part of that small minority who may benefit, “Yes, there’s a suggestion that [contralateral prophylactic mastectomy] will improve your disease-free survival, but if you do develop a contralateral breast cancer, there’s a very good chance it will be cured, so your overall life expectancy is not affected. These are hard concepts to communicate to patients.”
“Our challenge,” she emphasized, “is presenting information to patients so that they choose approaches other than [contralateral prophylactic mastectomy], and that if they do end up choosing contralateral prophylactic mastectomy, it is an informed decision.” ■
Disclosure: Drs. King and Bedrosian reported no potential conflicts of interest.
References
1. 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.
2. Kurian AW, Lichtensztain DY, Keegan THM, et al: Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998-2011. JAMA 312:902-914, 2013.
3. King TA, Sakr R, Patil S, et al: Clinical management factors contribute to the decision for contralateral prophylactic mastectomy. J Clin Oncol 29:2158-2164, 2011.
4. Reiner AS, John EM, Brooks JD, et al: Risk of asynchronous contralateral breast cancer in noncarriers of BRCA1 and BRCA2 mutations with a family history of breast cancer: A report from the Women’s Environmental Cancer and Radiation Epidemiology Study. J Clin Oncol 31:433-439, 2013.
5. Bedrosian I, Hu CY, Chang GJ: Population-based study of contralateral prophylactic mastectomy and survival outcomes of breast cancer patients. J Natl Cancer Inst 102:401-409, 2010.
6. Brewster AM, Bedrosian I, Parker PA, et al: Association between contralateral prophylactic mastectomy and breast cancer outcomes by hormone receptor status. Cancer 118:5637-5643, 2012.
7. Portschy PR, Kuntz KM, Tuttle TM, et al: Survival outcomes after contralateral prophylactic mastectomy: A decision analysis. J Natl Cancer Inst 106(8):dju160, 2014.
