Contralateral Prophylactic Mastectomy May Benefit Small Subgroup

Roxanne Nelson

March 04, 2010

March 4, 2010 — Contralateral prophylactic mastectomy (CPM) is associated with a small survival benefit in a subgroup of women with breast cancer. This association was primarily observed in women younger than 50 years with early-stage estrogen-receptor (ER)-negative breast cancer, according to a report published online February 25 in the Journal of the National Cancer Institute.

"We did identify a small group in which a benefit for CPM could be demonstrated," explained author George Chang, MD, MS, assistant professor in the Department of Surgical Oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

For the subgroup showing a benefit, the 5-year adjusted breast cancer survival rate increased by 4.8% in those who underwent CPM. The authors note that a combination of factors appears to create "optimal conditions" in which to consider CPM. These include a high absolute lifetime risk for contralateral breast cancer, a lack of available chemoprevention options, and a low risk for death from the index tumor.

On the basis of the these results, clinicians are now able to provide patients with more information about their options, Dr. Chang said.

"Physicians can now give patients further data, such as if they fall within the population that is mostly likely to benefit from CPM," he told Medscape Oncology. "There is an absolute benefit of almost 5% at 5 years for some women, and the benefit may even be higher at 10 years."

Rising Rates, Benefit Unclear

The rates of CPM have been increasing, even though most patients with unilateral tumors will not develop contralateral breast cancer during their lifetimes. Nevertheless, the overall rate of CPM more than doubled from 1998 to 2003 (J Clin Oncol. 2007;25:5203-5209). As previously reported by Medscape Oncology, the number of women with unilateral ductal carcinoma in situ who undergo CPM in the United States also markedly increased from 1998 to 2005.

The rising rates are both patient and provider driven, Dr. Chang told Medscape Oncology.

Factors Influencing Benefit of CPM

The authors note that their observation that lower breast-cancer-specific mortality is associated with CPM in younger women might be due, at least in part, to the larger absolute lifetime risk for metachronous contralateral breast cancer combined with a low probability of competing causes of death. "For older women, such as [those older than] 60 years, there is a greater chance of comorbidities," said Dr. Chang. "The risk of dying from a different comorbidity may outweigh the risk of dying from another breast cancer."

Among patients with advanced disease, the data suggest that the risk for death from a potential contralateral tumor is outweighed by the mortality risk from their initial breast cancer. "That isn't to say that none of these patients will benefit from CPM," he said, "but we did not see a survival benefit for this group."

The findings are also consistent with the established role of antiestrogen therapy in reducing the risk for contralateral breast cancer. Although the authors note that their analysis could not directly incorporate the use of antiestrogen therapies, the finding that ER-positive women had a 50% reduction in the rate of subsequent contralateral breast cancer, compared with ER-negative patients, "is consistent with the known clinical benefits of tamoxifen therapy."

Improved Survival Limited to Subgroup

Dr. Chang and colleagues used the Surveillance, Epidemiology, and End Results database to identify 107,106 women with breast cancer who had undergone mastectomy between 1998 and 2003. A subset of 8902 women who underwent CPM during this same time period was also identified. The researchers then estimated the association of CPM with breast-cancer-specific survival, with further analyses by age, disease stage, and ER status.

In a univariate analysis, CPM was associated with improved disease-specific survival for women with stages I to III breast cancer (hazard ratio [HR] for death, 0.63; 95% confidence interval [CI], 0.57 - 0.69; P < .001). Risk-stratified analysis showed that this association was due to a reduction in breast-cancer-specific mortality among patients between the ages of 18 and 49 years with stages I or II ER-negative cancer (HR for death, 0.68; 95% CI, 0.53 - 0.88; P = .004).

The 5-year adjusted breast cancer survival for women in this subgroup improved with CPM, compared with those who did not undergo the procedure (88.5% vs 83.7%). Conversely, the authors did not find a reduction in breast-cancer-related death associated with CPM in any of the subgroups of women older than 60 years.

Among women 50 to 59 years of age, CPM was associated with improved breast-cancer-specific survival in those with early-stage ER-negative disease (HR for death, 0.66; 95% CI, 0.45 - 0.97; P = .04) and with later-stage ER-positive disease (HR for death, 0.54; 95% CI, 0.32 - 0.92; P = .02). These findings, the authors note, most likely "reflect the mixed effects of a true association with CPM and unexplained model variance that are caused by differences in the health status among women in this group."

Dr. Chang emphasized that because this was an observational study and not a randomized trial, "a causal relationship between survival and CPM cannot be proved, so we cannot say that there was a benefit or that there was no benefit with CPM."

It is highly unlikely that a randomized trial will be conducted, he pointed out. "But in a large observational study such as this one, we can still show associations with CPM and control for confounders.

The study was funded by the American Society of Clinical Oncology Career Development Award. The authors have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online February 25, 2010. Abstract

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