Mastectomy Benefits Questioned in Stage IV Breast Cancer

Neil Osterweil

December 12, 2013

SAN ANTONIO — Mastectomy might not be the best choice for all women with metastatic breast cancer, contend investigators here at the 36th Annual San Antonio Breast Cancer Symposium.

In a randomized clinical trial of 350 women with metastatic breast cancer, those who underwent mastectomy and removal of axillary lymph nodes (plus radiation therapy) did not have better overall survival rates than women treated with medication alone, reported Rajendra Badwe, MD, director of the Tata Memorial Hospital in Mumbai, India.

At 72 months, overall survival was 20.5% for patients treated with locoregional therapy and 19.2% for those treated without it. The hazard ratio (HR) for surgery was 1.04 and was not significant.

Although local progression-free survival was better with surgery/radiation (HR, 0.16), distant progression-free survival was worse (HR, 1.42; P = .01). The results suggest that removing the primary tumor enabled or somehow fostered the growth of distant metastases, Dr. Badwe reported at a symposium press briefing.

"The clinical conclusion would be that locoregional treatment of the primary tumor in women presenting with metastatic breast cancer did not result in any overall survival benefit, and hence should not be offered as a routine practice," he concluded.

"The biological fallout of this study is that surgical removal of the primary tumor in these women appears to confer a growth advantage on distant metastases," he added.

The findings are likely to be practice changing, said Kent Osborne, MD, director of the Dan Duncan Cancer Center at the Baylor College of Medicine in Houston, who moderated the briefing.

Going forward, it is possible that mastectomy will be reserved for women with fungating and/or heavily bleeding masses.

"This is not to say that we shouldn't do mastectomies in the appropriate patient, but this trial would argue against doing it as a routine in all patients, but only perhaps in patients in whom it is going to be a cosmetic problem on the chest wall with a large, infected mass," Dr. Osborne explained.

Prospective Data Say Otherwise

But a breast cancer surgeon who was not involved in the study cautioned against too hasty an interpretation of the findings.

Other data from the Translational Breast Cancer Research Consortium prospective registry "do not show the same thing at all," said Tari A. King, MD, associate professor of surgery at Weill-Cornell Medical College and associate attending surgeon at the Memorial Sloan-Kettering Cancer in New York City.

She and her colleagues conducted a nested study within this registry and prospectively looked at 127 women with stage IV breast cancer at first diagnosis. The team analyzed outcomes for women who did not have surgery, which is the usual approach for such patients, and for those who did. Some of the women who did have surgery in the registry study were unexpectedly diagnosed with metastatic disease after surgery for what was thought to be localized disease.

None of the women in this group had died of metastatic disease at 2-year follow-up, and more than 60% had not progressed, she told Medscape Medical News. In other words, surgery did not seem to worsen their metastatic disease, she explained.

Dr. King noted that the women in the study from India did not have the benefit of targeted hormonal or anti-HER2 therapy.

"We know that [drug therapy] has led to the improvement in overall survival in the metastatic setting. I fear that if we lose sight of that in interpreting the results from Dr. Badwe's team, we're losing the opportunity to really identify the subset of women who may potentially benefit from local therapy," she said.

Were Fisher et al Right?

Dr. Badwe explained that these are the first data in humans supporting the research work of Bernard Fisher, MD, and colleagues from the University of Pittsburgh. In 1989, they reported that the removal of a primary tumor in mice with metastases released a growth factor that contributed to the growth of distant tumor (Cancer Res. 1989;49:1996-2001).

Dr. Fisher and his coauthors wrote that "the findings presented refute the premise that removal of a primary tumor is a local phenomenon with no other biological consequences. They indicate that, following primary tumor removal, metastatic behavior may be affected by an interplay of growth factor(s) which can influence the outcome of a host to its tumor."

Dr. Badwe noted that the practice of offering mastectomy to women with metastatic disease is based on retrospective nonrandomized studies that suggested there was a possible benefit from locoregional therapy.

In their study, Dr. Badwe and colleagues evaluated 350 women with stage IV breast cancer. After a course of anthracyclines, with or without taxanes, patients were stratified by metastatic site, number of metastases, and hormone-receptor status, and then randomized to either locoregional therapy or no locoregional therapy.

A total of 173 were randomized to locoregional therapy — surgery plus radiotherapy — and 177 to hormonal therapy as indicated, including ovarian ablation. No HER2-positive patients received trastuzumab or any other HER2-targeted therapy.

In a subgroup analysis, there was no difference in benefit according to menopausal status, metastatic site, number of metastases, or hormonal or HER2 status.

The study was funded by the Tata Memorial Center and the Department of Atomic Energy Clinical Trial Center in India. The study authors have disclosed no relevant financial relationships.

36th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S2-02. Presented December 11, 2013.

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