Survival Not Extended by Locoregional Treatment of MBC

Photo Courtesy © SABCS/Todd Buchanan 2013

Rajendra Badwe, MD

According to the results of a prospective, randomized, controlled trial, in women with metastatic breast cancer that responds to frontline chemotherapy, locoregional treatment (LRT) of the primary tumor and axillary nodes does not produce an increase in overall survival (OS).

Locoregional treatment should therefore not be offered to such patients in routine clinical practice, said Rajendra Badwe, MD, in discussing clinical trial findings at the 2013 San Antonio Breast Cancer Symposium. Instead, the indication for surgery would be confined to palliation for fungating or bleeding primary breast tumors.

In the United States, 5% to 10% of women with breast cancer present with metastatic disease, a percentage that has changed little in the past decade, and retrospective analyses of LRT for this patient population have yielded conflicting results, said Badwe, director of the Tata Memorial Hospital in Mumbai, India, during a press briefing Wednesday. He suggested that oncologists who do not recommend LRT for such patients could now feel more comfortable avoiding surgery.

In fact, preclinical evidence dating to 1989 suggests that removal of a primary tumor may facilitate growth of metastatic disease, said Badwe. Fisher et al found that metastasis increased in mice after tumor removal due to a serum growth factor capable of stimulating distant cells (Cancer Res. 1989;49(8):1996-2001).

Retrospective institutional series and population-based series in clinical cohorts, in contrast, suggest favorable impact of surgery and/or local radiotherapy in these patients. The retrospective analyses, however, “were fraught with selection bias,” said Badwe, director of the Tata Memorial Hospital in Mumbai, India.

To assess the impact of locoregional treatment on outcome in women with metastatic breast cancer at initial diagnosis, Badwe and colleagues recruited 350 women with metastatic breast cancer and an objective partial or complete tumor response to six cycles of chemotherapy (anthracyclines ± taxanes). Patients were randomized to either LRT or no LRT. Patients randomized to LRT underwent breast conservation or total mastectomy and surgical removal of axillary lymph nodes, followed by radiotherapy. Patients in either arm with estrogen receptor-positive tumors received standard endocrine therapy if appropriate. The two arms were matched for age, clinical tumor size, hormone receptor, and HER2 receptor status, and the number of metastases.

The primary endpoint of the study was OS. During a median follow-up of 17 months, no difference was observed in OS between those who received LRT and those who did not receive LRT; the OS rates were 19.2% and 20.5%, respectively, (HR = 1.04; 95%CI, 0.80-1.34;P= 0.79). The median OS rates in the LRT and no-LRT arms were 18.8 months and 20.5 months, respectively. OS after 2 years was 40% in the LRT arm and 43.3% in the no-LRT arm. There was no advantage to LRT in any of the subgroups examined by menopausal status, metastatic site, number of metastases, hormone receptor status, and HER2 status.

“The lack of a survival benefit is due to a trade-off between local control and distant disease progression,” said Badwe. Progression of distant disease was 42% more likely (P= .01) in the LRT arm whereas the risk of local progression was 84% lower with LRT.

“Fisher showed that when a mouse with metastatic and primary tumors has the primary tumor removed, the metastatic tumor grows faster. This suggests that the primary tumor has an inhibitory effect,” said Kent Osborne, MD, director of the Dan L. Duncan Cancer Center and the Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, who moderated the press briefing. “We know that tumors grow rapidly, and when they reach a certain volume, they plateau and grow more slowly. Maybe with large metastatic disease they are at that plateau, and by lowering the volume [of the primary tumor], they’re able to grow faster again. The factor responsible for this is unknown.”

Badwe R, Parmar V, Hawaldar R, et al. Surgical removal of primary breast tumor and axillary lymph nodes in women with metastatic breast cancer at first presentation: a randomized controlled trial. Presented at: 2013 San Antonio Breast Cancer Symposium; December 10-14, 2013; San Antonio, TX. Abstract S2-02.

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