ATLANTA-Surgical resection of the primary tumor may offer a significant survival advantage for women with HER2-positive (HER2+) stage IV breast cancer, according to data presented at the American Association for Cancer Research annual meeting.

Researchers found that women who underwent surgery had 44 percent longer survival than those who did not, according to Ross Mudgway, a third-year medical student at the University of California, Riverside School of Medicine (Abstract 4873).

With senior author Sharon Lum, MD, Professor of Surgical Oncology and Medical Director of the Breast Health Center at Loma Linda University, the investigators also found significant surgical disparities between insured and uninsured women.

Those with Medicare or private insurance coverage were more likely to have surgery and less likely to die of their disease than were those with other coverage or no insurance. In addition, Caucasian women were also more likely than non-Hispanic (NH) African-American women to have surgery and less likely to die of their cancer.

"In the current era, where HER2-targeted therapy has led to improved survival for HER2-positive metastatic breast cancer, our study suggests that surgery may be associated with even better survival," said Mudgway. "Our results suggest that providers must consider patients individually when considering surgery and be aware that disparities in who receives surgery exist and should be addressed."

Lum said HER2 status has been reported in large registry datasets since the early 2000s, but the impact of surgery on this type of breast cancer has not been well-documented across hospital systems. Between 20 and 30 percent of new stage IV breast cancer patients are HER2+. Prior analyses of survival rates have provided mixed results, but treatment advances are changing that, she noted.

"Until recently, patients diagnosed with HER2+ stage IV breast cancer had poor survival rates. However, with recent advances in systemic treatment survival rates have improved," Lum explained.

"Our findings should be considered in the context of all other factors," Mudgway added. "For patients, the decision to undergo breast surgery, especially a mastectomy, can often be life-changing as it affects both physical and emotional health. The patient's own feelings about whether or not she wishes to have surgery should be considered."

Numerous factors may contribute to a physician's decision with regard to recommending surgery, including comorbidities, response to other forms of treatment, and overall life expectancy. The retrospective study may not be fully representative of women facing the decision of whether to have surgery, the researchers said. For example, doctors may be most willing to operate on women who are healthier overall and, therefore, are more likely to experience a positive outcome.

Methodology, Other Findings

The research team retrospectively examined data on 3,231 women with HER2+ stage IV breast cancer in the National Cancer Database from 2010 to 2012. They found that 89.4 percent had received chemotherapy or targeted therapies, 37.7 percent had received endocrine therapy, and 31.8 percent had received radiation. Overall, 1,130 women, or 35 percent, received surgery.

Of the 3,231 patients, 71.3 percent were NH white; 18.4 percent were NH black; and 5.8 percent were Hispanic. In 25 percent of the cases, metastases were only seen in bone. The mean age of those who had surgery was 56.0 years compared to 59.1 years who did not, and the median follow-up was 21.2 months.

Among factors associated with increased odds of surgery were having private insurance (42.3%), Medicare/government coverage (30.5%), and having undergone radiation therapy (47.4%) versus 28.8 percent who did not. Among women who had surgery, 36.5 percent also received chemotherapy or immunotherapy versus 22 percent who did not. Patients who received endocrine therapy were also more likely to undergo surgery at 41.3 percent compared to 31.3 percent.

Women treated at an academic institution were less likely to have undergone surgery than those treated in a community practice (29.1% vs. 37.1%). By age, those between 20 and 39 years had a 44.4 percent likelihood of undergoing surgery, versus 36.9 percent in women 40 and 59 years of age, and 30.9 percent of women over the age of 60, the researchers found.

Commentary

Karen Sokolov, MD, Assistant Professor of Radiation Oncology at City of Hope, South Bay, in Torrance, Calif., said the findings provide "hopeful evidence" that should lead to future prospective studies to test the validity of these results.

Although advances in targeted systemic therapies have, on their own, significantly improved survival rates in these patients, surgical treatment of local disease in metastatic patients remains controversial in the case of stage IV breast cancer, she told Oncology Times.

"For patients faced with HER2+ stage IV breast cancer, the findings signify a possible improvement in prognosis with the addition of surgery to remove the primary breast tumor, especially when compared with the current standard of care of only systemic therapy," she said. "Although numerous factors need to be taken into consideration when proceeding with local surgery in metastatic disease, patients can discuss with their oncologists the possibility of surgery in addition to standard systemic therapies."

Sokolov said that conclusive evidence from prospective randomized studies would need to precede any alteration to the present standard of care for patients.

"The suggestion of a 44 percent increase in survival with the addition of surgery is encouraging; however, many selection biases can be present in a retrospective review that may impact this result. Patients offered surgery tend to be younger and healthier, exhibit a favorable response to systemic therapy, have a lower disease burden, or have a more favorable histology."

She also said the study findings were limited by lack of information on timing of surgery or details of other therapies received by these patients, all factors which would need to be considered and controlled for in order to determine if surgery is truly improving outcomes and to what magnitude.

Sokolov noted the findings that patients from disadvantaged communities were less likely to have surgery, and have a poorer survival, were at least partly due to inferior insurance coverage.

"If future studies lead to a change in the standard of care to include surgical resection of the primary breast tumor, insurance plans would provide coverage of surgery. This would, in theory, help bridge the gap in quality of care provided to underprivileged communities."

Kurt Samson is a contributing writer.