Surgery Shows Potential Survival Benefit in Metastatic HER2+ Breast Cancer

Ross Mudgway

Data from a retrospective cohort study suggest that surgery for patients with stage IV metastatic HER2-positive breast cancer may be associated with a survival benefit, explained Ross Mudgway.

“We thought treating the primary tumor [in metastatic breast cancer] wasn't necessary; however, now that these patients are living longer with these targeted therapies, we are finding that maybe treating the primary tumor with excision may lead to some survival benefit,” said Mudgway, the lead author of the study, which was conducted at Loma Linda University.

At the 2019 AACR Annual Meeting, Mudgway, a medical student at the University of California, Riverside School of Medicine, presented research tackling the controversy surrounding treating patients with stage IV HER2-positive breast cancer with surgery after they receive targeted therapy, dependent on their response.

The retrospective cohort study looked at 3231 women. In that group, 89.4% received chemotherapy/immunotherapy, 37.7% received endocrine therapy, 31.8% received radiation, and 35% received surgery. Factors that contributed to a physician’s decision to offer a patient surgery included comorbidities, response to other therapies, and overall life expectancy.

Results showed that, at a median follow-up of 21.2 months (range, 0-52), the median overall survival for patients who had surgery was 25 months compared with 18 months in those who did not undergo resection, leading to a 44% reduction in the risk of death (HR, 0.56; 95% CI, 0.40-0.77; P = .0004).

The study also investigated factors associated with surgery. Patients with Medicare or private insurance were more likely to have surgery than those with Medicaid or no insurance. Caucasian patients were also more likely to receive surgery than African Americans. Further research, however, is needed to confirm the findings of this study.

“From our research, we want physicians to consider surgery to treat HER2-positive stage IV breast cancer; however, we want to bring to light and make sure physicians are aware there are a lot of health disparities that exist and need to be addressed,” said Mudgway. “Although surgery may have a survival benefit, we think it should be considered alongside systemic therapy and other standards of care to provide the best overall treatment to [patients with] breast cancer.”

In an interview with OncLive, Mudgway discussed the importance of considering surgery for patients with stage IV HER2-positive breast cancer and addressed disparities in healthcare among different social groups.

OncLive: What recent advances have been made in the treatment of patients with stage IV HER2-positive breast cancer?

Mudgway: Prior research on the role of surgery in treating patients with metastatic breast cancer has demonstrated mixed results on the role of surgery and survival for stage IV disease. Some prior studies have provided evidence that surgery may provide a survival benefit, while other studies have shown there is no survival benefit to surgery.

For example, a study in India found that surgery had no benefit at long-term follow-up. Meanwhile, one of the most significant studies in this field in Turkey showed that surgery did have a survival benefit.

How has treatment in the field shifted in recent years?

One of the most significant reasons why we decided to do this study was due to the explosion of the new medications that are used to treat HER2-positive cancer, such as trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), and ado-trastuzumab emtansine (T-DM1; Kadcyla). Because of all these studies, patients with HER2-positive breast cancer are now having longer survival and are living a lot longer than usual.

In the past, surgery was not considered one of the reasons to treat someone with metastatic breast cancer because it was thought that patients with metastatic breast cancer would succumb to their diseases from their metastases.

What is the role of surgery in patients with stage IV HER2-positive breast cancer?

The role of surgery is variable. It depends on what the patient is presenting with. At our clinic at Loma Linda University, when patients present with metastatic breast cancer, we first start them with systemic therapy involving chemotherapy, hormonal therapy, and targeted therapy and we see how they respond to the therapy.

If they respond positively, then we consider them for surgical excision. The surgery can vary depending on if it's a total mastectomy, partial mastectomy, nipple sparing, or skin sparing. It also depends on the extent of the breast cancer, and it ultimately comes down to a discussion between the entire oncology team and the patient. It's usually a case-by-case basis to see what the patient desires and how the surgery can not only improve their disease, but also their quality of life (QoL).

What was the rationale for this study?

In our clinic, we were finding that patients were responding positively to the HER2-positive targeted therapies. We started giving them surgeries because it was warranted after careful discussion among interdisciplinary oncology team and patients themselves. They were surviving and doing well; however, we found that we did not have any evidence to back up the rationale to do surgery in this patient population.

Preliminary findings from prior studies showed mixed results of surgery, and some showed that surgery may have a survival benefit. We wanted to analyze this further in a specific subset of stage IV patients with HER2-positive breast cancer. We were pleased to find surgery was associated with improved survival; however, we were not able to control all the variables. Future randomized control trials are needed so they can further elucidate the role of surgery.

Could you expand on the key findings from your research?

The first key finding is that surgery was overall associated with improved survival. That was one of our main outcomes, and that's what we are most interested in, so that was pleasing to hear. The second key finding is that health disparities were highlighted through the study. Some patients were more likely to have surgery and others were not. For example, we found that patients who were of an African-American race and of lower income were less likely to receive surgery.

We would like to point out that those findings with the disparities is not new. Those data have been corroborated through a lot of prior research on disparities in not just breast cancer, but cancer care as a whole. It was interesting that those disparities were highlighted again. We believe there are a lot of different factors that come into play regarding racial and social factors in treating care. Future studies can benefit from looking at racial and social factors more and including a diverse patient population so we can further address these health disparities.

What ways can the healthcare field address disparities due to socioeconomic factors?

One way this can be done is by finding some way to mandate diversity in the patient accrual in different, randomized, controlled trials. Ensuring the patient population in the sample is as diverse as possible will be very helpful. There's so much that can be done via retrospective and prospective studies, where we can highlight these disparities and hopefully bring more awareness to decrease that gap in disparities. However, making a difference in addressing the health disparities should ultimately be done at a health policy level.

What factors that physicians should consider when deciding to recommend surgery?

First, physicians should look at the patient as a whole. It’s imperative that patients are first started on systemic therapy, which is the standard of care for treating patients with stage IV breast cancer. We need to look at them after they respond to chemotherapy, hormonal therapy, and targeted therapy based on their tumor status. After seeing how they respond to the treatment of systemic therapy, we need to look at them individually and see if they can benefit from surgery.

Although our findings show that surgery had a survival benefit in this patient population, we are aware that it is a very individual case-by-case basis. Some patients may not be expecting to live as long or they may not want to have surgery. There are so many risks and so many emotional decisions that come into play since surgery, especially breast surgery, can affect QoL. We want to make sure that providers in the future are encouraged to consider surgery as an option for treating patients with stage IV breast cancer, but it should be a long discussion with the provider and the patient.

Mudgway R, Chavez de Paz Villaneva C, Lin AC, et al. The impact of primary tumor surgery on survival in HER2 positive stage IV breast cancer patients in the current era of targeted therapy. Presented at: 2019 AACR Annual Meeting; March 29 to April 3, 2019; Atlanta, GA. Abstract 4873.