Surgery Tied to Improved Survival in Stage IV Breast Cancer

Alexander M. Castellino, PhD

April 03, 2019

ATLANTA — Women with human epidermal receptor 2–positive (HER2+) stage IV breast cancer who received surgery after systemic therapy were at a 44% reduced relative risk for death compared with women who did not undergo surgery. The finding comes from a retrospective analysis reported on April 3 at the American Association for Cancer Research (AACR) 2019 (abstract 4873).

"This suggests that in addition to standard HER2-targeted therapy and other adjuvant treatments, if a woman has stage IV HER2+ breast cancer, surgery to remove the primary breast tumor should be considered," said senior study author Sharon Lum, MD, medical director of the Breast Health Center at Loma Linda University, California.

Ross Mudgway

"For patients, the decision to undergo breast surgery, especially a mastectomy, can often be life-changing, as it affects both physical and mental health," lead author Ross Mudgway, a medical student at the University of California, Riverside, School of Medicine, said in an AACR statement. "The patient's own feelings about whether or not she wishes to have surgery should be considered," he added.

"This study should have no impact on clinical practice at this time," Monica Morrow, MD, chief of breast surgery at Memorial Sloan Kettering Cancer Center, New York City, told Medscape Medical News.

Whether surgery becomes routine practice for patients with stage IV breast cancer will depend on the results of the ECOG E2108 (NCT01242800) randomized trial, led by Seema Khan, MD, Morrow indicated. "The trial will answer the question whether surgery is beneficial in stage IV disease," she said. She noted that accrual for the trial is complete but that results have not yet been published.

Surgery in Stage IV Breast Cancer: Perspective From Breast Cancer Surgeons

Lum agreed that retrospective data do not offer good-quality evidence with respect to changes in guideline recommendations. The new study is hypothesis-generating, but having been a breast cancer surgeon for 20 years, she is convinced that these data already confirm the current trends among breast cancer surgeons, especially in the community setting.

"These data support what we do in clinical practice," she said.

"Clinical practice does not always wait for data from randomized clinical trials," Lum told Medscape Medical News. She pointed out that sentinel lymph node biopsy was in clinical practice long before randomized clinical trials provided confirmatory evidence.

Lum was drawn to the idea of surgery for women with metastatic breast cancer after observing that women who underwent surgery were living longer with no residual disease. Anecdotally, she pondered that perhaps her young, healthy patients would live longer after surgery, which would prevent the tumor from recurring in the breast of origin.

Morrow indicated that the question of whether surgery should play a role in the treatment of patients with stage IV breast cancer has been around for more than 15 years.

She explained that multiple retrospective studies such as the current one have shown a benefit in patients selected for surgery, but all of these studies were confounded by selection bias — the patients who underwent surgery were healthier and responded better to chemotherapy than those who did not receive surgery. "So, there is no way to know if they would have done equally well without the surgery," she said.

Lisa Newman, MD, chief of breast surgery at Weill Cornell Medicine and New York–Presbyterian Hospital, New York City, offered her own perspective on the study.

"That surgery improves survival makes sense in terms of the evolution of our thoughts on operating on women with stage IV disease," she said. Newman explained that historically, surgery has been undertaken in the palliative setting for bulky disease or in cases of bleeding in the metastatic setting.

"But because we have become successful in treating metastatic breast cancer with systemic therapy, which has been associated with longer survival times, there is a resurgence of interest beyond surgical intervention in the palliative setting," she told Medscape Medical News.

Newman agreed that results from retrospective studies have been mixed, perhaps because of selection bias, but also added, "Women who do best with surgery have low burden of disease and where best systemic therapies are available, as in HER2+ metastatic breast cancer."

"Offering surgery to these women may likely improve outcomes," she said.

Morrow noted that what is new about this study is that it evaluated in particular the subset of HER2+ patients for whom very effective drugs are available for treatment, making it particularly tempting to believe surgery is beneficial. "It is not part of our routine practice," she said. She explained that surgery was offered to women when they were participating in studies evaluating its benefit.

Newman noted that it is important to be thoughtful and apply sound judgment when offering surgery to these women. It is important to let the patient know whether surgery may provide benefit, and women have to be open to exercise their option, because surgery has associated risks and complications.

"At present, surgery in stage IV breast cancer is recommended only in cases where there is uncontrolled growth of the tumor in the breast," Morrow said. In this circumstance, it is performed to improve quality of life, she explained.

"In the majority of cases, if the metastatic sites are responding [to systemic therapy], so is the tumor in the breast, so surgery is uncommonly needed for this purpose," Morrow said.

Lum indicated that the opportunity to perform surgery in these patients is not a frequent occurrence, but it's definitely not a "never."

"In my practice, we do selective surgery on patients who have an opportunity for a longer survival," she remarked. "I perform surgery on a highly select group of patients," she said. She indicated that such individuals are typically young, healthy, and have no other risks for death. It is an option exercised through an open discussion first between the treating medical oncologist, who follows how the patient is responding to systemic therapy, the surgeon, and eventually the patients.

Newman shared similar opinions. For physicians who are likely to offer surgery to women with HER2+ stage IV cancer, she had some advice. "First, it is important to see that systemic therapy is working and see the evidence of the response. Surgery in these women may decrease disease burden. Women who have distant organ metastases are not candidates for surgery," she said.

Study Details

Mudgway and colleagues extracted information about surgery and survival for women with HER2+ stage IV breast cancer from the National Cancer Database from 2010, the year in which HER2 reporting started, to 2012.

Of more than 2.7 million women in the database, 58,867 had HER2+ invasive breast cancer; 3231 reported surgery designation (ie, whether or not the patient underwent surgery; 1130 underwent surgery) and were included in the analysis.

The database provided detailed demographic information on age, ethnicity, insurance status, clinical tumor and nodal stage, and the type of therapy patients received.

Overall, 71.3% of patients were non-Hispanic white, and 18.4% were non-Hispanic black; 46% had private insurance, 32% were covered by Medicare or other government insurance, and 23% were noninsured or were on Medicaid.

Also, 31% received radiotherapy, 89% of patients received chemotherapy and/or immunotherapy (ie, HER2-targeted therapy), and 38% received endocrine therapy. Surgery to the primary site was undertaken in 35% of patients.

Registry data offer an excellent source for teasing out disparities in care, Lum said.

The study found that patients with private insurance were more likely to have surgery and less likely to die of their disease compared with those with no insurance or those who received Medicaid. White women were more likely to receive surgery and live longer than black women.

In addition, women who underwent care at academic institutions and academic centers were less likely to receive surgery. This may run counter to trends in which patients are more likely to receive multimodal treatment at academic centers and research institutions than in community settings.

Lum suggested a reason why women who received treatment in comunity centers were more likely to undergo surgery: "With limited access to drugs and clinical trials at community centers, women in these places may have been offered surgery," she said.

After controlling for confounders, surgery was associated with improved survival (hazard ratio: 0.56; 95% confidence interval: 0.40 – 0.77).

"Even with propensity matching, we still cannot account for all selection bias, which may have accounted for improved outcomes with surgery," Lum told Medscape Medical News.

The authors have disclosed no relevant financial relationships.

American Association for Cancer Research (AACR) 2019: Abstract 4873. Presented April 3, 2019.

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