Real-World Data: Surgery Improves Survival in Treatment Responsive Metastatic Breast Cancer

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 284,200 new cases of breast cancer will be diagnosed in 2021 and about 44,130 individuals will die of the disease largely due to metastatic recurrence. Approximately 15-20% of invasive breast cancers overexpress HER2/neu oncogene and about 50% of HER2-positive breast cancers are Hormone Receptor positive. Patients with HER2-positive metastatic breast cancer are often treated with anti-HER2 targeted therapy along with chemotherapy, irrespective of hormone receptor status, and this has resulted in significantly improved treatment outcomes. Not all HER2-positive, Hormone Receptor positive metastatic breast cancer patients, are candidates for chemotherapy. These patients however may benefit from anti-HER2 targeted therapy given along with endocrine therapy.

Approximately 6% of newly diagnosed breast cancer patients present with Stage IV disease. Systemic therapy has been the cornerstone of treatment for patients with metastatic breast cancer. Breast surgery is often not a consideration for patients with metastatic breast cancer. However, breast surgery can be offered for palliation of symptoms, taking into consideration the risks and benefits of such intervention, in a patient with an ulcerated, bleeding, or a fungating tumor mass, that cannot be controlled with systemic therapy.

Surgical resection of metastatic disease is not a new concept. Previously published results from randomized controlled trials among patients with metastatic breast cancer concluded that there was no survival advantage with surgical intervention. However these results have been questioned because of the small number of participants, and did not take into account either the Hormone Receptor, HER-2 status or the sequence of chemotherapy in relation to the surgical intervention. It therefore remains unclear whether surgery, in addition to systemic treatments and radiation therapy, improves survival for certain patients with metastatic breast cancer.

The authors in this real-world study identified 12,838 patients with HER-2 overexpressing and Hormone Receptor positive, Stage IV breast cancer, from the NCI database. They then studied patients who had either systemic therapy alone, systemic therapy and surgery, or had systemic therapy, surgery and radiation, and evaluated whether certain biologic subtypes and timing of chemotherapy were associated with survival advantages. Specifically, they evaluated whether the Hormone Receptor status had an influence on surgical benefit, in these treatment-responsive breast cancer patients, understanding that triple negative breast cancers are not very responsive to treatment. The researchers excluded patients who died within six months of their diagnoses, in order to ensure that only treatment-responsive cancers were being studied. The goal of this study was to understand if surgery made a difference in metastatic breast cancers that were responsive to treatment.

The researchers noted that patients with a surgical intervention tended to have a longer survival, compared to patients with other treatment plans. Patients whose cancers were HER2-positive saw prolonged survival, especially when their treatment plan included surgery. Further, in addition to the benefit of surgery among treatment-responsive metastatic breast cancer patients, the authors noted that systemic therapy before surgery (preoperative systemic therapy which included chemotherapy and targeted therapies) had the greatest survival advantage in patients with positive HER-2 and Estrogen and Progesterone Receptor status.

It was concluded from this study that patients with Stage IV breast cancer responsive to systemic therapy may be able to benefit from the addition of surgery, regardless of their biologic subtype. The authors added that clinicians should evaluate real-world evidence, including this study, when choosing the optimal treatment for their patients with metastatic breast cancer, as it may be difficult to conduct randomized clinical trials in this patient population.

ASO Author Reflections: Surgery Offers Survival Advantage in Treatment-Responsive Metastatic Breast Cancer. Stahl K, Dodge D, and Shen C. Annals of Surgical Oncology, 2020; DOI: 10.1245/s10434-020-09286-9