Primary Breast Tumor Surgery Improves Overall Survival in HER2 Positive Advanced 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 268,600 new cases of invasive breast cancer will be diagnosed in 2019 and about 41,760 women will die of the disease. The HER or erbB family of receptors consist of HER1, HER2, HER3 and HER4. Approximately 15-20% of invasive breast cancers overexpress HER2/neu oncogene, which is a negative predictor of outcomes without systemic therapy. Approximately 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. HER2-targeted therapies include HERCEPTIN® (Trastuzumab), TYKERB® (Lapatinib), PERJETA® (Pertuzumab) and KADCYLA® (ado-Trastuzumab emtansine). Dual HER2 blockade with HERCEPTIN® and PERJETA®, given along with chemotherapy (with or without endocrine therapy), as first line treatment, in HER2 positive metastatic breast cancer patients, was shown to significantly improve Progression Free Survival (PFS) as well as Overall Survival. The superior benefit with dual HER2 blockade has been attributed to differing mechanisms of action and synergistic interaction between HER2 targeted therapies. 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.

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. A few previously published studies which evaluated the addition of surgical resection of the primary tumor to systemic therapy, among patients with metastatic HER2-positive breast cancer, have provided mixed results, with one study showing improved outcomes. The authors therefore conducted a retrospective study to examine the impact of primary breast tumor resection on survival, in HER2-positive Stage IV breast cancer patients, treated with HER2 targeted therapy.

This retrospective cohort study included records of 3,231 women with HER2 positive Stage IV breast cancer from the National Cancer Database, from 2010 to 2012. Of these women, 89.4% had received chemotherapy/anti-HER2 targeted therapies, 37.7% had received endocrine therapy, 31.8% had received radiation and 25% of the patients had bone only metastasis. Overall, 1,130 women (35%) underwent primary breast tumor resection. The mean age of those who had surgery was 56 years and the Primary endpoints were receipt of surgery and Overall Survival (OS).

At a median follow-up of 21.2 months, the median OS for patients who had surgery was 25 months compared with 18 months for those who did not undergo surgical resection (HR=0.56; P=0.0004). This suggested a 44% reduction in the risk of death with primary breast tumor resection. Patients having Medicare/other government or private insurance, as well as those who received radiation, chemotherapy/anti-HER2 targeted therapies and endocrine therapy were more likely to have surgery. Additionally, Caucasian women were also more likely than non-Hispanic black women, to have surgery. These findings suggested that women with Medicare or private insurance as well as white women were also more likely to have surgery and less likely to die of their disease, than non-Hispanic black women, and those with Medicaid or no insurance.

It was concluded that after controlling for independent variables, surgery of the primary site, in patients with metastatic HER2 positive breast cancer who are managed with present day contemporary treatment, is associated with improved Overall Survival. Breast surgery should therefore be discussed as a part of the treatment strategy, for qualified women, in this patient group. The impact of primary tumor surgery on survival in HER2 positive stage IV breast cancer patients in the current era of targeted therapy. Mudgway R, Chavez de Paz Villaneva C, Lin AC, et al. Presented at AACR Annual Meeting; March 29 to April 3, 2019; Atlanta, GA. Abstract 4873.