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KEY CONCEPTS

  • Metastatic breast cancer (MBC) most commonly arises from prior early-stage breast cancer and is incurable, with prognosis influenced by disease subtype (hormone receptor [HR] and HER2 receptor status).

  • Treatment of MBC is increasingly guided by disease biology, and the armamentarium of treatments includes several targeted agents, antibodies and antibody-drug conjugates, and checkpoint inhibitors.

  • Patients can live many years with MBC and preserving quality of life, minimizing toxicity, and shared patient-physician decision making are paramount in planning the best treatment strategy.

  • Endocrine therapy remains the backbone of treatment for HR-positive MBC and now includes CDK4/6 inhibitors as standard frontline treatment.

  • The clinical outcomes of patients with HER2-positive MBC continue to improve because of the efficacy of therapies that target the HER2 kinase pathway including pertuzumab, ado-trastuzumab emtansine, and tucatinib.

  • Metastatic triple-negative breast cancer remains the breast cancer subtype with the worst prognosis. However, multiple clinical trials are underway that incorporate immunotherapy, antibody-drug conjugates, and targeted therapies in an effort to improve outcomes over those achieved with standard chemotherapy.

INTRODUCTION

Breast cancer is the most common malignancy diagnosed in women in the United States and is a significant cause of morbidity and mortality. Approximately 268,600 new cases of invasive breast cancer occurred in the United States in 2019. Although lung cancer has surpassed breast cancer as the leading cause of cancer death among women, an estimated 41,760 deaths occurred from breast cancer in 2019.1

Since the 1970s, advances in combined-modality therapies have improved the outcomes of patients with early-stage breast cancer. Still, a significant proportion of patients with early-stage, localized breast cancer will have relapse with distant metastatic disease. The risk and timing of relapse varies widely among patients with breast cancer and is dependent on hormone receptor (HR) (estrogen receptor [ER] and progesterone receptor [PR]) and HER2/neu receptor (HER2) status as well as initial tumor (T) and nodal (N) staging. For example, among patients with ER-positive, stage T1 disease, the risk of distant recurrence at 20 years is 13% for patients without nodal involvement, 20% for 1 to 3 involved nodes, and 34% for 4 to 9 involved nodes, and the recurrence risk remains steady up to 20 years after diagnosis.2 For patients with HER2-positive or triple-negative breast cancer (TNBC), the risk of recurrence after treatment of a primary breast tumor is highest within the first 5 years of diagnosis and depends not only on the initial TN staging, but also on the degree of sensitivity to HER2-targeted treatment and/or chemotherapy. For example, in the HER2-positive, neoadjuvant TRYPHAENA trial, 3-year disease-free survival was 87% to 90% regardless of regimen; however, patients achieving a pathologic complete response (pCR) were far more likely to be disease-free at 3 years (hazard ratio 0.27; 95% CI 0.11–0.64). Patients with TNBC with a pCR or minimal residual disease after neoadjuvant chemotherapy have an 80% to 90% chance of cure, whereas patients with significant residual disease have a more ...

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