Skill Checkup: A 64-Year-Old Woman With a Breast Mass and Back and Hip Pain

Maurie Markman, MD

Disclosures

September 08, 2021

Correct Answer: A. Aromatase inhibitor plus a CDK4/6 inhibitor

Preferred first-line systemic endocrine-based therapy options, which are category 1 recommendations (based on phase 3 clinical trial evidence) per National Comprehensive Cancer Network (NCCN) clinical practice guidelines, include an aromatase inhibitor (ie, anastrozole, exemestane, or letrozole) in combination with a CDK4/6 inhibitor (ie, palbociclib, ribociclib, or abemaciclib); fulvestrant with or without a nonsteroidal aromatase inhibitor (ie, anastrozole or letrozole); or fulvestrant in combination with a CDK4/6 inhibitor.

Given that HR-positive/HER2-negative metastatic breast cancer will ultimately progress after first-line therapy, second-line systemic endocrine-based therapy options must be considered. Preferred second-line systemic endocrine-based therapy options, which are category 1 recommendations per the NCCN guidelines, include fulvestrant in combination with a CDK4/6 inhibitor (if a CDK4/6 inhibitor was not utilized in the first-line setting) or fulvestrant in combination with alpelisib (only in patients with PIK3CA mutations). Other preferred second-line systemic endocrine-based therapy options include everolimus in combination with exemestane, tamoxifen, or fulvestrant; fulvestrant monotherapy; nonsteroidal aromatase inhibitor monotherapy; or selective estrogen receptor modulator monotherapy.

A HER2 receptor antagonist, with or without chemotherapy, is used only for HER2-positive breast cancer. According to the NCCN guidelines, most women with HER2-positive breast cancer will receive one or more chemotherapy drugs plus trastuzumab, the anti-HER2 receptor antagonist. Many studies have shown that these treatments dramatically improve survival for women with HER2-positive breast cancer.

Currently, cytotoxic chemotherapy (eg, with a taxane) remains the mainstay of systemic treatment for triple-negative disease, although studies are investigating the use of other drug classes, including checkpoint inhibitors, agents that target the androgen receptor pathways, and antibody-drug conjugates.

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