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HRpos HER2neg ABC

CE / CME

Advancing the Care of Patients With High-Risk ​HR-Positive/HER2-Negative Advanced Breast Cancer

Physician Assistants/Physician Associates: 0.50 AAPA Category 1 CME credit

Nurse Practitioners/Nurses: 0.50 Nursing contact hour

Pharmacists: 0.50 contact hour (0.05 CEUs)

Physicians: maximum of 0.50 AMA PRA Category 1 Credit

Released: August 22, 2025

Expiration: February 21, 2026

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Patient Case: Metastatic Recurrence While ​Receiving Adjuvant ET​



  • 57-yr-old postmenopausal woman had history of high-risk node-positive ER+/HER2- ​
    early breast cancer in 2021; she underwent surgery, received adjuvant chemotherapy and adjuvant radiation therapy, and was started on letrozole ​

  • She also initiated adjuvant abemaciclib but did not tolerate due to poor appetite and diarrhea and stopped it in early 2022 after 6 months of treatment with 2 dose reductions​

  • She presents in spring 2025 with gradual fatigue and weight loss; imaging is notable for findings consistent with MBC, with lesions in bone, mediastinal lymph nodes, and 2 liver lesions​

  • Liver biopsy confirms MBC: ER 50%, PgR 30%, HER2 1+​

  • ctDNA evaluation shows an activating ESR1 mutation and an activating PIK3CA mutation​

  • Laboratory testing is normal; despite her symptoms, she continues to work full time and walks her dog daily​

Which first-line systemic therapy would you recommend?