How I Treat: A 63-Year-Old Woman With ER+/PR+/HER2-Negative Metastatic Breast Cancer

Neelima Vidula, MD I Massachusetts General Hospital I Boston, MA

Introduction. A 63-year-old woman with ER+/PR+/HER2-negative metastatic breast cancer presents to the clinic.

Patient history. At 50 years of age, she had a right breast ER+/PR+/HER2- breast cancer treated with surgery, radiation, and an aromatase inhibitor for 10 years. She has also developed back pain and was found to have bone metastases involving the spine without cord compression.

Diagnostic examination. The computed tomography (CT) chest-abdomen-pelvis (C/A/P) and bone scan demonstrated liver metastases and bone metastases. A biopsy of a liver metastasis demonstrates estrogen receptor (ER)-positive (90%)/progesterone receptor (PR)-positive (90%)/human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer (immunohistochemistry 2+, Fluorescence In Situ Hybridization-copy number 2.1, ratio 1.1). Tumor tissue genotyping of the liver mass shows FGFR1 and CCND1 mutations. Genetic testing is negative for BRCA1/2.

Treatment and management. She starts treatment with ribociclib/letrozole, which she was on for 2 years when CT imaging showed new liver metastases. Her liver enzymes are within normal ranges. She undergoes cell-free DNA testing, which has an ESR1 mutation. She started elacestrant and remained on treatment for 5 months, at which time, there are progressive liver metastases. She then switched to everolimus/exemestane followed by capecitabine with progressive liver metastases at this time.

Discussion. Patients with HR+/HER2-negative metastatic disease will eventually develop resistance to endocrine therapies, at which time, chemotherapy may be considered. However, we also have new antibody drug conjugates (ADCs) approved for HR+/HER2-negative metastatic breast cancer, including sacituzumab govitecan and trastuzumab deruxtecan.

The patient was started on trastuzumab deruxtecan 5.4 mg/kg IV every 3 weeks, given the HER2 low disease and one prior chemotherapy. In the DESTINY Breast-04 study, trastuzumab deruxtecan was associated with an improvement in both progression-free survival (PFS) and overall survival (OS) compared with chemotherapy of the physician’s choice.¹ In HR+ disease in this study, the median PFS was 10.1 months with trastuzumab deruxtecan vs 5.4 months with chemotherapy, and the median OS was 23.9 months with trastuzumab deruxtecan vs 17.5 months with chemotherapy. Trastuzumab deruxtecan is now approved for HR+/HER low metastatic disease after one prior chemotherapy.  

In the TROPICS-02 study evaluating sacituzumab govitecan vs chemotherapy of the physician’s choice in HR+/HER2- metastatic breast cancer, the median PFS was 5.5 months with sacituzumab govitecan vs 4.0 months with chemotherapy, and the median OS was 14.4 months with sacituzumab govitecan vs 11.2 months with chemotherapy.^2,3 Sacituzumab govitecan is FDA approved for HR+/HER2- metastatic breast cancer after prior endocrine therapy and 2+ prior systemic therapies in the metastatic setting.

Conclusion. I selected trastuzumab deruxtecan for this patient, given the compelling survival data in the presence of worsening liver metastases and one prior chemotherapy. In addition, the dosing schedule every 3 weeks was appealing to the patient. In my practice, I have certainly tried sequential ADCs, which is being studied.