See article, p. 198.

In breast cancer, some mutations in ERBB2 (encoding HER2) are associated with oncogenic addiction to HER2 signaling. Building on a phase II trial of single-agent treatment with the irreversible pan-HER inhibitor neratinib in patients with ERBB2-mutant solid tumors, Smyth and colleagues added a cohort of heavily pretreated patients with ERBB2-mutant metastatic breast cancer to evaluate the combination of neratinib with fulvestrant, a selective estrogen receptor (ER) degrader. Eighty-one patients were enrolled, including 47 (all HR+) treated with neratinib plus fulvestrant and 34 (23 HR+ and 11 HR−) treated with neratinib alone. Across both groups, unique ERBB2 mutations were identified in 22 patients, and the distribution of mutations was as expected for patients with breast cancer. The overall response rate (ORR) in the monotherapy group was 17.4% in patients with ER+ disease and 36.4% in patients with ER...

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