Pathologic complete response to neoadjuvant targeted therapy in locally advanced invasive lobular breast cancer

An 84-year-old woman with estrogen receptor-positive, progesterone receptor-negative, HER2-positive invasive lobular carcinoma (ILC) of the right breast achieved a pathologic complete response following neoadjuvant therapy with dual HER2 blockade (trastuzumab and pertuzumab) combined with letrozole. This report discusses key clinical and molecular factors, including tumor grade, Ki-67 proliferation index, and nodal response, that may influence sensitivity to combined HER2 and endocrine blockade. It explores biological indicators of sensitivity to endocrine and HER2-directed therapy, emphasizing how strong, uniform HER2 overexpression, low progesterone receptor expression, and a luminal B-like profile may together signal a tumor subtype that responds to dual blockade. This case illustrates the potential for chemotherapy-free regimens in select older adults with favorable tumor biology.