Effectiveness of neo-adjuvant systemic therapy with trastuzumab for basal HER2 type breast cancer: results from retrospective cohort study of Japan Breast Cancer Research Group (JBCRG)-C03

• Published in: Breast cancer research and treatment 2018-10, Vol.171 (3), p.675-683
• Main Authors: Sagara, Yasuaki, Takada, Masahiro, Ohi, Yasuyo, Ohtani, Shoichiro, Kurozumi, Sasagu, Inoue, Kenichi, Kosaka, Yoshimasa, Hattori, Masaya, Yamashita, Toshinari, Takao, Shintaro, Sato, Nobuaki, Iwata, Hiroji, Kurosumi, Masafumi, Toi, Masakazu
• Format: Article
• Language: English
• Subjects: Adjuvant chemotherapy; Analysis; Breast cancer; Cancer research; Cancer therapies; Care and treatment; Chemotherapy; Clinical Trial; Cohort analysis; Epidermal growth factor; Epidermal growth factor receptors; Epidermal growth factors; ErbB-2 protein; Gene expression; Genetic aspects; Immunotherapy; Medical prognosis; Medicine; Medicine & Public Health; Monoclonal antibodies; Oncology; Patients; Phenotypes; Prognosis; Targeted cancer therapy; Trastuzumab
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-018-4873-0

Purpose While human epidermal growth factor receptor 2 (HER2) target therapies have significantly improved the prognosis of patients with HER2-enriched breast cancer, differing clinical benefits and gene expression analyses suggest a divergent HER2 subgroup. We aimed to investigate whether the basal HER2 subtype of breast cancer has distinguished characteristics. Methods We performed a substudy by using data from a retrospective multi-institutional cohort of JBCRG-C03. Between 2001 and 2011, we identified 184 eligible patients who received concurrent neo-adjuvant chemotherapy (NAC) with trastuzumab for hormone receptor-negative and HER2-positive breast cancer. We defined basal HER2 subtype breast cancer as HER2-positive, ER/PgR-negative, and basal markers (EGFR, CK14 or CK5/6) positive by immunohistochemistrical evaluation. The pathologic complete response (pCR) and disease-free survival (DFS) rates were compared between the two subtypes. Results A total of 127 (69.0%) patients achieved pCR after NAC and 29 (15.8%) patients experienced events of DFS within a 42 month median follow-up period (interquartile range 26–58 months). Although the basal HER2 subtype was related with poor DFS (3 year DFS: non-basal HER2, 95.0%; basal HER2, 86.9%; adjusted HR 3.4; 95% CI 1.2–14.5), neither the subtype (pCR: non-basal HER2, 75%; basal HER2, 66.7%; adjusted OR 0.60; 95% CI 0.27–1.28) nor the degree of expression of basal markers was significantly related with the pCR rate. Conclusion Basal HER2 phenotype showed poor DFS, but equivalent pCR rate after concurrent neo-adjuvant chemotherapy with trastuzumab. A different treatment approach to basal-HER2 type is needed even for cases that achieved adequate clinical response after NAC.