Response to adjuvant chemotherapy in Luminal A patients

Purpose: Luminal A breast cancers have better prognosis than other molecular subtypes. Luminal A cancers may also be insensitive to adjuvant chemotherapy, although there is little high level evidence to confirm this concept. The primary hypothesis in this formal prospective-retrospective analysis was to assess interaction between subtype (Luminal A vs. other) and treatment (chemotherapy vs. not) for the primary endpoint (10-year invasive disease free survival) of a breast cancer trial randomizing women to adjuvant chemotherapy, analyzed in multivariate Cox proportional hazards models using the Wald interaction test. Experimental Design:The Danish Breast Cancer Cooperative Group 77B clinical trial randomized 1072 premenopausal women to no systematic treatment (control), levamisole, cyclophosphamide or cyclophosphamide-methotrexate-fluorouracil arms. All arms included radiotherapy but no endocrine therapy. Researchers with no access to clinical data performed intrinsic subtype analysis on tissue microarrays using published immunohistochemical methods based on estrogen receptor, progesterone receptor, HER2, Ki67 and basal markers. Results:709 patients had tissue available; chemotherapy benefit in these patients was similar to the original trial (hazard ratio (HR) 0.56). Immunohistochemistry classified 165 as Luminal A, 319 Luminal B, 58 HER2-enriched and 82 core basal (among 91 triple negative). Patients with Luminal A breast tumors did not benefit from chemotherapy (HR 1.06, 95% confidence interval 0.53-2.14, p = 0.86), whereas patients with non-luminal A subtypes did (HR 0.50, 95% confidence interval 0.38-0.66, p < 0.001); p (interaction) = 0.048. Conclusions: In a prospective-retrospective analysis of a randomized trial, patients with Luminal A breast cancers did not benefit from adjuvant cyclophosphamide-based chemotherapy.

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