Department of Medicine, Research Unit in Medical Senology, and Division of Pathology and Laboratory Medicine, European Institute of Oncology, Università degli Studi di Milano, Milan; Department of Pathological Anatomy, University of Bari, Bari; Centro di Riferimento Oncologico, Aviano, Italy; Department of Mathematics and Statistics, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT; International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard School of Public Health, Boston, MA; Oncology Institute of Southern Switzerland, Bellinzona; International Breast Cancer Study Group, Bern, Switzerland; University of Sydney, Sydney, Australia; and Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom.
J Clin Oncol. 2010 May 10.
Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents.
Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present.
Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor-absent, and endocrine receptor-present subtypes. No clear chemotherapy benefit was observed in endocrine receptor-present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor-present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor-absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor-present disease).
The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.
PMID: 20458051 [PubMed - as supplied by publisher] Source: National Library of Medicine.
