Prognosis of early breast cancer by immunohistochemistry defined intrinsic sub-types in patients treated with adjuvant chemotherapy in the NEAT/BR9601 trial.

Abstract

Breast cancer can be classified into molecular sub-types that have distinct survival patterns. We evaluated the prognostic significance of breast cancer sub-types in a cohort of women taking part in the NEAT and BR9601 clinical trials comparing cyclophosphamide, methotrexate and fluorouracil (CMF) with ECMF (epirubicin and CMF). Furthermore, we evaluated whether the sub-types were predictive of the added benefit of epirubicin in these trials. Tumour tissue microarrays were stained and scored for ER, PR, HER2, EGFR and CK5/6. These were used to classify the tumours into six intrinsic sub-types. We used Cox regression to compare overall survival (OS), breast cancer-specific survival (BCSS) and relapse-free survival (RFS) in the different sub-groups. We also compared the effect of ECMF with CMF by sub-group. Immunohistochemistry data were available for 1,725 cases of whom 805 were luminal 1-basal negative. Median follow-up time was 7 years. The luminal 1-basal negative tumours were associated with the best prognosis in five years after surgery and the HER2-like tumours were associated with the poorest prognosis. There was little evidence for significant heterogeneity of this effect by tumour sub-type (OS p = 0.40, BCSS p = 0.53 RFS p = 0.50) - the largest additional benefit of epirubicin was in women with tumours of the 5-negative phenotype (OS HR = 0.39 95% CI: 0.21-0.73) and the smallest was in Luminal 1-basal negative tumours (OS HR = 0.86 95% CI: 0.64-1.16). We confirmed that breast cancer sub-types show distinct behaviour with differences in short- and long-term survival. The benefit of ECMF over CMF was statistically similar in all disease sub-types.

• Authors: Alaa M Ali, Elena Provenzano, John M S Bartlett, Jean Abraham, Kristy Driver, Alison F Munro, Christopher Twelves, Christopher J Poole, Louise Hiller, Janet A Dunn, Helena M Earl, Carlos Caldas, Paul D Pharoah
• Journal: International journal of cancer (Int J Cancer) Vol. 133 Issue 6 Pg. 1470-8 (Sep 15 2013) ISSN: 1097-0215 [Electronic] United States
• PMID: 23483540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 UICC.

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (chemistry, drug therapy, mortality, pathology)
• Chemotherapy, Adjuvant
• Clinical Trials as Topic
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasm Staging
• Prognosis
• Proportional Hazards Models