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Medline ® Abstract for Reference 27

of 'Prognostic and predictive factors in metastatic breast cancer'

27
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Prognostic Value of Intrinsic Subtypes in Hormone Receptor-Positive Metastatic Breast Cancer Treated With Letrozole With or Without Lapatinib.
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Prat A, Cheang MC, Galván P, Nuciforo P, ParéL, Adamo B, Muñoz M, Viladot M, Press MF, Gagnon R, Ellis C, Johnston S
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JAMA Oncol. 2016 Oct;2(10):1287-1294.
 
Importance: The value of the intrinsic subtypes of breast cancer (luminal A, luminal B, human epidermal growth factor receptor 2 [currently known as ERBB2, but referred to as HER2 in this study]-enriched, and basal-like) in the metastatic setting is currently unknown.
Objective: To evaluate the association of the intrinsic subtypes of breast cancer with outcome and/or benefit in hormone receptor (HR)-positive metastatic breast cancer.
Design, Setting, and Participants: Unplanned retrospective analysis of 821 tumor samples (85.7% primary and 14.3% metastatic) from the EGF30008 phase 3 clinical trial (NCT00073528), in which postmenopausal women with HR-positive invasive breast cancer and no prior therapy for advanced or metastatic disease were randomized to letrozole with or without lapatinib, an epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor. Tumor samples were classified into each subtype using the research-based PAM50 classifier. Prior neoadjuvant/adjuvant antiestrogen therapy was allowed. Patients with extensive symptomatic visceral disease were excluded. Treatment effects were evaluated using interaction tests.
Main Outcomes and Measures: Primary and secondary end points were progression-free survival and overall survival.
Results: The median (range) age was 62 (31-94) years. Intrinsic subtype was the strongest prognostic factor independently associated with progression-free survival and overall survival in all patients, and in patients with HER2-negative (n = 644) or HER2-positive (n = 157) diseases. Median progression-free survival differed across the intrinsic subtypes of clinically HER2-negative disease: luminal A (16.9 [95% CI, 14.1-19.9]months), luminal B (11.0 [95% CI, 9.6-13.6]months), HER2-enriched (4.7 [95% CI, 2.7-10.8]months), and basal-like (4.1 [95% CI, 2.5-13.8]months). Median OS also differed across the intrinsic subtypes: luminal A (45 [95% CI, 41-not applicable {NA}]months), luminal B (37 [95% CI, 31-42]months), HER2-enriched (16 [95% CI, 10-NA]months), and basal-like (23 [95% CI, 12-NA]months). Patients with HER2-negative/HER2-enriched disease benefited from lapatinib therapy (median PFS, 6.49 vs 2.60 months; progression-free survival hazard ratio, 0.238 [95% CI, 0.066-0.863]; interaction P = .02).
Conclusions and Relevance: This is the first study to reveal an association between intrinsic subtype and outcome in first-line HR-positive metastatic breast cancer. Patients with HR-positive/HER2-negative disease with a HER2-enriched profile may benefit from lapatinib in combination with endocrine therapy. The clinical value of intrinsic subtyping in hormone receptor-positive metastatic breast cancer warrants further investigation, but patients with luminal A/HER2-negative metastatic breast cancer might be good candidates for letrozole monotherapy in the first-line setting regardless of visceral disease and number of metastases.
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Translational Genomics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain2Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain3Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain.
PMID