Genomic index of sensitivity to endocrine therapy for breast cancer

W. Fraser Symmans, Christos Hatzis, Christos Sotiriou, Fabrice Andre, Florentia Peintinger, Peter Regitnig, Guenter Daxenbichler, Christine Desmedt, Julien Domont, Christian Marth, Suzette Delaloge, Thomas Bauernhofer, Vicente Valero, Daniel J. Booser, Gabriel N. Hortobagyi, Lajos Pusztai

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    Abstract

    Purpose: We hypothesize that measurement of gene expression related to estrogen receptor α (ER; gene name ESR1) within a breast cancer sample represents intrinsic tumoral sensitivity to adjuvant endocrine therapy. Methods: A genomic index for sensitivity to endocrine therapy (SET) index was defined from genes coexpressed with ESR1 in 437 microarray profiles from newly diagnosed breast cancer, unrelated to treatment or outcome. The association of SET index and ESR1 levels with distant relapse risk was evaluated from microarrays of ER-positive breast cancer in two cohorts who received 5 years of tamoxifen alone as adjuvant endocrine therapy (n = 225 and 298, respectively), a cohort who received neoadjuvant chemotherapy followed by tamoxifen and/or aromatase inhibition (n = 122), and two cohorts who received no adjuvant systemic therapy (n = 208 and 133, respectively). Results: The SET index (165 genes) was significantly associated with distant relapse or death risk in both tamoxifen-treated cohorts (hazard ratio [HR] = 0.70, 95% CI, 0.56 to 0.88, P = .002; and HR = 0.76, 95% CI, 0.63 to 0.93, P = .007) and in the chemo-endocrine-treated cohort (HR = 0.19; 95% CI, 0.05 to 0.69, P = .011) independently from pathologic response to chemotherapy, but was not prognostic in two untreated cohorts. No distant relapse or death was observed after tamoxifen alone if node-negative and high SET or after chemo-endocrine therapy if intermediate or high SET. Conclusion: The SET index of ER-related transcription predicted survival benefit from adjuvant endocrine therapy, not inherent prognosis. Prior chemotherapy seemed to enhance the efficacy of adjuvant endocrine therapy related to SET index.

    Original languageEnglish
    Pages (from-to)4111-4119
    Number of pages9
    JournalJournal of Clinical Oncology
    Volume28
    Issue number27
    DOIs
    Publication statusPublished - 20 Sept 2010

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