Nuvera assay for predicting endocrine therapy response published in Journal of Clinical Oncology
September 7, 2010, Woburn, MA.
Nuvera Biosciences, a company developing novel molecular diagnostics for therapy response, announced today the publication of its work in prediction of endocrine therapy response, "Genomic Index of Sensitivity to Endocrine Therapy for Breast Cancer," in the August 9 online issue of the Journal of Clinical Oncology. The authors include Dr. Christos Hatzis, co-founder and VP, Technology at Nuvera, and collaborators from leading cancer institutions worldwide.
Existing genomic tests for breast cancer provide information about future risk of recurrence in general, but are not informative of the likely benefit from specific treatment options for each individual. For example, about 70% of breast cancers express the estrogen receptor (ER), however, anti-estrogen therapies, such as tamoxifen, only benefit half of these patients. A genomic index for sensitivity to endocrine therapy (SET) was defined from genes co-expressed with the estrogen receptor using 437 newly diagnosed breast cancer samples, unrelated to treatment or outcome.
The SET index consisting of 165 genes was evaluated for predicting relapse risk in ER-positive breast cancer patients who received different treatment strategies: (i) two cohorts of patients who received 5 years of tamoxifen alone as adjuvant endocrine therapy (n=225 and n=298, respectively), (ii) a cohort who received neoadjuvant chemotherapy followed by tamoxifen and/or aromatase inhibition (n=122), and (iii) two cohorts who received no adjuvant systemic therapy (n=208 and n=133, respectively).
The SET index was significantly associated with distant relapse in both tamoxifen-treated cohorts (hazard ratio=0.70, P=.002; and HR=0.76, P=.007) and in the chemo-endocrine–treated cohort (HR=0.19; P=.011) but was not prognostic in two untreated cohorts.
The investigators report the first genomic assay that provides independent prediction about the likely benefit from adjuvant hormonal therapy. “Better understanding of a patient’s sensitivity to endocrine therapy would help decide on a particular hormonal treatment and whether to rely on hormonal therapy alone or precede it with chemotherapy,” says lead author Dr. Symmans.
An editorial accompanying the publication (Oesterreich S, Lee AV, Davidson NE, J. Clin Oncol. 2010 Aug 9) states that the need to improve decision-making about the success of endocrine therapy and to refine the choice of agent remains paramount. That the SET index is predictive of benefit from endocrine therapy but that it does not predict for prognosis is different from many other previously reported gene signatures, which are largely prognostic of outcome in the absence of therapy. There is little doubt that multigene tests will continue to revolutionize our ability to estimate breast cancer prognosis and predict therapy response. Studies like the one by Symmans et al bring us closer to replacing ER and PR IHC with more accurate tests of higher positive predictive value.
Ultimately, explains Dr. Hatzis, predictors such as this will help guide the decision whether to follow surgery with chemotherapy, endocrine therapy, both, or neither. “When a patient’s tumor is predicted to have a low risk of recurrence and is also shown as insensitive to both chemo- and endocrine therapies, the best option is surgery alone. However, sensitivity to therapy independent of the risk of recurrence is important because a patient might elect to receive further therapy if her cancer is known to be highly susceptible to treatment.”
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