Abstract PS2-07-19: Proteomic subtyping of stage II/III TNBC from the I-SPY2 TRIAL reveals a druggable steroid hormone receptor signature (SRS) that is associated with poor outcome and enriched in non-pCR patients’ residual disease
Abstract
I-SPY Triple Negative Breast Cancer (TNBC) Response Predictive Subtypes (RPS) predict for benefit from immunotherapy and DNA damaging agents in Immune+ and DNA Repair Deficient (DRD) subgroups. We explored TNBC subtyping based on functional protein/phosphoprotein architecture and previously described a subset of TNBC that expresses high relative levels of estrogen receptor alpha (ERα)1. These ERα “high” TNBC express a steroid hormone receptor signature (SRS) characterized by co-incidentally increased expression of ERα, activated glucocorticoid receptor (pGR S211) and total androgen receptor (AR), present in ∼30% of TNBC. We have now investigated the drug target activation architecture of SRS-positive (SRS+) TNBC and associations of SRS+ status with outcomes in I-SPY2 patients not responding to neoadjuvant therapy.
Quantitative reverse phase protein array (RPPA) data from laser capture microdissection-enriched tumor epithelium comprised of 153 proteins/phosphoproteins, including ERα, AR, and pGR S211, were obtained from 253 I-SPY2 TNBC patients at pre-treatment baseline1 as well as in patient-matched surgical residual disease samples from 48 non-pCR TNBC patients. The SRS score was determined based on the equally weighted rank-sum addition of the 3 SRS analytes. SRS scores above and below the population median were considered SRS+ and SRS-negative (SRS-), respectively. Clinical information was provided by Quantum Leap Health Care Collaborative. For survival status and…
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