Abstract P2-08-10: Similarities between low hormone receptor positive and hormone receptor negative breast cancer: An analysis of 4366 patients from multicenter clinical trials
Authors: SL Villegas, B Lederer, M Untch, F Holms, H-U Ulmer, K Diebold, PA Fasching, K Weber, WD Schmitt, H Tesch, M Rezai, F Marmé, B Sinn, J Hackmann, A Schneeweiss, A Tannapfel, V Nekljudova, C Denkert, S Loibl
Journal: Cancer Research (2019)

Abstract Background: Currently, patients with breast cancer (BC) with hormone receptor (HR) immunohistochemical expression between 1-9% are eligible to receive endocrine therapy. However, recent data suggest that these tumors express a basal-like molecular phenotype associated with triple negative BC (TNBC) rather than luminal phenotype associated with HR positive BC. Here, we aimed to determine the differences between strong HR positive, low HR positive and negative HR BC, in regard to responsiveness to neoadjuvant chemotherapy (NACT) and disease free survival (DFS) in large cohorts from GBG clinical trials. Methods: In this retrospective analysis of data from women with BC treated in the neoadjuvant GeparQuinto (n=2572), GeparSixto (n=588) and GeparSepto (n=1206) clinical trials, we compared patients with three HR phenotypes: low positive (ER and/or PR= 1-9%), strong positive (ER or PR= 10-100%), and negative (ER and PR= &amp;lt;1%), regarding pathological complete response (pCR, ypT0 ypN0) and DFS. A logistic regression model for endpoint pCR was performed on pooled data from all trials. Cox regression was used to model DFS for patients participating in GeparQuinto and GeparSixto trial, including 71 with low HR positive phenotype. The models were adjusted by age, tumor and nodal status, grading, Her2 status, histological type, stromal and tumor infiltrating lymphocytes and clinical trial. The survival model was additionally adjusted by pCR after NACT. Results: Patients median age was 49 years, the majority had clinical tumor stage 2 (54.1%), negative nodal status (54.7%), and Her2 negative tumors (72.4%). 85.1% of women had BC classified as no special histological type. The pCR rate across the studies was 26.2%. 145 (3.4%) patients had low HR positive, 2417 (57.3%) strong HR positive and 1658 (39.3%) HR negative tumors. After NACT, 16.3% of patients with strong HR positive BC achieved a pCR, while among those with HR negative and low HR positive tumors, pCR rates were 40.2% and 37.9%, respectively (p&amp;lt;0.001). In the adjusted logistic regression model, there was no statistically significant difference between low HR positive and HR negative tumors (OR: 1.34, 95%-CI: (0.84-2.13), p=0.222). But strong HR positive tumors had a significantly lower chance of achieving a pCR compared to low HR positives (OR 0.48, 95%-CI: 0.30-0.76, p=0.002). Patients with strong HR positive BC had a better DFS than patients with low HR positive tumors (hazard ratio 0.35, 95%-CI: 0.18-0.70, p=0.003). DFS was not significantly different between patients with HR negative and low HR positive tumors (hazard ratio 0.74, 95%-CI: 0.38-1.43, p=0.370). Conclusions: Similarly to patients with negative HR tumors, patients with low HR positive tumors have a better responsiveness to NACT and worse survival rates, compared to patients with strongly HR positive BC. We suggest that studies on treatment options for basal-like/TNBC, should also consider including patients with low HR positive tumors. Citation Format: Villegas SL, Lederer B, Untch M, Holms F, Ulmer H-U, Diebold K, Fasching PA, Weber K, Schmitt WD, Tesch H, Rezai M, Marmé F, Sinn B, Hackmann J, Schneeweiss A, Tannapfel A, Nekljudova V, Denkert C, Loibl S. Similarities between low hormone receptor positive and hormone receptor negative breast cancer: An analysis of 4366 patients from multicenter clinical trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-10.