Clinical features of early-stage (I-III) triple-negative breast cancer (TNBC) patients with tumours exhibiting low-overall change in molecular profile after neoadjuvant therapy

Abstract Background Seth et al. (ASCO 19) identified four biologic classes based on longitudinal molecular profiling of TNBC tumors pre- and post- neoadjuvant adriamycin/cyclophosphamide (AC). The four groups were defined based on the enriched and depleted hallmark pathways that were observed. The low-overall change (LOC) group was defined as having no significant change in the pathways in pre- and post-AC biopsies. Of note, this group of patients had lower pathological complete response (pCR) rates. The aim of this study is to describe the clinical features of early-stage (I-III) TNBC patients with tumors exhibiting LOC in their biopsies with neoadjuvant therapy. Methods We analyzed the clinical characteristics of 48 patients with early stage (I-III) TNBC enrolled in the ARTEMIS trial (NCT02276443). All patients received neoadjuvant AC; 48% of patients were subsequently treated on a clinical trial and 52% received standard taxane-based chemotherapy. We compared the clinical characteristics of 17 patients in the LOC group with 31 patients in the other three biologic classes. Two-group comparison was performed using Chi-squared test. Results Age at diagnosis, histology, Vanderbilt subtype, Ki-67, sTIL levels and vimentin expression were similar between the groups. Median age at diagnosis in the LOC group was 58 (range, 27-74). All patients in this group were stage II-III, with no stage I identified. 59% of patients in the LOC group had stage III disease compared with 26% in the other groups (p = 0.02), Also, 47% of patients in this group had AR ≥ 10% compared to 19% in the other biological groups (p = 0.04). Table . 252P Variable Group Low-Overall Change Group (n = 17) % Other Biologic Classes (n = 31) % p Age at diagnosis ≤60 10 59 25 81 0.10 >60 7 41 6 19 Stage I 0 0 6 19 N/A II 7 41 17 55 0.36 III 10 59 8 26 0.02 Histology Invasive ductal 15 88 26 84 0.23 Metaplastic 0 0 4 13 Apocrine 1 6 0 0 Other 1 6 1 3 Vanderbilt subtype BL 3 18 8 26 0.24 LAR 4 24 2 6 M/MSL 3 18 11 35 IM 2 12 4 12 Ki-67 (%) ≥ 50 8 47 21 68 0.16 9 53 10 32 Androgen Receptor Expression (%) ≥ 10 8 47 6 19 0.04 9 53 25 81 Vimentin Expression (%) ≥50 2 12 4 13 0.91 15 88 27 87 sTIL Low ( 7 41 15 48 0.37 Moderate (≥5-30) 9 52 11 35 High (>30) 0 0 1 3 Conclusions Patients with low-overall change in their tumors had later-stage disease and higher AR expression. Previous analysis by Seth et al. has demonstrated a lower pCR rate in this group with standard neoadjuvant chemotherapy. This analysis highlights the potential role of androgen deprivation in this class of tumors. Legal entity responsible for the study The authors. Funding The University of Texas MD Anderson Cancer Center Moonshots Program and a CPRIT Multi-Investigator Research Award (MIRA). Disclosure S. Moulder: Research grant / Funding (self): Pfizer; Research grant / Funding (self): Genentech; Research grant / Funding (self): Novartis; Research grant / Funding (self): Seattle Genetics; Research grant / Funding (self): EMD Serono; Research grant / Funding (self): Bayer; Research grant / Funding (self): AstraZeneca. All other authors have declared no conflicts of interest.