Abstract P3-11-14: Is pathologic complete response (pCR) a valid marker of outcome even in large breast cancer? Clinical results from a neoadjuvant trial using a combination of epirubicin, docetaxel and bevacizumab (PROMIX)
Authors: Hatschek Thomas , Bjöhle Judith , Lidbrink Elisabet , Lekberg Tobias , Loman Niklas , von Wachenfeldt Väppling Anna , Söderberg Martin , Einbeigi Zakaria , Carlsson Lena , Lindman Henrik , Fredriksson Irma , Frisell Jan , Löfgren Lars , Rydén Lisa , Hellström Mats , Fernö Mårten , Bergh Jonas 
Published: May 2015

Abstract
Background: Several randomized trials have proven that preoperative chemotherapy is equivalent to adjuvant treatment, and allows for clinical and radiological assessment of efficacy in vivo. Recent results show that response-guided neoadjuvant therapy is a favorable policy for hormone receptor positive tumors, while pCR predicts prognosis for triple-negative (TNBC) and HER2 positive breast cancer (von Minckwitz 2013; Cortazar 2014). Since 2012 the FDA accepts pCR (ypT0 ypN0) as endpoint for accelerated drug approval.
Methods: In total, 150 women 18 years or older with verified HER2 negative breast cancer suitable for primary medical treatment were included in the trial between September 2008 and December 2011. The patients received two courses of epirubicin and docetaxel (Taxotere®), both 75mg/m2 for the 1st two courses, followed by the same treatment with addition of bevacizumab (Avastin®) 15 mg/kg for 4 additional courses. Clinical and radiological evaluations with mammography and ultrasound were performed before start and after courses 2, 4 and 6. Core biopsies were taken before start, after 2 courses, and at time of surgery. Blood samples were drawn before and 24 hours after the first 4 courses.
Results: Median age was 49 years, range: 27 to 70 years; 73% were reported as ductal, 15% as lobular, and 12% as rare histological types. Mean tumor size was 59 mm, median 55 mm, range: 20-180 mm; 3 tumors (2.0%) were reported as inflammatory, and 13 (8.7%) presented with skin involvement (T4b). Enlarged axillary nodes were found in 102 patients (68%) before start of treatment, 77 of these (64%) verified as metastatic. SNB in cases of normal axillary status was performed in 16 cases, in 9 cases (8%) with positive finding. Supra- or infraclavicular node involvement was verified in 20 cases (13%). 25% of all tumors were ER- and/or PR-negative, tumor grade based on a diagnostic biopsy was evaluable in only 83 cases. Of these, 4 (5%) were grade I, 46 (55%) grade II, and 33 (40%) grade III. Mean proliferation count (Ki67) was 37%, median 30%, range 1-90%. Breakdown into intrinsic subtypes based on immunohistochemistry defined 68 (46%) as luminal A-like, 36 (24%) as luminal B-like, and 44 (30%) as TNBC. pCR was achieved in 20 cases, 3 (2%) luminal A-like, 5 (3.4%) luminal B-like and 12 (8.2%) TNBC. After 2.2 years of follow-up, 35 patients (23.3%) have experienced recurrence and 18 of these (12%) have deceased due to breast cancer, among these 6 despite pCR, 2 classified as luminal B-like, and 4 as TNBC. The molecular subtype of the tumor predicted outcome, but pCR was not in our material, even after adjustment for tumor size at diagnosis, a predictor of favorable outcome. The number of events in relation to molecular subtypes is however limited. Updated outcome data will be presented.
Conclusions: The present trial does not confirm previously reported observations that pCR is a marker of favorable prognosis. One possible explanation is that unfavorable biological characteristics, particularly heterogeneity, may increase with tumor burden. Genomic and proteomic analyses are currently ongoing.
Citation Format: Thomas Hatschek, Judith Bjöhle, Elisabet Lidbrink, Tobias Lekberg, Niklas Loman, Anna von Wachenfeldt Väppling, Martin Söderberg, Zakaria Einbeigi, Lena Carlsson, Henrik Lindman, Irma Fredriksson, Jan Frisell, Lars Löfgren, Lisa Rydén, Mats Hellström, Mårten Fernö, Jonas Bergh. Is pathologic complete response (pCR) a valid marker of outcome even in large breast cancer? Clinical results from a neoadjuvant trial using a combination of epirubicin, docetaxel and bevacizumab (PROMIX) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-14.