Abstract P6-14-09: Clinical outcomes of triple negative inflammatory breast cancer treated with contemporary anthracycline and taxane preoperative therapy support further investigation of therapeutic targets

Abstract

Abstract Background: Approximately 40-50% of inflammatory breast cancer (IBC) is triple negative (TN), defined as estrogen and progesterone receptor and HER2 negative. The poor prognosis associated with TN- IBC lends itself to active investigation of novel therapies to improve outcome. Dr. Kornelia Polyak’s laboratory has demonstrated a significant association of JAK2/STAT3 pathway activity in TN-IBC (Overmoyer, Cancer Res 2012). In preparation of designing a clinical trial investigating the effect of JAK2 inhibition by ruxolitinib on biologic parameters and subsequent use in neoadjuvant chemotherapy (NAC) for TN-IBC, we determined historical outcomes resulting from a single institution’s contemporary standard treatment of TN-IBC. Methods: Among the 273 pts enrolled in the IRB approved IBC database at the Dana Farber Cancer Institute, 28 pts were identified with Stage III (T4d,NX,M0)TN-IBC diagnosed from 1/1/1999 to 12/31/2011 who were treated with standard NAC including anthracycline, cyclophosphamide and taxane. Time to treatment failure (TTF) was defined from diagnosis (dx) to first progression or recurrence; time to distant metastasis (TDM) was defined from dx to first metastasis at a distant site; overall survival was defined from dx to death from any cause. Subsequent to NAC, 25 pts underwent modified radical mastectomy (MRM) and radiation. For those 25 pts, disease-free survival (DFS) was defined from MRM to first recurrence or death; time to local/regional recurrence (LRR) was defined from MRM with death as competing risk. All time-to event endpoints were censored at the date last known alive if an event was not observed. Results: Among 28 patients, the median TTF was 19 months (mo) with 67% free from progression/recurrence at 1 year (yr) after dx (95% CI, 51-87%). Median TDM was 20 mo with 78% free from distant metastases at 1 yr (CI 64-95%). Most patients (13/21) had multiple sites of first distant metastasis including: lung (7), contralateral axilla (7), bone (6), liver (3) and CNS (3). Median OS was 34 mo since dx (Table). Among 25 patients who underwent MRM, median DFS was 15 mo with 1-yr DFS of 58% (42-82%); the cumulative probability of LRR was 13% and 33% at 1 and 2 yr. table1 OS probability95% CI1-year96%89%-100%2-year73%57%-92%3-year49%32%-75% Conclusions: This retrospective analysis of clinical outcomes of Stage III TN-IBC treated with contemporary anthracycline/taxane regimes is consistent with previously reported outcomes using historical NAC regimens. (Li, et al, the Oncologist 2012). These dismal rates of 49% 3-year OS from diagnosis and 58% 1-yr DFS following MRM demand more active investigation into novel targeting agents which can be combined with standard NAC specifically for the treatment of TN-IBC; a disease that has no known therapeutic target. For this reason DFCI is actively investigating the role of inhibiting the JAK2/STAT3 pathway using ruxolitinib in conjunction with standard weekly paclitaxel followed by AC as NAC for TN-IBC. Clinical trial information: NCT01796197. Citation Format: Beth Overmoyer, Hao Guo, Laura E Warren, Jennifer R Bellon, Kornelia Polyak, Faina Nakhlis, Judith Hirshfield-Bartek, Heather Jacene, Eren D Yeh, Meredith Regan, Inflammatory Breast Cancer International Consortium. Clinical outcomes of triple negative inflammatory breast cancer treated with contemporary anthracycline and taxane preoperative therapy support further investigation of therapeutic targets [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 P6-14-09.