Abstract P6-12-05: The impact of residual disease after preoperative systemic therapy on clinical outcomes in patients with inflammatory breast cancer
Authors: Nakhlis F , Regan MM , Warren LE , Bellon JR , Yeh ED , Jacene HA , Golshan M , Duggan MM , Dominici LS , Hirshfield-Bartek J , Mullaney EE , Overmoyer BA 
Published: August 2014

Introduction. Inflammatory breast cancer (IBC) is a rare and aggressive subtype of breast cancer treated with multimodality therapy consisting of preoperative systemic therapy (PST) followed by modified radical mastectomy (MRM) and chest wall and regional nodal radiation and if appropriate extended biologic therapy and/or endocrine therapy. In non-IBC patients (pts) the degree of pathologic response to PST has been shown to correlate with time to recurrence (TTR) and overall survival (OS). We sought to determine if the degree of pathologic response predicts clinical outcomes in IBC pts.

Methods. With IRB approval, we reviewed the records of IBC pts seen at Dana Farber/Brigham and Women's Cancer Center between 1997 and 2012. From 117 IBC pts, all of whom have had PST, followed by MRM and radiotherapy, 98 pts with stage III disease were analyzed. Statistical analysis: TTR - time from surgery until first locoregional or distant recurrence, or censored at date of last follow-up or death of other causes. OS - time from surgery until death from any cause or censored at date the pt last known to be alive. Pathologic complete response (pCR) - no residual invasive disease in the breast and axillary lymph nodes. Pathologic response to PST, disease characteristics (estrogen (ER), progesterone receptor (PR), Her2 status, grade, histology) and receipt of Her2-directed PST when indicated were evaluated as predictors of TTR and OS by Cox model.

Results 42 (43%) of 98 pts have experienced recurrence (1 local, 4 locoregional+distant, 31 distant). Median TTR = 5.1yrs. 40 pts died; 4 of other causes; median OS = 5.1yrs. pCR was associated with improved TTR (HR = 0.22, 95% CI 0.07-0.70, p = 0.011 univariate analysis); 5yr freedom from recurrence was 81% vs 40% with vs without pCR. The association remained after adjusting for disease and treatment characteristics (HR = 0.25, 95% CI 0.07-0.85, p = 0.026 multivariable). pCR was associated with better OS (HR = 0.35, 0.12-1.03, p = 0.06 multivariable).

TTR and OS according to pCR or no pCRFreedom from recurrenceno pCRpCRAll2-yr58%88%64%2-yr47%81%55%5-yr40%81%51%Median TTR2.8 yrsnot reached5.1 yrsOSno pCRpCRAll2-yr81%100%85%3-yr62%87%67%5-yr44%72%50%Median OS3.9 yrsnot reached5.1 yrs

In multivariable modeling of TTR, lower tumor grade was associated with better outcome. Pts with ER, PR and Her2 negative or HER2+ disease without preoperative trastuzumab (H) had worse outcome (median TTR 0.9yr and 1.4yr); those with ER+ and/or PR+ HER2- disease and those with HER2+ disease who received preoperative H had 5yr freedom from recurrence 74% and 82%.

TTR and OS according to ER, PR and Her2 status and receipt of neoadjuvant trastuzumab (H)Freedom from recurrenceER/PR/Her2-ER/PR+, HER2-ER/PR+, HER2+ no HER/PR+, HER2+ yes H2-yr25%80%38%92%3-yr25%74%0%82%5-yr15%74%0%82%Median TTR0.9 yrs11 yrs1.4 yrsnot reached

Conclusions. Hormone receptor and HER2 status are independent prognostic features in IBC, similar to those seen in non-IBC. In addition, anti-Her2-directed preoperative therapy is important to improve outcomes of IBC pts with HER2+ disease. Understanding these features should help in the development of optimal therapies for IBC.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-05.