Abstract P6-12-03: Predictors of poor clinical outcome among patients with inflammatory breast cancer (IBC) who did and did not achieve pathological complete response (pCR) after neoadjuvant systemic chemotherapy
Authors: Masuda H , Chavez-Mac Gregor M , Liu DD , Alvarez RH , Krishnamurthy S , Lucci A , Woodward W , Gildy B , Mittendorf EA , DeSnyder SM , Shen Y , Willey JS , Hortobagyi GN , Valero V , Ueno NT 
Published: August 2014

BACKGROUND: Pathological complete response (pCR) after neoadjuvant systemic chemotherapy (NST) is strongly associated with improved long-term clinical outcomes, even among the patients with inflammatory breast cancer (IBC). In this study, we examined the clinical factors determining long-term outcome in patients with IBC who did and did not achieve pCR.

METHODS: We identified patients with primary IBC treated with NST who received definitive surgery within 1 year and were evaluable for pathological tumor response, and whose hormone receptor and HER2 status was available at baseline. pCR was defined as no evidence of invasive cancer in the breast and ipsilateral axillary lymph nodes. We also investigated the relationship between clinical outcome and the ratio of positive to excised lymph nodes (lymph node ratio) in the non-pCR group. The Kaplan-Meier method was used to estimate disease-free survival (DFS) and overall survival (OS); groups were compared using the log-rank test. Multivariate Cox proportional hazards models were fit to identify predictors of DFS and OS.

RESULTS: Among 517 patients treated at MDACC between 1998 and 2011, 79 (15.2%) achieved pCR. A total of 50.3% had hormone receptor-positive disease, 37.5% had HER2-positive disease, and 26.3% had triple-negative disease. NST included an anthracycline and a taxane in 72.9% of the patients, an anthracycline only in 17.3% and others in 9.8%. A total of 83.7% of patients received adjuvant radiation therapy. The median follow-up period was 3.9 years in the pCR group and 2.4 years in the non-pCR group. Two-year DFS for pCR and non-pCR groups are 74% and 40%, respectively (p&lt;.0001). In the pCR group, only triple-negative disease was significantly associated with decreased OS (P = 0.006) and DFS (P = 0.024). In the non-pCR group, high lymph node ratio, triple-negative disease, vascular invasion, and positive surgical margins were associated with decreased OS and DFS, and adjuvant radiation and hormonal therapies were associated with increased OS and DFS in the multivariate model. As shown in the table, increased lymph node ratios were associated with increased estimated hazard ratios for OS and DFS in the non-pCR group.

Relationship between node ratio increase and clinical outcome Hazard ratio (95% confidence interval)Increase in node ratio,%OSDFS101.07 (1.02-1.12)1.09 (1.05-1.14)201.15 (1.05-1.25)1.20 (1.11-1.29)301.23 (1.08-1.41)1.32 (1.17-1.48)401.32 (1.11-1.58)1.45 (1.24-1.68)501.42 (1.14-1.77)1.59 (1.31-1.92)

CONCLUSIONS: In patients who do not achieve pCR, high lymph node ratio and positive surgical margins predict poor outcome after NST. Use of an optimized tri-modality treatment plan (chemotherapy, surgery, radiation therapy) is important to achieve the best outcomes in patients with IBC; Surgery including total mastectomy with clear margins and axillary dissection to remove all nodal tissue are critical for achieving optimal clinical outcomes in IBC. Even in the pCR group, some patients with triple negative disease still had a poor prognosis suggesting a need for more effective systemic therapy such as innovative agents tailored to the Lehmann subtypes.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-03.