Abstract

Abstract Introduction: Evaluation of the benefit of primary chemotherapy (PC) is not easy to establish. Pathologic complete response (pCR) has been considered the main surrogate prognostic factor of patient's survival. However, patients achieving a pCR are not the only ones who benefit from PC. The purpose of our study is to find a measure of response that includes the maximum of patients that benefit from PC in terms of survival. Patients and methods: 224 breast cancer patients were treated in Breast Cancer Unit from Institut Català d'Oncologia (ICO) L'Hospitalet with taxans and antracyclines-based PC +/- trastuzumab between 2009 and 2011. pCR was defined as no invasive carcinoma found in the tumor and in the axillary lymph nodes (ypT0/ypTis ypN0). Tumor and nodal downstaging (TNDS) was calculated according to the "neoadjuvant response index" (NRI) from Rodenhuis and also as a dichotomic variable: Positive includes those patients achieving dowstaging of both T and N plus T downstaging N0 and negatives those patients without downstaging in any of both variables. Those parameters were related to patient's overall survival (OS). Statistical analysis was performed with SPSS version 15. Results: Median age 45.5 years (24-83). Main tumor characteristics: T2 (62.6%); N1 (50%); ductal infiltrating carcinoma (95.5%) and grade III (57.1%). Biological sub-type according to the last St Gallen classification: luminal A: 28 patients (pts); luminal B/Her2-: 61 pts; luminal B/HER2+: 34 pts; HER2+: 33 pts and triple negative: 69 pts. Pathologic complete response was achieved in 49 pts (22.5%). TNDS was evaluated in 181 patients and of those 90 was positive. According to NRI 74 patients presented cut-off> 0.5 and 52 pts > 0.7. Parameters related to OS were: biological subtype (P: 0.007); achieving a pCR (p: 0.007); NRI cut-off 0.5 (P: 0.001) and TNDS (p:0.000). In the multivariate analysis only TNDS and biological subtype remained statistically significant. When comparing those patients with positive vs. negative TNDS, the HR for recurrence was of 10.05 (IC 2.33 -43.57). The median OS of the series has not been reached. OS at 5y was 82.7% (IC: 77.1%-88%) and specific breast cancer OS at 5 y was 85% (IC:79.5%-90%). The number of events (breast cancer deaths) for each biological subtype according to positive vs. negative TNDS was: luminal A: 0/5 vs. 0/18; luminal B Her2-: 0/10 vs. 8/43; luminal B HER2+:0/23 vs. 2/9; HER2+: 0/22 vs. 0/2 and TN: 2/30 vs. 8/18. Survival data per subtypes and TNDS is immature due to the scarce number of events. Estimated 5y OS for TNDS positive vs. negative in luminal A: 100% vs. 100%; luminal B Her2-: 100% vs. 82%; luminal B HER2+:100 vs.77.7%; HER2+: 100% vs. 100% and TN: 93% vs. 55%, respectively. Conclusion: In our series, TNDS measured either with the NRI from Rodenhuis or as a dichotomic variable was the best parameter to evaluate response to PC in terms of OS. OS of luminal A and luminal B/Her2 negative is less influenced by PC than the rest of subgroups. In fact both subgroups have good prognosis despite their poor sensitivity to chemotherapy. Those tumors that benefit most from PC were luminal B/ Her2+; Her2+ and triple negative patients who achieved a positive TNDS. Citation Format: Falo C, Ventura LM, Petit A, Perez J, Cañellas J, Perez L, Loayza C, Gil M, Varela M, Garcia A, Pla MJ, Lopez A, Guma A, Pernas S. Tumor and axillar downstaging as a prognostic factor and evaluation of effectiveness to primary chemotherapy in breast cancer: A retrospective analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-31.

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