Pathological response in a triple negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann's refined classification

Purpose: Triple-negative breast cancer (TNBC) requires the identification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of TNBC patients treated with neoadjuvant carboplatin and docetaxel (TCb). Methods: TNBC patients were accrued in a non-randomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for 6 cycles. Response was evaluated in terms of pathological complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans et al. Lehmann's subtyping was performed using the TNBCtype online tool from RNAseq data, and germline sequencing of a panel of 7 DNA damage repair genes was conducted. Results: 94 out of the 121 patients enrolled in the trial had RNAseq available. The overall pCR rate was 44.7%. Lehmann subtype distribution was: 34.0% BL1, 20.2% BL2, 23.4% M, 14.9% LAR and 7.4% were classified as ER+. Response to NACT with TCb was significantly associated with Lehmann subtype (p=0.027), even in multivariate analysis including tumor size and nodal involvement, with BL1 patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M (36.4%) and LAR (21.4%). BL1 was associated with a significant younger age at diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30% were BL1, 40% were BL2 and 30% were M. Conclusions: TNBCtype-4 is associated with a significantly different pCR rates for the different subtypes, with BL1 and LAR displaying the best and worse responses to NACT respectively.

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