Abstract PS16-07: Tumor infiltrating lymphocyte stratification refines AJCC TNM staging based outcomes of early-stage triple negative breast cancer treated with neoadjuvant anthracycline-free, docetaxel and carboplatin chemotherapy
Cancer Research(2024)
摘要
Abstract Background: Stromal tumor-infiltrating lymphocytes (sTILs) quantification is associated with pathological response to neoadjuvant chemotherapy (NAC) and long term outcomes in setting of adjuvant anthracycline based chemotherapy. A previous study in TNBC patients treated with adjuvant anthracycline chemotherapy shows that at a cut point of 30%, sTILs can up and downstage traditional AJCC stage groups. Additive impact of sTILs on refining outcomes beyond pathological response and TNM stage for patients treated with anthracycline-free chemotherapy is not known. This study aimed to investigate impact of sTILs on outcomes in a large cohort of TNBC patients treated with Docetaxel plus carboplatin NAC. Methods: Patients with stage I (T size > 1cm) to III TNBC scheduled to receive 6 cycles of NAC docetaxel (75 mg/m2) plus carboplatin (AUC 6) (TCb) every 3 weeks from two studies (NCT01560663 and NCT02302742) were combined for this analysis. sTILs were evaluated on pre-treatment H&E slide using standard criteria centrally by one of the investigators (RS). Pathological complete response (pCR) was defined as ypT0/is ypN0. Logistic regression analysis was used to examine the effect of multiple variables on Event free survival (EFS) and overall survival (OS). Results: For 474 patients included in this analysis, median age was 52 years, 8% were Black, 13% had germline BRCA1/2 mutation, 44% had clinical Lymph node (LN) positive disease and 13%, 62% and 25% respectively had TNM stage I, II and III disease. Median sTILs were 5% (range 1-95%) and 25% had >30% sTILs. pCR and RCB 0+1 rates were 50.2% and 60.4% respectively. On multivariable analysis, T stage (OR=0.51, p=0.030), nodal status (OR=0.56, p=0.028), Ki67 (OR=2.74, p< 0.001) and sTILs (OR=2.01, p=0.014) were associated with pCR. pCR rate in those with sTILs < 30 vs sTILs >30 was 45.9% and 63.9% respectively (p=0.0014). At median follow-up of 58 months, 5 years EFS was 81.05% in all patients, 93.94% in those with pCR and 68.67% in those without pCR, 5 year OS was 84.83% in all patients, 96.53% in those with pCR and 74.13% in those with residual disease. On multivariate analysis lower T stage, negative LN status and increasing sTILS were associated with better EFS (T stage: HR =1.98, p=0.018; LN status: HR=2.92, p< 0.001; sTILs: HR:0.46, p=0.04) and OS (T stage: HR=1.89, p=0.040; LN status: HR=3.13, p=0.001; sTILs: HR=0.30, p=0.008). At a cut-point of 30%, sTILs up and downstaged anatomic AJCC TNM stage groups (table 1). Conclusions and Relevance: In patients treated with anthracycline-free TCb chemotherapy, sTILs were independent predictors of EFS and OS beyond clinicopathological features. Notably, 30% sTILs cut-point stratified outcomes beyond anatomical TNM staging. These, findings can aid in patient stratification for chemotherapy backbone de-escalation in future trials and have the potential to inform patient selection for adjuvant treatment escalation and de-escalation trials. Tumor infiltrating lymphocyte stratification refines AJCC TNM staging based outcomes of early-stage triple negative breast cancer treated with neoadjuvant anthracycline-free, docetaxel and carboplatin chemotherapy. Table. Citation Format: Miguel Martín, Rachel Yoder, Roberto Salgado, María del Monte-Millán, Enrique Álvarez, Isabel Echavarria, Joshua Staley, Coralia Bueno-Muiño, Yolanda Jerez Gilarranz, Andrew Godwin, María Cebollero, Oscar Bueno, José Ángel García-Sáenz, Fernando Moreno Antón, Uriel Bohn, Henry L Gómez, Tatiana Massarrah, Sara López-Tarruella, Priyanka Sharma. Tumor infiltrating lymphocyte stratification refines AJCC TNM staging based outcomes of early-stage triple negative breast cancer treated with neoadjuvant anthracycline-free, docetaxel and carboplatin chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS16-07.
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