Abstract P2-08-31: Predictive and prognostic value of stromal tumor-infiltrating lymphocytes before and after neoadjuvant therapy in triple negative and HER2-positive breast cancer
Authors: Ochi T , Giampaolo B , Murai M , Nozaki F , Kobayashi D , Iwamoto T , Niikura N , Suzuki K , Yamauchi H , Hayashi N 
Published: May 2019

Background: Lymphocyte predominant breast cancer subgroup, defined as ≥ 50% stromal tumor-infiltrating lymphocytes (sTILs), is associated with high pathological complete response (pCR) rate after neoadjuvant therapy (NAT) and favorable outcome. In a cohort of triple negative (TNBC) and HER2+ breast cancer (BC) patients treated with NAT, we aimed to assess the predictive and prognostic value of pre- and post-NAT sTILs and the information provided by the change in sTILs during NAT.

Materials and methods: Two-hundred and nine consecutive patients (n=80 TNBC; and n=129 HER2+) who received NAT between 2001 and 2009 in our institution were evaluated. Pre-NAT sTILs were assessed on biopsy sample (baseline) and post-NAT sTILs on surgical specimens just for non-pCR patients. sTILs level was categorized as low 0-9%, intermediate 10-49%, and high ≥50%. The change in sTILs during NAT was calculated as the absolute difference between pre- and post-NAT sTILs. We evaluated the association of pre-NAT sTILs and pCR, and the association between pre- and post-NAT sTILs, and their change with relapse-free survival (RFS).

Results: Overall pCR rate was 37.8% (31.3% for TNBC, 41.2% for ER+/HER2+BC, 42.3% for ER-/HER2+BC). In each subtype, pre-NAT low sTILs group was significantly associated with lower pCR rate. During the median follow-up period of 98 months, 44 recurrences (21.1%) were observed. For TNBC, low pre-NAT sTILs group was associated with higher recurrence risk compared with int/high sTILs (HR=4.675 [2.013-10.859], p&lt;0.001). For only non-pCR patients, both pre- and post-NAT sTILs were significantly associated with RFS. The risk of recurrence was higher in the group with low pre-NAT sTILs (HR=5.333 [1.731-16.427], p=0.004), and the group of low post-NAT sTILs (HR=4.271 [1.498-12.173], p=0.007). Patients with the change of sTILs increase during NAT were not associated with RFS, compared with decrease or equal group (log-rank p=0.163). In multivariate analysis including both pre- and post-NAT sTILs, only pre-NAT sTILs retained significance (HR=3.844 [1.190-12.421], p=0.024). Low post-NAT sTILs group showed only a borderline significant association with shorter RFS (HR=2.836 [0.951-8.457], p=0.061), but it suggests that both pre- and post-NAT sTILs might provide independent prognostic information. In ER+/HER2+BC, low pre-NAT sTILs were associated with short RFS (p=0.036), but this association was not significant when only non-pCR patients were considered. In ER−/HER2+BC, sTILs were not significantly associated with RFS.

Conclusion: In TN and HER2+ BCs, tumors with low pre-NAT sTILs have a low likelihood to achieve a pCR (predictive marker). In TNBC, low pre-NAT sTILs were associated with higher recurrence risk. In non-pCR TNBC patients, both low pre- and post-NAT sTILs were associated with shorter RFS. These results suggest that sTILs information should be taken into account when additional post-surgery treatments are considered in non-pCR patients.

Citation Format: Ochi T, Giampaolo B, Murai M, Nozaki F, Kobayashi D, Iwamoto T, Niikura N, Suzuki K, Yamauchi H, Hayashi N. Predictive and prognostic value of stromal tumor-infiltrating lymphocytes before and after neoadjuvant therapy in triple negative and HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-31.