Pre-Treatment Stromal Tumour-Infiltrating Lymphocytes (S-Tils) Are Correlated With Complete Response (Cr) To Chemotherapy (Chemo) Plus Trastuzumab (T) In Her2-Positive (H Plus ) Metastatic Breast Cancer (Mbc)
CANCER RESEARCH(2016)
Abstract
Background. We have previously reported that ChemoT produces durable (u003e5 years) CR in a minority of pts with H+MBC, prompting a search for predictive markers. Extensive lymphocytic infiltration of cancers is correlated with high levels of immune gene signatures. International consensus guidelines on TILs define lymphocyte-predominant at a threshold of S-TILs of 50-60% versus tumour cells. High levels of S-TILs has been correlated with improved outcome in HER2+ early stage BC pts treated with ChemoT. We investigated the degree of S-TIL infiltration in metastatic biopsies from pts with HER2+MBC prior to ChemoT, and attempted to determine whether S-TILs predicted CR in HER2+MBC. Methods. We searched a database of all pts with HER2+ MBC treated at our institution with anti-HER2 therapy over 15yrs to identify pts who achieved CR according to RECIST 1.0 criteria, which lasted for at least 6 months. We matched them with an equal number of pts from the database who were treated during the same period, but who had progressive (POD) or stable disease (SD) as best response to T. Pts must have at least one pre-treatment tumour sample available for S-TILs assessment, and adequate clinical and follow-up information. S-TILs (mononuclear cells including lymphocytes and plasma cells) contained within the boundaries of invasive tumour were identified on a representative haematoxylin and eosin stained slide and scored as a percentage of the stromal area alone, according to the International TILs Working Group 2014 methodology [Salgado R, 2015]. S-TILs were assessed specifically for this study by a senior pathologist who scored the samples and who was blinded to pts response and clinical details. Results. Out of 246 MBC pts registered in the HER2+ database we identified 31 CR pts with at least one available pre-treatment metastatic sample. A cohort of 31 matching POD-SD pts was randomly obtained from the same database. In 8 cases (7 CR / 1 POD-SD) S-TILs could not be assessed due to inadequate material, or for other technical reasons. The final study sample is 54 pts (24 CR / 30 POD-SD). Pts characteristics are as follows: median age (range): CR 55 (29-78) / POD-SD 56 (26-89), hormone receptor (HR) pos: CR 12 (50%) / POD-SD 18 (60%), De Novo MBC at diagnosis: CR 13 (54%) / POD-SD 8 (27%) [p 50% were statistically significantly more frequent in CR (50% of pts) than POD/SD (20%) [chi-square p=0.02]. No statistically significant difference in the HR status was observed between the two groups (CR vs POD-SD) or between the high and low S-TILs pts. Conclusions. S-TILs u003e50% in the pre-treatment tumour biopsy of HER2+MBC were significantly correlated with subsequent CR to ChemoT, supporting the hypothesis that the immunological effects of T may play a role in determining response. Speculatively, S-TILs might identify pts with a higher likelihood of benefit from T. Further study of the potential role of S-TILs as predictors of T benefit are required. Citation Format: Gullo G, Quinn C, Zacchia A, Fennelly D, Defrein A, Ballot J, Zanoni D, Walshe J, Maltese M, McDermott E, Crown J. Pre-treatment stromal tumour-infiltrating lymphocytes (S-TILs) are correlated with complete response (CR) to chemotherapy (Chemo) plus trastuzumab (T) in HER2-positive (H+) metastatic breast cancer (MBC). [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 P4-14-15.
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