Tumor Infiltrating Lymphocytes Predict Response to Neoadjuvant Chemotherapy in Breast Cancer

A high level of tumor infiltrating lymphocytes (TILs) may be a marker of pathologic complete response (pCR) to neoadjuvant chemotherapy in breast cancer, especially in patients with triple-negative or HER2-positive disease, said Yan Mao, PhD candidate, at the 2014 Breast Cancer Symposium.

She and colleagues at Shanghai Jiatong University in China conducted a systematic review and meta-analysis of 13 studies that included 3555 patients with the goal of examining the relationship between TILs and pCR associated with neoadjuvant chemotherapy for breast cancer. Studies included were those in which the predictive significance of intratumoral and/or stromal TILs and/or CD3+, CD4+, CD8+, and FOXP3+ lymphocytes was determined.

In a pooled analysis, a high number of TILs in the pretreatment biopsy correlated with a higher pCR rate with neoadjuvant chemotherapy, with an overall odds ratio (OR) for pCR of 3.82. The result was consistent across studies, regardless of the tumor site selected. “Whether in the tumor stroma or the center, or combined together, the presence of TILs indicated a good pCR rate,” said Mao. The OR for a pCR with neoadjuvant chemotherapy for intratumoral TILs was 3.32, for TILs in the stroma, 4.15, and for TILs in combined sites, 8.98.

The presence of TILs predicted a higher pCR rate in triple-negative breast cancer (OR = 5.03) and in HER2-positive disease (OR = 5.54), but not in hormone receptor—positive/HER2-negative disease (OR = 2.57; 95% CI, 0.20-33.24).

An analysis of specific subsets of TILs showed that CD8+ T-lymphocytes (OR = 5.07) and FOXP3+ T-lymphocytes (OR = 2.82) predicted pathologic response to neoadjuvant chemotherapy in the pretreatment biopsy but a lower number of CD8+ cells (OR = 2.85) and FOXP3+ cells (OR = 4.27) predicted a response when tested after neoadjuvant chemotherapy. “The reason is unclear; translational or basic research is needed to shed some light on this finding,” Mao said.

The predictive role of CD3+ and CD4+ T-lymphocytes was also examined but results are not conclusive, as each was assessed in only one study.

One limitation to the meta-analysis was that the determination of cutoff points varied between the studies, said Mao. Some studies used 10% TILs as a positive cutoff value, whereas others used absence versus presence of TILs.

“This abstract further supports existing data that high levels of TILs at diagnosis in early triple-negative breast cancer and HER2-positive breast cancer is associated with higher rates of pCR or higher sensitivity to chemotherapy and better outcomes,” said Sherene Loi, MBBS, PhD, who was lead investigator of one of the studies included but was not involved in the meta-analysis.

She added that the potential added prognostic value of various TILs subsets over TILs as a whole is unknown and could be minimal. “The question remains on how we can potentially boost host antitumor immunity in those who don’t have TILs at baseline and if we can optimize the immune response by adding other immunotherapies in addition to chemotherapy to those who do have TILs in their tumor at diagnosis,” said Loi, head of the Translational Breast Cancer Genomics Laboratory at the Peter MacCallum Cancer Centre in East Melbourne, Victoria, Australia.

Mao Y, Qu Q, Zhang Y, et al. Tumor infiltrating lymphocytes (TIL) to predict response to neoadjuvant chemotherapy in breast cancer: A systemic review and meta-analysis. J Clin Oncol. 2014;32(suppl 26; abstr 138).