Evaluation of tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis as predictive markers for response to neoadjuvant chemotherapy in triple-negative breast cancer

Abstract

559 Background: Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor (ER), progesterone receptor (PgR) and HER-2. Pathological complete response (pCR) of TNBC to neoadjuvant chemotherapy (NAC) is correlated with excellent clinical outcome. We examined the value of histological parameters including tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis as surrogate markers for pCR in TNBC. Methods: Of 474 patients who received NAC and subsequent surgical therapy to stage II-III invasive breast carcinoma between 1999 and 2007, 102 (22%) had TNBC, and 92 core needle biopsy (CNB) specimens before NAC were available. We first immunohistochemically confirmed TNBC and basal-like subtype by current criteria for ER, PgR, and HER-2, cytokeratin (CK) 5/6, CK14, EGFR, and p53. All cases were TNBC, and 54 tumors (59%) were basal-like subtype defined as expression of at least one of CK5/6, CK14 and EGFR in >1% of cancer cells. Totally, 26 tumors (28%) showed pCR. Thirteen histopathological parameters were examined, and their correlation with pCR rate was tested. These parameters were also examined in resected tumor specimens from 21 non-pCR cases. Results: The pCR rate was significantly higher in the patients with tumors with TIL (24 of 68, 35%) than in those without (2 of 24, 8%, p = 0.01), and higher in tumors with high-score apoptosis (9 of 19, 47%) than in those with low-score apoptosis (17 of 73, 23%, p = 0.04). Tumors showing medullary features and p53-negative tended to show pCR more frequently (38% and 35%) than those with non-medullary features and with p53-positive (25% and 24%), but the differences were not significant. Of 21 non-pCR cases, TIL was consistently negative before and after NAC in 8, but TIL emerged after NAC in 13. The pCR rate did not differ significantly between the basal-like type (31%) and non-basal-like type (24%). Conclusions: TIL and the level of tumor cell apoptosis appeared predictive markers for response to NAC in TNBC. Patients’ host factors correlated with immune response appears play a substantial role in the response to NAC in TNBC. No significant financial relationships to disclose.