title: Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer.
abstract: The purpose of the present study was to identify histological surrogate predictive markers of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC). Among 474 patients who received NAC and subsequent surgical therapy for stage II-III invasive breast carcinoma between 1999 and 2007, 102 (22%) had TNBC, and 92 core needle biopsy (CNB) specimens obtained before NAC were available. As controls, CNB specimens from 42 tumors of the hormone receptor-negative and HER2-positive (HR-/HER2+) subtype and 46 tumors of the hormone receptor-positive and HER2-negative (HR+/HER2-) subtype were also included. Histopathological examination including tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis, and immunohistochemical studies for basal markers were performed, and the correlation of these data with pathological therapeutic effect was analyzed. The rates of pCR at the primary site were higher for TNBC (32%) and the HR-/HER2+ subtype (21%) than for the HR+/HER2- subtype (7%) (P = 0.006). Expression of basal markers and p53, histological grade 3, high TIL scores, and apoptosis were more frequent in TNBC and the HR-/HER2+ subtype than in the HR+/HER2- subtype (P = 0.002 for TIL and P < 0.001 for others). In TNBC, the pCR rates of tumors showing a high TIL score and of those showing a high apoptosis score were 37 and 47%, respectively, and significantly higher or tended to be higher than those of the tumors showing a low TIL score and of the tumors showing a low apoptosis score (16 and 27%, respectively, P = 0.05 and 0.10). In a total of 180 breast cancers, the pCR rates of the tumors showing a high TIL score (34%) and of those showing a high apoptosis score (35%) were significantly higher than those of the tumors showing a low TIL score (10%) and those of the tumors showing a low apoptosis score (19%) (P = 0.0001 and 0.04, respectively). Histological grade and basal marker expression were not correlated with pCR. Although the whole analysis was exploratory, the degree of TIL correlated with immune response appear to play a substantial role in the response to NAC in TNBC.
authors.affiliation: Breast and Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Ono
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Chikako
authors.initials: C
authors.lastname: Shimizu
authors.forename: Sohei
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Harukaze
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Taizo
authors.initials: T
authors.lastname: Hirata
authors.forename: Kan
authors.initials: K
authors.lastname: Yonemori
authors.forename: Masashi
authors.initials: M
authors.lastname: Ando
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008214:Lymphocytes / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human