Optimal threshold for stromal tumor-infiltrating lymphocytes: its predictive and prognostic value in HER2-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy.
The purpose of the present study was to determine the optimal threshold for stromal tumor-infiltrating lymphocytes (TILs) and investigate its predictive and prognostic value in HER2-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC). Levels of stromal TILs were evaluated using hematoxylin and eosin-stained sections of core biopsies from 116 patients. We investigated the correlation between stromal TILs and pathological response to identify its optimal threshold. Using receiver operating characteristic curve analysis, a 30 % threshold best discriminated pathological complete response (pCR) from non-pCR subgroups (P < 0.001). Lymphocyte-rich breast cancer (LRBC) was defined as having ≥30 % stromal TILs level, and was used for analysis. For analyses of predictive factors, multivariate analysis indicated that LRBC was a strong predictor of pCR with an odds ratio of 5.23 (P < 0.001). Negative hormone receptor (HR) status was also significantly associated with pCR (P = 0.028). LRBC significantly predicted pCR in both HR-positive and HR-negative tumors (P = 0.016 and 0.006, respectively). For survival analyses, LRBC was the only independent predictor of improved event-free survival (EFS) among baseline clinicopathological factors in multivariate analysis (P = 0.012). When pathological response was included, both LRBC and pCR were independent predictors of better EFS (P = 0.040 and 0.045, respectively). LRBC significantly predicted longer EFS in the non-pCR subgroup (P = 0.018), whereas LRBC was not significantly associated with EFS in the pCR subgroup (P = 0.825). A 30 % threshold for stromal TILs optimally identified response to trastuzumab-based NAC in HER2-positive breast cancer; its predictive and prognostic value was also validated in our study.
Breast Disease Center, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Shiwei
S
Liu
Breast Disease Center, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China. 18600441365@163.com.
Xuening
X
Duan
Breast Disease Center, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Ling
L
Xu
Breast Disease Center, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Ling
L
Xin
Breast Disease Center, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Yuanjia
Y
Cheng
Breast Disease Center, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Qian
Q
Liu
Breast Disease Center, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Jingming
J
Ye
Department of Pathology, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Shuang
S
Zhang
Department of Pathology, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Hong
H
Zhang
Department of Medical Statistics, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Sainan
S
Zhu
Department of Pathology, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Ting
T
Li
Breast Disease Center, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
Yinhua
Y
Liu
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D062005:Biopsy, Large-Core Needle; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
Breast cancer; HER2; Neoadjuvant chemotherapy; Predictive factors; Prognostic factors; Tumor-infiltrating lymphocytes