Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer. 2012

Makiko Ono, and Hitoshi Tsuda, and Chikako Shimizu, and Sohei Yamamoto, and Tatsuhiro Shibata, and Harukaze Yamamoto, and Taizo Hirata, and Kan Yonemori, and Masashi Ando, and Kenji Tamura, and Noriyuki Katsumata, and Takayuki Kinoshita, and Yuichi Takiguchi, and Hideki Tanzawa, and Yasuhiro Fujiwara
Breast and Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

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.

UI MeSH Term Description Entries
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D009367 Neoplasm Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Cancer Staging,Staging, Neoplasm,Tumor Staging,TNM Classification,TNM Staging,TNM Staging System,Classification, TNM,Classifications, TNM,Staging System, TNM,Staging Systems, TNM,Staging, Cancer,Staging, TNM,Staging, Tumor,System, TNM Staging,Systems, TNM Staging,TNM Classifications,TNM Staging Systems
D011960 Receptors, Estrogen Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important. Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
D011980 Receptors, Progesterone Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives. Progesterone Receptors,Progestin Receptor,Progestin Receptors,Receptor, Progesterone,Receptors, Progestin,Progesterone Receptor,Receptor, Progestin
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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