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Immune microenvironment, homologous recombination deficiency, and therapeutic response to neoadjuvant chemotherapy in triple-negative breast cancer: Japan Breast Cancer Research Group (JBCRG)22 TR.
Ueno, Takayuki; Kitano, Shigehisa; Masuda, Norikazu; Ikarashi, Daiki; Yamashita, Makiko; Chiba, Tomohiro; Kadoya, Takayuki; Bando, Hiroko; Yamanaka, Takashi; Ohtani, Shoichiro; Nagai, Shigenori; Nakayama, Takahiro; Takahashi, Masato; Saji, Shigehira; Aogi, Kenjiro; Velaga, Ravi; Kawaguchi, Kosuke; Morita, Satoshi; Haga, Hironori; Ohno, Shinji; Toi, Masakazu.
Afiliación
  • Ueno T; Breast Surgical Oncology, The Cancer Institute Hospital of JFCR, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. takayuki.ueno@jfcr.or.jp.
  • Kitano S; Division of Cancer Genomic Medicine Development, Advanced Medical Development Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan. takayuki.ueno@jfcr.or.jp.
  • Masuda N; Division of Cancer Immunotherapy Development, Advanced Medical Development Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan.
  • Ikarashi D; Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Yamashita M; Division of Cancer Immunotherapy Development, Advanced Medical Development Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan.
  • Chiba T; Division of Cancer Immunotherapy Development, Advanced Medical Development Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan.
  • Kadoya T; Division of Pathology, The Cancer Institute Hospital of JFCR, Tokyo, Japan.
  • Bando H; Department of Breast Surgery, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan.
  • Yamanaka T; Breast and Endocrine Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
  • Ohtani S; Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan.
  • Nagai S; Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
  • Nakayama T; Division of Breast Oncology, Saitama Cancer Center, Saitama, Japan.
  • Takahashi M; Department of Breast and Endocrine Surgery, Osaka International Cancer Institute, Osako, Japan.
  • Saji S; Department of Breast Surgery, NHO Hokkaido Cancer Center, Sapporo, Japan.
  • Aogi K; Department of Medical Oncology, Fukushima Medical University Hospital, Fukushima, Japan.
  • Velaga R; Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan.
  • Kawaguchi K; Department of Breast Surgery, Kyoto University Hospital, Kyoto, Japan.
  • Morita S; Department of Breast Surgery, Kyoto University Hospital, Kyoto, Japan.
  • Haga H; Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Ohno S; Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
  • Toi M; Breast Oncology Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan.
BMC Med ; 20(1): 136, 2022 04 25.
Article en En | MEDLINE | ID: mdl-35462552
ABSTRACT

BACKGROUND:

Triple-negative breast cancer (TNBC) is a biologically diverse disease, with characteristics such as homologous recombination deficiency (HRD), gene mutation, and immune reactions. Japan Breast Cancer Research Group 22 is a multicenter trial examining TNBC's response to neoadjuvant chemotherapy (NAC) according to the HRD status. This translational research investigated the clinical significance of the immune microenvironment of TNBC in association with HRD, tumor BRCA1/2 (tBRCA1/2) mutation, and response to NAC.

METHODS:

Patients aged below 65 years with high HRD or germline BRCA1/2 (gBRCA1/2) mutation randomly received paclitaxel + carboplatin (group A1) or eribulin + carboplatin (A2), followed by anthracycline. Patients aged below 65 years with low HRD or those aged 65 years or older without gBRCA1/2 mutation randomly received eribulin + cyclophosphamide (B1) or eribulin + capecitabine (B2); nonresponders to the first four cycles of the therapy received anthracycline. A pathological complete response (pCR) was defined as the absence of residual cancer cells in the tissues. Pretreatment biopsy specimens were stained by multiplexed fluorescent immunohistochemistry using antibodies against CD3, CD4, CD8, Foxp3, CD204, and pan-cytokeratin. Immune cells with specific phenotypes were counted per mm2 in cancer cell nests (intratumor) and stromal regions. The immune cell densities were compared with clinicopathological and genetic factors including tumor response.

RESULTS:

This study analyzed 66 samples. T1 tumors had a significantly higher density of intratumoral CD8+ T cells than T2 or larger tumors. The tBRCA1/2 mutation or HRD status was not associated with the density of any immune cell. The density of intratumoral and stromal CD4+ T cells was higher in patients showing pCR than in those without pCR. In a multivariate analysis, intratumoral and stromal CD4+ T cell density significantly predicted pCR independent of age, chemotherapy dose, HRD status, and treatment groups (P = 0.009 and 0.0057, respectively). In a subgroup analysis, the predictive value of intratumoral and stromal CD4+ T cell density persisted in the platinum-containing chemotherapy group (A1+A2) but not in the non-platinum-containing group (B1+B2).

CONCLUSIONS:

Intratumoral and stromal CD4+ T cell density was an independent predictor of pCR in patients with TNBC. A larger study is warranted to confirm the results. TRIAL REGISTRATION UMIN000023162.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Humans País/Región como asunto: Asia Idioma: En Revista: BMC Med Asunto de la revista: MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Humans País/Región como asunto: Asia Idioma: En Revista: BMC Med Asunto de la revista: MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Japón