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01.12.2014 | Preclinical study

Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer: its correlation with pathological complete response to neoadjuvant chemotherapy

verfasst von: Minoru Miyashita, Hironobu Sasano, Kentaro Tamaki, Monica Chan, Hisashi Hirakawa, Akihiko Suzuki, Hiroshi Tada, Go Watanabe, Noriko Nemoto, Saki Nakagawa, Takanori Ishida, Noriaki Ohuchi

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2014

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Abstract

The anti-tumor immune response was recently reported to play a critical role in the chemotherapeutic sensitivity of breast cancer. Therefore, we investigated the correlation between CD8+ and FOXP3+ tumor-infiltrating lymphocytes and the pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), in conjunction with neoangiogenesis, basal and proliferation markers. CD8+ and FOXP3+ lymphocytes were assessed in biopsy specimens by double-staining immunohistochemistry, in combination with immunostaining of vasohibin-1, CD31, EGFR, CK5/6, and Ki-67. Earlier age, pre-menopausal status, smaller tumor size, and high Ki-67 were significantly associated with pCR, as in high CD8+, high CD8+/FOXP3+ ratio, and low vasohibin-1 positive ratio. Multivariate analysis did reveal that a high CD8+/FOXP3+ ratio was a strong predictor of pCR with an odds ratio of 5.32 (P = 0.005). High Ki-67 was also significantly associated with pCR (P = 0.002). TNBCs with a high CD8+/FOXP3+ ratio and high Ki-67 had the highest pCR rate (70 %) following NAC. However, the pCR rate of the patients with low CD8+/FOXP3+ ratio and low Ki-67 was only 5 %. The pCR rates of a high CD8+/FOXP3+ ratio and low Ki-67 patients and those with a low CD8+/FOXP3+ ratio and high Ki-67 were 24 and 21 %, respectively. TNBCs with a high CD8+/FOXP3+ ratio were more sensitive to anthracycline and taxane-based chemotherapeutic regimens, and the CD8+/FOXP3+ ratio in conjunction with Ki-67 could predict pCR following NAC in TNBC. This predictor may represent a new surrogate for testing the efficacy of investigational agents in the neoadjuvant setting.

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Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRef

Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMedCentralPubMedCrossRef

Sorlie T, Tibshirani R, Parker J et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423PubMedCentralPubMedCrossRef

Cortazar P, Zhang L, Untch M et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172PubMedCrossRef

Liedtke C, Mazouni C, Hess KR et al (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26:1275–1281PubMedCrossRef

Darb-Esfahani S, Loibl S, Muller BM et al (2009) Identification of biology-based breast cancer types with distinct predictive and prognostic features: role of steroid hormone and HER2 receptor expression in patients treated with neoadjuvant anthracycline/taxane-based chemotherapy. Breast Cancer Res 11:R69PubMedCentralPubMedCrossRef

Denkert C, Loibl S, Muller BM et al (2013) Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol 24:2786–2793PubMedCrossRef

Lehmann BD, Bauer JA, Chen X et al (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Investig 121:2750–2767PubMedCentralPubMedCrossRef

Masuda H, Baggerly KA, Wang Y et al (2013) Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res 19:5533–5540PubMedCrossRef

10.

Apetoh L, Ghiringhelli F, Tesniere A et al (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13:1050–1059PubMedCrossRef

11.

Andre F, Dieci MV, Dubsky P et al (2013) Molecular pathways: involvement of immune pathways in the therapeutic response and outcome in breast cancer. Clin Cancer Res 19:28–33PubMedCrossRef

12.

Liu F, Lang R, Zhao J et al (2011) CD8(+) cytotoxic T cell and FOXP3(+) regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes. Breast Cancer Res Treat 130:645–655PubMedCrossRef

13.

Liu S, Lachapelle J, Leung S, Gao D, Foulkes WD, Nielsen TO (2012) CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer. Breast Cancer Res 14:R48PubMedCentralPubMedCrossRef

14.

Ali HR, Provenzano E, Dawson SJ et al (2014) Association between CD8+ T-cell infiltration and breast cancer survival in 12 439 patients. Ann Oncol 25:1536–1543PubMedCrossRef

15.

Liyanage UK, Moore TT, Joo HG et al (2002) Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 169:2756–2761PubMedCrossRef

16.

Viguier M, Lemaitre F, Verola O et al (2004) Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol 173:1444–1453PubMedCrossRef

17.

Mahmoud SM, Paish EC, Powe DG et al (2011) An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer. Breast Cancer Res Treat 127:99–108PubMedCrossRef

18.

Oda N, Shimazu K, Naoi Y et al (2012) Intratumoral regulatory T cells as an independent predictive factor for pathological complete response to neoadjuvant paclitaxel followed by 5-FU/epirubicin/cyclophosphamide in breast cancer patients. Breast Cancer Res Treat 136:107–116PubMedCrossRef

19.

West NR, Kost SE, Martin SD et al (2013) Tumour-infiltrating FOXP3+ lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer. Br J Cancer 108:155–162PubMedCentralPubMedCrossRef

20.

Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med 324:1–8PubMedCrossRef

21.

Weidner N, Folkman J, Pozza F et al (1992) Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84:1875–1887PubMedCrossRef

22.

Bevilacqua P, Barbareschi M, Verderio P et al (1995) Prognostic value of intratumoral microvessel density, a measure of tumor angiogenesis, in node-negative breast carcinoma—results of a multiparametric study. Breast Cancer Res Treat 36:205–217PubMedCrossRef

23.

Chan MS, Wang L, Chanplakorn N et al (2012) Effects of estrogen depletion on angiogenesis in estrogen-receptor-positive breast carcinoma—an immunohistochemical study of vasohibin-1 and CD31 with correlation to pathobiological response of the patients in neoadjuvant aromatase inhibitor therapy. Expert Opin Ther Targets 16(Suppl 1):S69–S78PubMedCrossRef

24.

Fu J, Xu D, Liu Z et al (2007) Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology 132:2328–2339PubMedCrossRef

25.

Mahmoud SM, Paish EC, Powe DG et al (2011) Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 29:1949–1955PubMedCrossRef

26.

Tamaki K, Moriya T, Sato Y et al (2009) Vasohibin-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis. Cancer Sci 100:88–94PubMedCrossRef

27.

Tamaki K, Sasano H, Maruo Y et al (2010) Vasohibin-1 as a potential predictor of aggressive behavior of ductal carcinoma in situ of the breast. Cancer Sci 101:1051–1058PubMedCrossRef

28.

Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145PubMedCrossRef

29.

Urruticoechea A, Smith IE, Dowsett M (2005) Proliferation marker Ki-67 in early breast cancer. J Clin Oncol 23:7212–7220PubMedCrossRef

30.

de Azambuja E, Cardoso F, de Castro Jr G et al (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer 96:1504–1513PubMedCentralPubMedCrossRef

31.

Lerma E, Peiro G, Ramon T et al (2007) Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2/neu (basal-like breast carcinomas). Mod Pathol 20:1200–1207PubMedCrossRef

32.

Rakha EA, Reis-Filho JS, Ellis IO (2008) Basal-like breast cancer: a critical review. J Clin Oncol 26:2568–2581PubMedCrossRef

33.

Bertucci F, Finetti P, Rougemont J et al (2005) Gene expression profiling identifies molecular subtypes of inflammatory breast cancer. Cancer Res 65:2170–2178PubMedCrossRef

34.

Bertucci F, Finetti P, Cervera N et al (2006) Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res 66:4636–4644PubMedCrossRef

35.

Ladoire S, Arnould L, Apetoh L et al (2008) Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3+ regulatory T cells. Clin Cancer Res 14:2413–2420PubMedCrossRef

36.

Goldhirsch A, Winer EP, Coates AS et al (2013) Personalized the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24:2206–2223PubMedCentralPubMedCrossRef

37.

Doedens AL, Stockmann C, Rubinstein MP et al (2010) Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res 70:7465–7475PubMedCentralPubMedCrossRef

38.

Tartour E, Pere H, Maillere B et al (2011) Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy. Cancer Metastasis Rev 30:83–95PubMedCrossRef

Titel: Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer: its correlation with pathological complete response to neoadjuvant chemotherapy
verfasst von: Minoru Miyashita
Hironobu Sasano
Kentaro Tamaki
Monica Chan
Hisashi Hirakawa
Akihiko Suzuki
Hiroshi Tada
Go Watanabe
Noriko Nemoto
Saki Nakagawa
Takanori Ishida
Noriaki Ohuchi
Publikationsdatum: 01.12.2014
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2014
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-014-3197-y

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Abstract

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