ANDROGEN RECEPTOR EXPRESSION IN TRIPLE NEGATIVE BREAST CANCER AND ITS RELATIONSHIP TO PROGNOSTIC FACTORS

Authors

  • Maximiliano Cassilha Kneubil Hospital Geral de Caxias do Sul
  • Alessandra Eifler Guerra Godoy Universidade de Caxias do Sul
  • Guilherme Portela Coelho Universidade de Caxias do Sul
  • Fábio Firmbach Pasqualotto Universidade de Caxias do Sul
  • José Mauro Madi Universidade de Caxias do Sul
  • Janaína Brollo Hospital Geral de Caxias do Sul

Abstract

Objective: Triple negative breast cancer (TNBC) is a subset of tumors with an aggressive intrinsic biology, resulting in poor prognosis. Androgen receptor (AR) is currently one of the most studied biomarkers in TNBC, playing a role in the genesis and development of breast cancer. Methods: In this cross-sectional study, we retrospectively reviewed the medical records of all patients with TNBC who received care from 2012 to 2014 at a single health center in southern Brazil. Histological material from breast tumors was analyzed by immunohistochemistry for AR expression and related to age, histological grade, tumor-infiltrating lymphocytes (TILs), and Ki-67. Results: Of 34 TNBC cases identified, 23 (67.6%) were AR negative and 11 (32.4%) were AR positive. The average age of the patients was 51.9 years (range: 30–82 years). Among positive cases, AR was weakly expressed in 6 and strongly expressed in 5 cases. Most patients (n=28; 82.0%) had poorly differentiated tumors. Mean Ki-67 expression was 65.0% in AR-negative and 43.6% in AR-positive cases (p<0.05). There was a significant association between age and AR expression (p<0.005), which was associated with mean age 70.8 years in the strongly AR-positive group and 42.3 years in the weakly AR-positive group. The mean percentage of TILs was 38.6% in AR-positive and 39.1% in AR-negative cases (p=0.391). Conclusion: There was no significant association between AR expression and histological grade or TILs. AR positivity in TNBC was associated with older age and tumors with lower Ki-67 expression, indicating two subgroups with distinct phenotypes in patients with TNBC.

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References

Brasil. Ministério da Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. Estimativa 2016 - Incidência de Câncer no Brasil. 2015 [cited on 2016 Apr 13]. Available from: http://www.inca.gov.br/estimativa/2016/estimativa-2016-v11.pdf

Curigliano G, Goldhirsch A. The triple-negative subtype: new ideas for the poorest prognosis breast cancer. J Natl Cancer Inst Monogr. 2011;2011(43):108-10.

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes, and

survival in the Carolina Breast Cancer Study. JAMA. 2006;295(21):2492-502.

Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10(16):5367-74.

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci. 2003;100(14):8418-23.

Pistelli M, Caramanti M, Biscotti T, Santinelli A, Pagliacci A, De Lisa M, et al. Androgen receptor expression in early triplenegative breast cancer: clinical significance and prognostic associations. Cancers (Basel). 2014;6(3):1351-62.

Collins LC, Cole KS, Marotti JD, Hu R, Schnitt SJ, Tamimi RM. Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the Nurses’ Health Study. Mod Pathol. 2011;24(7):924-31.

Park S, Koo J, Park HS, Kim JH, Choi SY, Lee JH, et al. Expression of androgen receptors in primary breast cancer. Ann Oncol. 2010;21(3):488-92.

Lakhani S. WHO Classification of Tumours of the Breast. Lyon: International Agency for Research on Cancer; 2012.

Atkins D, Reiffen KA, Tegtmeier CL, Winther H, Bonato MS, Storkel S. Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem. 2004;52:893-901.

Deyarmin B, Kane JL, Valente AL, van Laar R, Gallagher C, Shriver CD, et al. Effect of ASCO/CAP guidelines for determining ER status on molecular subtype. Ann Surg Oncol. 2013;20(1):87-93.

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997-4013.

Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Research and Treatment. 2013;139(2):539-52. doi: 10.1007/s10549-013-2560-8

Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, et al. Prognostic value od tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trial: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959-66.

Lakhani S, Ellis I, Schnitt S, Tan PH, Vijver MJV. WHO Classification of Tumours of the Breast. 4ª edition. Lyon: IARC Press; 2012.

Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, et al. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res. 2011;17(7):1867-74.

Honma N, Horii R, Iwase T, Saji S, Younes M, Ito Y, et al. Clinical importance of androgen receptor in breast cancer patients treated with adjuvant tamoxifen monotherapy. Breast Cancer. 2012;20:323-30.

Hickey TE, Robinson JL, Carroll JS, Tilley WD. Minireview: The 1androgen receptor in breast tissues: growth inhibitor, tumor suppressor, oncogene? Mol Endocrinol. 2012;26(8):1252-67.

Moore NL, Buchanan G, Harris JM, Selth LA, Bianco-Miotto T, Hanson AR, et al. An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity. Endocr Relat Cancer. 2012;19(4):599-613.

Iggo RD. New insights into the role of androgen and estrogen receptors in molecular apocrine breast tumours. Breast Cancer Res. 2011;13(6):318.

Naderi A, Chia KM, Liu J. Synergy between inhibitors of androgen receptor and MEK has therapeutic implications in estrogen receptor-negative breast cancer. Breast Cancer Res. 2011;13(2):R36.

He J, Peng R, Yuan Z, Wang S, Peng J, Lin G, et al. Prognostic value of androgen receptor expression in operable triplenegative breast cancer: a retrospective analysis based on a tissue microarray. Med Oncol. 2012;29(2):406-10.

Wang C, Pan B, Zhu H, Zhou Y, Mao F, Lin Y, et al. Prognostic value of androgen receptor in triple negative breast cancer: a meta-analysis. Oncotarget. 2016;7(29):46482-91.

Qi JP, Yang YL, Zhu H, Wang J, Jia Y, Liu N, et al. Expression of the androgen receptor and its correlation with molecular subtypes in 980 Chinese breast cancer patients. Breast Cancer (Auckl). 2012;6:1-8.

Jiang HS, Kuang XY, Sun WL, Xu Y, Zheng YZ, Liu YR, et al. Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status. Oncotarget. 2016;7(27):41285-93.

Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31(1):13-20.

Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized

adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959-66.

Pietri E, Conteduca V, Andreis D, Massa I, Melegari E, Sarti S, et al. Androgen receptor signaling pathways as a target for breast cancer treatment. Endocr Relat Cancer. 2016;23(10):R485-98.

Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016 May 17;13(11)674-90.

Kach J, Conzen SD, Szmulewitz RZ. Targeting the glucocorticoid receptor in breast and prostate cancers. Sci

Transl Med. 2015;7(305):305ps19.

Romero Q, Bendahl PO, Ferno M, Grabau D, Borgquist S. A novel model for Ki67 assessment in breast cancer. Diagn Pathol. 2014;9:118.

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Published

2017-07-02

How to Cite

Kneubil, M. C., Godoy, A. E. G., Coelho, G. P., Pasqualotto, F. F., Madi, J. M., & Brollo, J. (2017). ANDROGEN RECEPTOR EXPRESSION IN TRIPLE NEGATIVE BREAST CANCER AND ITS RELATIONSHIP TO PROGNOSTIC FACTORS. Mastology, 27(3), 199–205. Retrieved from https://revistamastology.emnuvens.com.br/revista/article/view/497

Issue

Vol. 27 No. 3 (2017)

Section

Original Articles

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Copyright (c) 2017 Maximiliano Cassilha Kneubil, Alessandra Eifler Guerra Godoy, Guilherme Portela Coelho, Fábio Firmbach Pasqualotto, José Mauro Madi, Janaína Brollo

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This work is licensed under a Creative Commons Attribution 4.0 International License.