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Incidence and Prognostic Significance of Androgen Receptors (AR) in Indian Triple-Negative Breast Cancer (TNBC)

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Abstract

Background

Molecular sub-characterization of triple-negative breast cancer (TNBC) has great therapeutic and possibly prognostic implications. The primary aim of this study was to investigate the incidence of luminal androgen receptor (LAR) subtype of TNBC and secondary aims were sub-categorization and clinico-pathologic correlation of LAR breast cancers. Retrospective study (January 2008 and 31st of December 2018) consisting of 157 TNBC patients. Androgen receptor (AR) expression was measured by immunohistochemical analysis. One percent cutoff was set as a positive expression. Sub-categorization was done on the basis of EGFR (> 15% of tumor cells) and Ki-67 expression (low- < 11%, intermediate- 11–20%, and high- > 21%). AR expression was correlated with various clinico-pathologic features and outcomes of the patients. The incidence of AR expression in TNBC was 24.8%. Considering different thresholds of > 5%, > 10%, and > 20% immunostaining, the incidence of AR positivity was 18.4, 15.2, and 11.5% respectively. The incidence of Ki-67 (p = 0.89) and EGFR (p = 0.643) expression did not differ significantly in AR-positive and -negative TNBC. Based on EGFR expression 19, 67 and 14% patients were categorized as low, intermediate, and high risk respectively. Low-risk (p ≤ 0.001) and low-grade (p = 0.014) tumors were more likely to have > 10% AR expression. Clinico-pathological profile, response to neoadjuvant chemotherapy, disease-free survival (p = 0.458), and overall survival (p = 0.806) did not significantly differ between AR expressing and negative TNBC. On multivariate analysis, only tumor staging was a significant predictor of survival (p = 0.012) and AR expression of > 10% revealed a trend towards improved survival (p = 0.07). When considering only AR-positive TNBC, AR expression of > 10% (p = 0.038), distant metastases (p = 0.003), and EGFR status (p = 0.024) were significantly associated with survival. AR expression does not seem to very strongly correlate with prognosis in TNBC and further studies could focus more on its predictive role in deciding anti-androgen therapy.

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References

  1. Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363(20):1938–1948. https://doi.org/10.1056/NEJMra1001389

    Article  CAS  PubMed  Google Scholar 

  2. Kassam F, Enright K, Dent R, Dranitsaris G, Myers J, Flynn C et al (2009) Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin Breast Cancer 9:29–33. https://doi.org/10.3816/CBC.2009.n.005

    Article  PubMed  Google Scholar 

  3. Agarwal G, Nanda G, Lal P, Mishra A, Agarwal A, Agrawal V, Krishnani N (2016) Outcomes of Triple-Negative Breast Cancers (TNBC) Compared with non-TNBC: does the survival vary for all stages? World J Surg. https://doi.org/10.1007/s00268-016-3422-4

    Article  PubMed  Google Scholar 

  4. Lehman BD, Jovanović B, Chen X, Estrada MV, Johnson KN, Shyr W et al (2016) Refinement of triple-negative breast cancer molecular subtypes: implications for Neoadjuvant Chemotherapy Selection. PLoS ONE. https://doi.org/10.1371/journal.pone.0157368

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jézéquel P, Loussouarn D, Guérin-Charbonnel C, Campion L, Vanier A, Gouraud W et al (2015) Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response. Breast Cancer Res 17:43. https://doi.org/10.1186/s13058-015-0550-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yu KD, Zhu R, Zhan M, Rodriguez AA, Yang W, Wong S et al (2013) Identification of prognosis-relevant subgroups in patients with chemoresistant triple-negative breast cancer. Clin Cancer Res 19(10):2723–2733. https://doi.org/10.1158/1078-0432.CCR-12-2986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Prat A, Adamo B, Cheang MC, Anders CK, Carey LA, Perou CM (2013) Molecular characterization of basal-like and non-basal-like triple-negative breast cancer. Oncologist 18:123–133. https://doi.org/10.1634/theoncologist.2012-0397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tang D, Xu S, Zhang Q, Zhao W (2012) The expression and clinical significance of the androgen receptor and E-cadherin in triple-negative breast cancer. Med Oncol 29:526–533. https://doi.org/10.1007/s12032-011-9948-2

    Article  CAS  PubMed  Google Scholar 

  9. Sutton LM, Cao D, Sarode V, Molberg KH, Torgbe K, Haley B et al (2012) Decreased androgen receptor expression is associated with distant metastases in patients with androgen receptor-expressing triple-negative breast carcinoma. Am J Clin Pathol 138:511–516. https://doi.org/10.1309/AJCP8AVF8FDPTZLH

    Article  PubMed  Google Scholar 

  10. Mirzania M (2016) Approach to the triple negative breast cancer in new drugs area. Int J Hematol Oncol Stem Cell Res 10(2):115–119

    PubMed  PubMed Central  Google Scholar 

  11. Park S, Koo J, Park HS, Kim JH, Choi SY, Lee JH et al (2010) Expression of androgen receptors in primary breast cancer. Ann Oncol 21(3):488–492. https://doi.org/10.1093/annonc/mdp510

    Article  CAS  PubMed  Google Scholar 

  12. Gasparini P, Fassan M, Cascione L, Guler G, Balci S, Irkkan C et al (2014) Androgen receptor status is a prognostic marker in non-basal triple negative breast cancers and determines novel therapeutic options. PLoS ONE 9(2):e88525. https://doi.org/10.1371/journal.pone.0088525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mrklić I, Pogorelić Z, Capkun V, Tomić S (2013) Expression of androgen receptors in triple negative breast carcinomas. Acta Histochem 115(4):344–348. https://doi.org/10.1016/j.acthis.2012.09.006

    Article  CAS  PubMed  Google Scholar 

  14. Gerratana L, Basile D, Buono G, De Placido S, Giuliano M, Minichillo S et al (2018) Androgen receptor in triple negative breast cancer: a potential target for the targetless subtype. Cancer Treat Rev 68:102–110. https://doi.org/10.1016/j.ctrv.2018.06.005

    Article  CAS  PubMed  Google Scholar 

  15. Luo X, Shi YX, Li ZM, Jiang WQ (2010) Expression and clinical significance of androgen receptor in triple negative breast cancer. Chin J Cancer 29(6):585–590

    Article  CAS  PubMed  Google Scholar 

  16. Park S, Koo JS, Kim MS, Park HS, Lee JS, Kim SI et al (2011) Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers. Ann Oncol 22:1755–1762. https://doi.org/10.1093/annonc/mdq678

    Article  CAS  PubMed  Google Scholar 

  17. Niemeier LA, Dabbs DJ, Beriwal S, Striebel JM, Bhargava R (2010) Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. Mod Pathol 23:205–212. https://doi.org/10.1038/modpathol.2009.159

    Article  CAS  PubMed  Google Scholar 

  18. Rampurwala M, Wisinski KB, O’Regan R (2016) Role of the androgen receptor in triple-negative breast cancer. Clin Adv Hematol Oncol 4:186–193

    Google Scholar 

  19. Astvatsaturyan K, Yue Y, Walts AE, Bose S (2018) Androgen receptor positive triple negative breast cancer: clinicopathologic, prognostic, and predictive features. PLoS One. 13(6):e0197827. https://doi.org/10.1371/journal.pone.0197827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hickey TE, Robinson JL, Carroll JS, Tilley WD (2012) Mini review: The androgen receptor in breast tissues: growth inhibitor, tumor suppressor, oncogene? Mol Endocrinol 26(8):1252–1267. https://doi.org/10.1210/me.2012-1107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pistelli M, Caramanti M, Biscotti T, Santinelli A, Pagliacci A, De Lisa M et al (2014) Androgen receptor expression in early triple-negative breast cancer: clinical significance and prognostic associations. Cancers (Basel) 6:1351–1362. https://doi.org/10.3390/cancers6031351

    Article  CAS  PubMed  Google Scholar 

  22. Barton VN, D’Amato NC, Gordon MA, Lind HT, Spoelstra NS, Babbs BL et al (2015) Multiple molecular subtypes of triple-negative breast cancer critically rely on androgen receptor and respond to enzalutamide in vivo. Mol Cancer Ther 14(3):769–778. https://doi.org/10.1158/1535-7163.MCT-14-0926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM et al (2000) Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arc Pathol Lab Med 124(7):966–978

    Article  CAS  Google Scholar 

  24. Garay JP, Karakas B, Abukhdeir AM, Cosgrove DP, Gustin JP, Higgins MJ et al (2012) The growth response to androgen receptor signaling in ER-negative human breast cells is dependent on p21 and mediated by MAPK activation. Breast Cancer Res 9:14

    Google Scholar 

  25. Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109:25–32. https://doi.org/10.1002/cncr.22381

    Article  CAS  PubMed  Google Scholar 

  26. Birell SN, Hall RE, Tilley WD (1998) Role of the androgen receptor in human breast cancer. J Mammary Gland Biol Neoplasia 3:95–103. https://doi.org/10.1023/A:1018730519839

    Article  Google Scholar 

  27. Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C et al (2006) An estrogen receptor negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 25:3994–4008. https://doi.org/10.1038/sj.onc.1209415

    Article  CAS  PubMed  Google Scholar 

  28. Choi JE, Kang SH, Lee SJ, Bae YK (2015) Androgen receptor expression predicts decreased survival in early- stage triple-negative breast cancer. Ann Surg Oncol 22:82–89. https://doi.org/10.1245/s10434-014-3984-z

    Article  PubMed  Google Scholar 

  29. Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, Shaughnessy JO (2018) Enzalutamide for the treatment of androgen receptor–expressing triple-negative breast cancer. J Clin Oncol 36:884–890. https://doi.org/10.1200/JCO.2016.71.3495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mirzania M (2016) Approach to the triple negative breast cancer in new drugs area. Int J Hematol Oncol Stem Cell Res 10(2):115–119

    PubMed  PubMed Central  Google Scholar 

  31. Ogawa Y, Hai E, Matsumoto K, Ikeda K, Tokunaga S, Nagahara H et al (2008) Androgen receptor expression in breast cancer: relationship with clinicopathological factors and biomarkers. Int J Clin Oncol 13:431–435. https://doi.org/10.1007/s10147-008-0770-6

    Article  CAS  PubMed  Google Scholar 

  32. Marotti JD, de Abreu FB, Wells WA, Tsongalis GJ (2017) Triple-negative breast cancer next-generation sequencing for target identification. Am J Pathol 187:2133–2138. https://doi.org/10.1016/j.ajpath.2017.05.018

    Article  CAS  PubMed  Google Scholar 

  33. McGhan LJ, McCullough AE, Protheroe CA, Dueck AC, Lee JJ, Nunez-Nateras R et al (2013) Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype. Ann Surg Oncol 21:367. https://doi.org/10.1245/s10434-013-3260-7

    Article  Google Scholar 

  34. Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA et al (2013) Translational Breast Cancer Research Consortium (TBCRC 011) Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin Cancer Res 19(19):5505–5512. https://doi.org/10.1158/1078-0432.CCR-12-332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. He J, Peng R, Yuan Z, Wang S, Peng J, Lin G et al (2012) Prognostic value of androgen receptor expression in operable triple-negative breast cancer: a retrospective analysis based on a tissue microarray. Med Oncol 29:406–410. https://doi.org/10.1007/s12032-011-9832-0

    Article  CAS  PubMed  Google Scholar 

  36. Hu R, Dawood S, Holmes MD et al (2011) Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res 17(7):1867–1874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Choi JE, Kang SH, Lee SJ, Bae YK (2015) Androgen receptor expression predicts decreased survival in early- stage triple-negative breast cancer. Ann Surg Oncol 22(1):82–89

    Article  PubMed  Google Scholar 

  38. Lehmann-Che J, Hamy AS, Porcher R et al (2013) Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors overexpressing either HER2 or GCDFP15. Breast Cancer Res 15(3):R37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by an intramural grant (A-13-PGI/IMP/80/2019) from Sanjay Gandhi Postgraduate Institute of Medical Sciences.

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Authors

Contributions

AM: (1) conception and design of the study, acquisition of data, and analysis and interpretation of data, (2) drafting the article and revising it critically for important intellectual content, (3) final approval of the version to be submitted.

SKM: (1) lab work, acquisition and analysis of data (2) revising manuscript critically for important intellectual content, (3) final approval of the version to be submitted.

VS: (1) acquisition and analysis of data (2) revising the article critically for important intellectual content, (3) final approval of the version to be submitted.

NK: (1) conception and design of the study, and analysis and interpretation of data, (2) revising the article critically for important intellectual content, (3) final approval of the version to be submitted.

NK: (1) conception and design of the study and analysis and interpretation of data, (2) revising the article critically for important intellectual content, (3) final approval of the version to be submitted.

GA: (1) the conception and design of the study (2) revising the article critically for important intellectual content, (3) final approval of the version to be submitted.

Corresponding author

Correspondence to Anjali Mishra.

Ethics declarations

The abstract based on this study was presented as poster presentation in the BSI section of the 49th World Congress of International Society of Surgery ISS/SIC, International Surgical Week 2022 (ISW 2022) held in Vienna, Austria between August 15 to 18, 2022.

Informed Consent

Informed consent was obtained from all individual participants for collection of specimens. For review consent waiver was granted by the Institute Ethics Committee. The study was approved by the Institute Ethics Committee (IEC 2019–106-IMP-EXP-9).

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The authors declare no competing interests.

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Mishra, A., Mishra, S.K., Sharanappa, V. et al. Incidence and Prognostic Significance of Androgen Receptors (AR) in Indian Triple-Negative Breast Cancer (TNBC). Indian J Surg Oncol 15, 250–257 (2024). https://doi.org/10.1007/s13193-024-01877-2

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