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Androgen deprivation by adrenal suppression using low-dose hydrocortisone for the treatment of breast carcinoma with apocrine features: a case report illustrating this new paradigm

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Abstract

We report on a postmenopausal patient with a secondary metastatic apocrine breast cancer successfully treated with low-dose hydrocortisone only following several lines of chemotherapy. The tumor cells in the primary and metastatic lesion exhibited a ‘triple-negative’ status (estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative); the androgen receptor (AR) was strongly expressed. Twenty milligrams of hydrocortisone, a low substitution dose known to suppress adrenal steroid production, twice daily led to a clinical benefit lasting for one year, with symptom control, radiologically stable disease, and steady decrease in CA15.3. Our observation demonstrates that an AR-expressing apocrine breast cancer may respond to androgen deprivation, as an ER-positive breast cancer may benefit from estrogen deprivation. It highlights the importance of further research targeting the AR pathway in apocrine carcinoma, for which androgens represent the sole (known) steroid hormone stimulating tumor growth. Future clinical trials should not only focus on AR inhibitors like enzalutamide, but also on ablative modalities like low-dose hydrocortisone aiming at medical adrenalectomy. This method of androgen deprivation is largely available, cheap, and nearly devoid of toxicity.

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References

  1. Eusebi V, Millis RR, Cattani MG, Bussolati G, Azzopardi JG (1986) Apocrine carcinoma of the breast. A morphologic and immunocytochemical study. Am J Pathol 123(3):532–541

    PubMed Central  CAS  PubMed  Google Scholar 

  2. Dellapasqua S, Maisonneuve P, Viale G, Pruneri G, Mazzarol G, Ghisini R, Mazza M, Iorfida M, Rotmensz N, Veronesi P et al (2013) Immunohistochemically defined subtypes and outcome of apocrine breast cancer. Clin Breast Cancer 13(2):95–102

    Article  CAS  PubMed  Google Scholar 

  3. Vranic S, Schmitt F, Sapino A, Costa JL, Reddy S, Castro M, Gatalica Z (2013) Apocrine carcinoma of the breast: a comprehensive review. Histol Histopathol 28(11):1393–1409

    PubMed  Google Scholar 

  4. Vranic S, Marchiò C, Castellano I, Botta C, Scalzo MS, Bender RP, Payan-Gomez C, di Cantogno LV, Gugliotta P, Tondat F et al (2015) Immunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breast. Hum Pathol 46(9):1350–1359

    Article  CAS  PubMed  Google Scholar 

  5. O’Malley FP, Bane A (2008) An update on apocrine lesions of the breast. Histopathology 52(1):3–10

    Article  PubMed  Google Scholar 

  6. Shao MM, Chan SK, Yu AM, Lam CC, Tsang JY, Lui PC, Law BK, Tan PH, Tse GM (2012) Keratin expression in breast cancers. Virchows Arch 461(3):313–322

    Article  CAS  PubMed  Google Scholar 

  7. Lehmann-Che J, Hamy AS, Porcher R, Barritault M, Bouhidel F, Habuellelah H, Leman-Detours S, de Roquancourt A, Cahen-Doidy L, Bourstyn E et al (2013) Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors over expressing either HER2 or GCDFP15. Breast Cancer Res 15(3):R37

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Birrell SN, Bentel JM, Hickey TE, Ricciardelli C, Weger MA, Horsfall DJ, Tilley WD (1995) Androgens induce divergent proliferative responses in human breast cancer cell lines. J Steroid Biochem Mol Biol 52(5):459–467

    Article  CAS  PubMed  Google Scholar 

  9. Safarpour D, Pakneshan S, Tavassoli FA (2014) Androgen receptor (AR) expression in 400 breast carcinomas: is routine AR assessment justified? Am J Cancer Res 4(4):353–368

    PubMed Central  PubMed  Google Scholar 

  10. Hickey TE, Robinson JL, Carroll JS, Tilley WD (2012) Minireview: the androgen receptor in breast tissues: growth inhibitor, tumor suppressor, oncogene? Mol Endocrinol 26(8):1252–1267

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Yu Q, Niu Y, Liu N, Zhang JZ, Liu TJ, Zhang RJ, Wang SL, Ding XM, Xiao XQ (2011) Expression of androgen receptor in breast cancer and its significance as a prognostic factor. Ann Oncol 22(6):1288–1294

    Article  CAS  PubMed  Google Scholar 

  12. Gonzalez LO, Corte MD, Vazquez J, Junquera S, Sanchez R, Alvarez AC, Rodriguez JC, Lamelas ML, Vizoso FJ (2008) Androgen receptor expression in breast cancer: relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors. BMC Cancer 8:149

    Article  PubMed Central  PubMed  Google Scholar 

  13. Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A et al (2013) Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer Res 19(19):5505–5512

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Traina TA: Stage 1 results from a 2-stage study of enzalutamide, an androgen receptor (AR) inhibitor, in advanced AR + triple-negative breast cancer (TNBC). In: SABCS 2014. San Antonio, Texas, USA; 2014

  15. Cochrane DR, Bernales S, Jacobsen BM, Cittelly DM, Howe EN, D’Amato NC, Spoelstra NS, Edgerton SM, Jean A, Guerrero J et al (2014) Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Res 16(1):R7

    Article  PubMed Central  PubMed  Google Scholar 

  16. Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M (2011) Targeting androgen receptor in estrogen receptor-negative breast cancer. Cancer Cell 20(1):119–131

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C, Gerald WL (2006) An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 25(28):3994–4008

    Article  CAS  PubMed  Google Scholar 

  18. Thike AA, Yong-Zheng Chong L, Cheok PY, Li HH, Wai-Cheong Yip G, Huat Bay B, Tse GM, Iqbal J, Tan PH (2014) Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer. Mod Pathol 27(3):352–360

    CAS  PubMed  Google Scholar 

  19. Peters AA, Buchanan G, Ricciardelli C, Bianco-Miotto T, Centenera MM, Harris JM, Jindal S, Segara D, Jia L, Moore NL et al (2009) Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. Cancer Res 69(15):6131–6140

    Article  CAS  PubMed  Google Scholar 

  20. Agoff SN, Swanson PE, Linden H, Hawes SE, Lawton TJ (2003) Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol 120(5):725–731

    Article  CAS  PubMed  Google Scholar 

  21. Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, Marotti JD, Hankinson SE, Colditz GA, Tamimi RM (2011) Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res 17(7):1867–1874

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Iversen P, McLeod DG, See WA, Morris T, Armstrong J, Wirth MP (2010) Group CEPCT: Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer: final results from the bicalutamide Early Prostate Cancer programme at a median follow-up of 9.7 years. BJU Int 105(8):1074–1081

    Article  CAS  PubMed  Google Scholar 

  23. Arce-Salinas C, Riesco-Martinez MC, Hanna W, Bedard P, Warner E (2014) Complete response of metastatic androgen receptor-positive breast cancer to bicalutamide: case report and review of the literature. J Clin Oncol

  24. Santen RJ, Lipton A, Kendall J (1974) Successful medical adrenalectomy with amino-glutethimide. Role of altered drug metabolism. JAMA 230(12):1661–1665

    Article  CAS  PubMed  Google Scholar 

  25. Vermeulen A, Paridaens R, Heuson JC (1983) Effects of aminoglutethimide on adrenal steroid secretion. Clin Endocrinol (Oxf) 19(6):673–682

    Article  CAS  Google Scholar 

  26. Kirschner MA, Knorr DW (1972) Suppression of androgen and oestrogen production in normal men. Acta Endocrinol (Copenh) 70(2):342–350

    CAS  Google Scholar 

  27. Montgomery B, Cheng HH, Drechsler J, Mostaghel EA (2014) Glucocorticoids and prostate cancer treatment: friend or foe? Asian J Androl 16(3):354–358

    Article  PubMed Central  PubMed  Google Scholar 

  28. Wagner AD, Thomssen C, Haerting J, Unverzagt S (2012) Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer. Cochrane Database Syst Rev, 7:CD008941

  29. Tarulli GA, Butler LM, Tilley WD, Hickey TE (2014) Bringing androgens up a NOTCH in breast cancer. Endocr Relat Cancer 21(4):T183–202

    Article  CAS  PubMed  Google Scholar 

  30. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368(2):138–148

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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    Authors and Affiliations

    1. Department of Oncology, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium

      Lynn Jongen, Robert Paridaens, Hans Wildiers & Patrick Neven

    2. Department of General Medical Oncology, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium

      Robert Paridaens & Hans Wildiers

    3. Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research, KU Leuven - University of Leuven, Leuven, Belgium

      Giuseppe Floris

    4. Department of Pathology, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium

      Giuseppe Floris

    5. Department of Gynecology and Obstetrics, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium

      Patrick Neven

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    1. Lynn Jongen
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    2. Robert Paridaens
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    Correspondence to Lynn Jongen.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the UZ Leuven committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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    Lynn Jongen and Robert Paridaens have contributed equally to this work.

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    Jongen, L., Paridaens, R., Floris, G. et al. Androgen deprivation by adrenal suppression using low-dose hydrocortisone for the treatment of breast carcinoma with apocrine features: a case report illustrating this new paradigm. Breast Cancer Res Treat 155, 603–607 (2016). https://doi.org/10.1007/s10549-016-3708-0

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    • DOI: https://doi.org/10.1007/s10549-016-3708-0

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