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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Case report

Hormone signaling via androgen receptor affects breast cancer and prostate cancer in a male patient: A case report

Authors: Haruko Takuwa, Wakako Tsuji, Masayuki Shintaku, Fumiaki Yotsumoto

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Male breast cancer (MBC) is rare, accounting for only around 1% of all breast cancers. Most MBCs are hormone-driven. Not only the estrogen receptor (ER), but also other steroid hormone receptors, including the androgen receptor (AR) and progesterone receptor (PgR) are expressed in MBC. AR activation in breast cancer cells facilitates downstream gene expression that drives tumorigenesis in a similar manner to ER. AR-mediated signalling works paradoxically in breast cancer and prostate cancer, and cancer cells expressing the AR are endocrine-sensitive.

Case presentation

We describe a case of double cancer of MBC and prostate cancer. A 69-year-old man was referred to our hospital with a lump in his left breast in the 1990s. The patient had cT3N3M0, stage IIIC breast cancer, and underwent a mastectomy and axillary lymph node dissection. Though adjuvant chemotherapy was administered, he experienced pleural metastasis 2 months after the surgery. Two years after the recurrence during endocrine therapy with oral 5-fluorouracil, he complained of frequent urination. Radiological and histological examinations revealed that the patient had cT3N0M0, stage III primary prostate cancer with a prostate-specific antigen (PSA) level of 40.5 ng/mL. Germline mutations in the BRCA1 and BRCA2 genes were not tested. He received multidisciplinary, continuous therapy for both breast and prostate cancer; however, 5 and 3 years after each diagnosis, respectively, he experienced a deep vein thrombosis in his right leg related to the endocrine therapy. Liver metastasis progressed after he stopped breast cancer therapy. However, long-term disease control had been achieved with anti-estrogen therapy for breast cancer and estrogen replacement therapy for prostate cancer.

Conclusions

Several studies have shown that estrogen exposure after estrogen depletion likely causes apoptosis of ER-positive breast cancer cells. Our findings indicate that this also applies to the environment in male body. AR dominant signaling prevents breast cancer recurrence and metastasis, especially in MBC patients.
Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.CrossRef
2.
go back to reference Ruddy KJ, Winer EP. Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. Ann Oncol Off J Eur Soc Med Oncol. 2013;24:1434–43.CrossRef Ruddy KJ, Winer EP. Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. Ann Oncol Off J Eur Soc Med Oncol. 2013;24:1434–43.CrossRef
3.
go back to reference Rizzolo P, Silvestri V, Tommasi S, Pinto R, Danza K, Falchetti M, et al. Male breast cancer: genetics, epigenetics, and ethical aspects. Ann Oncol Off J Eur Soc Med Oncol. 2013;24(Suppl 8):viii75–82. Rizzolo P, Silvestri V, Tommasi S, Pinto R, Danza K, Falchetti M, et al. Male breast cancer: genetics, epigenetics, and ethical aspects. Ann Oncol Off J Eur Soc Med Oncol. 2013;24(Suppl 8):viii75–82.
4.
go back to reference Speirs V, Shaaban AM. The rising incidence of male breast cancer. Breast Cancer Res Treat. 2009;115:429–30.CrossRef Speirs V, Shaaban AM. The rising incidence of male breast cancer. Breast Cancer Res Treat. 2009;115:429–30.CrossRef
5.
go back to reference Severson TM, Zwart W. A review of estrogen receptor/androgen receptor genomics in male breast cancer. Endocr Relat Cancer. 2017;24:R27–34.CrossRef Severson TM, Zwart W. A review of estrogen receptor/androgen receptor genomics in male breast cancer. Endocr Relat Cancer. 2017;24:R27–34.CrossRef
6.
go back to reference Nilsson C, Koliadi A, Johansson I, Ahlin C, Thorstenson S, Bergkvist L, et al. High proliferation is associated with inferior outcome in male breast cancer patients. Mod Pathol. 2013;26:87–94.CrossRef Nilsson C, Koliadi A, Johansson I, Ahlin C, Thorstenson S, Bergkvist L, et al. High proliferation is associated with inferior outcome in male breast cancer patients. Mod Pathol. 2013;26:87–94.CrossRef
7.
go back to reference Anderson WF, Jatoi I, Tse J, Rosenberg PS. Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol. 2010;28:232–9.CrossRef Anderson WF, Jatoi I, Tse J, Rosenberg PS. Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol. 2010;28:232–9.CrossRef
8.
go back to reference White J, Kearins O, Dodwell D, Horgan K, Hanby AM, Speirs V. Male breast carcinoma: increased awareness needed. Breast Cancer Res. 2011;13:219.CrossRef White J, Kearins O, Dodwell D, Horgan K, Hanby AM, Speirs V. Male breast carcinoma: increased awareness needed. Breast Cancer Res. 2011;13:219.CrossRef
9.
go back to reference Peters AA, Buchanan G, Ricciardelli C, Bianco-Miotto T, Centenera MM, Harris JM, et al. Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. Cancer Res. 2009;69:6131–40.CrossRef Peters AA, Buchanan G, Ricciardelli C, Bianco-Miotto T, Centenera MM, Harris JM, et al. Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. Cancer Res. 2009;69:6131–40.CrossRef
10.
go back to reference Chia K, O’Brien M, Brown M, Lim E. Targeting the androgen receptor in breast cancer. Curr Oncol Rep. 2015;17:4.CrossRef Chia K, O’Brien M, Brown M, Lim E. Targeting the androgen receptor in breast cancer. Curr Oncol Rep. 2015;17:4.CrossRef
11.
go back to reference Cardoso F, Bartlett JMS, Slaets L, van Deurzen CHM, van Leeuwen-Stok E, Porter P, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG international male breast Cancer program. Ann Oncol Off J Eur Soc Med Oncol. 2018;29:405–17. Cardoso F, Bartlett JMS, Slaets L, van Deurzen CHM, van Leeuwen-Stok E, Porter P, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG international male breast Cancer program. Ann Oncol Off J Eur Soc Med Oncol. 2018;29:405–17.
12.
go back to reference Evans DB, Crichlow RW. Carcinoma of the male breast and Klinefelter’s syndrome: is there an association? CA Cancer J Clin. 1987;37:246–51.CrossRef Evans DB, Crichlow RW. Carcinoma of the male breast and Klinefelter’s syndrome: is there an association? CA Cancer J Clin. 1987;37:246–51.CrossRef
13.
go back to reference Ewertz M, Holmberg L, Tretli S, Pedersen BV, Kristensen A. Risk factors for male breast cancer--a case-control study from Scandinavia. Acta Oncol. 2001;40:467–71.CrossRef Ewertz M, Holmberg L, Tretli S, Pedersen BV, Kristensen A. Risk factors for male breast cancer--a case-control study from Scandinavia. Acta Oncol. 2001;40:467–71.CrossRef
14.
go back to reference Liede A, Karlan BY, Narod SA. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol. 2004;22:735–42.CrossRef Liede A, Karlan BY, Narod SA. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol. 2004;22:735–42.CrossRef
15.
go back to reference Korde LA, Zujewski JA, Kamin L, Giordano S, Domchek S, Anderson WF, et al. Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol. 2010;28:2114–22.CrossRef Korde LA, Zujewski JA, Kamin L, Giordano S, Domchek S, Anderson WF, et al. Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol. 2010;28:2114–22.CrossRef
16.
go back to reference Ibrahim M, Yadav S, Ogunleye F, Zakalik D. Male BRCA mutation carriers: clinical characteristics and cancer spectrum. BMC Cancer. 2018;18:179.CrossRef Ibrahim M, Yadav S, Ogunleye F, Zakalik D. Male BRCA mutation carriers: clinical characteristics and cancer spectrum. BMC Cancer. 2018;18:179.CrossRef
17.
go back to reference Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, et al. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002;31:55–9.CrossRef Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, et al. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002;31:55–9.CrossRef
18.
go back to reference Adamo B, Ricciardi GRR, Ieni A, Franchina T, Fazzari C, Sanò MV, et al. The prognostic significance of combined androgen receptor, E-cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget. 2017;8:76974–86.PubMedPubMedCentral Adamo B, Ricciardi GRR, Ieni A, Franchina T, Fazzari C, Sanò MV, et al. The prognostic significance of combined androgen receptor, E-cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget. 2017;8:76974–86.PubMedPubMedCentral
19.
go back to reference Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinänen R, Palmberg C, et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet. 1995;9:401–6.CrossRef Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinänen R, Palmberg C, et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet. 1995;9:401–6.CrossRef
20.
go back to reference Harris WP, Mostaghel EA, Nelson PS, Montgomery B. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion. Nat Clin Pract Urol. 2009;6:76–85.CrossRef Harris WP, Mostaghel EA, Nelson PS, Montgomery B. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion. Nat Clin Pract Urol. 2009;6:76–85.CrossRef
21.
go back to reference Cai C, He HH, Chen S, Coleman I, Wang H, Fang Z, et al. Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1. Cancer Cell. 2011;20:457–71.CrossRef Cai C, He HH, Chen S, Coleman I, Wang H, Fang Z, et al. Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1. Cancer Cell. 2011;20:457–71.CrossRef
22.
go back to reference Guo W, Keener AL, Jing Y, Cai L, Ai J, Zhang J, et al. FOXA1 modulates EAF2 regulation of AR transcriptional activity, cell proliferation, and migration in prostate cancer cells. Prostate. 2015;75:976–87.CrossRef Guo W, Keener AL, Jing Y, Cai L, Ai J, Zhang J, et al. FOXA1 modulates EAF2 regulation of AR transcriptional activity, cell proliferation, and migration in prostate cancer cells. Prostate. 2015;75:976–87.CrossRef
23.
go back to reference Union for International Cancer Control-TNM classification, 8th edition. 2016. Union for International Cancer Control-TNM classification, 8th edition. 2016.
24.
go back to reference Giordano SH. A review of the diagnosis and management of male breast cancer. Oncologist. 2005;10:471–9.CrossRef Giordano SH. A review of the diagnosis and management of male breast cancer. Oncologist. 2005;10:471–9.CrossRef
25.
go back to reference Rivera E, Gomez H. Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone. Breast Cancer Res. 2010;12(Suppl 2):S2.CrossRef Rivera E, Gomez H. Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone. Breast Cancer Res. 2010;12(Suppl 2):S2.CrossRef
26.
go back to reference Hamilton A, Roy JA, Beex L, Piccart M, Mauriac L, Coleman R, et al. EORTC 10941: a phase II study of liarozole in postmenopausal patients with ‘chemotherapy-resistant’ or ‘potentially hormone sensitive’ metastatic breast cancer. Breast Cancer Res Treat. 2000;60:181–8.CrossRef Hamilton A, Roy JA, Beex L, Piccart M, Mauriac L, Coleman R, et al. EORTC 10941: a phase II study of liarozole in postmenopausal patients with ‘chemotherapy-resistant’ or ‘potentially hormone sensitive’ metastatic breast cancer. Breast Cancer Res Treat. 2000;60:181–8.CrossRef
27.
go back to reference Sawaki M, Wada M, Sato Y, Mizuno Y, Kobayashi H, Yokoi K, et al. High-dose toremifene as first-line treatment of metastatic breast cancer resistant to adjuvant aromatase inhibitor: a multicenter phase II study. Oncol Lett. 2012;3:61–5.CrossRef Sawaki M, Wada M, Sato Y, Mizuno Y, Kobayashi H, Yokoi K, et al. High-dose toremifene as first-line treatment of metastatic breast cancer resistant to adjuvant aromatase inhibitor: a multicenter phase II study. Oncol Lett. 2012;3:61–5.CrossRef
28.
go back to reference Yamamoto Y, Masuda N, Ohtake T, Yamashita H, Saji S, Kimijima I, et al. Clinical usefulness of high-dose toremifene in patients relapsed on treatment with an aromatase inhibitor. Breast Cancer. 2010;17:254–60.CrossRef Yamamoto Y, Masuda N, Ohtake T, Yamashita H, Saji S, Kimijima I, et al. Clinical usefulness of high-dose toremifene in patients relapsed on treatment with an aromatase inhibitor. Breast Cancer. 2010;17:254–60.CrossRef
29.
go back to reference Stenbygaard LE, Herrstedt J, Thomsen JF, Svendsen KR, Engelholm SA, Dombernowsky P. Toremifene and tamoxifen in advanced breast cancer--a double-blind cross-over trial. Breast Cancer Res Treat. 1993;25:57–63.CrossRef Stenbygaard LE, Herrstedt J, Thomsen JF, Svendsen KR, Engelholm SA, Dombernowsky P. Toremifene and tamoxifen in advanced breast cancer--a double-blind cross-over trial. Breast Cancer Res Treat. 1993;25:57–63.CrossRef
30.
go back to reference Binkhorst L, Mathijssen RHJ, Jager A, van Gelder T. Individualization of tamoxifen therapy: much more than just CYP2D6 genotyping. Cancer Treat Rev. 2015;41:289–99.CrossRef Binkhorst L, Mathijssen RHJ, Jager A, van Gelder T. Individualization of tamoxifen therapy: much more than just CYP2D6 genotyping. Cancer Treat Rev. 2015;41:289–99.CrossRef
31.
go back to reference Kim JY, Han W, Moon HG, Ahn SK, Kim J, Lee JW, et al. Prognostic effect of preoperative serum estradiol level in postmenopausal breast cancer. BMC Cancer. 2013;13:503.CrossRef Kim JY, Han W, Moon HG, Ahn SK, Kim J, Lee JW, et al. Prognostic effect of preoperative serum estradiol level in postmenopausal breast cancer. BMC Cancer. 2013;13:503.CrossRef
32.
go back to reference Iwase H, Yamamoto Y, Yamamoto-Ibusuki M, Murakami KI, Okumura Y, Tomita S, et al. Ethinylestradiol is beneficial for postmenopausal patients with heavily pre-treated metastatic breast cancer after prior aromatase inhibitor treatment: a prospective study. Br J Cancer. 2013;109:1537–42.CrossRef Iwase H, Yamamoto Y, Yamamoto-Ibusuki M, Murakami KI, Okumura Y, Tomita S, et al. Ethinylestradiol is beneficial for postmenopausal patients with heavily pre-treated metastatic breast cancer after prior aromatase inhibitor treatment: a prospective study. Br J Cancer. 2013;109:1537–42.CrossRef
33.
go back to reference Lewis JS, Meeke K, Osipo C, Ross EA, Kidawi N, Li T, et al. Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation. J Natl Cancer Inst. 2005;97:1746–59.CrossRef Lewis JS, Meeke K, Osipo C, Ross EA, Kidawi N, Li T, et al. Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation. J Natl Cancer Inst. 2005;97:1746–59.CrossRef
34.
go back to reference Takuwa H, Saji S, Takada M, Takahara S, Yamauchi, A. The relationship between serum E2 levels and recurrence in premenopausal, ER-positive breast cancer patients: a retrospective study. Breast Dis 2018; Epub ahead of print. doi:https://doi.org/10.3233/BD-170307. Takuwa H, Saji S, Takada M, Takahara S, Yamauchi, A. The relationship between serum E2 levels and recurrence in premenopausal, ER-positive breast cancer patients: a retrospective study. Breast Dis 2018; Epub ahead of print. doi:https://​doi.​org/​10.​3233/​BD-170307.
35.
go back to reference Gunnarsson PO, Forshell GP. Clinical pharmacokinetics of estramustine phosphate. Urology. 1984;23:22–7.CrossRef Gunnarsson PO, Forshell GP. Clinical pharmacokinetics of estramustine phosphate. Urology. 1984;23:22–7.CrossRef
36.
go back to reference Imamov O, Lopatkin NA, Gustafsson JA. Estrogen receptor beta in prostate cancer. N Engl J Med. 2004;351:2773–4.CrossRef Imamov O, Lopatkin NA, Gustafsson JA. Estrogen receptor beta in prostate cancer. N Engl J Med. 2004;351:2773–4.CrossRef
37.
go back to reference Lai J, Myers SA, Lawrence MG, Odorico DM, Clements JA. Direct progesterone receptor and indirect androgen receptor interactions with the kallikrein-related peptidase 4 gene promoter in breast and prostate cancer. Mol Cancer Res. 2009;7:129–41.CrossRef Lai J, Myers SA, Lawrence MG, Odorico DM, Clements JA. Direct progesterone receptor and indirect androgen receptor interactions with the kallikrein-related peptidase 4 gene promoter in breast and prostate cancer. Mol Cancer Res. 2009;7:129–41.CrossRef
38.
go back to reference Gui B, Hsieh CL, Kantoff PW, Kibel AS, Jia L. Androgen receptor-mediated downregulation of microRNA-221 and -222 in castration-resistant prostate cancer. PLoS One. 2017;12:e0184166.CrossRef Gui B, Hsieh CL, Kantoff PW, Kibel AS, Jia L. Androgen receptor-mediated downregulation of microRNA-221 and -222 in castration-resistant prostate cancer. PLoS One. 2017;12:e0184166.CrossRef
Metadata
Title
Hormone signaling via androgen receptor affects breast cancer and prostate cancer in a male patient: A case report
Authors
Haruko Takuwa
Wakako Tsuji
Masayuki Shintaku
Fumiaki Yotsumoto
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5216-6

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