Skip to main content

Advertisement

SpringerLink
Log in

Aromatase inhibitors for metastatic male breast cancer: molecular, endocrine, and clinical considerations

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Male breast cancer is a rare condition. Aromatase inhibitors are widely used for treating metastatic male breast cancer patients. In this setting, their use is not substantiated by prospective clinical trials, but is rather driven by similarities supposedly existing with breast cancer in postmenopausal women. This oversimplified approach was questioned by studies addressing the molecular and endocrine roots of the disease. In this manuscript, we discuss relevant aspects of the current use of aromatase inhibitors in metastatic male breast cancer in light of the most updated evidence on the molecular landscape of the disease and the specific changes in the hormonal background occurring with aging. We further point to strategies for blocking multiple hormonal pathway nodes with the goal of improving their therapeutic potential. We searched PubMed from its inception until March 2014 for relevant literature on the use of aromatase inhibitors in metastatic male breast cancer. Selected terms were combined and used both as medical headings and text words. The reference list of the suitable manuscripts was inspected for further publications. Aromatase inhibitors represent the mainstay of treatment in the metastatic setting. Yet, efforts aimed at sharpening the therapeutic potential of aromatase inhibitors still pose a challenge due to the paucity of data. The choice of dual hormonal (or sequential) therapy combining aromatase inhibitors with a GnRH analogue may represent a valid alterative, particularly if informed by cancer- and patient-related features including molecular, endocrine, and clinic characteristics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN (2004) Breast carcinoma in men: a population-based study. Cancer 101:51–57

    Article  PubMed  Google Scholar 

  2. Ruddy KJ, Winer EP (2013) Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. Ann Oncol 24:1434–1443

    Article  CAS  PubMed  Google Scholar 

  3. Brinton LA, Cook MB, McCormack V, Johnson KC, Olsson H, Casagrande JT, et al (2014) Anthropometric and hormonal risk factors for male breast cancer: male breast cancer pooling project results. J Natl Cancer Inst 106:doi: 10.1093/jnci/djt465

  4. Anderson WF, Jatoi I, Tse J, Rosenberg PS (2010) Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol 28:232–239

    Article  PubMed Central  PubMed  Google Scholar 

  5. Cardoso F, Bischoff J, Brain E, Zotano ÁG, Lück HJ, Tjan-Heijnen VC et al (2013) A review of the treatment of endocrine responsive metastatic breast cancer in postmenopausal women. Cancer Treat Rev 39:457–465

    Article  CAS  PubMed  Google Scholar 

  6. Johansson I, Nilsson C, Berglund P, Lauss M, Ringnér M, Olsson H et al (2012) Gene expression profiling of primary male breast cancers reveals two unique subgroups and identifies Nacetyltransferase-1 (NAT1) as a novel prognostic biomarker. Breast Cancer Res 14:R31

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Callari M, Cappelletti V, De Cecco L, Musella V, Miodini P, Veneroni S et al (2011) Gene expression analysis reveals a different transcriptomic landscape in female and male breast cancer. Breast Cancer Res Treat 127:601–610

    Article  CAS  PubMed  Google Scholar 

  8. Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I (2002) Estradiol in elderly men. Aging Male 5:98–102

    Article  CAS  PubMed  Google Scholar 

  9. Eggemann H, Ignatov A, Smith BJ, Altmann U, von Minckwitz G, Röhl FW et al (2013) Adjuvant therapy with tamoxifen compared to aromatase inhibitors for 257 male breast cancer patients. Breast Cancer Res Treat 137:465–470

    Article  CAS  PubMed  Google Scholar 

  10. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874

    Article  PubMed Central  PubMed  Google Scholar 

  11. Huo D, Ikpatt F, Khramtsov A, Dangou JM, Nanda R, Dignam J et al (2009) Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer. J Clin Oncol 27:4515–4521

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70

    Article  Google Scholar 

  13. Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ et al (2012) The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486:346–352

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C et al (2013) Mutational landscape and significance across 12 major cancer types. Nature 502:333–339

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Rudlowski C, Schulten HJ, Golas MM, Sander B, Barwing R, Palandt JE et al (2006) Comparative genomic hybridization analysis on male breast cancer. Int J Cancer 118:2455–2460

    Article  CAS  PubMed  Google Scholar 

  16. Kornegoor R, Moelans CB, Verschuur-Maes AH, Hogenes MC, de Bruin PC, Oudejans JJ et al (2012) Promoter hypermethylation in male breast cancer: analysis by multiplex ligation-dependent probe amplification. Breast Cancer Res 14:R101

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Kornegoor R, Moelans CB, Verschuur-Maes AH, Hogenes MC, de Bruin PC, Oudejans JJ et al (2012) Oncogene amplification in male breast cancer: analysis by multiplex ligation-dependent probe amplification. Breast Cancer Res Treat 135:49–58

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Johansson I, Nilsson C, Berglund P, Strand C, Jönsson G, Staaf J et al (2011) High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer. Breast Cancer Res Treat 129:747–760

    Article  PubMed  Google Scholar 

  19. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331:1565–1570

    Article  CAS  PubMed  Google Scholar 

  20. Shaaban AM, Ball GR, Brannan RA, Cserni G, Di Benedetto A, Dent J et al (2012) A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. Breast Cancer Res Treat 133:949–958

    Article  CAS  PubMed  Google Scholar 

  21. Fassan M, Baffa R, Palazzo JP, Lloyd J, Crosariol M, Liu CG et al (2009) MicroRNA expression profiling of male breast cancer. Breast Cancer Res 11:R58

    Article  PubMed Central  PubMed  Google Scholar 

  22. Johansson I, Ringnér M, Hedenfalk I (2013) The landscape of candidate driver genes differs between male and female breast cancer. PLoS ONE 8:e78299

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Patani N, Martin LA (2014) Understanding response and resistance to oestrogen deprivation in ER-positive breast cancer. Mol Cell Endocrinol 382:683–694

    Article  CAS  PubMed  Google Scholar 

  24. Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X et al (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45:1446–1451

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Toy W, Shen Y, Won H, Green B, Sakr RA, Will M et al (2013) ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 45:1439–1445

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Li S, Shen D, Shao J, Crowder R, Liu W, Prat A et al (2013) Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. Cell Rep 4:1116–1130

    Article  CAS  PubMed  Google Scholar 

  27. Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A, Dvir A, Soussan-Gutman L, Jeselsohn R et al (2013) D538G mutation in estrogen receptor-α: a novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res 73:6856–6864

    Article  CAS  PubMed  Google Scholar 

  28. Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T et al (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366:520–529

    Article  CAS  PubMed  Google Scholar 

  29. Turner KJ, Morley M, Atanassova N, Swanston ID, Sharpe RM (2000) Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility. J Endocrinol 164:225–238

    Article  CAS  PubMed  Google Scholar 

  30. Mauras N, O’Brien KO, Klein KO, Hayes V (2000) Estrogen suppression in males: metabolic effects. J Clin Endocrinol Metab 85:2370–2377

    CAS  PubMed  Google Scholar 

  31. T’Sjoen GG, Giagulli VA, Delva H, Crabbe P, De Bacquer D, Kaufman JM (2005) Comparative assessment in young and elderly men of the gonadotropin response to aromatase inhibition. J Clin Endocrinol Metab 90:5717–5722

    Article  PubMed  Google Scholar 

  32. Bighin C, Lunardi G, Del Mastro L, Marroni P, Taveggia P, Levaggi A et al (2010) Estrone sulphate, FSH, and testosterone levels in two male breast cancer patients treated with aromatase inhibitors. Oncologist 15:1270–1272

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C (2004) Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. J Clin Endocrinol Metab 89:1174–1180

    Article  CAS  PubMed  Google Scholar 

  34. Burnett-Bowie SA, Roupenian KC, Dere ME, Lee H, Leder BZ (2009) Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol 70:116–123

    Article  CAS  Google Scholar 

  35. Lopez M, Di Lauro L, Lazzaro B, Papaldo P (1985) Hormonal treatment of disseminated male breast cancer. Oncology 42:345–349

    Article  CAS  PubMed  Google Scholar 

  36. Lopez M (1985) Cyproterone acetate in the treatment of metastatic cancer of the male breast. Cancer 55:2334–2336

    Article  CAS  PubMed  Google Scholar 

  37. Lopez M, Natali M, Di Lauro L, Vici P, Pignatti F, Carpano S (1993) Combined treatment with buserelin and cyproterone acetate in metastatic male breast cancer. Cancer 72:502–505

    Article  CAS  PubMed  Google Scholar 

  38. Dakin Haché K, Gray S, Barnes PJ, Dewar R, Younis T, Rayson D et al (2007) Clinical and pathological correlations in male breast cancer: intratumoral aromatase expression via tissue microarray. Breast Cancer Res Treat 105:169–175

    Article  PubMed  Google Scholar 

  39. Takagi K, Moriya T, Kurosumi M, Oka K, Miki Y, Ebata A et al (2013) Intratumoral estrogen concentration and expression of estrogen-induced genes in male breast carcinoma: comparison with female breast carcinoma. Horm Cancer 4:1–11

    Article  CAS  PubMed  Google Scholar 

  40. White J, Kearins O, Dodwell D, Horgan K, Hanby AM, Speirs V (2011) Male breast carcinoma: increased awareness needed. Breast Cancer Res 13:219

    Article  PubMed Central  PubMed  Google Scholar 

  41. Anelli TF, Anelli A, Tran KN, Lebwohl DE, Borgen PI (1994) Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer 74:74–77

    Article  CAS  PubMed  Google Scholar 

  42. Visram H, Kanji F, Dent SF (2010) Endocrine therapy for male breast cancer: rates of toxicity and adherence. Curr Oncol 17:17–21

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Pemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH (2012) Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol 23:1471–1474

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Giordano SH, Valero V, Buzdar AU, Hortobagyi GN (2002) Efficacy of anastrozole in male breast cancer. Am J Clin Oncol 25:235–237

    Article  PubMed  Google Scholar 

  45. Zabolotny BP, Zalai CV, Meterissian SH (2005) Successful use of letrozole in male breast cancer: a case report and review of hormonal therapy for male breast cancer. J Surg Oncol 90:26–30

    Article  PubMed  Google Scholar 

  46. Arriola E, Hui E, Dowsett M, Smith IE (2007) Aromatase inhibitors and male breast cancer. Clin Transl Oncol 9:192–194

    Article  CAS  PubMed  Google Scholar 

  47. Doyen J, Italiano A, Largillier R, Ferrero JM, Fontana X, Thyss A (2010) Aromatase inhibition in male breast cancer patients: biological and clinical implications. Ann Oncol 21:1243–1245

    Article  CAS  PubMed  Google Scholar 

  48. Giordano SH, Hortobagyi GN (2006) Leuprolide acetate plus aromatase inhibition for male breast cancer. J Clin Oncol 24:e42–e43

    Article  PubMed  Google Scholar 

  49. Zagouri F, Sergentanis TN, Koutoulidis V, Sparber C, Steger GG, Dubsky P et al (2013) Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series. Br J Cancer 108:2259–2263

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Di Lauro L, Vici P, Del Medico P, Laudadio L, Tomao S, Giannarelli D et al (2013) Letrozole combined with gonadotropin-releasing hormone analog for metastatic male breast cancer. Breast Cancer Res Treat 141:119–123

    Article  PubMed  Google Scholar 

  51. Korde LA, Zujewski JA, Kamin L, Giordano S, Domchek S, Anderson WF et al (2010) Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol 28:2114–2122

    Article  PubMed Central  PubMed  Google Scholar 

  52. Lopez M, Di Lauro L, Papaldo P, Lazzaro B (1985) Chemotherapy in metastatic male breast cancer. Oncology 42:205–209

    Article  CAS  PubMed  Google Scholar 

  53. Zagouri F, Sergentanis TN, Chrysikos D, Zografos E, Rudas M, Steger G et al (2013) Fulvestrant and male breast cancer: a case series. Ann Oncol 24:265–266

    Article  CAS  PubMed  Google Scholar 

  54. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995–2005

    Article  PubMed Central  PubMed  Google Scholar 

  55. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–1197

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Tania Merlino and Ana Maria Edlisca for technical assistance.

Conflict of interest

The authors have declared no conflicts of interest.

Author information

Authors and Affiliations

  1. Division of Medical Oncology B, “Regina Elena” National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy

    Marcello Maugeri-Saccà, Maddalena Barba, Patrizia Vici, Laura Pizzuti, Domenico Sergi & Luigi Di Lauro

  2. Scientific Direction, “Regina Elena” National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy

    Marcello Maugeri-Saccà & Ruggero De Maria

Authors
  1. Marcello Maugeri-Saccà
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maddalena Barba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrizia Vici
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laura Pizzuti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Domenico Sergi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ruggero De Maria
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Luigi Di Lauro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcello Maugeri-Saccà.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maugeri-Saccà, M., Barba, M., Vici, P. et al. Aromatase inhibitors for metastatic male breast cancer: molecular, endocrine, and clinical considerations. Breast Cancer Res Treat 147, 227–235 (2014). https://doi.org/10.1007/s10549-014-3087-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-014-3087-3

Keywords

Search

Navigation