Steroidal Hormone Receptor Expression in Male Breast Cancer

Authors

1 Associate Professor, Department of Radiotherapy-Oncology, Omid and Ghaem Hospitals, Mashhad University of Medical Sciences, Mashhad, Iran

2 Oncologist, Department of Radiaiotherapy-Oncology, Omid and Ghaem Hospitals, Mashhad University of Medical Sciences, Mashhad, Iran

3 Associate Professor, Department of Pathology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Introduction: The etiology of male breast cancer is unclear, but hormonal levels may play a role in development of this disease. It seems that the risk of male breast cancer related to increased lifelong exposure to estrogen or reduced androgen. The aim of this study was to investigate the expression of the steroid hormone receptors including estrogen receptor (ER) and progesterone receptor (PR) in Iranian cases with male breast cancer.
Methods: This is a prospective review of 18 cases of male breast cancer in in Omid Hospital, Mashhad, North East of Iran, between October 2001 and October 2006. ER and PR were measured by immunohistochemistry. Clinicopathologic features and family history were obtained by interview. Data were analyzed with SPSS 13 using descriptive statistics.
 Results: The median age was 63.2 year. All the cases were infiltrating ductal carcinoma. A high rate of expression of ER (88.8%) and PR (66.6%) was found in the studied cases.
Conclusion: Cancers of the male breast are significantly more likely than cancers of the female breast to express hormonal receptors.

Keywords


 

 Introduction

 

Introduction

Male breast cancer typically occurs at a much lower rate, compared with female breast cancer; however, its prevalence varies depend-ing on geographical location. Similar to female breast cancer, the risk of male breast cancer appears to be related to increased lifelong exposure to estrogen or reduced androgen. Klinefelter's syndrome, history of mumps orchitis, undescended testis, or testicular injury are among the risk factors in men, perhaps due to an imbalance in the estrogen-testosterone ratio. Feminization, whether genetically or due to environmental exposure, appears to increase the risk of this cancer, as reported in transse-xuals receiving exogenous estrogens. The majority of male breast cancers are ER positive, and a few studies have examined the contrib-ution of markers such as HER2/neu and p53 (1).

This prospective study investigates the expression of steroid hormone receptors (estro-

gen receptor (ER) and progesterone receptor (PR)) in male breast cancer in Mashhad, Iran.

Materials and Methods

Specimens were collected from 18 patients with male breast cancer in Omid University Hospital, between October 2001 and October 2006. The steroid hormone receptors (ER and PR) were measured by immunohistochemistry, and the patients’ clinicopathologic characteri-stics, especially their family history were recor-ded via interviews. Results were analyzed using SPSS Version 13.

Results

During the study, of 803 patients with mam-mary carcinomas who referred to Radiation Oncology Department of Omid Hospital, 2.24% (18 cases) presented with male breast cancer. The characteristics of patients with breast cancer are presented in Table 1.

The median age was 63.2 years, and all cases had infiltrating ductal carcinoma. The family history of breast cancer was negative in 17 cases, and in one case, the sibling (sister) suffered from breast cancer. Staging was compa-red with TNM (Tumor, Node, Metastasis) syst-em, and the most frequent stages were II and III.

The mean of metastatic axillary lymph nodes was 4.74 nodes (from 0 to 17).

*Among 18 subjects, 2, 7, 4, and 3 patients were in stages I, II, III, and IV, respectively; how-ever, the stages of two patients were unknown.

ER and PR were positive in 88.8% and 66.6% of the patients, respectively (ER and PR were negative in base on 0% of IHC staining).

Discussion

In 2005, an estimated number of 1600 new cases of male breast cancer were diagnosed in U.S.A (3). The mean age for diagnosis of male breast cancer is 67 years, which is 5 years more than the average in women (2). In this review, the median age of diagnosis was reported as 63.2 years old.

Breast cancer affects Iranian women at least one decade earlier than their counterparts in developed countries (4); though, this has not been proven for male patients.

Data show that 93.7% of male breast canc-er are ductal or unclassified carcinomas; 2.6%, 1.8% and 1.5% are papillary, mucinous and lobular, respectively (2). In the present review, 100% of cases present with ductal carcinoma.

Although the etiology of male breast can-cer is unclear, hormonal levels may play a role in the development of this disease. Male breast ca-ncer has a high rate of hormone receptor expr-ession, and approximately 90 % and 81% of male breast cancers express the estrogen and progesterone receptors, respectively (2). In this review, 88.8 % of male breast cancers express ER, and 66.6.% express PR. Male breast cancers are significantly more likely to express hormo-nal receptors in comparison with female breast cancers (2).

The presented data in this review add to the body of information regarding steroid receptor expression in male breast cancer.

Males have lower circulating levels of estradiol than females. The extremely-high level of hormone receptor expression observed in male breast cancer is quite intriguing. Without sufficient legend to bind to and activate their cognate receptors, it seems that there is no selective advantage for male breast tumors to express hormone receptors. This might be expl-ained considering the hormonal environment in post-menopausal women, where the production of ovarian hormones has virtually ceased.

The in situ production of estrogens in breast carcinoma is considered to play an impo-rtant role in the proliferation of breast cancer cells, as it has been demonstrated that breast tumors possess enzyme systems required to produce bioactive estrogens in situ from circula-ting precursors androstenedione or oestrone sulphate (16). In post-menopausal women, these systems are active, and the same might be expected in males.

Male breast cancers are known to over-express intratumoral aromatuse (18), which is likely to contribute to in situ estrogen biosyn-thesis. Thus, the availability of bioactive estrog-ens in a male environment, characterized by relatively low serum levels of estrogen will presumably provide a growth advantage for ER-positive tumors (15).

Finally, due to the rarity of male breast cancer, a significant problem in studying this disease is finding sufficiently large numbers to allow multivariate analysis of possible progno-stic markers.

Conclusion

In our study, expression of hormone receptors in male breast cancer was high, like to the others studies.

Conflict of Interest

No conflict of interest exists.

Acknowledgment

This study was supported by Cancer Res-earch Center of Mashhad University of Medical Science (82025). We would like to thank the staff of Radiation Oncology Department of Mashhad University. We also express our deepest gratitude to Dr. G. Noferesty and Dr. R. Partovi for their assistance and introducing the study cases.

 1. DeVita VT, Lawrence TS, Rosenberg SA. Devita, Hellman, and Rosenberg's Cancer principles and practice of oncology. 9th ed. Philadelphia Pa: Lippincott Williams & Wilkins; 2011.

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

3. Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics, 2004. CA: a cancer journal for clinicians. 2004; 54(1): 8-29.

4. Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, et al. Breast cancer in Iran: An Epidemiological Review. The breast journal. 2007; 13(4): 383-391.

5. Rayson D, Erlichman C, Suman VJ, Roche PC, Wold LE, Ingle JN, et al. Molecular markers in male breast cancer. Cancer. 1998; 83(9): 1947-1955.

6. Munoz de toro MM, Maffini MV, kass L, Luque EH. proliferative activity and steroid hormone receptor status in male breast carcinoma. Journal of steroid biochemistry and molecular biology. 1998; 67(4): 333-339.

7. Pich A, Margaria E, Chiusa L, Candelaresi G, Dal Canton O. Androgen receptor expression in male breast carcinoma: lack of clinicopatholoqical association. British journal of cancer. 1999; 79(5-6): 959-964.

8. Pich A, Margaria E, chiasa L. Oncogenes and male breast carcinoma: c-erbB-2 and p53 coexpression predicts a poor survival. Journal of clinical oncology. 2000; 18(16): 2948-2956.

9. Andra S, Fonseca I, Pinto AE, Cardoso P, Pereira T, Soares J. Male breast cancer--a reappraisal of clinical and biologic indications of prognosis, Acta oncologica. 2001; 40(4): 472-478.

10. Mourao Netto M, Logallo AF, Nonogali eral S. Expression of c-erb-2, p53 and c-myc proteins in male breast carcinoma comparison with traditional prognostic factors and survival. Brazilian Journal of Medical and Biological Research. 2001; 34: 887-894.

11. Wang-Rodriguez J, Cross K, Gallagher S, Djahanban M, Armstrong JM, Wiedner N, et al. Male breast carcinoma: correlation of ER, PR, Ki-67, Her2-Neu, and p53 with treatment and survival, a study of 65 cases. Modern pathology. 2002; 15(8):853-861.

12. Muir D, kanthan R, kanthar SC. Male versus female breast cancers. A population based comparative immunohistochemical analysis. Archives of pathology & laboratory medicine. 2003; 127 (1): 36-41.

13. Bärlund M, Kuukasjärvi T, Syrjäkoski K, Auvinen A, Kallioniemi A. Frequent amplification and overexpression of CCND1 in male breast cancer. International Journal of Cancer. 2004; 111(6): 968-971.

14. Rudlowski C, friedrichs N, faridi A, Füzesi L, Moll R, Bastert G, et al. HER-2enu Gene amplification and protein expression in primary male breast cancer. Breast cancer Research and treatment. 2004; 84(3): 215-223.

15. Mwphy CE, carder PJ, Lansdown MR, Speirs V. Steroid hormone receptal expression in male breast cancer. European journal of surgical oncology. 2006; 32(1): 44-47.

16. Benchellah Z, Wagner A, Harchaoui Y, Huten N, Body G. Male Breast Cancer, 19 case reports. Annales de chirurgie. 2002; 127:619-623.

17. Pasqualini JR, Cheerice G, Nguyen BL, Maloche C, Delalonde L, Talbi M, et al. Estrone sulfate-sulfatase and 17  hydroxyl steroid dehydrogenase activieies: a hypothesis for their role in the evaluation of human breast cancer from hormone–dependence to hormone independence. The Journal of steroid biochemistry and molecular biology. 1995; 53(1-6): 407-412.

18. Pasqualini JR. The selective estrogen enzyme modulators in breast cancer: a review. Biochimica et biophysica acta. 2004; 1654 (2): 123-143.