Androgen receptors and serum testosterone levels identify different subsets of postmenopausal breast cancers

BMC Cancer

Volumn 12, Issue , 2012, Pages

  Secreto, Giorgio ^a   Venturelli, Elisabetta ^a   Meneghini, Elisabetta ^a   Carcangiu, Maria Luisa ^a   Paolini, Biagio ^a   Agresti, Roberto ^a   Pellitteri, Cristina ^a   Berrino, Franco ^a   Gion, Massimo ^b   Cogliati, Patrizia ^a   Saragò, Giuseppina ^a   Micheli, Andrea ^a  

^a NATIONAL CANCER INSTITUTE   (Italy)

^b Regional Hospital   (Italy)

Author keywords

Androgen receptors; Androgens; Postmenopausal breast cancer; Testosterone levels

Indexed keywords

ANDROGEN; ANDROGEN RECEPTOR; ESTROGEN RECEPTOR; PROGESTERONE RECEPTOR; TESTOSTERONE;

ADULT; AGE; AGED; ARTICLE; AXILLARY LYMPH NODE; BODY MASS; BREAST CANCER; CANCER CLASSIFICATION; CANCER GRADING; CANCER GROWTH; CANCER PATIENT; COHORT ANALYSIS; DISEASE ASSOCIATION; FEMALE; GROWTH STIMULATION; HISTOPATHOLOGY; HORMONE SYNTHESIS; HUMAN; IMMUNOHISTOCHEMISTRY; LYMPH NODE METASTASIS; MAJOR CLINICAL STUDY; POSTMENOPAUSE; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; SAMPLE SIZE; TESTOSTERONE BLOOD LEVEL; TREND STUDY; TUMOR VOLUME;

ADULT; AGED; AGED, 80 AND OVER; BREAST NEOPLASMS; COHORT STUDIES; CROSS-SECTIONAL STUDIES; FEMALE; HUMANS; IMMUNOHISTOCHEMISTRY; LOGISTIC MODELS; MIDDLE AGED; NEOPLASM PROTEINS; POSTMENOPAUSE; RECEPTORS, ANDROGEN; TESTOSTERONE;

EID: 84870861698     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-12-599     Document Type: Article

References (58)

1. Søreide JA, Lea OA, Varhaug JE, Skarstein A, Kvinnsland S. Androgen receptors in operable breast cancer: relation to other steroid hormone receptors, correlations to prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. Eur J Surg Oncol 1992, 18:112-118.
2. Isola JJ. Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. J Pathol 1993, 170:31-35. 10.1002/path.1711700106, 8100853.
3. Hall RE, Aspinall JO, Horsfall DJ, Birrell SN, Bentel JM, Sutherland RL, Tilley WD. Expression of the androgen receptor and an androgen-responsive protein, apolipoprotein D, in human breast cancer. Br J Cancer 1996, 74:1175-1180. 10.1038/bjc.1996.513, 2075941, 8883401.
4. Kuenen-Boumeester V, Van der Kwast TH, Claassen CC, Look MP, Liem GS, Klijn JG, Henzen-Logmans SC. The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer 1996, 32A:1560-1565.
5. Moinfar F, Okcu M, Tsybrovskyy O, Regitnig P, Lax SF, Weybora W, Ratschek M, Tavassoli FA, Denk H. Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer 2003, 98:703-711. 10.1002/cncr.11532, 12910513.
6. Agoff SN, Swanson PE, Linden H, Hawes SE, Lawton TJ. Androgen receptor expression in estrogen receptor-negative breast ancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol 2003, 120:725-731. 10.1309/42F00D0DJD0J5EDT, 14608899.
7. Ogawa Y, Hai E, Matsumoto K, Ikeda K, Tokunaga S, Nagahara H, Sakurai K, Inoue T, Nishiguchi Y. Androgen receptor expression in breast cancer: relationship with clinicopathological factors and biomarkers. Int J Clin Oncol 2008, 13:431-435. 10.1007/s10147-008-0770-6, 18946753.
8. Park S, Koo J, Park HS, Kim JH, Choi SY, Lee JH, Park BW, Lee KS. Expression of androgen receptors in primary breast cancer. Ann Oncol 2010, 21:488-492. 10.1093/annonc/mdp510, 19887463.
9. Niemeier LA, Dabbs DJ, Beriwal S, Striebel JM, Bhargava R. Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. Mod Pathol 2010, 23:205-212. 10.1038/modpathol.2009.159, 19898421.
10. Yu Q, Niu Y, Liu N, Zhang JZ, Liu TJ, Zhang RJ, Wang SL, Ding XM, Xiao XQ. Expression of androgen receptor in breast cancer and its significance as a prognostic factor. Ann Oncol 2011, 22:1288-1294. 10.1093/annonc/mdq586, 21109569.
11. Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, Marotti JD, Hankinson SE, Colditz GA, Tamimi RM. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res 2011, 17:1867-1874. 10.1158/1078-0432.CCR-10-2021, 3076683, 21325075.
12. Gonzales-Angulo AM, Stemke-Hale K, Palla SL, Carey M, Agarwal R, Meric-Berstam F, Traina TA, Hudis C, Hortobagyi GN, Gerald WL, Mills GB, Hennessy BT. Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer. Clin Cancer Res 2009, 15:2472-2478. 10.1158/1078-0432.CCR-08-1763, 19276248.
13. Secreto G, Venturelli E, Meneghini E, Greco M, Ferraris C, Gion M, Zancan M, Fabricio AS, Berrino F, Cavalleri A, Micheli A. Testosterone and biological characteristics of breast cancers in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2009, 18:2942-2948. 10.1158/1055-9965.EPI-09-0540, 19843675.
14. Secreto G, Meneghini E, Venturelli E, Cogliati P, Agresti R, Ferraris C, Gion M, Zancan M, Fabricio AS, Berrino F, Cavalleri A, Micheli A. Circulating sex hormones and tumor characteristics in postmenopausal breast cancer patients. A cross-sectional study. Int J Biol Markers 2011, 26:241-246.
15. Hammond ME, Hayes DF, Wolff AC, Mangu PB, Temin S. American society of clinical oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract 2010, 6:195-197. 10.1200/JOP.777003, 2900870, 21037871.
16. Micello D, Marando A, Sahnane N, Riva C, Capella C, Sessa F. Androgen receptor is frequently expressed in HER2-positive, ER/PR-negative breast cancers. Virchows Arch 2010, 457:467-476. 10.1007/s00428-010-0964-y, 20809337.
17. Denduluri N, Ershler WB. Aging biology and cancer. Semin Oncol 2004, 31:137-148. 10.1053/j.seminoncol.2003.12.025, 15112145.
18. Edwards BK, Howe HL, Ries LA, Thun MJ, Rosenberg HM, Yancik R, Wingo PA, Jemal A, Feigal EG. Annual report to the nation on the status of cancer, 1973-1999, featuring implications of age and aging on U.S. cancer burden. Cancer 2002, 94:2766-2792. 10.1002/cncr.10593, 12173348.
19. Kirschner MA. Hirsutism and virilism in women. Spec Top Endocrinol Metab 1984, 6:55-93.
20. van Landeghem AA, Poortman J, Nabuurs M, Thijssen JH. Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res 1985, 45:2900-2906.
21. Vermeulen A, Deslypere JP, Paridaens R, Leclercq G, Roy F, Heuson JC. Aromatase, 17beta-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women. Eur J Cancer Clin Oncol 1986, 22:515-525. 10.1016/0277-5379(86)90121-5, 3015631.
22. Santen RJ. Determinants of tissue oestradiol levels in human breast cancer. Cancer Surv 1986, 5:597-616.
23. Thijssen JHH, Blankenstein MA. Endogenous oestrogens and androgens in normal and malignant endometrial and mammary tissues. Eur J Cancer Clin Oncol 1989, 25:1953-1959. 10.1016/0277-5379(89)90377-5, 2632276.
24. Mistry P, Griffiths K, Maynard PV. Endogenous C19-steroids and oestradiol levels in human primary breast tumour tissues and their correlation with androgen and oestrogen receptors. J Steroid Biochem 1986, 24:1117-1125. 10.1016/0022-4731(86)90372-9, 3736038.
25. Recchione C, Venturelli E, Manzari A, Cavalleri A, Martinetti A, Secreto G. Testosterone, dihydrotestosterone and oestradiol levels in postmenopausal breast cancer tissues. J Steroid Biochem Molec Biol 1995, 52:541-546. 10.1016/0960-0760(95)00017-T, 7779758.
26. Shibuya R, Suzuki T, Miki Y, Yoshida K, Moriya T, Ono K, Akahira J, Ishida T, Hirakawa H, Evans DB, Sasano H. Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast. Endocr Relat Cancer 2008, 15:113-124. 10.1677/ERC-07-0092, 18310280.
27. Sasano H, Miki Y, Nagasaki S, Suzuki T. In situ estrogen production and its regulation in human breast carcinoma: from endocrinology to intracrinology. Pathol Int 2009, 59:777-789. 10.1111/j.1440-1827.2009.02444.x, 19883428.
28. Bulun SE, Lin Z, Imir G, Amin S, Demura M, Yilmaz B, Martin R, Utsunomiya H, Thung S, Gurates B, Tamura M, Langoi D, Deb S. Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment. Pharmacol Rev 2005, 57:359-383. 10.1124/pr.57.3.6, 16109840.
29. Suzuki T, Miki Y, Moriya T, Akahira J, Ishida T, Hirakawa H, Yamaguchi Y, Hayashi S, Sasano H. 5Alpha-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production. Int J Cancer 2007, 120:285-291. 10.1002/ijc.22317, 17066438.
30. Suzuki T, Miki Y, Akahira J, Moriya T, Ohuchi N, Sasano H. Aromatase in human breast carcinoma as a key regulator of intratumural sex steroid concentrations. Endocr J 2008, 55:455-463. 10.1507/endocrj.K07E-053, 18480557.
31. Santen RJ, Brodie H, Simpson ER, Siiteri PK, Brodie A. History of aromatase: saga of an important biological mediator and therapeutic target. Endocr Rev 2009, 30:343-375. 10.1210/er.2008-0016, 19389994.
32. Suzuki T, Miki Y, Takagi K, Hirakawa H, Moriya T, Ohuchi N, Sasano H. Androgens in human breast carcinoma. Med Mol Morphol 2010, 43:75-81. 10.1007/s00795-010-0494-3, 20683693.
33. Suzuki T, Miki Y, Nakata T, Shiotsu Y, Akinaga S, Inoue K, Ishida T, Kimura M, Moriya T, Sasano H. Steroid sulfatase and estrogen sulfotransferase in normal human tissue and breast carcinoma. J Steroid Biochem Molec Biol 2003, 86:449-454. 10.1016/S0960-0760(03)00356-X, 14623543.
34. Suzuki T, Nakata T, Miki Y, Kaneko C, Moriya T, Ishida T, Akinaga S, Hirakawa H, Kimura M, Sasano H. Estrogen sulfotransferase and steroid sulfatase in human breast carcinoma. Cancer Res 2003, 63:2762-2770.
35. Nagasaki S, Miki Y, Akahira J, Suzuki T, Sasano H. 17beta-hydroxysteroid dehydrogenases in human breast cancer. Ann N Y Acad Sci 2009, 1155:25-32. 10.1111/j.1749-6632.2008.03682.x, 19250189.
36. Pascall JC. Post-transcriptional regulation of gene expression by androgens: recent observations from the epidermal growth factor gene. J Mol Endocrinol 1997, 18:177-180. 10.1677/jme.0.0180177, 9195471.
37. Harris AL, Nicholson S, Sainsbury JR, Farndon J, Wright C. Epidermal growth factor receptors in breast cancer: association with early relapse and death, poor response to hormones and interactions with neu. J Steroid Biochem 1989, 34:123-131. 10.1016/0022-4731(89)90072-1, 2576295.
38. Bolla M, Chedin M, Souvignet C, Marron J, Arnould C, Chambaz E. Estimation of epidermal growth factor receptor in 177 breast cancers: correlation with prognostic factors. Breast Cancer Res Treat 1990, 16:97-102. 10.1007/BF01809293, 2176111.
39. Toi M, Osaki A, Yamada H, Toge T. Epidermal growth factor receptor expression as a prognostic indicator in breast cancer. Eur J Cancer 1991, 27:977-980. 10.1016/0277-5379(91)90262-C, 1832907.
40. Tsutsui S, Kataoka A, Ohno S, Murakami S, Kinoshita J, Hachitanda Y. Prognostic and predictive value of epidermal growth factor receptor in recurrent breast cancer. Clin Cancer Res 2002, 8:3454-3460.
41. Meche A, Cîmpean AM, Raica M. Immunohistochemical expression and significance of epidermal growth factor receptor (EGFR) in breast cancer. Romanian J Morphol Embryol 2009, 50:217-221.
42. Bhargava R, Gerald WL, Li AR, Pan Q, Lal P, Ladanyi M, Chen B. EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. Mod Pathol 2005, 18:1027-1033. 10.1038/modpathol.3800438, 15920544.
43. Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D, Duss S, Nicoulaz AL, Brisken C, Fiche M, Delorenzi M, Iggo R. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 2005, 24:4660-4671. 10.1038/sj.onc.1208561, 15897907.
44. Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C, Gerald WL. An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 2006, 25:3994-4008. 10.1038/sj.onc.1209415, 16491124.
45. Naderi A, Hughes-Davies L. A functionally significant cross-talk between androgen receptor and ErbB2 pathways in estrogen receptor negative breast cancer. Neoplasia 2008, 10:542-548. 2386539, 18516291.
46. Dimitrakakis C, Zhou J, Wang J, Belanger A, Labrie F, Cheng C, Powell D, Bondy C. A physiologic role for testosterone in limiting estrogenic stimulation of the breast. Menopause 2003, 10:292-298. 10.1097/01.GME.0000055522.67459.89, 12851512.
47. Labrie F, Luu-The V, Labrie C, Bélanger A, Simard J, Lin SX, Pelletier G. Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev 2003, 24:152-182. 10.1210/er.2001-0031, 12700178.
48. Liao DJ, Dickson RB. Roles of androgens in the development, growth, and carcinogenesis of the mammary gland. J Steroid Biochem Mol Biol 2002, 80:175-189. 10.1016/S0960-0760(01)00185-6, 11897502.
49. Labrie F, Luu-The V, Bélanger A, Lin S-X, Simard J, Pelletier G, Labrie C. Is dehydroepiandrosterone a hormone?. J Endocrinol 2005, 187:169-196. 10.1677/joe.1.06264, 16293766.
50. Labrie F, Bélanger A, Bélanger P, Bérubé R, Martel C, Cusan L, Gomez J, Candas B, Chaussade V, Castiel I, Deloche C, Leclaire J. Metabolism of DHEA in postmenopausal women following percutaneous administration. J Steroid Biochem Mol Biol 2007, 103:178-188. 10.1016/j.jsbmb.2006.09.034, 17084625.
51. Labrie F, Martel C, Balser J. Wide distribution of the serum dehydroepiandrosterone and sex steroid levels in postmenopausal women: role of the ovary?. Menopause 2011, 18:30-43. 10.1097/gme.0b013e3181e195a6, 20683211.
52. Grattarola R. Androgens in breast cancer. I. Atypical endometrial hyperplasia and breast cancer in married premenopausal women. Am J Obstet Gynecol 1973, 116:423-428.
53. Grattarola R. Ovariectomy alone or in combination with dexamethasone in patients with advanced breast cancer and high levels of testosterone excretion. J Natl Cancer Inst 1976, 56:11-16.
54. Secreto G, Zumoff B. Paradoxical effects associated with supranormal urinary testosterone excretion in premenopausal women with breast cancer: increased risk of postmastectomy recurrence and higher remission rate after ovariectomy. Cancer Res 1983, 43:3408-3411.
55. Secreto G, Oriana S, Recchione C. variectomy alone or in combination with dexamethasone in patients with advanced breast cancer and high levels of testosterone or androstanediol secretion. Endocr Relat Cancer 1984, 14:55-58.
56. van Landeghem AA, Poortman J, Nabuurs M, Thijssen JH. Endogenous concentration and subcellular distribution of androgens in normal and malignant human breast tissue. Cancer Res 1985, 45:2907-2912.
57. Secreto G. Endocrine classification of postmenopausal breast cancers. The Androgen-Excess Theory of Breast Cancer 2012, Trivandrum, Kerala, India: Research Signpost, Secreto G, Zumoff B, http://www.trnres.com/ebook.php.
58. Nahleh Z. Androgen receptor as a target for the treatment of hormone receptor-negative breast cancer: an unchartered territory. Future Oncol 2008, 4:15-21. 10.2217/14796694.4.1.15, 18240997.