Skip to main content
Top
Published in: Breast Cancer Research and Treatment 3/2007

01-11-2007 | Epidemiology

Serum prolactin levels are positively associated with mammographic density in postmenopausal women

Authors: Gail A. Greendale, Mei-Hua Huang, Giske Ursin, Sue Ingles, Frank Stanczyk, Carolyn Crandall, Gail A. Laughlin, Elizabeth Barrett-Connor, Arun Karlamangla

Published in: Breast Cancer Research and Treatment | Issue 3/2007

Login to get access

Abstract

Background

Prolactin is a polypeptide hormone that promotes normal breast proliferation and differentiation, but it is also implicated in the development and growth of mammary tumors. Mammographic density is a strong, independent predictor of breast cancer and, therefore, a potential surrogate indicator of breast cancer risk.

Methods

To test the hypothesis that serum prolactin is positively related to mammographic density, we conducted a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Mammographic Density Study. Based on prior work, we further hypothesized that this association would be apparent only in women who had not recently used postmenopausal hormone therapy (HT).

Results

In linear regression models adjusted for age, body mass index, race, smoking, alcohol use, parity and physical activity, among the 400 women who were not recent users of HT, prolactin was positively and statistically significantly associated with mammographic density (Beta log base 2 prolactin 0.0369 [95% CI: 0.0094–0.0645]. Thus, for each doubling of serum prolactin, there was an absolute increase in mammographic density of 3.69%. Additional adjustment for serum levels of estradiol, progesterone, sex hormone binding globulin and age at first pregnancy did not affect this result. There was no association between prolactin and mammographic density among the 169 participants who had recently used HT.

Conclusion

The correspondence between higher prolactin and higher mammographic density is consistent with prolactin’s mitogenic properties and the associations between prolactin and breast tumor promotion. These results support the thesis that prolactin deserves investigation as a target for breast cancer risk reduction.
Literature
1.
go back to reference Wolfe JN, Saftlas AF, Salane M (1987) Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case–control study. Am J Radiol 148:1087–1092 Wolfe JN, Saftlas AF, Salane M (1987) Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case–control study. Am J Radiol 148:1087–1092
2.
go back to reference Boyd NF, Byng JW, Jong RA et al (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst 87:670–675PubMedCrossRef Boyd NF, Byng JW, Jong RA et al (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst 87:670–675PubMedCrossRef
3.
go back to reference Ursin G, Astrahan MA, Salane M et al (1998) The detection of changes in mammographic densities. Cancer Epidemiol Biomarkers Prev 7:43–47PubMed Ursin G, Astrahan MA, Salane M et al (1998) The detection of changes in mammographic densities. Cancer Epidemiol Biomarkers Prev 7:43–47PubMed
4.
go back to reference Saftlas AF, Szklo M (1987) Mammographic parenchymal patterns and breast cancer risk. Epidemiol Rev 9:146–174PubMed Saftlas AF, Szklo M (1987) Mammographic parenchymal patterns and breast cancer risk. Epidemiol Rev 9:146–174PubMed
5.
go back to reference Oza AM, Boyd NF (1993) Mammographic parenchymal patterns: a marker of breast cancer risk. Epidemiol Rev 15:196–208PubMed Oza AM, Boyd NF (1993) Mammographic parenchymal patterns: a marker of breast cancer risk. Epidemiol Rev 15:196–208PubMed
6.
go back to reference Warner E, Lockwood G, Tritchler D, Boyd NF (1992) The risk of breast cancer associated with mammographic parenchymal patterns: a meta-analysis of the published literature to examine the effect of method of classification. Cancer Detect Prev 16:67–72PubMed Warner E, Lockwood G, Tritchler D, Boyd NF (1992) The risk of breast cancer associated with mammographic parenchymal patterns: a meta-analysis of the published literature to examine the effect of method of classification. Cancer Detect Prev 16:67–72PubMed
7.
go back to reference Boyd NF, Lockwood GA, Martin LG et al (1998) Mammographic densities and breast cancer risk. Breast Dis 10:126–133 Boyd NF, Lockwood GA, Martin LG et al (1998) Mammographic densities and breast cancer risk. Breast Dis 10:126–133
8.
go back to reference Byrne C, Schairer C, Wolfe J et al (1995) Mammographic features and breast cancer risk: effects with time, age and menopause status. J Natl Cancer Inst 87:1622–1629PubMedCrossRef Byrne C, Schairer C, Wolfe J et al (1995) Mammographic features and breast cancer risk: effects with time, age and menopause status. J Natl Cancer Inst 87:1622–1629PubMedCrossRef
9.
go back to reference Ursin G, Ma H, Wu AH et al (2003) Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomarkers Prev 12:332–338PubMed Ursin G, Ma H, Wu AH et al (2003) Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomarkers Prev 12:332–338PubMed
10.
go back to reference Bright RA, Morrison AS, Brisson J et al (1988) Relationship between mammographic and histologic features of breast tissue in women with benign biopsies. Cancer 61:266–271PubMedCrossRef Bright RA, Morrison AS, Brisson J et al (1988) Relationship between mammographic and histologic features of breast tissue in women with benign biopsies. Cancer 61:266–271PubMedCrossRef
11.
go back to reference Urbanski S, Jensen HM, Cooke G et al (1988) The association of histological and radiological indicators of breast cancer risk. Br J Cancer 58:474–479PubMed Urbanski S, Jensen HM, Cooke G et al (1988) The association of histological and radiological indicators of breast cancer risk. Br J Cancer 58:474–479PubMed
12.
go back to reference Bartow SA, Pathak DR, Mettler FA (1990) Radiographic microcalcification and parenchymal pattern as indicators of histologic “high-risk” benign breast disease. Cancer 66:1721–1725PubMedCrossRef Bartow SA, Pathak DR, Mettler FA (1990) Radiographic microcalcification and parenchymal pattern as indicators of histologic “high-risk” benign breast disease. Cancer 66:1721–1725PubMedCrossRef
13.
go back to reference Boyd NF, Jensen HM, Cooke G, Han HL (1992) Relationship between mammographic and histological risk factors for breast cancer. J Natl Cancer Inst 84:1170–1195PubMedCrossRef Boyd NF, Jensen HM, Cooke G, Han HL (1992) Relationship between mammographic and histological risk factors for breast cancer. J Natl Cancer Inst 84:1170–1195PubMedCrossRef
14.
go back to reference Wellings SR, Wolfe JN (1978) Correlative studies of the histological and radiographic appearance of the breast parenchyma. Radiology 129:299–306PubMed Wellings SR, Wolfe JN (1978) Correlative studies of the histological and radiographic appearance of the breast parenchyma. Radiology 129:299–306PubMed
15.
go back to reference Fisher ER, Palekar A, Kim WS, Redmond C (1978) The histopathology of mammographic patterns. Am J Clin Pathol 69:421–426PubMed Fisher ER, Palekar A, Kim WS, Redmond C (1978) The histopathology of mammographic patterns. Am J Clin Pathol 69:421–426PubMed
16.
go back to reference Moskowitz M, Gartside P, McLaughlin C (1980) Mammographic patterns as markers for high-risk benign breast disease and incident cancers. Radiology 134:293–295PubMed Moskowitz M, Gartside P, McLaughlin C (1980) Mammographic patterns as markers for high-risk benign breast disease and incident cancers. Radiology 134:293–295PubMed
17.
go back to reference Arthur JE, Ellis IO, Flowers C, Roebuck E, Elston CW, Blamey RW (1990) The relationship of “high risk” mammographic patterns to histological risk factors for development of cancer in the human breast. Br Radiol 63:845–849CrossRef Arthur JE, Ellis IO, Flowers C, Roebuck E, Elston CW, Blamey RW (1990) The relationship of “high risk” mammographic patterns to histological risk factors for development of cancer in the human breast. Br Radiol 63:845–849CrossRef
18.
go back to reference Pike MC, Bernstein L, Spicer DV (1993) Exogenous hormones and breast cancer risk. In: Niederhuber JE (ed) Current therapy in oncology, Mosbey, St. Louis Pike MC, Bernstein L, Spicer DV (1993) Exogenous hormones and breast cancer risk. In: Niederhuber JE (ed) Current therapy in oncology, Mosbey, St. Louis
19.
go back to reference Pike MC, Spicer DV, Dahmoush L, Press MF (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15:17–35PubMed Pike MC, Spicer DV, Dahmoush L, Press MF (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15:17–35PubMed
20.
go back to reference Vonderhaar BK. (1998) Prolactin: the forgotten hormone of human breast cancer. Pharmacol Ther 79:169–178PubMedCrossRef Vonderhaar BK. (1998) Prolactin: the forgotten hormone of human breast cancer. Pharmacol Ther 79:169–178PubMedCrossRef
21.
go back to reference Goffin V, Binart N, Touraine P, Kelly PA (2002) Prolactin: the new biology of an old hormone. Annu Rev Physiol 64:47–67PubMedCrossRef Goffin V, Binart N, Touraine P, Kelly PA (2002) Prolactin: the new biology of an old hormone. Annu Rev Physiol 64:47–67PubMedCrossRef
22.
go back to reference Harris J, Stanford PM, Oakes SR, Ormandy CJ (2004) Prolactin and the prolactin receptor: new targets of an old hormone. Ann Med 36:414–425PubMedCrossRef Harris J, Stanford PM, Oakes SR, Ormandy CJ (2004) Prolactin and the prolactin receptor: new targets of an old hormone. Ann Med 36:414–425PubMedCrossRef
23.
go back to reference Clevenger CV, Furth PA, Hankinson SE, Schuler LA (2003) The role of prolactin in mammary carcinoma. Endocr Rev 24:1–27PubMedCrossRef Clevenger CV, Furth PA, Hankinson SE, Schuler LA (2003) The role of prolactin in mammary carcinoma. Endocr Rev 24:1–27PubMedCrossRef
24.
go back to reference Hankinson SE, Willet WC, Michaud DS (1999) Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer I 91:629–634CrossRef Hankinson SE, Willet WC, Michaud DS (1999) Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer I 91:629–634CrossRef
25.
go back to reference Tworoger SS, Sluss P, Hankinson SE (2006) Association between plasma prolactin concentrations and risk of breast cancer among predominately premenopausal women. Cancer Res 66:2476–2482PubMedCrossRef Tworoger SS, Sluss P, Hankinson SE (2006) Association between plasma prolactin concentrations and risk of breast cancer among predominately premenopausal women. Cancer Res 66:2476–2482PubMedCrossRef
26.
go back to reference Greendale GA, Reboussin BA, Slone S et al (2003) Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst 95:30–37PubMedCrossRef Greendale GA, Reboussin BA, Slone S et al (2003) Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst 95:30–37PubMedCrossRef
27.
go back to reference Greendale GA, Palla SL, Ursin G et al (2005) The association of endogenous sex steroids and sex steroids binding proteins with mammographic density: results from the postmenopausal estrogen/progestin interventions mammographic density study. Am J Epidemiol 162:826–834PubMedCrossRef Greendale GA, Palla SL, Ursin G et al (2005) The association of endogenous sex steroids and sex steroids binding proteins with mammographic density: results from the postmenopausal estrogen/progestin interventions mammographic density study. Am J Epidemiol 162:826–834PubMedCrossRef
28.
go back to reference The PEPI Investigators (1995) Rationale, design and conduct of the PEPI Trial. Controlled Clin Trials 16:3S-19SCrossRef The PEPI Investigators (1995) Rationale, design and conduct of the PEPI Trial. Controlled Clin Trials 16:3S-19SCrossRef
29.
go back to reference Greendale GA, Bodin-Dunn L, Ingles S, Hail R, Barrett-Connor E (1996) Leisure, home and occupational physical activity and cardiovascular risk factors in postmenopausal women: the postmenopausal estrogen/progestins intervention (PEPI) study. Arch Intern Med 156:418–424PubMedCrossRef Greendale GA, Bodin-Dunn L, Ingles S, Hail R, Barrett-Connor E (1996) Leisure, home and occupational physical activity and cardiovascular risk factors in postmenopausal women: the postmenopausal estrogen/progestins intervention (PEPI) study. Arch Intern Med 156:418–424PubMedCrossRef
30.
go back to reference Greendale GA, James MK, Espeland M, Barrett-Connor E (1997) Can we measure postmenopausal estrogen/progestin use? The postmenopausal estrogen/progestin interventions trial. Am J Epidemiol 146:763–770PubMed Greendale GA, James MK, Espeland M, Barrett-Connor E (1997) Can we measure postmenopausal estrogen/progestin use? The postmenopausal estrogen/progestin interventions trial. Am J Epidemiol 146:763–770PubMed
31.
go back to reference Block G, Hartman AM, Dresser CM et al (1986) A data-based approach to diet questionnaire design and testing. Am J Epidemiol 124:453–469PubMed Block G, Hartman AM, Dresser CM et al (1986) A data-based approach to diet questionnaire design and testing. Am J Epidemiol 124:453–469PubMed
32.
go back to reference Anderson DC, Hopper BR, Lasley BL, Yen SS (1976) A simple method for the assay of eight steroids in small volumes of plasma. Steroids 28:179PubMedCrossRef Anderson DC, Hopper BR, Lasley BL, Yen SS (1976) A simple method for the assay of eight steroids in small volumes of plasma. Steroids 28:179PubMedCrossRef
33.
go back to reference Tremblay RR, Dube JY (1974) Plasma concentrations of free and non-TeBG bound testosterone in women on oral contraceptives. Contraception 10:599PubMedCrossRef Tremblay RR, Dube JY (1974) Plasma concentrations of free and non-TeBG bound testosterone in women on oral contraceptives. Contraception 10:599PubMedCrossRef
34.
go back to reference Greendale GA, Reboussin BA, Sie A et al (1999) Effects of estrogen and estrogen–progestin on mammographic parenchymal density. Ann Intern Med 130:262–269PubMed Greendale GA, Reboussin BA, Sie A et al (1999) Effects of estrogen and estrogen–progestin on mammographic parenchymal density. Ann Intern Med 130:262–269PubMed
35.
go back to reference Byng JW, Boyd NF, Little L et al (1996) Symmetry of projection in the quantitative analyses of mammographic images. Eur J Cancer Prev 5:319–327PubMedCrossRef Byng JW, Boyd NF, Little L et al (1996) Symmetry of projection in the quantitative analyses of mammographic images. Eur J Cancer Prev 5:319–327PubMedCrossRef
36.
go back to reference Crandall C, Palla S, Reboussin BA, Ursin G, Greendale G (2005) Positive association between mammographic breast density and bone mineral density in the Postmenopausal Estrogen/Progestin Interventions Study. Breast Cancer Res 7:R922–R928PubMedCrossRef Crandall C, Palla S, Reboussin BA, Ursin G, Greendale G (2005) Positive association between mammographic breast density and bone mineral density in the Postmenopausal Estrogen/Progestin Interventions Study. Breast Cancer Res 7:R922–R928PubMedCrossRef
37.
go back to reference Wang DY, de Stavola BL, Bulbrook RD et al (1988) The permanent effect of reproductive events on blood prolactin levels and its relation to breast cancer risk: a population study of postmenopausal women. Eur J Cancer Clin Oncol 24:1225–1231PubMedCrossRef Wang DY, de Stavola BL, Bulbrook RD et al (1988) The permanent effect of reproductive events on blood prolactin levels and its relation to breast cancer risk: a population study of postmenopausal women. Eur J Cancer Clin Oncol 24:1225–1231PubMedCrossRef
38.
go back to reference Heuson JC, Coune A, Staquet M (1972) Clinical trial of 2-BR-alpha-ergocryptine (CB154) in advanced breast cancer. Eur J Cancer 8:155–156 Heuson JC, Coune A, Staquet M (1972) Clinical trial of 2-BR-alpha-ergocryptine (CB154) in advanced breast cancer. Eur J Cancer 8:155–156
39.
go back to reference Peyrat JP, Vennin PH, Bonneterre J et al (1984) Effect of bromocriptine treatment on prolactin and steroid and steroid receptor levels in human breast cancer. Eur J Cancer Clin Oncol 20:1363–1367PubMedCrossRef Peyrat JP, Vennin PH, Bonneterre J et al (1984) Effect of bromocriptine treatment on prolactin and steroid and steroid receptor levels in human breast cancer. Eur J Cancer Clin Oncol 20:1363–1367PubMedCrossRef
40.
go back to reference Gill S, Peston D, Vonderhaar BK, Shousha S (2001) Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study. J Clin Pathol 54:956–960PubMed Gill S, Peston D, Vonderhaar BK, Shousha S (2001) Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study. J Clin Pathol 54:956–960PubMed
41.
go back to reference Mertani HC, Garcia-Cabellero T, Lambert A et al (1998) Cellular expression of growth hormone and prolactin receptors in human breast disorders. Int J Cancer 79:202–211PubMedCrossRef Mertani HC, Garcia-Cabellero T, Lambert A et al (1998) Cellular expression of growth hormone and prolactin receptors in human breast disorders. Int J Cancer 79:202–211PubMedCrossRef
42.
go back to reference Reynolds C, Montone KT, Powell CM, Tomaszewski JE, Clevenger CV (1997) Expression of prolactin and its receptor in human breast carcinoma. Endocrinology 138:5555–5559PubMedCrossRef Reynolds C, Montone KT, Powell CM, Tomaszewski JE, Clevenger CV (1997) Expression of prolactin and its receptor in human breast carcinoma. Endocrinology 138:5555–5559PubMedCrossRef
43.
go back to reference Touraine P, Martini JF, Zafrani B et al (1998) Increased expression of prolactin gene assessed by quantitative polymerase chain reaction in human breast tumors versus normal breast tissues. J Clin Endocr Metab 83:667–674PubMedCrossRef Touraine P, Martini JF, Zafrani B et al (1998) Increased expression of prolactin gene assessed by quantitative polymerase chain reaction in human breast tumors versus normal breast tissues. J Clin Endocr Metab 83:667–674PubMedCrossRef
44.
go back to reference Ingram DM, Nortage EM, Roberts AN (1990) Prolactin and breast cancer risk. Med J Aust 153:469–473PubMed Ingram DM, Nortage EM, Roberts AN (1990) Prolactin and breast cancer risk. Med J Aust 153:469–473PubMed
45.
go back to reference Boyd NF, Stone J, Martin LJ et al (2002) The association of breast mitogens with mammographic densities. Br J Cancer 87:876–882PubMedCrossRef Boyd NF, Stone J, Martin LJ et al (2002) The association of breast mitogens with mammographic densities. Br J Cancer 87:876–882PubMedCrossRef
46.
go back to reference Tamimi RM, Hankinson SE, Colditz GA, Byrne C (2005) Endogenous sex hormone levels and mammgraphic density among postmenopausal women. Cancer Epidem Biomar 14:2641–2647CrossRef Tamimi RM, Hankinson SE, Colditz GA, Byrne C (2005) Endogenous sex hormone levels and mammgraphic density among postmenopausal women. Cancer Epidem Biomar 14:2641–2647CrossRef
47.
go back to reference Hankinson SE, Willet WC, Manson JE et al (1995) Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. J Natl Cancer I 87:1297–1302CrossRef Hankinson SE, Willet WC, Manson JE et al (1995) Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. J Natl Cancer I 87:1297–1302CrossRef
48.
go back to reference Koenig KL, Toniolo P, Bruning PF et al (1993) Reliability of serum prolactin measurements in women. Cancer Epidem Biomar 2:411–414 Koenig KL, Toniolo P, Bruning PF et al (1993) Reliability of serum prolactin measurements in women. Cancer Epidem Biomar 2:411–414
49.
go back to reference Muti P, Trevisan M, Micheli A et al (1996) Reliability of serum hormones in premenopausal and postmenopausal women over a one-year period. Cancer Epidem Biomar 5:917–922 Muti P, Trevisan M, Micheli A et al (1996) Reliability of serum hormones in premenopausal and postmenopausal women over a one-year period. Cancer Epidem Biomar 5:917–922
50.
go back to reference Ehara Y, Siler TM, Yen SS (1976) Effects of large doses of estrogen on prolactin and growth hormone release. Am J Obstet Gynecol 125:455–458PubMed Ehara Y, Siler TM, Yen SS (1976) Effects of large doses of estrogen on prolactin and growth hormone release. Am J Obstet Gynecol 125:455–458PubMed
51.
go back to reference Yen SS, Ehara Y, Siler TM Augmentation of prolactin secretion by estrogen in hypogonadal women. J Clin Invest 53:652–655 Yen SS, Ehara Y, Siler TM Augmentation of prolactin secretion by estrogen in hypogonadal women. J Clin Invest 53:652–655
52.
go back to reference Chang RJ, Davidson BJ, Carlson HE, Judd HL (1982) Circadian pattern of prolactin secretion in postmenopausal women receiving estrogen with or without progestin. Am J Obstet Gynec 144:402–407PubMed Chang RJ, Davidson BJ, Carlson HE, Judd HL (1982) Circadian pattern of prolactin secretion in postmenopausal women receiving estrogen with or without progestin. Am J Obstet Gynec 144:402–407PubMed
53.
go back to reference Yen SS, Lasley B, Wang C, Ehara Y (1975) Steroid modulation of the hypothalamic-pituitary system in the secretion of reproductive hormones. J Steroid Biochem 6:1047–1053PubMedCrossRef Yen SS, Lasley B, Wang C, Ehara Y (1975) Steroid modulation of the hypothalamic-pituitary system in the secretion of reproductive hormones. J Steroid Biochem 6:1047–1053PubMedCrossRef
Metadata
Title
Serum prolactin levels are positively associated with mammographic density in postmenopausal women
Authors
Gail A. Greendale
Mei-Hua Huang
Giske Ursin
Sue Ingles
Frank Stanczyk
Carolyn Crandall
Gail A. Laughlin
Elizabeth Barrett-Connor
Arun Karlamangla
Publication date
01-11-2007
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2007
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-006-9454-y

Other articles of this Issue 3/2007

Breast Cancer Research and Treatment 3/2007 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine