Top

Breast Cancer Research and Treatment

Published in:

01-08-2020 | Breast Cancer | Review

Hormone replacement therapy and mammographic density: a systematic literature review

Authors: Shadi Azam, Katja Kemp Jacobsen, Arja R. Aro, Elsebeth Lynge, Zorana Jovanovic Andersen

Published in: Breast Cancer Research and Treatment | Issue 3/2020

Abstract

Purpose

Hormone replacement therapy (HRT) is used to reduce climacteric symptoms of menopause and prevent osteoporosis; however, it increases risk of breast cancer. Mammographic density (MD) is also a strong risk factor for breast cancer. We conducted this review to investigate the association between HRT use and MD and to assess the effect of different HRT regimens on MD.

Methods

Two of authors examined articles published between 2002 and 2019 from PubMed, Embase, and OVID using Covidence systematic review platform. Any disagreements were discussed until consensus was reached. The protocol used in this review was created in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality of each eligible study was assessed using the Oxford Center for Evidence-Based Medicine (OCEBM) hierarchy.

Results

Twenty-two studies met the inclusion criteria. Six studies showed that using estrogen plus progestin (E + P) HRT was associated with higher MD than estrogen alone. Four studies reported that continuous estrogen plus progestin (CEP) users had higher MD than sequential estrogen plus progestin (SEP) and estrogen alone users. However, two studies showed that SEP users had slightly higher MD than CEP users and estrogen alone users.

Conclusions

Epidemiological evidence is rather consistent suggesting that there is a positive association between HRT use and MD with the highest increase in MD among current users, and CEP users. Our results suggest that due to increase in MD and masking effect, current E + P users may require additional screening procedures, shorter screening intervals, or using advanced imaging techniques.

Available only for authorised users

Jensen PB, Jensen J, Riis BJ, Rodbro P, Strom V, Christiansen C (1987) Climacteric symptoms after oral and percutaneous hormone replacement therapy. Maturitas 9(3):207–215CrossRefPubMed

Gallagher JC (2001) Role of estrogens in the management of postmenopausal bone loss. Rheum Dis Clin North Am 27(1):143–162CrossRefPubMed

Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 288(3):321–333CrossRefPubMed

Marchesoni D, Driul L, Ianni A, Fabiani G, Della Martina M, Zuiani C, Bazzocchi M (2006) Postmenopausal hormone therapy and mammographic breast density. Maturitas 53(1):59–64. https://doi.org/10.1016/j.maturitas.2005.02.010 CrossRefPubMed

Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A (2003) Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA 289(24):3243–3253. https://doi.org/10.1001/jama.289.24.3243 CrossRef

Beral V (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet (London, England) 362(9382):419–427CrossRef

Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, Edwards BK, Berry DA (2007) The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med 356(16):1670–1674. https://doi.org/10.1056/NEJMsr070105 CrossRefPubMed

Boyd NF, Martin LJ, Yaffe MJ, Minkin S (2011) Mammographic density and breast cancer risk: current understanding and future prospects. Breast Cancer Res 13(6):223. https://doi.org/10.1186/bcr2942 CrossRefPubMedPubMedCentral

McCormack VA, dos Santos SI (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 15(6):1159–1169. https://doi.org/10.1158/1055-9965.epi-06-0034 CrossRef

10.

Hodge R, Hellmann SS, von Euler-Chelpin M, Vejborg I, Andersen ZJ (2014) Comparison of Danish dichotomous and BI-RADS classifications of mammographic density. Acta Radiol Short Rep 3(5):2047981614536558. https://doi.org/10.1177/2047981614536558 CrossRefPubMedPubMedCentral

11.

Martin LJ, Minkin S, Boyd NF (2009) Hormone therapy, mammographic density, and breast cancer risk. Maturitas 64(1):20–26. https://doi.org/10.1016/j.maturitas.2009.07.009 CrossRefPubMed

12.

Rice MS, Tamimi RM, Bertrand KA, Scott CG, Jensen MR, Norman AD, Visscher DW, Chen YY, Brandt KR, Couch FJ, Shepherd JA, Fan B, Wu FF, Ma L, Collins LC, Cummings SR, Kerlikowske K, Vachon CM (2018) Does mammographic density mediate risk factor associations with breast cancer? An analysis by tumor characteristics. Breast Cancer Res Treat 170(1):129–141. https://doi.org/10.1007/s10549-018-4735-9 CrossRefPubMedPubMedCentral

13.

World-class systematic review management - A Cochrane technology platform. Covidence (2019). https://www.covidence.org/home/

14.

Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ (Clinical Research Ed) 339:b2535. https://doi.org/10.1136/bmj.b2535 CrossRef

15.

Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C, Liberati A, Moschetti I, Phillips B, Thornton H. Explanation of the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence (Background Document). Oxford Centre for Evidence-Based Medicine. https://www.cebm.net/index.aspx?o=5653

16.

Boyd NF, Martin LJ, Li Q, Sun L, Chiarelli AM, Hislop G, Yaffe MJ, Minkin S (2006) Mammographic density as a surrogate marker for the effects of hormone therapy on risk of breast cancer. Cancer Epidemiol Biomark Prev 15(5):961–966. https://doi.org/10.1158/1055-9965.epi-05-0762 CrossRef

17.

Boyd NF, Melnichouk O, Martin LJ, Hislop G, Chiarelli AM, Yaffe MJ, Minkin S (2011) Mammographic density, response to hormones, and breast cancer risk. J Clin Oncol 29(22):2985–2992. https://doi.org/10.1200/jco.2010.33.7964 CrossRefPubMed

18.

Byrne C, Ursin G, Martin CF, Peck JD, Cole EB, Zeng D, Kim E, Yaffe MD, Boyd NF, Heiss G, McTiernan A, Chlebowski RT, Lane DS, Manson JE, Wactawski-Wende J, Pisano ED (2017) Mammographic density change with estrogen and progestin therapy and breast cancer risk. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djx001 CrossRefPubMedPubMedCentral

19.

Couto E, Qureshi SA, Hofvind S, Hilsen M, Aase H, Skaane P, Vatten L, Ursin G (2012) Hormone therapy use and mammographic density in postmenopausal Norwegian women. Breast Cancer Res Treat 132(1):297–305. https://doi.org/10.1007/s10549-011-1810-x CrossRefPubMed

20.

Crandall CJ, Aragaki AK, Cauley JA, McTiernan A, Manson JE, Anderson GL, Wactawski-Wende J, Chlebowski RT (2012) Breast tenderness after initiation of conjugated equine estrogens and mammographic density change. Breast Cancer Res Treat 131(3):969–979. https://doi.org/10.1007/s10549-011-1803-9 CrossRefPubMed

21.

Crandall CJ, Guan M, Laughlin GA, Ursin GA, Stanczyk FZ, Ingles SA, Barrett-Connor E, Greendale GA (2008) Increases in serum estrone sulfate level are associated with increased mammographic density during menopausal hormone therapy. Cancer Epidemiol Biomark Prev 17(7):1674–1681. https://doi.org/10.1158/1055-9965.epi-07-2779 CrossRef

22.

Crandall CJ, Karlamangla A, Huang MH, Ursin G, Guan M, Greendale GA (2006) Association of new-onset breast discomfort with an increase in mammographic density during hormone therapy. Arch Intern Med 166(15):1578–1584. https://doi.org/10.1001/archinte.166.15.1578 CrossRefPubMed

23.

Gapstur SM, Lopez P, Colangelo LA, Wolfman J, Van Horn L, Hendrick RE (2003) Associations of breast cancer risk factors with breast density in Hispanic women. Cancer Epidemiol Biomark Prev 12(10):1074–1080

24.

Harvey JA, Santen RJ, Petroni GR, Bovbjerg VE, Smolkin ME, Sheriff FS, Russo J (2008) Histologic changes in the breast with menopausal hormone therapy use: correlation with breast density, estrogen receptor, progesterone receptor, and proliferation indices. Menopause (New York, NY) 15(1):67–73. https://doi.org/10.1097/gme.0b013e318054e29a CrossRef

25.

Heng D, Gao F, Jong R, Fishell E, Yaffe M, Martin L, Li T, Stone J, Sun L, Hopper J, Boyd NF (2004) Risk factors for breast cancer associated with mammographic features in Singaporean chinese women. Cancer Epidemiol Biomark Prev 13(11 Pt 1):1751–1758

26.

McTiernan A, Martin CF, Peck JD, Aragaki AK, Chlebowski RT, Pisano ED, Wang CY, Brunner RL, Johnson KC, Manson JE, Lewis CE, Kotchen JM, Hulka BS (2005) Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's Health Initiative randomized trial. J Natl Cancer Inst 97(18):1366–1376. https://doi.org/10.1093/jnci/dji279 CrossRefPubMed

27.

van Duijnhoven FJ, Peeters PH, Warren RM, Bingham SA, van Noord PA, Monninkhof EM, Grobbee DE, van Gils CH (2007) Postmenopausal hormone therapy and changes in mammographic density. J Clin Oncol 25(11):1323–1328. https://doi.org/10.1200/jco.2005.04.7332 CrossRefPubMed

28.

Aiello EJ, Buist DS, White E (2006) Do breast cancer risk factors modify the association between hormone therapy and mammographic breast density? (United States). Cancer Causes Control: CCC 17(10):1227–1235. https://doi.org/10.1007/s10552-006-0073-z CrossRefPubMed

29.

Carmona-Sanchez E, Cuadros Lopez JL, Cuadros Celorrio AM, Perez-Roncero G, Gonzalez Ramirez AR, Fernandez Alonso AM (2013) Assessment of mammographic density in postmenopausal women during long term hormone replacement therapy. Gynecol Endocrinol 29(12):1067–1070. https://doi.org/10.3109/09513590.2013.831831 CrossRefPubMed

30.

Chen FP, Cheung YC, Soong YK (2010) Factors that influence changes in mammographic density with postmenopausal hormone therapy. Taiwan J Obstet Gynecol 49(4):413–418. https://doi.org/10.1016/s1028-4559(10)60091-5 CrossRefPubMed

31.

Greendale GA, Reboussin BA, Slone S, Wasilauskas C, Pike MC, Ursin G (2003) Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst 95(1):30–37CrossRefPubMed

32.

Jeon JH, Kang JH, Kim Y, Lee HY, Choi KS, Jun JK, Oh DK, Lee CY, Ko K, Park EC (2011) Reproductive and hormonal factors associated with fatty or dense breast patterns among Korean women. Cancer Res Treat 43(1):42–48. https://doi.org/10.4143/crt.2011.43.1.42 CrossRefPubMedPubMedCentral

33.

Olsson A, Sartor H, Borgquist S, Zackrisson S, Manjer J (2014) Breast density and mode of detection in relation to breast cancer specific survival: a cohort study. BMC Cancer 14:229. https://doi.org/10.1186/1471-2407-14-229 CrossRefPubMedPubMedCentral

34.

Topal NB, Ayhan S, Topal U, Bilgin T (2006) Effects of hormone replacement therapy regimens on mammographic breast density: the role of progestins. J Obstet Gynaecol Res 32(3):305–308. https://doi.org/10.1111/j.1447-0756.2006.00402.x CrossRefPubMed

35.

Yaghjyan L, Mahoney MC, Succop P, Wones R, Buckholz J, Pinney SM (2012) Relationship between breast cancer risk factors and mammographic breast density in the Fernald Community Cohort. Br J Cancer 106(5):996–1003. https://doi.org/10.1038/bjc.2012.1 CrossRefPubMedPubMedCentral

36.

Christodoulakos GE, Lambrinoudaki IV, Panoulis KP, Vourtsi AD, Vlachos L, Georgiou E, Creatsas GC (2003) The effect of various regimens of hormone replacement therapy on mammographic breast density. Maturitas 45(2):109–118CrossRefPubMed

37.

Marugg RC, van der Mooren MJ, Hendriks JH, Rolland R, Ruijs SH (1997) Mammographic changes in postmenopausal women on hormonal replacement therapy. Eur Radiol 7(5):749–755. https://doi.org/10.1007/bf02742938 CrossRefPubMed

38.

Sala E, Warren R, McCann J, Duffy S, Luben R, Day N (2000) High-risk mammographic parenchymal patterns, hormone replacement therapy and other risk factors: a Case–control study. Int J Epidemiol 29(4):629–636. https://doi.org/10.1093/ije/29.4.629 CrossRefPubMed

39.

Vachon CM, Sellers TA, Vierkant RA, Wu FF, Brandt KR (2002) Case–control study of increased mammographic breast density response to hormone replacement therapy. Cancer Epidemiol Biomark Prev 11(11):1382–1388

40.

Lundstrom E, Wilczek B, von Palffy Z, Soderqvist G, von Schoultz B (1999) Mammographic breast density during hormone replacement therapy: differences according to treatment. Am J Obstet Gynecol 181(2):348–352. https://doi.org/10.1016/s0002-9378(99)70560-0 CrossRefPubMed

41.

Persson I, Thurfjell E, Holmberg L (1997) Effect of estrogen and estrogen-progestin replacement regimens on mammographic breast parenchymal density. J Clin Oncol 15(10):3201–3207. https://doi.org/10.1200/jco.1997.15.10.3201 CrossRefPubMed

42.

Sendag F, Cosan Terek M, Ozsener S, Oztekin K, Bilgin O, Bilgen I, Memis A (2001) Mammographic density changes during different postmenopausal hormone replacement therapies. Fertil Steril 76(3):445–450. https://doi.org/10.1016/s0015-0282(01)01935-5 CrossRefPubMed

43.

Hofseth LJ, Raafat AM, Osuch JR, Pathak DR, Slomski CA, Haslam SZ (1999) Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast. J Clin Endocrinol Metab 84(12):4559–4565. https://doi.org/10.1210/jcem.84.12.6194 CrossRefPubMed

44.

American Cancer Society. Non-cancerous breast conditions. Hyperplasia of the breast (Ductal or Lobular). Version 10.08.2019. https://www.cancer.org/cancer/breast-cancer/non-cancerous-breast-conditions/hyperplasia-of-the-breast-ductal-or-lobular.html. Accessed 20 June 2020

45.

Longacre TA, Bartow SA (1986) A correlative morphologic study of human breast and endometrium in the menstrual cycle. Am J Surg Pathol 10(6):382–393. https://doi.org/10.1097/00000478-198606000-00003 CrossRefPubMed

Title: Hormone replacement therapy and mammographic density: a systematic literature review
Authors: Shadi Azam
Katja Kemp Jacobsen
Arja R. Aro
Elsebeth Lynge
Zorana Jovanovic Andersen
Publication date: 01-08-2020
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Estrogens
Progestin
Published in: Breast Cancer Research and Treatment / Issue 3/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05744-w

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2020

Re: Risk-reducing mastectomy: a case series of 124 procedures in Brazilian patients

High-Efficiency Same-Day Approach to Breast Reconstruction During the COVID-19 Crisis

PIBF1 suppresses the ATR/CHK1 signaling pathway and promotes proliferation and motility of triple-negative breast cancer cells

Surveillance, Epidemiology, and End Results program underestimates breast cancer-specific mortality after ductal carcinoma in situ diagnosis

Plasma DNA as a “liquid biopsy” incompletely complements tumor biopsy for identification of mutations in a case series of four patients with oligometastatic breast cancer

The bottom line for lesion localization in breast cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer