The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density

International Consortium on Mammographic Density

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BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk.

METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche.

RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (β√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (β√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (β√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (β√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups.

CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

Original languageEnglish
Article number49
Pages (from-to)49
JournalBreast Cancer Research
Issue number1
Publication statusPublished - 14 Jul 2022

Bibliographical note

Funding Information:
ML declares a non-restricted investigator-initiated grant from AstraZeneca and minor support from Swiss Re.

Funding Information:
The Melbourne Collaborative Cohort Study acknowledges that their cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. Isfahan University acknowledges assistance from Dr. Vida Razavi and Dr. Shamila Razavi. Instituto Nacional de Salud Pública acknowledges the Ministry of Education of Mexico and the Institute for Social Security and Services for State Workers’ Medical Directorate staff and regional office in Jalisco for technical and administrative support. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of these organizations.

Funding Information:
This work was supported by the US National Cancer Institute at the National Institutes of Health [R03CA167771]; the International Agency for Research on Cancer; the University of Western Australia [Research Collaboration Award] and the Cancer Council Western Australia [Capacity Building and Collaboration Grant]. Original studies were supported, according to country by: Australia VicHealth; Cancer Council Victoria; Australian National Health and Medical Research Council [209057, 251,553 and 504711]; Australian National Breast Cancer Foundation [to JSt]; Canada the National Cancer Institute of Canada [to NFB]; Chile Fondecyt [11100238 to MLG, 1120326, 1130277, 3130532]; World Cancer Research Fund [2010/245]; Ellison Medical Foundation Grant [to AP]; Iran Isfahan University of Medical Sciences; Israel The Israel Cancer Association; Republic of Korea Asan Medical Center [2010-0811]; Malaysia Sime Darby LPGA Tournament; Ministry of Education University Malaya [High Impact Research Grant UM.C/HIR/MOHE/06]; University Malaya [Research Grant UMRG RP046B-15HTM]; Mexico National Council of Science and Technology (Mexico); the American Institute for Cancer Research [10A035]; Netherlands EPIC-NL-Europe against Cancer Programme of the European Commission (SANCO); Dutch Ministry of Health; Dutch Cancer Society; ZonMW the Netherlands Organisation for Health Research and Development; World Cancer Research Fund (WCRF); Poland Polish-Norwegian Research Programme [PNRF-243-AI-1/07]; Singapore National Medical Research Council [Clinician Scientist Award]; National University Cancer Institute Singapore (NCIS) Centre grant programme from National Medical Research Council; South Africa Pink Drive; Spain Spain’s Health Research Fund (Fondo de Investigacion Santiaria) [PI060386 and PS09/0790]; Spanish Federation of Breast Cancer Patients (FECMA) [EPY1169-10]; Turkey- Roche Mustahzarlari San. A.S., Istanbul, Turkey; UK UK Engineering and Physical Sciences Research Council [EP/K020439/1 to JHi]; Breast Cancer Campaign [2007MayPR23], Cancer Research UK [G186/11 and C405/A14565]; Da Costa Foundation UK; USA National Cancer Institute [R01CA85265, R37 CA54281, R01 CA97396, P50 CA116201, R01 CA177150 and R01 CA140286]; Cancer Center Support Grant [CA15083; CA131332, CA124865, UM1 CA186107 and UM1 CA176726]; the Susan G. Komen Foundation.

Publisher Copyright:
© 2022, The Author(s).


  • Adult
  • Breast Density
  • Breast Neoplasms/diagnostic imaging
  • Cross-Sectional Studies
  • Female
  • Humans
  • Mammography/methods
  • Menarche
  • Population Groups
  • Pregnancy
  • Risk Factors


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