Mammographic density phenotypes and risk of breast cancer: A meta-analysis

Andreas Pettersson, Rebecca E. Graff, Giske Ursin, Isabel Dos Santos Silva, Valerie McCormack, Laura Baglietto, Celine M Vachon, Marije F. Bakker, Graham G. Giles, Kee Seng Chia, Kamila Czene, Louise Eriksson, Per Hall, Mikael Hartman, Ruth M L Warren, Greg Hislop, Anna M. Chiarelli, John L. Hopper, Kavitha Krishnan, Jingmei LiQing Li, Ian Pagano, Bernard A. Rosner, Chia Siong Wong, Christopher Scott, Jennifer Stone, Gertraud Maskarinec, Norman F. Boyd, Carla H. Van Gils, Rulla M. Tamimi

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Background Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk. Methods We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than. 05 considered to be statistically significant. Results Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity =. 02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity <. 01) for postmenopausal women. Conclusions The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.

Original languageEnglish (US)
Article numberdju078
JournalJournal of the National Cancer Institute
Volume106
Issue number5
DOIs
StatePublished - May 14 2014
Externally publishedYes

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Meta-Analysis
Confidence Intervals
Breast Neoplasms
Phenotype
Odds Ratio
Breast Density
Parity
Case-Control Studies
Breast
Body Mass Index
Logistic Models
Fats

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pettersson, A., Graff, R. E., Ursin, G., Dos Santos Silva, I., McCormack, V., Baglietto, L., ... Tamimi, R. M. (2014). Mammographic density phenotypes and risk of breast cancer: A meta-analysis. Journal of the National Cancer Institute, 106(5), [dju078]. https://doi.org/10.1093/jnci/dju078

Mammographic density phenotypes and risk of breast cancer : A meta-analysis. / Pettersson, Andreas; Graff, Rebecca E.; Ursin, Giske; Dos Santos Silva, Isabel; McCormack, Valerie; Baglietto, Laura; Vachon, Celine M; Bakker, Marije F.; Giles, Graham G.; Chia, Kee Seng; Czene, Kamila; Eriksson, Louise; Hall, Per; Hartman, Mikael; Warren, Ruth M L; Hislop, Greg; Chiarelli, Anna M.; Hopper, John L.; Krishnan, Kavitha; Li, Jingmei; Li, Qing; Pagano, Ian; Rosner, Bernard A.; Wong, Chia Siong; Scott, Christopher; Stone, Jennifer; Maskarinec, Gertraud; Boyd, Norman F.; Van Gils, Carla H.; Tamimi, Rulla M.

In: Journal of the National Cancer Institute, Vol. 106, No. 5, dju078, 14.05.2014.

Research output: Contribution to journalArticle

Pettersson, A, Graff, RE, Ursin, G, Dos Santos Silva, I, McCormack, V, Baglietto, L, Vachon, CM, Bakker, MF, Giles, GG, Chia, KS, Czene, K, Eriksson, L, Hall, P, Hartman, M, Warren, RML, Hislop, G, Chiarelli, AM, Hopper, JL, Krishnan, K, Li, J, Li, Q, Pagano, I, Rosner, BA, Wong, CS, Scott, C, Stone, J, Maskarinec, G, Boyd, NF, Van Gils, CH & Tamimi, RM 2014, 'Mammographic density phenotypes and risk of breast cancer: A meta-analysis', Journal of the National Cancer Institute, vol. 106, no. 5, dju078. https://doi.org/10.1093/jnci/dju078
Pettersson A, Graff RE, Ursin G, Dos Santos Silva I, McCormack V, Baglietto L et al. Mammographic density phenotypes and risk of breast cancer: A meta-analysis. Journal of the National Cancer Institute. 2014 May 14;106(5). dju078. https://doi.org/10.1093/jnci/dju078
Pettersson, Andreas ; Graff, Rebecca E. ; Ursin, Giske ; Dos Santos Silva, Isabel ; McCormack, Valerie ; Baglietto, Laura ; Vachon, Celine M ; Bakker, Marije F. ; Giles, Graham G. ; Chia, Kee Seng ; Czene, Kamila ; Eriksson, Louise ; Hall, Per ; Hartman, Mikael ; Warren, Ruth M L ; Hislop, Greg ; Chiarelli, Anna M. ; Hopper, John L. ; Krishnan, Kavitha ; Li, Jingmei ; Li, Qing ; Pagano, Ian ; Rosner, Bernard A. ; Wong, Chia Siong ; Scott, Christopher ; Stone, Jennifer ; Maskarinec, Gertraud ; Boyd, Norman F. ; Van Gils, Carla H. ; Tamimi, Rulla M. / Mammographic density phenotypes and risk of breast cancer : A meta-analysis. In: Journal of the National Cancer Institute. 2014 ; Vol. 106, No. 5.
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abstract = "Background Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk. Methods We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95{\%} confidence intervals (CIs). All tests were two-sided with P less than. 05 considered to be statistically significant. Results Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95{\%} CI = 1.29 to 1.47) for absolute dense area, 0.78 (95{\%} CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95{\%} CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95{\%} CI = 1.31 to 1.44), 0.79 (95{\%} CI = 0.73 to 0.85), and 1.53 (95{\%} CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95{\%} CI = 0.71 to 0.94; P heterogeneity =. 02) for premenopausal and 0.85 (95{\%} CI = 0.75 to 0.96; P heterogeneity <. 01) for postmenopausal women. Conclusions The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.",
author = "Andreas Pettersson and Graff, {Rebecca E.} and Giske Ursin and {Dos Santos Silva}, Isabel and Valerie McCormack and Laura Baglietto and Vachon, {Celine M} and Bakker, {Marije F.} and Giles, {Graham G.} and Chia, {Kee Seng} and Kamila Czene and Louise Eriksson and Per Hall and Mikael Hartman and Warren, {Ruth M L} and Greg Hislop and Chiarelli, {Anna M.} and Hopper, {John L.} and Kavitha Krishnan and Jingmei Li and Qing Li and Ian Pagano and Rosner, {Bernard A.} and Wong, {Chia Siong} and Christopher Scott and Jennifer Stone and Gertraud Maskarinec and Boyd, {Norman F.} and {Van Gils}, {Carla H.} and Tamimi, {Rulla M.}",
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T1 - Mammographic density phenotypes and risk of breast cancer

T2 - A meta-analysis

AU - Pettersson, Andreas

AU - Graff, Rebecca E.

AU - Ursin, Giske

AU - Dos Santos Silva, Isabel

AU - McCormack, Valerie

AU - Baglietto, Laura

AU - Vachon, Celine M

AU - Bakker, Marije F.

AU - Giles, Graham G.

AU - Chia, Kee Seng

AU - Czene, Kamila

AU - Eriksson, Louise

AU - Hall, Per

AU - Hartman, Mikael

AU - Warren, Ruth M L

AU - Hislop, Greg

AU - Chiarelli, Anna M.

AU - Hopper, John L.

AU - Krishnan, Kavitha

AU - Li, Jingmei

AU - Li, Qing

AU - Pagano, Ian

AU - Rosner, Bernard A.

AU - Wong, Chia Siong

AU - Scott, Christopher

AU - Stone, Jennifer

AU - Maskarinec, Gertraud

AU - Boyd, Norman F.

AU - Van Gils, Carla H.

AU - Tamimi, Rulla M.

PY - 2014/5/14

Y1 - 2014/5/14

N2 - Background Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk. Methods We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than. 05 considered to be statistically significant. Results Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity =. 02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity <. 01) for postmenopausal women. Conclusions The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.

AB - Background Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk. Methods We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than. 05 considered to be statistically significant. Results Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity =. 02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity <. 01) for postmenopausal women. Conclusions The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.

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