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Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes : Pooled Analysis of Population-Based Studies

Jung, Audrey Y ; Ahearn, Thomas U ; Behrens, Sabine ; Middha, Pooja ; Bolla, Manjeet K ; Wang, Qin ; Arndt, Volker ; Aronson, Kristan J ; Augustinsson, Annelie LU and Beane Freeman, Laura E , et al. (2022) In Journal of the National Cancer Institute 114(12). p.1706-1719
Abstract

BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.

METHODS: Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical... (More)

BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.

METHODS: Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided.

RESULTS: Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.

CONCLUSIONS: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

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Contribution to journal
publication status
published
subject
keywords
Female, Humans, Breast Neoplasms/etiology, Receptor, ErbB-2, Receptors, Progesterone, Receptors, Estrogen, Triple Negative Breast Neoplasms/epidemiology, Case-Control Studies, Risk Factors, Biomarkers, Tumor
in
Journal of the National Cancer Institute
volume
114
issue
12
pages
14 pages
publisher
Oxford University Press
external identifiers
  • scopus:85139114483
  • pmid:35723569
ISSN
1460-2105
DOI
10.1093/jnci/djac117
language
English
LU publication?
yes
additional info
© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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18ff896b-2840-4b29-bf5a-7475b9f76657
date added to LUP
2023-11-11 15:49:52
date last changed
2024-04-09 16:46:38
@article{18ff896b-2840-4b29-bf5a-7475b9f76657,
  abstract     = {{<p>BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.</p><p>METHODS: Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided.</p><p>RESULTS: Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity &lt; .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity &lt; .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.</p><p>CONCLUSIONS: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.</p>}},
  author       = {{Jung, Audrey Y and Ahearn, Thomas U and Behrens, Sabine and Middha, Pooja and Bolla, Manjeet K and Wang, Qin and Arndt, Volker and Aronson, Kristan J and Augustinsson, Annelie and Beane Freeman, Laura E and Becher, Heiko and Brenner, Hermann and Canzian, Federico and Carey, Lisa A and Czene, Kamila and Eliassen, A Heather and Eriksson, Mikael and Evans, D Gareth and Figueroa, Jonine D and Fritschi, Lin and Gabrielson, Marike and Giles, Graham G and Guénel, Pascal and Hadjisavvas, Andreas and Haiman, Christopher A and Håkansson, Niclas and Hall, Per and Hamann, Ute and Hoppe, Reiner and Hopper, John L and Howell, Anthony and Hunter, David J and Hüsing, Anika and Kaaks, Rudolf and Kosma, Veli-Matti and Koutros, Stella and Kraft, Peter and Lacey, James V and Le Marchand, Loic and Lissowska, Jolanta and Loizidou, Maria A and Mannermaa, Arto and Maurer, Tabea and Murphy, Rachel A and Olshan, Andrew F and Olsson, Håkan and Patel, Alpa V and Perou, Charles M and Rennert, Gad and Shibli, Rana}},
  issn         = {{1460-2105}},
  keywords     = {{Female; Humans; Breast Neoplasms/etiology; Receptor, ErbB-2; Receptors, Progesterone; Receptors, Estrogen; Triple Negative Breast Neoplasms/epidemiology; Case-Control Studies; Risk Factors; Biomarkers, Tumor}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{12}},
  pages        = {{1706--1719}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of the National Cancer Institute}},
  title        = {{Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes : Pooled Analysis of Population-Based Studies}},
  url          = {{http://dx.doi.org/10.1093/jnci/djac117}},
  doi          = {{10.1093/jnci/djac117}},
  volume       = {{114}},
  year         = {{2022}},
}