Citation
Jung, Audrey Y.; Ahearn, Thomas U.; Behrens, Sabine; Middha, Pooja; Bolla, Manjeet K.; Wang, Qin; Arndt, Volker; Aronson, Kristan J.; Augustinsson, Annelie; & Beane Freeman, Laura E., et al. (2022). Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies. Journal of the National Cancer Institute, 114(2), 1706-1719. PMCID: PMC9949579Abstract
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) and by invasiveness. All statistical tests were 2-sided.
RESULTS: Compared to 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-<25 years after last birth and 45-<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 < 30 years after last birth). Older age at first birth (P-heterogeneity<.001 for triple-negative compared to luminal-A like) and breastfeeding (P-heterogeneity<.001 for triple-negative compared to luminal-A like) were associated with lower risk of triple-negative 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.
CONCLUSION: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared to other subtypes, with implications for the understanding of disease etiology and risk prediction.
URL
http://dx.doi.org/10.1093/jnci/djac117Reference Type
Journal ArticleYear Published
2022Journal Title
Journal of the National Cancer InstituteAuthor(s)
Jung, Audrey Y.Ahearn, Thomas U.
Behrens, Sabine
Middha, Pooja
Bolla, Manjeet K.
Wang, Qin
Arndt, Volker
Aronson, Kristan J.
Augustinsson, Annelie
Beane Freeman, Laura E.
Becher, Heiko
Brenner, Hermann
Canzian, Federico
Carey, Lisa A., for the CTS Consortium
Czene, Kamila
Eliassen, A. Heather
Eriksson, Mikael
Evans, D. Gareth
Figueroa, Jonine
Fritschi, Lin
Gabrielson, Marike
Giles, Graham G.
Guénel, Pascal
Hadjisavvas, Andreas
Haiman, Christopher A.
Håkansson, Niclas
Hall, Per
Hamann, Ute
Hoppe, Reiner
Hopper, John L.
Howell, Anthony
Hunter, David J.
Hüsing, Anika
Kaaks, Rudolf
Kosma, Veli-Matti
Koutros, Stella
Kraft, Peter
Lacey, James V.
Le Marchand, Loic
Lissowska, Jolanta
Loizidou, Maria A.
Mannermaa, Arto
Maurer, Tabea
Murphy, Rachel A.
Olshan, Andrew F.
Olsson, Håkan
Patel, Alpa V.
Perou, Charles M.
Rennert, Gad
Shibli, Rana
Shu, Xiao-Ou
Southey, Melissa C.
Stone, Jennifer
Tamimi, Rulla M.
Teras, Lauren R.
Troester, Melissa A.
Truong, Thérèse
Vachon, Celine M.
Wang, Sophia S.
Wolk, Alicja
Wu, Anna H.
Yang, Xiaohong R.
Zheng, Wei
Dunning, Alison M.
Pharoah, Paul D. P.
Easton, Douglas F.
Milne, Roger L.
Chatterjee, Nilanjan
Schmidt, Marjanka K.
García-Closas, Montserrat
Chang-Claude, Jenny