Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes: pooled analysis of population-based studies

TY - JOUR

T1 - Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes: pooled analysis of population-based studies

AU - Jung, Audrey Y

AU - Ahearn, Thomas U

AU - Behrens, Sabine

AU - Middha, Pooja

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Arndt, Volker

AU - Aronson, Kristan J

AU - Augustinsson, Annelie

AU - Beane Freeman, Laura E

AU - Becher, Heiko

AU - Brenner, Hermann

AU - Canzian, Federico

AU - Carey, Lisa A

AU - Czene, Kamila

AU - Eliassen, A Heather

AU - Eriksson, Mikael

AU - Evans, D Gareth

AU - Figueroa, Jonine D

AU - Fritschi, Lin

AU - Gabrielson, Marike

AU - Giles, Graham G

AU - Guénel, Pascal

AU - Hadjisavvas, Andreas

AU - Haiman, Christopher A

AU - Håkansson, Niclas

AU - Hall, Per

AU - Hamann, Ute

AU - Hoppe, Reiner

AU - Hopper, John L

AU - Howell, Anthony

AU - Hunter, David J

AU - Hüsing, Anika

AU - Kaaks, Rudolf

AU - Kosma, Veli-Matti

AU - Koutros, Stella

AU - Kraft, Peter

AU - Lacey, James V

AU - Le Marchand, Loic

AU - Lissowska, Jolanta

AU - Loizidou, Maria A

AU - Mannermaa, Arto

AU - Maurer, Tabea

AU - Murphy, Rachel A

AU - Olshan, Andrew F

AU - Olsson, Håkan

AU - Patel, Alpa V

AU - Perou, Charles M

AU - Rennert, Gad

AU - Shibli, Rana

AU - Shu, Xiao-Ou

AU - Southey, Melissa C

AU - Stone, Jennifer

AU - Tamimi, Rulla M

AU - Teras, Lauren R

AU - Troester, Melissa A

AU - Truong, Thérèse

AU - Vachon, Celine M

AU - Wang, Sophia S

AU - Wolk, Alicja

AU - Wu, Anna H

AU - Yang, Xiaohong R

AU - Zheng, Wei

AU - Dunning, Alison M

AU - Pharoah, Paul D P

AU - Easton, Douglas F

AU - Milne, Roger L

AU - Chatterjee, Nilanjan

AU - Schmidt, Marjanka K

AU - García-Closas, Montserrat

AU - Chang-Claude, Jenny

AU - CTS Consortium

N1 - © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2022/12/8

Y1 - 2022/12/8

N2 - 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.

AB - 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.

U2 - 10.1093/jnci/djac117

DO - 10.1093/jnci/djac117

M3 - SCORING: Journal article

C2 - 35723569

VL - 114

SP - 1706

EP - 1719

JO - JNCI-J NATL CANCER I

JF - JNCI-J NATL CANCER I

SN - 0027-8874

IS - 12

ER -