Dataset Information

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

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 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.

SUBMITTER: Jung AY

PROVIDER: S-EPMC9949579 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Jung Audrey Y AY Ahearn Thomas U TU Behrens Sabine S Middha Pooja P Bolla Manjeet K MK Wang Qin Q Arndt Volker V Aronson Kristan J KJ Augustinsson Annelie A Beane Freeman Laura E LE Becher Heiko H Brenner Hermann H Canzian Federico F Carey Lisa A LA Czene Kamila K Eliassen A Heather AH Eriksson Mikael M Evans D Gareth DG Figueroa Jonine D JD Fritschi Lin L Gabrielson Marike M Giles Graham G GG Guénel Pascal P Hadjisavvas Andreas A Haiman Christopher A CA Håkansson Niclas N Hall Per P Hamann Ute U Hoppe Reiner R Hopper John L JL Howell Anthony A Hunter David J DJ Hüsing Anika A Kaaks Rudolf R Kosma Veli-Matti VM Koutros Stella S Kraft Peter P Lacey James V JV Le Marchand Loic L Lissowska Jolanta J Loizidou Maria A MA Mannermaa Arto A Maurer Tabea T Murphy Rachel A RA Olshan Andrew F AF Olsson Håkan H Patel Alpa V AV Perou Charles M CM Rennert Gad G Shibli Rana R Shu Xiao-Ou XO Southey Melissa C MC Stone Jennifer J Tamimi Rulla M RM Teras Lauren R LR Troester Melissa A MA Truong Thérèse T Vachon Celine M CM Wang Sophia S SS Wolk Alicja A Wu Anna H AH Yang Xiaohong R XR Zheng Wei W Dunning Alison M AM Pharoah Paul D P PDP Easton Douglas F DF Milne Roger L RL Chatterjee Nilanjan N Schmidt Marjanka K MK García-Closas Montserrat M Chang-Claude Jenny J

Journal of the National Cancer Institute 20221201 12

<h4>Background</h4>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.<h4>Methods</h4>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 esti ...[more]

PMID: 35723569

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Project description:BackgroundPrevious studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.MethodsWe pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided.ResultsIn case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors.ConclusionsThis study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

Project description:Aside from age, sex, and family history, risk of developing breast cancer is largely linked to reproductive factors, which characterize exposure to sex hormones. Given that, molecular testing at the tumor level is currently possible, clinical characterization of tumor subtypes is routinely conducted to guide treatment decisions. However, despite the vast amount of published data from observational studies on reproductive factor associations and breast cancer risk, relatively fewer reports have been published on associations specific to breast tumor subtypes. We conducted a review of the literature and summarized the results of associations between reproductive factors and risk or odds of three distinct tumor subtypes: estrogen receptor/progesterone receptor positive (hormone receptor positive, HR+ tumors), tumors overexpressing the human epidermal receptor 2 protein (HER2+), and triple negative breast cancer (TNBC), which lacks the three markers. Results show that the most consistent evidence for associations with reproductive risk factors exists for HR+ breast cancers, with nulliparity, current use of menopausal hormone therapy, and prolonged interval between menarche and age at first birth being the strongest risk factors; increased age at first birth and decreased age at menarche were fairly consistently associated with HR+ cancers; and though less consistent, older age at menopause was also positively associated, while lactation was inversely associated with HR+ tumors. Fewer consistent associations have been reported for TNBC. The single protective factor most consistently associated with TNBC was longer duration of breastfeeding. Increased parity, younger age at first birth, older age at menarche, and oral contraceptive use were less consistently shown to be associated with TNBC. No remarkable associations for HER2+ breast cancers were evident, although this was based on relatively scarce data. Findings suggest heterogeneity in reproductive risk factors for the distinct subtypes of breast tumors, which may have implications for recommended prevention strategies.

Project description:Prior studies reported the association of reproductive factors with breast cancer (BC), but the evidence is inconsistent. We conducted a pooled analysis of nine cohort studies in Japan to evaluate the impact of six reproductive factors (age at menarche/age at first birth/number of births/age at menopause/use of female hormones/breastfeeding) on BC incidence. We conducted analyses according to menopausal status at the baseline or at the diagnosis. Hazard ratio (HR) and 95% confidence interval (CI) were estimated by applying Cox proportional-hazards model in each study. These hazard ratios were integrated using a random-effects model. Among 187,999 women (premenopausal: 61,113, postmenopausal: 126,886), we observed 873 premenopausal and 1,456 postmenopausal cases. Among premenopausal women, use of female hormones significantly increased BC incidence (HR: 1.53 [1.04-2.25]). Although P value for trend was not significant for age at first birth and number of births (P for trend: 0.15 and 0.30, respectively), women giving first birth at ages ≥36 experienced significantly higher BC incidence than at ages 21-25 years, and women who had ≥2 births experienced significantly lower BC incidence than nulliparous women. Among postmenopausal women, more births significantly decreased BC incidence (P for trend: 0.03). Although P value for trend was not significant for age at first birth and age at menopause (P for trend: 0.30 and 0.37, respectively), women giving first birth at ages 26-35 years experienced significantly higher BC incidence than at ages 21-25 years, and women with age at menopause: ≥50 years experienced significantly higher BC incidence than age at menopause: ≤44 years. BC incidence was similar according to age at menarche or breastfeeding history among both premenopausal and postmenopausal women. In conclusion, among Japanese women, use of female hormones increased BC incidence in premenopausal women, and more births decreased BC incidence in postmenopausal women.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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