. 2023 Jun;199(2):323-334.

doi: 10.1007/s10549-023-06903-5. Epub 2023 Apr 5.

Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: a premenopausal breast cancer collaborative group analysis

Hazel B Nichols¹, Melissa G House², Rina Yarosh³, Sara Mitra⁴, Mandy Goldberg⁵, Kimberly A Bertrand⁶, A Heather Eliassen^{7

8}, Graham G Giles^{9

10

11}, Michael E Jones¹², Roger L Milne^{9

10

11}, Katie M O'Brien⁵, Julie R Palmer^{6

13}, Sven Sandin^{14

15

16}, Walter C Willett^{7

8

17}, Weiyao Yin^{14

18}, Dale P Sandler^#⁵, Anthony J Swerdlow^#^{12

19}, Minouk J Schoemaker^#^{12

20}

Affiliations

¹ Department of Epidemiology, Hazel B. Nichols, University of North Carolina at Chapel Hill Gillings School of Global Public Health, 2104F McGavran-Greenberg Hall, 135 Dauer Drive, Chapel Hill, Chapel Hill, NC, 27599-7435, USA. Hazel.Nichols@unc.edu.
² , Westat, USA.
³ Department of Epidemiology, Hazel B. Nichols, University of North Carolina at Chapel Hill Gillings School of Global Public Health, 2104F McGavran-Greenberg Hall, 135 Dauer Drive, Chapel Hill, Chapel Hill, NC, 27599-7435, USA.
⁴ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA.
⁵ Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, USA.
⁶ Slone Epidemiology Center, Boston University, Boston, USA.
⁷ Channing Division of Network Medicine, Department of Medicine Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
⁹ Cancer Epidemiology Division Cancer Council Victoria, Melbourne, Australia.
¹⁰ Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
¹¹ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia.
¹² Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
¹³ Boston University Chobanian & Avedisian School of Medicine, Boston University, Boston, USA.
¹⁴ Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Solna, Sweden.
¹⁵ Department of Psychiatry Icahn School of Medicine at Mount Sinai, New York, USA.
¹⁶ Seaver Autism Center for Research and Treatment at Mount Sinai Icahn School of Medicine at Mount Sinai, New York, USA.
¹⁷ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, USA.
¹⁸ Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
¹⁹ Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
²⁰ Real World Solutions IQVIA, Amsterdam, The Netherlands.

^# Contributed equally.

PMID: 37020102
PMCID: PMC11314296
DOI: 10.1007/s10549-023-06903-5

Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: a premenopausal breast cancer collaborative group analysis

Hazel B Nichols et al. Breast Cancer Res Treat. 2023 Jun.

. 2023 Jun;199(2):323-334.

doi: 10.1007/s10549-023-06903-5. Epub 2023 Apr 5.

Authors

Affiliations

¹ Department of Epidemiology, Hazel B. Nichols, University of North Carolina at Chapel Hill Gillings School of Global Public Health, 2104F McGavran-Greenberg Hall, 135 Dauer Drive, Chapel Hill, Chapel Hill, NC, 27599-7435, USA. Hazel.Nichols@unc.edu.
² , Westat, USA.
³ Department of Epidemiology, Hazel B. Nichols, University of North Carolina at Chapel Hill Gillings School of Global Public Health, 2104F McGavran-Greenberg Hall, 135 Dauer Drive, Chapel Hill, Chapel Hill, NC, 27599-7435, USA.
⁴ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA.
⁵ Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, USA.
⁶ Slone Epidemiology Center, Boston University, Boston, USA.
⁷ Channing Division of Network Medicine, Department of Medicine Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
⁹ Cancer Epidemiology Division Cancer Council Victoria, Melbourne, Australia.
¹⁰ Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
¹¹ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia.
¹² Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
¹³ Boston University Chobanian & Avedisian School of Medicine, Boston University, Boston, USA.
¹⁴ Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Solna, Sweden.
¹⁵ Department of Psychiatry Icahn School of Medicine at Mount Sinai, New York, USA.
¹⁶ Seaver Autism Center for Research and Treatment at Mount Sinai Icahn School of Medicine at Mount Sinai, New York, USA.
¹⁷ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, USA.
¹⁸ Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
¹⁹ Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
²⁰ Real World Solutions IQVIA, Amsterdam, The Netherlands.

^# Contributed equally.

PMID: 37020102
PMCID: PMC11314296
DOI: 10.1007/s10549-023-06903-5

Abstract

Purpose: Women with preeclampsia are more likely to deliver preterm. Reports of inverse associations between preeclampsia and breast cancer risk, and positive associations between preterm birth and breast cancer risk are difficult to reconcile. We investigated the co-occurrence of preeclampsia/gestational hypertension with preterm birth and breast cancer risk using data from the Premenopausal Breast Cancer Collaborative Group.

Methods: Across 6 cohorts, 3096 premenopausal breast cancers were diagnosed among 184,866 parous women. We estimated multivariable hazard ratios (HR) and 95% confidence intervals (CI) for premenopausal breast cancer risk using Cox proportional hazards regression.

Results: Overall, preterm birth was not associated (HR 1.02, 95% CI 0.92, 1.14), and preeclampsia was inversely associated (HR 0.86, 95% CI 0.76, 0.99), with premenopausal breast cancer risk. In stratified analyses using data from 3 cohorts, preterm birth associations with breast cancer risk were modified by hypertensive conditions in first pregnancies (P-interaction = 0.09). Preterm birth was positively associated with premenopausal breast cancer in strata of women with preeclampsia or gestational hypertension (HR 1.52, 95% CI: 1.06, 2.18), but not among women with normotensive pregnancy (HR = 1.09, 95% CI: 0.93, 1.28). When stratified by preterm birth, the inverse association with preeclampsia was more apparent, but not statistically different (P-interaction = 0.2), among women who did not deliver preterm (HR = 0.82, 95% CI 0.68, 1.00) than those who did (HR = 1.07, 95% CI 0.73, 1.56).

Conclusion: Findings support an overall inverse association of preeclampsia history with premenopausal breast cancer risk. Estimates for preterm birth and breast cancer may vary according to other conditions of pregnancy.

Keywords: Breast cancer; Cohort; Epidemiology.

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Figures

**Fig. 1**
Inclusion criteria for participating studies in the premenopausal breast cancer collaborative group with individual-level data available for pooled analyses of pregnancy complications and premenopausal breast cancer risk

**Fig. 2**
Hazard ratios (HR) and 95% confidence intervals (CI) for preterm birth (< 37 weeks) and hypertensive conditions of pregnancy in relation to premenopausal breast cancer risk. HRs are shown for the pooled analysis, and according to the individual study results in the Generations Study (GEN), Nurses’ Health Study II (NHS2), Sister Study (SIS), and Black Women’s Health Study (BWHS) cohorts

See this image and copyright information in PMC

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Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: a premenopausal breast cancer collaborative group analysis

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Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: a premenopausal breast cancer collaborative group analysis

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