Skip to main content

Advertisement

SpringerLink
Log in

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

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The data that support the findings of this study are not publicly available due to privacy or ethical restrictions. Study data may be shared upon reasonable request to senior authors.

Abbreviations

BP:

Blood pressure

BWHS:

Black Women’s Health Study

CI:

Confidence interval

ER:

Estrogen receptor

GEN:

Generations Study

HR:

Hazard ratio

MCCS:

Melbourne Collaborative Cohort Study

NHS2:

Nurses’ Health Study II

RR:

Relative risk

SIS:

Sister Study

SWLS:

Swedish Women’s Lifestyle and Health Study

UK:

United Kingdom

USA:

United States of America

References

  1. Roberts JM, Pearson GD, Cutler JA, Lindheimer MD, National Heart L, Blood I (2003) Summary of the NHLBI working group on research on hypertension during pregnancy. Hypertens Pregnancy 22(2):109–127

    PubMed  Google Scholar 

  2. Folk DM (2018) Hypertensive disorders of pregnancy: overview and current recommendations. J Midwifery Womens Health 63(3):289–300

    PubMed  Google Scholar 

  3. Ananth CV, Keyes KM, Wapner RJ (2013) Pre-eclampsia rates in the United States, 1980–2010: age-period-cohort analysis. BMJ 347:f6564

    PubMed  PubMed Central  Google Scholar 

  4. Wang F, Zhang W, Cheng W, Huo N, Zhang S (2021) Preeclampsia and cancer risk in women in later life: a systematic review and meta-analysis of cohort studies. Menopause 28(9):1070–1078

    PubMed  Google Scholar 

  5. Nechuta S, Paneth N, Velie EM (2010) Pregnancy characteristics and maternal breast cancer risk: a review of the epidemiologic literature. Cancer Causes Control 21(7):967–989

    PubMed  Google Scholar 

  6. Falk RT, Staff AC, Bradwin G, Karumanchi SA, Troisi R (2016) A prospective study of angiogenic markers and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Causes Control 27(8):1009–1017

    PubMed  PubMed Central  Google Scholar 

  7. Vatten LJ (2009) Romundstad PlR, jenum PlA, eskild a: angiogenic balance in pregnancy and subsequent breast cancer risk and survival: a population study. Cancer Epidemiol Biomark Prev 18(7):2074–2078

    CAS  Google Scholar 

  8. Preterm Birth [https://www.who.int/news-room/fact-sheets/detail/preterm-birth]

  9. Martin JAH BEO, J.K.: Births in the United States. In. Edited by Statistics NCfH. Hyattsville, MD; 2019.

  10. Wright LB, Schoemaker MJ, Jones ME, Ashworth A, Swerdlow AJ (2018) Breast cancer risk in relation to history of preeclampsia and hyperemesis gravidarum: prospective analysis in the generations Study. Int J Cancer 143(4):782–792

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hajiebrahimi M, Cnattingius S, Lambe M, Bahmanyar S (2016) Pregnancy history and risk of premenopausal breast cancer-a nested case-control study. Int J Epidemiol 45(3):816–824

    PubMed  Google Scholar 

  12. Hsieh CC, Wuu J, Lambe M, Trichopoulos D, Adami HO, Ekbom A (1999) Delivery of premature newborns and maternal breast-cancer risk. Lancet 353(9160):1239

    CAS  PubMed  Google Scholar 

  13. Innes KE, Byers TE (2004) First pregnancy characteristics and subsequent breast cancer risk among young women. Int J Cancer 112(2):306–311

    CAS  PubMed  Google Scholar 

  14. Melbye M, Wohlfahrt J, Andersen AM, Westergaard T, Andersen PK (1999) Preterm delivery and risk of breast cancer. Br J Cancer 80(3–4):609–613

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Troisi R, Gulbech Ording A, Grotmol T, Glimelius I, Engeland A, Gissler M, Trabert B, Ekbom A, Madanat-Harjuoja L, Sorensen HT et al (2018) Pregnancy complications and subsequent breast cancer risk in the mother: a Nordic population-based case-control study. Int J Cancer 143(8):1904–1913

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Vatten LJ, Romundstad PR, Trichopoulos D, Skjaerven R (2002) Pregnancy related protection against breast cancer depends on length of gestation. Br J Cancer 87(3):289–290

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Cnattingius S, Torrang A, Ekbom A, Granath F, Petersson G, Lambe M (2005) Pregnancy characteristics and maternal risk of breast cancer. JAMA 294(19):2474–2480

    CAS  PubMed  Google Scholar 

  18. Le Marchand L, Kolonel LN, Myers BC, Mi MP (1988) Birth characteristics of premenopausal women with breast cancer. Br J Cancer 57(4):437–439

    PubMed  PubMed Central  Google Scholar 

  19. Swerdlow AJ, Wright LB, Schoemaker MJ, Jones ME (2018) Maternal breast cancer risk in relation to birthweight and gestation of her offspring. Breast Cancer Res 20(1):110

    PubMed  PubMed Central  Google Scholar 

  20. Troisi R, Doody DR, Mueller BA (2013) A linked-registry study of gestational factors and subsequent breast cancer risk in the mother. Cancer Epidemiol Biomarkers Prev 22(5):835–847

    PubMed  PubMed Central  Google Scholar 

  21. Ardalan A, Bungum T (2016) Gestational age and the risk of maternal breast cancer: a population-based case-control study. Breast J 22(6):657–661

    PubMed  Google Scholar 

  22. Kessous R, Walfisch A, Meirovitz M, Davidson E, Sergienko R, Sheiner E (2017) Preterm delivery and future maternal risk of female malignancies. Arch Gynecol Obstet 295(1):205–210

    PubMed  Google Scholar 

  23. Polednak AP, Janerich DT (1983) Characteristics of first pregnancy in relation to early breast cancer. A case-control study J Reprod Med 28(5):314–318

    CAS  PubMed  Google Scholar 

  24. Lapillonne H, Golsteyn RM, Lapillonne A (1999) Duration of pregnancy and risk of breast cancer. Lancet 353(9169):2075

    CAS  PubMed  Google Scholar 

  25. Nichols HB, Schoemaker MJ, Wright LB, McGowan C, Brook MN, McClain KM, Jones ME, Adami HO, Agnoli C, Baglietto L et al (2017) The premenopausal breast cancer collaboration: a pooling project of studies participating in the national cancer institute cohort consortium. Cancer Epidemiol Biomarkers Prev 26(9):1360–1369

    PubMed  PubMed Central  Google Scholar 

  26. Roswall N, Sandin S, Adami HO, Weiderpass E (2017) Cohort profile: the Swedish women’s lifestyle and health cohort. Int J Epidemiol 46(2):e8

    PubMed  Google Scholar 

  27. Swerdlow AJ, Jones ME, Schoemaker MJ, Hemming J, Thomas D, Williamson J, Ashworth A (2011) The breakthrough generations study: design of a long-term uk cohort study to investigate breast cancer aetiology. Br J Cancer 105(7):911–917

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Giles GG, English DR (2002) The Melbourne collaborative cohort study. IARC Sci Publ 156:69–70

    CAS  PubMed  Google Scholar 

  29. Colditz GA, Hankinson SE (2005) The nurses’ health study: lifestyle and health among women. Nat Rev Cancer 5(5):388–396

    CAS  PubMed  Google Scholar 

  30. Sandler DP, Hodgson ME, Deming-Halverson SL, Juras PS, D’Aloisio AA, Suarez LM, Kleeberger CA, Shore DL, DeRoo LA, Taylor JA et al (2017) The sister study cohort: baseline methods and participant characteristics. Environ Health Perspect 125(12):127003

    PubMed  PubMed Central  Google Scholar 

  31. Rosenberg L, Adams-Campbell L, Palmer JR (1995) The black women’s health study: a follow-up study for causes and preventions of illness. J Am Med Womens Assoc (1972) 50(2):56–58

    CAS  PubMed  Google Scholar 

  32. Milne RL, Fletcher AS, MacInnis RJ, Hodge AM, Hopkins AH, Bassett JK, Bruinsma FJ, Lynch BM, Dugue PA, Jayasekara H et al (2017) Cohort profile: the melbourne collaborative cohort study (health 2020). Int J Epidemiol 46(6):1757–1757i

    CAS  PubMed  Google Scholar 

  33. Greenland S, Pearl J, Robins JM (1999) Causal diagrams for epidemiologic research. Epidemiology 10(1):37–48

    CAS  PubMed  Google Scholar 

  34. Buse A (1982) The likelihood ratio, wald, and lagrange multiplier tests: an expository note. Am Stat 36(3):153–157

    Google Scholar 

  35. Schoenfeld D (1980) Chi-squared goodness-of-fit tests for the proportional hazards regression model. Biometrika 67(1):145–153

    Google Scholar 

  36. Harville DA (1977) Maximum likelihood approaches to variance component estimation and to related problems. J Am Stat Assoc 72(358):320–338

    Google Scholar 

  37. Laird NM, Ware JH (1982) Random-effects models for longitudinal data. Biometrics 38(4):963–974

    CAS  PubMed  Google Scholar 

  38. Smith-Warner SA, Spiegelman D, Ritz J, Albanes D, Beeson WL, Bernstein L, Berrino F, van den Brandt PA, Buring JE, Cho E et al (2006) Methods for pooling results of epidemiologic studies: the pooling project of prospective studies of diet and cancer. Am J Epidemiol 163(11):1053–1064

    PubMed  Google Scholar 

  39. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10(1):101–129

    Google Scholar 

  40. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    CAS  PubMed  Google Scholar 

  41. Higgins J, Thompson S, Deeks J, Altman D (2002) Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice. J Health Serv Res Policy 7(1):51–61

    PubMed  Google Scholar 

  42. Vatten LJ, Romundstad PR, Trichopoulos D, Skjaerven R (2002) Pre-eclampsia in pregnancy and subsequent risk for breast cancer. Br J Cancer 87(9):971–973

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Opdahl S, Romundstad PR, Alsaker MD, Vatten LJ (2012) Hypertensive diseases in pregnancy and breast cancer risk. Br J Cancer 107(1):176–182

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Pacheco NL, Andersen AM, Kamper-Jorgensen M (2015) Preeclampsia and breast cancer: the influence of birth characteristics. Breast 24(5):613–617

    PubMed  Google Scholar 

  45. Schoemaker MJ, Nichols HB, Wright LB, Brook MN, Jones ME, O’Brien KM, Adami HO, Baglietto L, Bernstein L et al Premenopausal Breast Cancer Collaborative (2018) Association of body mass index and age with subsequent breast cancer risk in premenopausal women. JAMA Oncol 4(11):e181771

    PubMed  PubMed Central  Google Scholar 

  46. Levine RJ, Maynard SE, Qian C, Lim K-H, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH et al (2004) Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 350(7):672–683

    CAS  PubMed  Google Scholar 

  47. Valensise H, Vasapollo B, Gagliardi G, Novelli GP (2008) Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease. Hypertension 52(5):873–880

    CAS  PubMed  Google Scholar 

  48. Bertrand KA, O’Brien KM, Wright LB, Palmer JR, Blot WJ, Eliassen AH, Rosenberg L, Sandin S, Tobias D, Weiderpass E et al (2020) Gestational diabetes and risk of breast cancer before after 55. Int J Epidemiol. https://doi.org/10.1093/ije/dyab165

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all study participants, staff, and participating cancer registries. The Nurses' Health Study II thank study participants, staff, and the following state cancer registries: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IA, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The Black Women's Health Study obtained pathology data on breast cancer from state cancer registries in AZ, CA, CO, CT, DE, DC, FL, GA, IL, IN, KY, LA, MD, MA, MI, NJ, NY, NC, OK, PA, SC, TN, TX, and VA. The Melbourne Collaborative Cohort Study cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the Australian Cancer Database. The authors assume full responsibility for analyses and interpretation of these data. They thank the National Cancer Institute Cohort Consortium for facilitating this collaboration.

Funding

Support for this research comes, in part, by the National Institutes of Health (R01CA204258; R01CA058420; U01CA164974; P01CA151135; U01CA176726; UM1CA186107; R01CA50385) and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES044005); the Avon Foundation (02–2014-080); the National Center for Advancing Translational Sciences (KL2-TR001109); the National Program of Cancer Registries of the Centers for Disease Control and Prevention and the Department of Energy; Breast Cancer Now and the United Kingdom National Health Service funding to the Royal Marsden/Institute of Cancer Research National Institute for Health Research Biomedical Research Centre; the Institute of Cancer Research (02–2014-080); Karolinska Institutet Distinguished Professor Award (2368/10–221); VicHealth, Cancer Council Victoria and the Australia National Health and Medical Research Council (209057, 396414, and 1074383); Breast Cancer Research Foundation (17–138); the Swedish Research Council and Swedish Cancer Foundation; The coordination of EPIC (the European Prospective Investigation into Cancer and Nutrition) is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Swedish Cancer Society, Swedish Research Council, and county councils of Skåne and Va¨ sterbotten (Sweden); and grant 14136 to European Prospective Study into Cancer and Nutrition (EPIC)–Norfolk and grants C570/A16491 and C8221/A19170 to EPIC-Oxford from Cancer Research UK and grant 1000143 to EPIC-Norfolk and MR/M012190/1 to EPIC-Oxford from the Medical Research Council (United Kingdom).

Author information

Author notes

  1. Dale P. Sandler, Anthony J. Swerdlow and Minouk J. Schoemaker have contributed equally to this work.

Authors and 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 B. Nichols & Rina Yarosh

  2. Westat, USA

    Melissa G. House

  3. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA

    Sara Mitra

  4. Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, USA

    Mandy Goldberg, Katie M. O’Brien & Dale P. Sandler

  5. Slone Epidemiology Center, Boston University, Boston, USA

    Kimberly A. Bertrand & Julie R. Palmer

  6. Channing Division of Network Medicine, Department of Medicine Brigham and Women’s Hospital and Harvard Medical School, Boston, USA

    A. Heather Eliassen & Walter C. Willett

  7. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA

    A. Heather Eliassen & Walter C. Willett

  8. Cancer Epidemiology Division Cancer Council Victoria, Melbourne, Australia

    Graham G. Giles & Roger L. Milne

  9. Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia

    Graham G. Giles & Roger L. Milne

  10. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia

    Graham G. Giles & Roger L. Milne

  11. Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK

    Michael E. Jones, Anthony J. Swerdlow & Minouk J. Schoemaker

  12. Boston University Chobanian & Avedisian School of Medicine, Boston University, Boston, USA

    Julie R. Palmer

  13. Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Solna, Sweden

    Sven Sandin & Weiyao Yin

  14. Department of Psychiatry Icahn School of Medicine at Mount Sinai, New York, USA

    Sven Sandin

  15. Seaver Autism Center for Research and Treatment at Mount Sinai Icahn School of Medicine at Mount Sinai, New York, USA

    Sven Sandin

  16. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, USA

    Walter C. Willett

  17. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China

    Weiyao Yin

  18. Division of Breast Cancer Research, The Institute of Cancer Research, London, UK

    Anthony J. Swerdlow

  19. Real World Solutions IQVIA, Amsterdam, The Netherlands

    Minouk J. Schoemaker

Authors
  1. Hazel B. Nichols
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Melissa G. House
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rina Yarosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sara Mitra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mandy Goldberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kimberly A. Bertrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Heather Eliassen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Graham G. Giles
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael E. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Roger L. Milne
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Katie M. O’Brien
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Julie R. Palmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Sven Sandin
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Walter C. Willett
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Weiyao Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Dale P. Sandler
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Anthony J. Swerdlow
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Minouk J. Schoemaker
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The work reported in the paper has been performed by the authors, unless clearly specified in the text. HBN, DPS, AJS, and MJS contributed to study conceptualization, methodology, and supervision. HBN and MH conducted the formal analysis. HBN drafted the original manuscript, which was critically reviewed and approved by all authors.

Corresponding author

Correspondence to Hazel B. Nichols.

Ethics declarations

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Individual study protocols were approved by the relevant institutional review boards and obtained informed consent from participants.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file 1 (DOCX 25 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nichols, H.B., House, M.G., Yarosh, R. et al. Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: a premenopausal breast cancer collaborative group analysis. Breast Cancer Res Treat 199, 323–334 (2023). https://doi.org/10.1007/s10549-023-06903-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-023-06903-5

Keywords

Search

Navigation