University of Oulu

Katuwal, S., Tapanainen, J.S., Pukkala, E. et al. The effect of length of birth interval on the risk of breast cancer by subtype in grand multiparous women. BMC Cancer 19, 199 (2019).

The effect of length of birth interval on the risk of breast cancer by subtype in grand multiparous women

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Author: Katuwal, Sushmita1; Tapanainen, Juha S.2,3,4; Pukkala, Eero1,5;
Organizations: 1Faculty of Social Sciences, University of Tampere, Kauppi Campus, Arvo Ylpön Street 34, 33520, Tampere, Finland
2Department of Obstetrics and Gynecology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
3Department of Obstetrics and Gynecology, Oulu University Hospital, University of Oulu, Medical Research Center Oulu, Oulu, Finland
4Department of Obstetrics and Gynecology, University of Oulu and Oulu University Hospital, Medical Research Center, PEDEGO Research Unit, Oulu, Finland
5Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
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Language: English
Published: Springer Nature, 2019
Publish Date: 2020-04-09


Background: The length of interval between successive childbirths (birth interval) might influence the incidence of breast cancer, either by stimulating or by inhibiting the factors that are responsible for the initiation of breast cancer or its early development.

Methods: This is a case-control study nested in a cohort of 47,479 Finnish grand-multiparous (GM) women born after 1934, and registered as having had at least five births before 2013. The 1354 women with breast cancer diagnosis were compared with controls (1:5) matched by parity and date of birth of the mother. Conditional logistic regression was used to estimate odds ratios of the risk of ductal and lobular breast cancer subtypes associated with each of the intervals between the 1st and 5th birth, stratified by age at diagnosis. Age at first and last birth before index date were used as covariates.

Results: Increased intervals between the 1st and 5th births were associated with an increased risk of lobular breast cancer. In contrast, regarding ductal cancer, premenopausal women with shorter length of interval (< 2 years) between the 1st and 2nd birth had greater risk and longer intervals (3+ years) were associated with reduced risk. Spacing between the 2nd and 5th birth did not influence the risk of ductal breast cancer.

Conclusion: The findings of our study suggest that the effect of the length of birth interval on breast cancer depends on the age and histology. The protective effect of shorter birth intervals on lobular breast among postmenopausal women and the opposite effect on ductal cancer in premenopausal women may reflect distinct differentiation and functional roles of lobular and ductal cells, and possibly also different response to hormonal exposure.

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Series: BMC cancer
ISSN: 1471-2407
ISSN-E: 1471-2407
ISSN-L: 1471-2407
Volume: 19
Article number: 199
DOI: 10.1186/s12885-019-5404-z
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
3123 Gynaecology and paediatrics
Funding: This study was supported by the grants from Sigrid Jusélius Foundation, the Academy of Finland (295760), and Helsinki University Hospital Funds. The funding body had no role in the design of the study, collection, analysis, and interpretation of the data or in writing the manuscript.
Copyright information: © The Author(s). 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.