Abstract
BackgroundThe 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.MethodsThis 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.ResultsIncreased 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.ConclusionThe 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.
Highlights
The length of interval between successive childbirths 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
Overall, 76% of women with ductal breast cancer subtype and 86% of women with lobular breast cancer subtype in our study were diagnosed at the age 50 years or above (Table 1)
The women with different breast cancer subtypes were similar in terms of average age at 1st birth (22.0 years for ductal breast cancer group and 22.8 years in the lobular breast cancer group), and age at 5th birth (33.6 and 34.8 years for ductal and lobular breast cancer groups, respectively)
Summary
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. Age at first birth and the number of pregnancies are well-known risk factors of breast cancer [1,2,3,4,5,6], and each pregnancy after the first one induces an additional long-lasting risk reduction until the eighth pregnancy (6). Pregnancies have dual effects on breast cancer: the long-lasting protective effect of a pregnancy at a young age is preceded by a transient increase in risk (up to 3–10 years) after the birth [2, 4,5,6,7]. A Reproductive events and their timing can affect breast tissue differentiation through hormonal mechanisms [8,9,10,11].
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