By Tarja I Kinnunen; Riitta Luoto; Mika Gissler; Elina Hemminki; Leena Hilakivi-Clarke
Abstract and Introduction
Abstract
Background: Elevated pregnancy estrogen levels are associated with increased risk of developing breast cancer in mothers. We studied whether pregnancy weight gain that has been linked to high circulating estrogen levels, affects a mother’s breast cancer risk.
Methods: Our cohort consisted of women who were pregnant between 1954-1963 in Helsinki, Finland, 2,089 of which were eligible for the study. Pregnancy data were collected from patient records of maternity centers. 123 subsequent breast cancer cases were identified through a record linkage to the Finnish Cancer Registry, and the mean age at diagnosis was 56 years (range 35 – 74). A sample of 979 women (123 cases, 856 controls) from the cohort was linked to the Hospital Inpatient Registry to obtain information on the women’s stay in hospitals.
Results: Mothers in the upper tertile of pregnancy weight gain (>15 kg) had a 1.62-fold (95% CI 1.03-2.53) higher breast cancer risk than mothers who gained the recommended amount (the middle tertile, mean: 12.9 kg, range 11-15 kg), after adjusting for mother’s age at menarche, age at first birth, age at index pregnancy, parity at the index birth, and body mass index (BMI) before the index pregnancy. In a separate nested case-control study (n = 65 cases and 431 controls), adjustment for BMI at the time of breast cancer diagnosis did not modify the findings.
Conclusions: Our study suggests that high pregnancy weight gain increases later breast cancer risk, independently from body weight at the time of diagnosis.
Background
Sensitivity of the breast to hormones and environmental exposures varies throughout a woman’s life span.[1] During pregnancy, the breast undergoes extensive changes in preparation for lactation. High estrogenicity during pregnancy causes marked cellular proliferation, in both in the normal and tumor cells. Normal breast cells differentiate to milk-secreting alveoli, while tumor cells, if present, continue to multiple and eventually form a detectable tumor. These two events probably explain the dual effect of pregnancy on breast cancer risk: pregnancy before age 20 reduces, whereas first pregnancy after age 30 increases, breast cancer risk.[2] In young women, pregnancy may eliminate future targets for neoplastic changes by differentiating target cells;[3] the breast tissue of older first time mothers is more likely to have acquired malignant cells that are stimulated by high pregnancy hormonal environment.
Women whose pregnancy estrogen levels are elevated are at an increased risk of breast cancer. For example, women who took the synthetic estrogen diethylstilbestrol (DES) during pregnancy are at an increased risk of developing breast cancer,[4] as are women who suffered from severe pregnancy nausea[5] or who gave birth to heavy newborns.[6] Both nausea in pregnancy and high birth weight are linked to elevated pregnancy estrogen levels.[7,8] Conversely, pregnant women having high alpha feto-albumin levels,[9,10] or suffering from hypertension or pre-eclampsia,[11,12] exhibit a reduced risk. Alpha feto-protein has direct antiestrogenic activity and binds estrogens, reducing their biological availability.[13,14] Hypertension during pregnancy is linked to reduced estrogen and increased testosterone levels.[15] A recent study in which estrogen levels were measured in stored blood samples of pregnant women later diagnosed with breast cancer, provides direct evidence in support of high estrogen and low progesterone levels in increasing maternal breast cancer risk.[16] However, some studies have failed to find an association between pregnancy estrogen levels, determined indirectly, and maternal breast cancer risk.[11,17]
Adipose tissue aromatizes androgens to estrogens, and thus high body mass index (BMI) is linked to elevated estrogen levels in postmenopausal women.[18] Some studies suggest that high pregnancy weight gain may be associated with increased pregnancy estrogen levels,[19] although this has not been confirmed in more recent studies.[20,21] The goal of this study was to determine whether high pregnancy weight gain affects breast cancer risk.
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Section 1 of 4 Next Page: Methods
Tarja I Kinnunen,1, 2 Riitta Luoto,1, 2 Mika Gissler,3 Elina Hemminki,3 and Leena Hilakivi-Clarke,4
1Tampere School of Public Health, 33014 University of Tampere, Finland; 2UKK Institute, PL 30, 33501 Tampere, Finland; 3National Research and Development Centre for Welfare and Health, PL 220, 00531 Helsinki, Finland; 4Lombardi Cancer Center and Department of Oncology, Georgetown University, 3970 Reservoir Rd, NW, Washington, DC 20057, USA
Competing Interests: The author(s) declare that they have no competing interests.
Authors’ Contributions: TK: PhD student who collected and put together all the material for the study, managed the data and did statistical analysis, and participated in writing the manuscript.
MG: Participated in statistical analysis of the data and writing the manuscript.
EH: Collected the original data base of pregnant women and was in charge of linking the data base to cancer registry, participated in statistical analysis planning and writing the manuscript.
RL: Generated the idea of testing the hypothesis in the Hemminki data base, and participated in all stages of the study and in writing the manuscript.
LH-C: Generated the hypothesis, obtained funding for the study, and was in charge of writing the manuscript.
