Pregnancy weight gain and breast cancer risk
BMC Women's Health
Pregnancy weight gain and breast cancer risk
Tarja I Kinnunen 1 2
Riitta Luoto 1 2
Mika Gissler 0
Elina Hemminki 0
Leena Hilakivi-Clarke 3
0 National Research and Development Centre for Welfare and Health , PL 220, 00531 Helsinki , Finland
1 UKK Institute , PL 30, 33501 Tampere , Finland
2 Tampere School of Public Health, 33014 University of Tampere , Finland
3 Lombardi Cancer Center and Department of Oncology, Georgetown University , 3970 Reservoir Rd, NW, Washington, DC 20057 , USA
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
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.
Methods
The cohort
The study population was a historic cohort of women
pregnant between 1954 and 1963 in Helsinki, Finland (n
= 4,090). The cohort was a sample gathered for a study on
hormone exposure, including 2,022 exposed, 2,062
controls and 6 women with unknown hormone exposure
status. Information on the cohort was collected from the
maternity cards of municipal maternity centers, wh (...truncated)