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Early-Onset Breast Cancer Possibly Linked to Preeclamptic Pregnancy, High Birth Weight


With little research on the subject, the investigators sought out a connection between certain perinatal factors and risk of young-onset breast cancer in a sister-matched case-control study.

Certain perinatal factors have been shown to possibly exert influence over an increased risk of developing early-onset breast cancer, reported a study published in Breast Cancer Research.

Mother’s preeclampsia in pregnancy, smoking status during pregnancy, gestational hypertension, prenatal diethylstilbestrol (DES) use, gestational diabetes, low birth weight (<5.5 lb), high birth weight (>8.8 lb), short gestational length (<38 weeks), and being breastfed or fed soy formula were the outcome variables evaluated. All factors were self-reported.

Gestational diabetes status was ultimately excluded from the final analysis because so few of the women reported it, the authors noted.

Initial estimates showed positive associations between short gestational length (odds ratio [OR], 1.26; 95% CI, 0.83-1.92) and having smoked during pregnancy (OR, 1.19; 95% CI, 0.81-1.74) with greater risk for early-onset breast cancer. However, the results of conditional logistic regression analyses show that the following factors were associated with an overall higher risk of developing young-onset breast cancer:

  • High birth weight (OR, 1.59; 95% CI, 1.07-2.36)
  • Preeclampsia (adjusted OR, 1.92; 95% CI, 0.82-4.51)

For preeclampsia especially, the link was even stronger in women who went on to develop invasive breast cancer (OR, 2.87; 95% CI, 1.08-7.59).

Patients enrolled in this trial (n = 1759), The Two Sister Study, between 2008 and 2010 had either ductal carcinoma in situ or invasive breast cancer diagnosed before age 50 and within the past 4 years. Their mean (SD) age at diagnosis was 45.0 (3.9) years. They also had to have 1 or more sisters without the disease.

The control group (n = 1672) consisted of their sisters, enrolled between 2003 and 2009 who were case-matched with no history of breast cancer up to the age of their sister’s diagnosis. Their mean (SD) age at their sister’s diagnosis was 46.3 (6.0) years.

Both groups of sisters received the same computer-assisted telephone interviews on their disease status. All also had to give their consent for medical record and pathology report retrieval. Most diagnoses (88.7%) were confirmed by this information.

The authors also carried out case-only analyses to determine a possible causal link from being born to a mother with a preeclamptic pregnancy, and they determined that these women with young-onset breast cancer had a higher risk of estrogen receptor (ER)-negative disease (OR, 2.27; 95% CI, 1.05-4.92). Also, the risk of ER-positive disease persisted for women born with a high birth weight (OR, 1.68; 95% CI, 1.07-2.62).

These odds were reduced for high birth weight (OR, 0.64; 95% CI, 0.35-1.17), and near-null associations were shown between ER-negative tumors and prenatal exposure to DES (OR, 0.91; 95% CI, 0.38-2.21) and smoking during pregnancy (OR, 1.08; 95% CI, 0.81-1.45).

Additional results show:

  • More of the case group were born at less than 38 weeks vs their sisters: 15.2% vs 11.5%
  • There was a lower risk of breast cancer from prenatal exposure to DES (OR, 0.82; 95% CI, 0.44-1.54) and having been breastfed (OR, 0.76; 95% CI, 0.58-1.00)
  • Getting soy formula (OR, 1.04; 95% CI, 0.66-1.65) and being of a low birth weight (OR, 1.05; 95% CI, 0.70-1.59) were not associated with greater early-onset breast cancer risk

“These results provide indirect support for the hypothesis that prenatal exposures affect the subsequent risk of breast cancer in young women,” they concluded. “Future epidemiological research on the connection between maternal hypertensive disorders, birth weight, and young-onset breast cancer is warranted to help us gain a better understanding of the etiology of the disease."


Diaz-Santana MV, O’Brien KM, D’Aloisio AA, Regalado G, Sandler DP, Weinberg CR. Perinatal and postnatal exposures and risk of young-onset breast cancer. Breast Cancer Res. Published online August 13, 2020. doi:10.1186/s13058-020-01317-3

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