AACR: High Levels of Pregnancy Hormones Linked to Increased Risk of HR-Negative Breast Cancer
Specifically, increased concentrations of estradiol, estrone, and progesterone—circulating concentrations of which rise as pregnancy progresses—were associated with greater risk of maternal hormone-receptor (HR)-negative breast cancer diagnosed before the age of 50 years, Annekatrin Lukanova, MD, PhD, of the German Cancer Research Center, Heidelberg, Germany, and colleagues noted.
“For hormones with similar concentrations during early pregnancy and in the non-pregnant state (testosterone and insulin-like growth factor I [IGF-I]), direct associations with HR-positive breast cancer were observed, in line with most available epidemiological data in non-pregnant women,” she noted.
The study, nested within the Northern Sweden Maternity Cohort, included 417 controls and 223 women who had donated blood samples during their first trimester of pregnancy and were later diagnosed with breast cancer. Estradiol, estrone, progesterone, and testosterone were measured by high-performance liquid chromatography tandem mass spectrometry. Sex hormone-binding globulin (SHBG) and IGF-I were measured by immunoassays.
The majority of cases had HR-positive disease: 171 (77%) were estrogen receptor-positive (ER+), 157 (70%) were progesterone receptor-positive (PR+) and 152 (68%) had ER+/PR+ tumors. For HR-positive tumors, a significant direct association was observed with circulating concentrations of testosterone (OR for ER+ in the top vs bottom tertile 1.8; 95% CI 1.1–3.0; P<0.02) and IGF-I (OR 2.0; 95% CI 1.2–3.3; P<0.01). For HR-negative disease, risk estimates did not reach statistical significance, with the exception of progesterone for PR-negative tumors (OR 2.0; 95% CI 1.0–3.9; P<0.04).
In analyses limited to ER-negative tumors diagnosed up to age 50 years (n=38), the associations were stronger, “but only of borderline significance,” Dr. Lukanova noted. For PR-negative tumors diagnosed up to age 50 years (n=49), the associations were significant for estradiol (OR 1.8; 95% CI 1.0–3.1; P<0.04), progesterone (OR 2.6; 95% CI 1.1–6.1; P<0.03) and SHBG (OR 1.8; 95% CI 1.0–3.0; P<0.04).
“Adjustments for maternal height, weight, smoking, hypertension during pregnancy, child's sex, weight and length had negligible effect on risk estimates,” she stated.
Noting this study was small and the hormones were measured only during the first trimester of pregnancy, “larger studies are necessary to characterize the association of pregnancy hormones with risk of hormone-defined maternal breast cancer,” she concluded.