Hormonal factors play a key role in the development of breast cancer, according to background information in the article. Early menarche (first menstruation), late menopause, and long-term use of hormone therapy have been shown to be associated with increased risk of breast cancer. Serum levels of estrogens, progesterone and placental growth hormones are many times higher during pregnancy than during other periods of life, and pregnant women also are exposed to elevated levels of insulin-like growth factors. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. It has been hypothesized that placental weight could be an indirect measure of hormone exposure during pregnancy.
Sven Cnattingius, M.D., Ph.D., of Karolinska Institutet, Stockholm, Sweden, and colleagues investigated the possible associations between indirect markers of hormonal exposures during pregnancy, such as placental weight, offspring's birth weight, pregnancy complications, and subsequent maternal risk of developing breast cancer. The researchers used data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. The study included women in the Sweden Birth Register who delivered single births between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001).
Of 314,019 women in the cohort, 2,216 (0.7 percent) developed breast cancer during the follow-up through 2001, of whom 2,100 (95 percent) were diagnosed before age 50 years. The researchers found that compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies. A high birth weight (4000 g or greater) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates. Compared with women who had a placental weight of less than 500 g, women who had a placental weight of at least 700 g had a 38 percent increase in risk of breast cancer.
"Our finding of a positive association between placental weight and breast cancer risk may reflect that exposures to elevated levels of pregnancy hormones influence the risk of breast cancer. The role of estrogens in breast carcinogenesis is well established, and serum estrogen levels are at least 10 times higher during pregnancy compared with other times of life," the authors write.
"In addition, placental weight appears to be a better indicator of the hormonal milieu than birth weight or other included birth parameters. Underlying biological mechanisms responsible for the observed associations may not only be limited to a direct growth enhancing effect on breast cells during childbearing, but also may be due to maternal characteristics or genetic factors associated with placental growth," the researchers conclude. (JAMA.2005; 294:2474-2480. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: This study was financially supported through a grant from the U.S. Army Breast Cancer Research Program.