Teens Having a Cow: Red Meat and Breast Cancer
Abstract & Commentary
By Russell H. Greenfield, MD. Dr. Greenfield is Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, and Visiting Professor, University of Arizona, College of Medicine, Tucson; he reports no financial relationship relevant to this field of study.
Source: Linos E, at al. Red meat consumption during adolescence among premenopausal women and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2008;17:2146-2151.
Concerns have long been raised about an association between animal protein intake, specifically red meat, and risk of breast cancer. Red meat consumption during early adulthood has been associated with an increased risk of premenopausal breast cancer, while data for postmenopausal breast cancer risk are less consistent. This study focused on the dietary habits of adolescents, both because there is a paucity of data on this group and later risk of breast cancer, and because some experts believe adolescence may be a period of increased susceptibility to environmental factors leading to later development of breast cancer due to the regular occurrence of undifferentiated cell division until first pregnancy.
The authors of this prospective cohort trial (part of the Nurses' Health Study II, NHS II) had access to information supplied by more than 39,000 women aged 25-43 years in 1989, who in 1998 (mean age, 44 years) completed a validated food frequency questionnaire (FFQ) on their diet during high school. The FFQ assessing dietary habits during high school was completed in 1998, and specifically included reference to foods commonly available from 1960 to 1980. Subjects were followed for seven years or until either a diagnosis of breast cancer was made or death occurred. Specific nutrient and caloric intakes were calculated, as were breast cancer rates.
At trial's end the researchers identified a total of 455 cases of invasive premenopausal breast cancer from the cohort. Subjects who ate the most red meat during high school had a significantly increased risk of breast cancer (relative risk = 1.34) in energy-adjusted and multivariate-adjusted models compared with those who ate the least red meat during adolescence. This association persisted after adjustment for intake of heme iron and animal fat. Risk of breast cancer increased 20% for every 100 g of red meat ingested daily, with the association being slightly stronger for ER- and PR-positive tumors. In contrast, no association between breast cancer risk and red meat consumption was identified for red meat intake during adulthood. As regards types of red meat and breast cancer risk, the association was greatest for frequent consumption of hot dogs. A borderline significant association was also identified for consumption of processed meat.
The researchers conclude that high levels of red meat intake during the teenage years may increase the risk of premenopausal breast cancer by 30-40%.
Recent years have seen a greater degree of attention being paid to early life exposures and later risk of cancer, with data accumulating that raise the specter of windows of significant susceptibility. The conclusions of the current study are extremely concerning, but at least one shortcoming impacts the reliability of their findings, that being the potential for recall bias. The authors used a validated and reproducible retrospective questionnaire, and even contacted participants' mothers where available, but subjects still had to try to recreate their diets from 16 to 35 years past. In addition, only half the available cohort completed the questionnaire. Significant flaws aside, the findings merit our attention because the methodological strengths of the trial outweigh its weaknesses. The prospective nature of the investigation, its large sample size and high compliance rate, and multivariate modeling make for an impressive work.
Diet is one of the few potentially modifiable risk factors for cancer, and data like these help us shape the recommendations for our young patients and their parents. As the authors note, possible ways that regular red meat intake might promote carcinogenesis include increased iron load (animal data suggest that dietary iron may increase estrogen carcinogenicity), increased exposure to hormones used in the raising of cattle, and increased risk with select methods of preparation (e.g., formation of heterocyclic amines at high temperatures, which are estrogenic in vitro). We do not yet know the exact times of increased susceptibility if present, nor exactly to which agents people may be sensitive, but in light of the risk associated with regular hot dog intake, one area of investigation should be the processing of meats and associated physiologic effects after ingestion. Until more data are available, it seems prudent to recommend that young girls be exposed to red meat products less often than they typically are now.