Sasco, AJ. 2001. Epidemiology of breast cancer: an environmental disease? APMIS 109:321-32.

[mixtures severely constrain current epidemiological studies]

Sasco reviews studies through 2001 on the human epidemiology of breast cancer. Her main points:

  • Breast cancer is the commonest cancer in women in the world, in both industrialized and developing countries. In 1999, 467,000 women's deaths were attributed to breast cancer (1.7% of all female deaths).
  • Breast cancer incidence rates are increasing in many countries, although mortality rates are stable or slightly declining in some.
       
  • Countries vary significantly. Rates are high in North America, North Europe and Oceania; intermediate rates in Central and South America, and South and East Europe; low rates in Africa and Asia.
  • Only a small portion of breast cancer cases can be explained by known risk factors.
  • Sasco writes in her concluding remarks that "there is a crucial need to better define time windows of exposure. Vulnerability periods correspond to in utero life, as well as prepubertal period both for girls and boys. In women, perimenopause may also be particularly relevant." A number of studies indicate that conditions in utero can influence the risk of breast cancer later in life. These include work on twins, which concludes that breast cancer risk may be affected both by the type of twinning (identical vs. fraternal) and the sex of the fraternal twin.
  • Identified risk factors include:
 

Family history (genetics). Identified gene mutations represent a tiny fraction of all breast cancers, "much less than 10% overall." But if present, they "confer considerable life-time risk ... compared to the general population."

Reproductive and hormonal life, e.g., early menarche, not having been pregnant or late age at first birth, late menopause, hormonal factors such as high levels of free estrogen; long-term use of oral contraceptives or menopausal hormone replacement, or other factors that increase life-time exposure to estrogen. "Risk of cancer is influenced by the endogenous hormonal mileau."

Lifestyle, particularly diet. "High intake of fruits and vegetables is probably associated with a slightly reduced risk of breast cancer." Rapid growth and/or high body mass are risk factors, thought to be related to high total caloric intake, particularly if not balanced by caloric expenditure. Meat consumption is possibly associated with an increased risk, as is alcohol consumption. The impact of tobacco smoke is even less clear. Most studies examining physical activity indicate a slight reduction in risk with more activity.

Exposures. "Only limited data are available on specific exposures in relation to breast cancer." Studies of the aftermath of atomic explosions in Japan reveal an increased risk of breast cancer, "particularly for women having been exposed around puberty." A few studies show elevated risk in relation to exposure to electromagnetic fields. With respect to chemicals, "Suggestive associations were found for styrene, several organic solvents, such as methylene chloride, carbon tetrachloride, formaldehyde, as well as for several metals, metal oxides and acid mists." But some surprisingly, "systematic reviews on occupation and breast cancer are stil few and much work remains to be done. Little evidence is available on virus exposures, although in mice a virus is a recognized cause that is transmitted from mother to daughters via milk.

Hormones and endocrine disruptors. Because of the established role of life-time estrogen levels as a breast cancer risk factor, considerable attention has been paid to possible impacts of exogenous estrogens on risk. Long-term use of oral contraceptives is associated with a small increase in risk.

Studies of organochlorines show contradictory results. Older studies of PCBs and DDE found higher levels in breast-cancer patients than controls, but newer, larger studies contradict this (see also Gammon et al 2002, published since Sasco wrote her review). It is important to note (which Sasco does not, that the persistent PCBs and DDE measured in these studies are not xenoestrogens, but instead anti-estrogens and anti-androgens, respectively. Thus negative findings with them are irrelevant to the hypothesis that xenoestrogens elevate breast cancer risk. More...

Another organochlorine, dieldrin, is associated with an increase in risk and an increased breast cancer mortality rate once diagnosed.