Exposure to organic solvents and breast cancer in women: a hypothesis

Incidence rates for breast cancer have increased steadily over the last 25 years, particularly among postmenopausal women. Secular changes in accepted and suspected risk factors can explain only a part of this increase. Given the increasing number of women in the workforce, it is possible that increases in breast cancer incidence may be caused by occupational exposure to hazardous agents. In particular, we hypothesize that organic solvents act directly as genotoxic agents or indirectly through their metabolites. Most organic solvents are highly lipophilic and are readily absorbed and distributed throughout the body via the bloodstream. Organic solvents are biotransformed mostly in the liver and the kidneys through a series of oxidative and reductive reactions, some of them resulting in bioactivation. There are indications of P-450 enzymatic oxidative activity in the breast parenchyma, but there appears to be limited detoxification of highly reactive metabolites. The physiology of the breast may also accentuate the accumulation of chemicals: breast parenchyma is embedded in a fat depot capable of storing lipophilic xenobiotics; it is conceivable that organic solvents and their metabolites, once stored in fat tissues, migrate to the breast parenchyma and are then transferred to the mammary lobules through continuous apocrine secretions. These secretions may reside in the ductular system long enough for the solvents and their bioactivated metabolites to locally exert detrimental effects. The evidence supporting this hypothesis is that many organic solvents have been detected in breast milk, the majority of carcinomas occur in the ductular system, and some organic solvents have been shown to produce mammary gland cancer in experiments on rodents. Further toxicological and epidemiologic studies are required to test this hypothesis, to elucidate the mechanisms, and to identify specific carcinogenic organic solvents.