Hormone replacement therapy: pathobiological aspects of hormone-sensitive cancers in women relevant to epidemiological studies on HRT: a mini-review

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Abstract
Hormone replacement therapy (HRT) has gained widespread and in some areas indiscriminate use. In reference to recent epidemiological studies which showed unexpected and controversial associations of HRT use with malignant tumours, here we review the current understanding of the dynamics of tumour growth. The pathomorphological characteristics and sex hormone sensitivity of cancers of the breast, endometrium, ovary and colon are discussed. The development of cancer from the first malignant tumour cell to clinical diagnosis takes many years. Hormones can influence tumour growth, but it is questionable whether hormones induce malignant tumours de novo. It is much more likely that hormones ‘merely’ promote the growth of already existing tumour cells. The long developmental process of tumours is in apparent contradiction to results of some epidemiological studies that describe an increased cancer risk, implying primary initiation, in HRT users within observation periods of 1–6 years. The mechanisms of initiation versus promotion of hormone-sensitive cancers, particularly breast cancer, are only partly understood. The conventional methods of epidemiological studies cannot detect potential risk factors without bias if they do not include a pathomorphological component on growth characteristics. The results of previous studies should be interpreted with great caution with regard to tumour biology.