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

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.

Prospective Study on Physical Activity and Risk of In Situ Breast Cancer

“…Postmenopausal women who are physically active in comparison with inactive women may have lower concentrations of serum estrone, estradiol, and androgens (34,35) and higher sex hormone-binding globulin (36). Furthermore, substantial epidemiologic, clinical, and experimental evidence has clearly established a late-stage growth promoting effect of estrogens (37), which would be in line with our findings.…”

MDM2 SNP309 Accelerates Tumor Formation in a Gender-Specific and Hormone-Dependent Manner

“…Estrogen signaling manipulation has been shown to alter both cancer incidence and progression (42)(43)(44). This study suggests that women with a G/G genotype for SNP309 could be affected differently by estrogen signaling manipulation than women with a T/T genotype.…”

Reduction in hormone replacement therapy use and declining breast cancer incidence in the Belgian province of Limburg

“…This suggests that exogenous hormones stimulate growth of occult tumours rather than act as initiators of carcinogenesis [33]. Biologically, it seems indeed that exogenous hormones do not induce malignant tumours de novo, but accelerates the growth of already existing tumour cells [34]. In another study the decrease in proliferation was limited to ER-positive, but not ER-negative tumours upon withdrawal of HRT, and this within a month after stopping [35].…”