Hormone replacement therapy (HRT), breast cancer and tumor pathology

Within an average observation period of 5–6 years, several clinical trials reported an increased risk of breast cancer due to hormone replacement therapy (HRT). However, it remains disputable, whether the increased rate of breast cancers detected within the given time frame is indeed due to newly induced tumors and thus constitutes HRT-initiated primary breast cancers. Onco-pathologically speaking it appears more likely that HRT stimulates the growth of already existing small tumor nests which – due to their small size – would otherwise go undiagnosed. The major arguments are:1.Cancer research has established that malignant tumors, including breast cancer, need an average of 5–10 years to expand from a single malignant cell to a lesion of 5–10 mm diameter. A time period of only 5 years, as covered by the respective studies, may well be too short to permit the detection of tumors primarily induced by HRT.2.This calculation is a worst-case scenario which can only be accurate if the tumor is a fast growing aggressive lesion without cell loss during its progression. Both characteristics are not true for the HRT-associated breast cancer, on the contrary: in the majority of cases the lesions are well differentiated slowly growing tumors.3.With regard to the relatively short period of observation one has to assume that the HRT drugs – a physiological substance in (sub-) physiological doses – would have to transform a normal breast epithelial cell into a malignant tumor cell in the early phase of treatment. There is no plausible explanation for such immediate effects of steroid hormones.4.Both the Women's Health Initiative (WHI) and Million Women Study (MWS) report that the increase of breast cancer cases starts immediately after the initiation of the HRT. If HRT would really instigate de novo breast cancers, the rise in incidences would be expected to occur much later. Yet, the growth rate rapidly declined after HRT was discontinued. This is also remarkable because the curve of normalization would be expected to decrease over a much longer period of time given the unlimited growth potential of malignant cells.In summary, HRT is hence more likely to be a tumor promoter than a de novo-inducer of breast cancers.