One effect and two causes: Growth acceleration and breast cancer risk after hormone replacement therapy

BackgroundHormone replacement therapy (HRT) is currently linked to increased breast cancer (BC) diagnoses. While this appears paradox to an estimated 15-year development period of hormone receptor-positive BC, the discrepancy can be explained if HRT has two effects. MethodsWe modelled cohorts of 100,000 women using two parameters: HRT caused accelerated tumour growth and increased incidence. A reference cohort used age-specific incidence, a 15-year growth period, and life expectancy. Treatment cohorts with faster growth and higher incidence were simulated over 30 years. Study endpoints were cumulative and annual BC incidence. Using data from the Womens Health Initiative (WHI), we estimated the factors that reproduce the WHI long-term outcomes. ResultsThe data indicate that HRT accelerates the growth of previously undetected BC, causing them to appear as seemingly new cases. The timing and duration of HRT determine when this rise occurs. After roughly 15 years of tumour development, an inherent HRT-related risk becomes apparent and overlaps with the expected baseline risk of aging women. The WHI results were reproduced with a growth acceleration factor of 1.4 and an initiation risk factor of 2, consistent with an approximate 10% drop in BC incidence in the United States around 2002 following reduced HRT use. ConclusionEstimates of about one million additional HRT-associated BCs may largely reflect accelerated growth of pre-existing BCs. Risk-adapted screening strategies could diagnosis newly initiated tumours early. By communicating these short- and long-term effects of HRT on cancer risk patients and physicians could make an informed decision on the risks and benefits of HRT-use.