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

Background An increased risk for breast cancer (BC) following hormone replacement therapy (HT) with estrogen and progesterone in women has been reported in several studies. However, HTs are associated with two distinct effects, a BC risk (RF) and an acceleration of BC growth (GAF). The interaction of both effects is analyzed. Methods Using data from the U.S. population on BC incidence and life expectancy specific cohorts and their disease trajectories are modelled. First, age-specific BCs are randomly generated for the age interval 50-80 years based on public data. Second, this simulated cohort subsequently receives a HT over 4 years that accelerates the growth of prevalent BCs. In a third cohort additional BCs are simulated caused by HT under treatment. The cumulative incidence of BCs is modelled for up to 30 years using different assumptions on BC growth duration, GAF and RF, as well as the duration of HT. The Women’s Health Initiative Study (WHI-S) is also simulated in a fourth cohort assuming a GAF 1.4 and RF 2.0. Results Studies modelling the risk of BC after HT imply two main findings: First, the growth of prevalent BCs is accelerated in parallel to the start of HT. This results in an increased BC incidence where the relative risk is equivalent to the GAF. The duration of HT defines the turning point of this increase. The second finding demonstrates that during the 15 years of BC growth an inherent RF for BC through HTs becomes observable only after a comparable delay. The combined effect results in an overlap of age-specific BCs, which develop at the same time, both growing faster under HT. Varying parameters can explain different results in the WHI-S. According to the WHI almost 6 million women decided to discontinue or not to start HT. This offers a valid explanation (assuming a GAF 2) for the 10% decline in incidence around 2002. Estimates which report one million additional BCs associated with HT in Western countries since 1990 can thus, for the most part, be attributed to more rapidly growing prevalent BCs. Conclusion HT accelerates the growth of prevalent BCs and can also cause BCs which become symptomatic after 10 or more years. In combination these effects increase BC incidence. Differentiated information on these inherent risks and benefits should support shared decision-making for HT.