Incidence and temporal patterns of true recurrences and second primaries in women with breast cancer: a 10-year competing risk-adjusted analysis

Abstract

Abstract Background The data available regarding the risk and timing of true breast cancer (BC) recurrences and second primaries are limited. Methods We carried out a one-time, detailed manual review of multiple medical charts of 1988 eligible BC patients from the Emilia-Romagna Cancer Registry (northern Italy) (2000-2013). The occurrence and timing of all types of first true recurrences (TRs, including local, regional and distant recurrences) and second BCs (SBCs, including ipsilateral SBC and contralateral SBC) during 10 years of follow-up were evaluated. The types of recurrences were defined according to the Maastricht Delphi consensus. A competing risk-adjusted analysis was performed. The median recurrence-free interval, the smoothed subhazard functions, the subhazards (actuarial life table approach) and the cumulative incidence function of follow-up events were estimated. Prognostic factors for TRs and SBCs were identified using the Fine and Gray model. The observed total number of BC episodes was compared with the expected number of BCs based on registered incidence rates in the general population with the calculation of the age-standardised incidence ratio. Results The median time to detection was 3.4 years for TRs versus 5.1 years for SBCs. The risk of total TRs had two peaks, one between the 2nd and the 3rd year of follow-up and another, of smaller size, between the 7th and the 8th year. The subhazard of SBCs fluctuated for 5 years, had a drop between the 6th and the 7th year and a marked peak between the 8th and the 9th. Prognostic factors for TRs included tumour stage, tumour grade, lymph node status and residual disease. Factors associated with the risk of SBCs included patient age and hormone therapy (inverse association). The excess incidence of total BC episodes as compared with the expected incidence of BC was huge in the first two years and no longer significant in the 9th/10th year. Conclusions The novel and multifaceted evidence provided by this study warrants further research into the risk and timing of all types of recurrences during the follow-up of primary BC.