Abstract P2-06-07: Risk of metastases after ipsilateral breast tumour recurrence changes overtime according to patient and tumour characteristics: Implications for treatment
Authors: Gennaro M , Di Cosimo S , Ardoino I , Veneroni S , Mariani L , de Braud F , Daidone MG , Biganzoli E , Demicheli R 
Published: March 2017

Abstract
To evaluate the risk of systemic disease of early breast cancer (EBC) patients undergoing breast conservative surgery between 1970 - 2000 and experiencing ipsilateral breast tumour recurrence (IBTR). Patients and Methods The study population included EBC patients randomly assigned onto 5 Milan prospective trials (n= 915) or comparably treated outside clinical trials (n= 1060) with quadrantectomy followed by radiotherapy and with known primary tumor characteristics. Multivariable regression analysis was performed via the piecewise exponential. The model accounts other than known prognostic factors, including age, menopausal status, pathologic size, nodal status and time dependent effect for estrogen receptor (ER) for the IBTR occurrence as time dependent covariate (i.e. switching from 0 to 1 at the time of surgery for IBTR). Also the new time scale induced by IBTR occurrence, namely time elapsed since surgery for IBTR to the end-point of interest, was accounted for in the model.
Results Median follow-up was 124 months (IQ Range 96.6 – 179). At the time of analysis, 504 patients were died, 470 presented with systemic disease and 150 with IBTR as first breast cancer event. IBTR was associated with a high risk of systemic disease. This risk was dependent on primary tumor characteristics, including T size, 2 versus 1 (HR 1.79 95% CI 1.46 – 2.21), and nodal status, N1 versus N0 (HR 1.61, 95% CI 1.32 – 1.98), and N2 versus N0 (HR 3.91, 95% CI 3.13 – 4.89). Of note, ER-negative cohort had a slightly earlier and higher hazard of events overtime compared with ER-positive cohort, which, instead, presented higher hazard estimates over the long follow-up period. The most important finding concerned the new timescale induced by IBTR occurrence that revealed to have definite prognostic value, and suggest that patients with IBTR as compared with patients with no IBTR have a sudden and at least 5-fold increase of risk of systemic disease within 2 years following second surgery; of note, this risk decreases thereafter, though it never desappears. Conclusion Breast cancer patients experiencing IBTR are at increased risk of systemic disease. This risk changes overtime and is different according to initial patient and primary tumor characteristics, and hormonal receptor status. The definition of different patterns of BC recurrence can improve BC care through surveillance guidelines and can guide the design of tailored clinical studies.
Citation Format: Gennaro M, Di Cosimo S, Ardoino I, Veneroni S, Mariani L, de Braud F, Daidone MG, Biganzoli E, Demicheli R. Risk of metastases after ipsilateral breast tumour recurrence changes overtime according to patient and tumour characteristics: Implications for treatment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-06-07.