Abstract PD6-08: PD6-08 Mortality risks over 20 years in men with stage I-III hormone receptor-positive breast cancer
Authors: Leone Julieta , Hassett Michael J. , Freedman Rachel , Tolaney Sara , Graham Noah , Tayob Nabihah , Vallejo Carlos T. , Winer Eric , Lin Nancy U. , Leone Jose P. 
Published: March 2023

Abstract
Background: In women with hormone receptor-positive (HR+) breast cancer, the risk of distant recurrence and death persists for at least 20 years (y) from diagnosis. The risk of late mortality in men with HR+ breast cancer has not been reported. The aims of this study were to evaluate long-term risks of breast cancer-specific mortality (BCSM) and non-BCSM in men with stage I-III HR+ breast cancer. In addition, we aimed to identify factors associated with late deaths from breast cancer in men.
Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program, we identified men diagnosed with stage I-III HR+ breast cancer between 1990-2008. We used cumulative incidence function to estimate the effect of baseline clinical and pathologic variables including age at diagnosis, stage, tumor size (T), nodal status (N), and tumor grade, on cumulative risks of BCSM and non-BCSM over time. We estimated annual rate of events per 100 person-years. We plotted smoothed hazard estimates over time for BCSM by stage and nodal status. Fine and Gray multivariable regression was used to evaluate the association of pre-selected variables with BCSM, conditional on having survived 5 y.
Results: We included 2,836 patients (pts) with a median follow-up of 15.41 y. Median age at diagnosis was 67 y (IQR 57-76 y). Stage distribution was: 34.5% stage I, 46% stage II, and 19.5% stage III. The table shows risks of BCSM and non-BCSM and annual event rates by stage, N status, and grade. The cumulative risk of BCSM in y 0-20 was 12.4% for stage I, 26.2% for stage II and 46.0% for stage III. In contrast, the cumulative risk of non-BCSM over the same period ranged from 42.8% in stage III to 52.4% in stage I. Of all BCSM events, the proportion that occurred 0-&lt; 5y, 5-&lt; 10y and ≥10y was: For stage I 22.55%, 50% and 27.45%; For stage II 37.58%, 38.93% and 23.49%, For stage III 49.15%, 31.62% and 19.23%; respectively (p&lt; 0.001). Among pts with stage II breast cancer, we observed a peak in the risk of BCSM at 6 y with a hazard rate of 3%, followed by a minimal decline in risk thereafter. However, among pts with stage III (n=554), and those with N3 (n=160), we observed a risk of BCSM that peaked first at 4-5 y (hazard rates: 6.3% and 9.9% for stage III and N3, respectively) followed by a small decline and then peaked again at 11-12 y (hazard rates: 7.5% and 12.7% for stage III and N3, respectively). In adjusted Fine and Gray regression conditional on having survived 5 y, risks of BCSM were higher for pts aged &lt; 50 y vs &gt;64 y (Hazard ratio [HzR] 1.59; 95% CI, [1.17 – 2.16]), grade III/IV vs grade I (HzR 1.85; 95% CI, [1.22 – 2.79]), and stage III vs stage I (HzR 3.93; 95% CI, [2.93 – 5.26]).
Conclusions: In HR+ male breast cancer, risks of BCSM persist for at least 20 y after diagnosis and depend on traditional clinicopathologic factors such as age, tumor stage and tumor grade. Among the relatively small group of men with higher stages of disease, we observed a prolonged risk of BCSM with an early and late peak, which is different from the risk that is reported in women (Leone JP, BCRT 2021). Whether the observed trends in hazards over time reflect biologic differences in tumor characteristics, tumor dormancy, and/or host factors between male and female breast cancer cannot be elucidated from these data. Better adjuvant therapies are warranted to reduce early and late BCSM risks.
Risks of BCSM, non-BCSM and annual event rates in men with stage I-III hormone receptor-positive breast cancer
Citation Format: Julieta Leone, Michael J. Hassett, Rachel Freedman, Sara Tolaney, Noah Graham, Nabihah Tayob, Carlos T. Vallejo, Eric Winer, Nancy U. Lin, Jose P. Leone. PD6-08 Mortality risks over 20 years in men with stage I-III hormone receptor-positive breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-08.