Abstract P5-08-27: Treatment patterns and clinical outcomes in patients with hormone receptor (HR)+ HER2+ metastatic breast cancer and low vs high levels of HR positivity from the SystHERs Registry
Authors: Jahanzeb M , Tripathy D , Rugo H , Swain S , Kaufman PA , Mayer M , Hurvitz S , O'Shaughnessy J , Mason G , Yardley DA , Brufsky A , Chu L , Antao V , Beattie M , Yoo B , Cobleigh M 
Published: March 2017

Abstract
Introduction In 2010, the cutoff for HR positivity in breast cancer was established as ≥1% of cells staining HR+, previously having varied from 1% to 10%. The impact of this change on treatment patterns and outcomes is poorly understood. SystHERs is a prospective, observational cohort registry of patients (pts) with HER2+ metastatic breast cancer (MBC) that commenced enrollment in 2012. To our knowledge, SystHERs is the largest registry to collect and analyze data for the HER2+ subgroup. We report baseline characteristics, treatment patterns, and early outcomes by %HR+ (1–9% vs 10–100%).
Methods SystHERs enrolled pts aged ≥18 years and within 6 months of HER2+ MBC diagnosis. For pts with locally-determined HR+ disease, defined as HR+ in primary or metastatic tissue, %HR+ is the highest percentage of ER+ or PR+ tissue in early breast cancer or MBC. The percentage of ER+ or PR+ cells was not reported for pts considered HR– by the investigator. Median overall survival (OS; Kaplan–Meier) and hazard ratios (Cox regression) were estimated.
Results As of Feb 1, 2016, data were available for 872 eligible pts with known HR status, of whom 608 (70%) had HR+ disease. Of the 608 pts, 53 (9%) had 1–9%HR+ and 496 (82%) had 10–100%HR+; %HR+ was not reported for 59 pts. Baseline characteristics were similar between %HR+ subgroups (Table 1).
As shown in Table 2, the 1–9%HR+ subgroup was less likely to receive first-line hormonal therapy (26%) than the 10–100%HR+ subgroup (56%). 87% and 79% of pts received chemotherapy, respectively.
Median time from MBC diagnosis was 16.5 months (range, 0.4–49.4 months). Median OS was not reached at the data cutoff. The number of deaths was 13 (25%) in the 1–9%HR+ subgroup, and 68 (14%) in the 10–100%HR+ subgroup (log-rank P=0.025). The OS hazard ratio (0.514, 95% CI 0.283–0.931) favored the 10–100%HR+ subgroup. OS did not differ significantly between pts with 1–9%HR+ vs HR– disease (log-rank P=0.582, hazard ratio 1.185, 95% CI 0.647–2.169).
Table 1. Baseline characteristics 1-9%HR+ (n=53)10-100%HR+ (n=496)HR– (n=264)Age at MBC diagnosis, median yrs (range)54 (30–86)57 (21–86)55 (28–88)Race, % White838372Black151320Premenopausal, %282522ECOG performance status, % 04654441463942≥2878MBC diagnosis type, % De novo404958Recurrent605142Visceral, %*686275*Non-hepatic abdominal, ascites, CNS, liver, lung, or pleural effusion sites of metastasis
Table 2. First-line treatment 1-9%HR+ (n=53)10-100%HR+ (n=496)HR– (n=264)HER2-targeted therapy, %969391Chemotherapy, %877989Hormonal therapy, %26564
Conclusions These preliminary observational data suggest potential differences in treatment patterns and survival outcomes in low vs moderate/high HR+ expressers, with the former being less likely to receive hormonal therapy (26% vs 56%). Furthermore, low HR positivity was associated with poorer OS and was similar to OS observed in pts with HR– disease.
Citation Format: Jahanzeb M, Tripathy D, Rugo H, Swain S, Kaufman PA, Mayer M, Hurvitz S, O'Shaughnessy J, Mason G, Yardley DA, Brufsky A, Chu L, Antao V, Beattie M, Yoo B, Cobleigh M. Treatment patterns and clinical outcomes in patients with hormone receptor (HR)+ HER2+ metastatic breast cancer and low vs high levels of HR positivity from the SystHERs Registry [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 P5-08-27.