Abstract P6-08-40: Survival of metastatic hormone receptor (HR) positive/HER2 negative; HER2+; and triple negative (TN) breast cancer based on initial presentation
Authors: den Brok Wendie-Lou D , Speers Caroline , Lovedeep Gondara , Baxter Emily , Tyldesley Scott , Caroline Lohrisch 
Published: May 2015

Abstract
Introduction: Median overall survival (OS) for patients (pts) with metastatic breast cancer (MBC) is described as 2-3 years, but few reports compare OS for de novo versus relapsed disease. The recognized clinical subtypes of breast cancer (HR positive[+] /HER2 negative; HER2+; TN) are known to have variable OS clinically, but this has not been systematically documented. We hypothesized that pts relapsing from a non MBC stage (relapsed) might have different OS than those presenting initially with metastases (de novo), and that OS would differ for the three clinical biomarker subgroups.
Methods: Using the Breast Cancer Outcomes Unit database, we identified all women diagnosed with MBC, de novo or relapsed, in British Columbia between 01/2001 and 12/2009 and referred to the BC Cancer Agency. Review of medical records confirmed ER, PR and HER2 status. Survival from MBC diagnosis was calculated for relapsed vs de novo in the three biomarker subgroups.
Results: After excluding pts with a synchronous or prior contralateral disease, we identified 3645 women with known ER. Median follow up was 91 months. HER2 known (n=3010) and unknown (n=635, 17%) cases had the same median OS (17 months [m]) and HR status (72% ER+). Trastuzumab (T) was standard in MBC during this era, but fewer than 10% had adjuvant T (introduced mid 2005) which explains the high number of HER2+ MBC cases. We previously reported longer OS for HER2+ disease relapsing after adjuvant therapy without T (older cohort) than after adjuvant T (SABCS 2013 Lohrisch). HER2 unknown pts were excluded from further survival analyses. Three percent of cases with known PR were ER negative/PR +. Therefore ER was used as the main determinant of HR status.
For the entire cohort and all biomarker groups, OS was longer for denovo than for relapsed MBC.
Overall Survival - relapsed vs de novo MBC for each biomarker subtype Relapsed MBCDe novo MBC SubgroupsN dead/totalMedian OS, mN dead/totalMedian OS, mP-valueAll cases with known ER2124/231115593/69926&lt;.0001HR+/ HER2 negAll821/91224290/36434&lt;.0001PR known414/47720251/31934&lt;.0001PR unknown407/4352839/45330.1315TNBCAll368/3919110/126150.0001HER2+All935/100811193/209170.0061ER neg268/278758/609.50.2191ER+667/73015135/149250.0088
OS was longest for denovo HR+/HER2 negative (34m) and shortest for HER2+/ER negative (7m) and TN (9m) relapsers. The difference in OS for relapsed vs denovo HER2+ disease was significant for HR+ but not HR negative cases, likely due to small numbers in the latter subset.
Conclusion: Relapsers experience shorter OS than their denovo biomarker counterparts, possibly due to the selective pressure of adjuvant therapy on disease biology. When restricted to pts who received systemic therapy for MBC, OS figures may be higher. Novel therapies may decrease the total number of relapsers, and improve OS in MBC for all, but are unlikely to narrow the OS gap between relapsed and denovo groups. Trials exploring therapies for MBC of all biomarker types should therefore stratify by stage at initial diagnosis.
Citation Format: Wendie-Lou D den Brok, Caroline Speers, Gondara Lovedeep, Emily Baxter, Scott Tyldesley, Lohrisch Caroline. Survival of metastatic hormone receptor (HR) positive/HER2 negative; HER2+; and triple negative (TN) breast cancer based on initial presentation [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-40.