Abstract P5-04-02: Biopsy of metastases impacts treatment choice and patient outcome in breast cancer – Final results of the WSG/DETECT PRIMET study
Authors: Wuerstlein R , Kates R , Heitz F , Gluz O , Ortmann M , Freudenberger M , du Bois A , Bensmann E , Pelz E , Mallmann P , Fehm T , Nitz U , Liedtke C , Harbeck N 
Published: August 2014

Abstract
Background: Changes in tumor biology (e.g., hormone receptor (HR) / HER2 status or grading) between primary tumor (PT) and metastatic tissue (MT) could impact outcome and treatment choice following first recurrence in breast cancer (BC).
Methods: PRIMET is a prospectively planned, retrospective multicenter quality assurance study comparing BC phenotype in tissue from PT, involved lymph nodes (LN) of primary disease, and disease recurrence (DR). PRIMET comprises 635 patients from WSG and DETECT trial groups (11 centers), whose BC was diagnosed between 1980 and 2010; follow-up continued until mid-2012. Patients with unilateral primary BC suffering subsequent local-regional and / or distant DR (LDR / DDR) were included. Clinical data including ER, PR, HER2, and grade were obtained from a systematic chart review in PT and DR; in two centers, these factors were also measured in LN by central pathology. Dependence of post-recurrence survival (PRS) on changes in tumor biological factors was analyzed.
Results: Data from 635 patients (including 592 cM0, of whom 46% had LDR only) were available for analysis. Median follow-up in patients alive at analysis was 101 months. Considering cM0 patients, median overall survival (OS) was 176 months; median recurrence-free survival (RFS) was 48 months (DDR present: 45 months; LDR only: 50 months). Median PRS was 59 months (DDR present: 45 months; LDR only: 127 months). In patients with first DR within 18 months, median PRS was 29 months, in others 79 months. HR status in PT/MT was: 61.5% (+/+), 13.2% (+/-), 5.5% (-/+) 19.8% (-/-). Of the HR “switches” in either direction with LN biopsy available, about half already occurred in lymph nodes. HER2 status in PT/MT was: 14.6% (+/+), 6.7% (+/-), 14.9% (-/+) 63.8% (-/-). With LN biopsy available, most losses of HER2 overexpression were already observed in LN tissue, whereas acquired HER2 overexpression was observed in about half of LN biopsies. Triple negative (TN: HR-, HER2-) percentages were 74.4% (non-TN/non-TN), 9.0% (non-TN/TN), 6.1% (TN/non-TN), 10.5% (TN/TN).
Compared to HR+/+, loss of HR+ status (HR+/-) was significantly associated with poorer PRS (hazard ratio: 1.62; p = 0.01). Significantly better PRS was associated with a switch from G3 to G1/2 (hazard ratio: 0.47; p = 0.02). Tumors that switched to TN or that lost HER2 overexpression showed trends toward poorer PRS. Persistent TN was associated with poorer PRS than other combinations.
Among patients with DDR, metastasis in bone only was associated with better PRS than primary or visceral (CNS, lung, liver, etc.) metastasis. Among patients with visceral metastasis, negative HR status in metastasis was associated with poorer survival than in HR+/+ not only for HR-/- (p = 0.02), but also for HR+/- (p = 0.04).
Conclusions:
Tumor biology of primary and metastatic tissue differed in a substantial fraction of patients (HR: 19%; HER2: 22%, TN: 18%); more than half of all changes occurred already in LN. Status changes particularly loss of HR+ status, had significant prognostic impact. We can expect a switch in HR or HER2 status (or both) in about 38% of metastatic tissue biopsies, with presumably important clinical therapeutic consequences, in particular regarding targeted therapies.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-04-02.