It was originally assumed that breast cancer receptors remained constant over time and during progression to metastasis. However, there is mounting evidence that receptor status changes can occur. Differences in estrogen (ER), progesterone (PR), or human epidermal growth factor receptor 2 (HER2) status between the original tumor and corresponding metastases (including lymph node metastases) is known as “discordance.” Changes in receptor status can be a marker of increased disease aggressiveness.
Treatment decisions concerning patients with metastatic breast cancer typically are based on the receptor status of the original (primary) tumor. However, biopsy of metastases is technically feasible in most cases and consensus is growing that treatment decisions should be informed by the receptor status of any metastases. Now a new study has reported that breast cancer patients have longer progression-free survival when treatment matches the HER2 status of metastases rather than that of the primary tumor if they are discordant.

Latest research finds treatment should match HER2 status of mets

The retrospective study referenced above was designed to investigate the effectiveness of treatment for breast cancer in which there may be discordance in HER2 expression between the primary tumor and metastatic sites. To conduct the study, the authors assessed progression-free and overall survival according to HER2 concordance when treating women with taxane chemotherapy + trastuzumab (Herceptin), with or without pertuzumab (Perjeta), in first- or second-line treatment and trastuzumab-emtansine (T-DM1) or capecitabine–lapatinib in subsequent lines.
All breast cancer patients receiving trastuzumab between January 2002 and September 2017 at the University Hospital in Leuven, Belgium were identified. Of these, 74 stage IV patients with available HER2 status in both primary and metastatic sites were included in the study. The analysis was corrected for any use of pertuzumab. Of the 74 study participants; 46 (62%) had an unchanged HER2 status (primary tumor HER2+ → metastases HER2+), 9 (12%) lost HER2 overexpression (HER2+ → HER2-), and 19 (26%) acquired HER2 amplification (HER2- → HER2+). The primary tumor in the majority (25 out of 28) of cases with discordant HER2 status had ER+ and/or PR+ hormone receptor status.
HER2+ → HER2- patients were found to have significantly lower progression-free survival (5.5 months) under taxane–trastuzumab–(pertuzumab) treatment than HER2+ → HER2+ (i.e., no discordance) (9 months) and HER2- → HER2+ (14 months) cases. Progression-free survival for the 30 patients who underwent later line T-DM1 treatment was significantly longer for those without discordance (6.0 months) than for the discordant groups HER2- → HER2+ (1.0 month) and HER2+ → HER2- (1.5 months). After correcting for possible confounders (variables that could cause a spurious association), the HER2+ → HER2- group was found to have significantly worse overall survival than the HER2+ → HER2+ and HER2- → HER2+ groups.
The authors conclude that, in contrast with patients with loss of HER2 overexpression, patients with a positive conversion of HER2 status benefited significantly from first-line treatment with taxane–trastuzumab–(pertuzumab). This finding highlights the importance of biopsying metastatic lesions and matching treatment with the last HER2 result.
Please see our article on discordance for more information.