COMPARISON OF HER-2 STATUS IN PRIMARY BREAST CANCER AND METASTATIC SITES: RESULTS FROM A SINGLE INSTITUTION ANALYSIS

Introduction:HER-2 overexpression occurs in 15-20% of breast cancer; the assessment of HER2 status is necessary to select patients who are candidate to receive anti-HER2 agents, such as trastuzumab. The evaluation of HER2 is generally carried out in primary tumor. However, it is controversial if it would be more appropriate to reassess HER2 status in the metastatic lesion. Aim of the present analysis is to compare the HER2 status in primary tumors versus metastatic sites in metastatic breast cancer patients. Patients and Methods: The Archive of the Pathology Division was searched to identify all the biopsies performed since 2004 resulted positive for metastases from breast cancer. Among these patients, only those with available samples from primary tumor and followed at our department were considered for this analysis. Therefore, 68 out of the previously 89 identified patients are included in the present study. HER-2 overexpression was evaluated by IHC and/or by FISH. Overall, samples were considered positive for HER2 in case of IHC 3+, or 2+ and FISH amplification, or FISH amplification. In case of discordance between IHC and FISH, HER 2 status was defined according to the FISH result. Results: Median age at diagnosis was 53 years (range 27-74). Among the 49 patients evaluable by IHC, 40 (82%) were negative (0-1+); 3 (6%) were IHC 2+, and 6 (12%) were 3+. Among the 38 patients evaluable by FISH, 32 (84%) were non-amplified, and 6 (16%) were amplified. Overall, at diagnosis, 15% of tumors were HER2 positive. Sites of biopsied metastases were: soft tissues (n=22), liver (n=20), chest wall (n=13), CNS (n=4), bronchus (n=4), bone (n=1), bone marrow (n=2), and other (n=2). On paired metastases, HER2 status was found to be unchanged in 57 out of the 68 (84%) evaluable patients, while a change in HER2 status was observed in 11 cases (16%). All the discordant cases were assessed both by IHC and FISH whenever possible, or by using the same modality. Surprisingly, only 2 patients changed from HER2 positivity to HER2 negativity (without receiving anti HER2 therapy prior to metastatic site biopsies), while in 9 patients her2 was negative on primary tumors and overexpressed in paired metastases. Conclusion. The unexpected discordance observed in our analysis, with particular regard to those tumors that convert from negative to positive HER2 status, warrants further studies with larger series. However, based on these data, when feasible with minimal invasiveness, a biopsy of metastatic disease might increase treatment options for a significant proportion of patients.