PD05-05: Meta Analysis of Discordant HER2 Status in Matched Primary and Metastatic Breast Cancer.

Abstract

Background: The status of HER2 amplification in breast cancer is an important prognostic and predictive indicator. Only those tumors exhibiting HER2 overamplification are candidates for HER2 targeted therapy. It remains controversial how accurately HER2 status of primary tumors reflects HER2 status in distant metastases. Discordance between primary and metastatic tumors can impact significantly on patient management and suitability for HER2 targeted therapies in the setting of recurrent distant disease. Methods: A literature search of the PubMed database was performed to identify all primary studies comparing HER2 status in matched primary and distant metastatic tumors between January 2005 and February 2011. Review and data extraction was performed by two independent reviewers. Eligible studies evaluated HER2 status by current ASCO guidelines. Studies comparing paired primary and axillary lymph nodes or synchronous primaries and metastases were excluded. Weighted pooled estimates were calculated. Results: The original search strategy retrieved 1703 studies for which there were 62 eligible studies for full evaluation. Metastatic sites included bone, brain, lung and liver. Traztuzumab was received in three studies. Weighted summary estimate for negative to positive discordance was 23% (95% CI, 16.0-28%). Positive to negative discordance had a weighted summary estimate of 4% (95% CI, 0.0-6%). Discussion: Meta analysis of studies adhering to ASCO guidelines for HER2 status determination revealed a significant rate of change to HER2 positive metastatic disease in HER2 unamplified primary breast cancers. This data suggests that nearly one quarter of patients may be denied the benefit of HER2 targeted therapy if HER2 primary status alone is used a the sole measure in determining therapeutic options upon distant recurrence. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-05.

Discordance rate of HER2 status in primary breast carcinomas versus synchronous axillary lymph node metastases: a multicenter retrospective investigation

“…Thus, we may suppose that the HER2 discordance rate of 4.72% between the primary BC and their synchronous nodal metastases could not be due to doubtful HER2 assessment. In accordance with the relevant literature, we found both positive and negative conversion of HER2 status between the primary tumor and the lymph node metastases 1,25,28,29…”

“…In accordance with the relevant literature, we found both positive and negative conversion of HER2 status between the primary tumor and the lymph node metastases. 1 , 25 , 28 , 29 …”

Characteristics of Breast Cancer Metastasizing to Bone in a Mediterranean Population

“…More specifically, studies indicate that PR loss was the main change observed [25][26][27][28], a finding that is congruent with the results of our study in which the most prevalent change of status in discordant cases was the change of PR from positive to negative. However, among the HER2 discordant cases, our study showed that more patients lost the HER2 expression than those who became HER2-overexpressed, which contradicts the findings of a meta-analysis highlighting contrary results [29].…”

Association of Biomarker Discrepancy and Treatment Decision, Disease Outcome in Recurrent/Metastatic Breast Cancer Patients

“…Moreover, among these receptor statuses, the lowest concordance rate was observed in PR (8,11,22,23) and HER2 status is the most stable one between primary and recurrent/ metastatic lesions (24). For patients with HER2 discrepancy, more patients were "HER2 gain" (from HER2-negative to positive) rather than "HER2-loss" (from HER2-positive to negative), according to another meta-analysis (25). McAnena et al demonstrated in a retrospective study of 132 recurrent breast cancer patients that biomarker discrepancy was observed more in visceral metastasis than bone or soft tissues metastasis (22.0% vs 15.2%) (26).…”