Measuring the impact of the American College of Surgeons Oncology Group Z0011 trial on breast cancer surgery in a community health system.

BACKGROUND: The American College of Surgeons Oncology Group Z0011 trial has been lauded as practice changing. We sought to identify its impact on breast cancer surgery in the community hospital setting. METHODS: A retrospective review was performed from 8 community hospitals identifying patients with invasive breast cancer meeting the Z0011 criteria. The primary outcome measures were the rate of completion axillary lymph node dissection (ALND) and performance of intraoperative sentinel lymph node (SLN) analysis over time. RESULTS: A total of 1,125 lumpectomies with SLN biopsies were performed with 180 subjects meeting inclusion criteria. Performance of ALND (P < .0001) and intraoperative SLN analysis (P < .0001) declined during each time period. Patients more likely to undergo ALND included those with extracapsular extension (odds ratio [OR] 12.8, 95% confidence interval [CI] 2.5 to 67.1) and those who underwent reoperative surgery (OR 10.8, 95% CI 2.6 to 44.4) or intraoperative SLN analysis (OR 5.1, 95% CI 1.2 to 21.9). CONCLUSION: American College of Surgeons Oncology Group Z0011 trial has been rapidly practice changing in the community hospital setting.

MET and ERBB2 are coexpressed in ERBB2+ breast cancer and contribute to innate resistance.

UNLABELLED: Breast cancer displays significant intratumoral heterogeneity, which has been shown to have a substantial impact on both innate and acquired resistance to tyrosine kinase inhibitors. The heterogeneous expression of multiple receptor tyrosine kinases (RTK) in cancers supports tumor signaling robustness and plays a significant role in resistance to targeted inhibition. Recent studies have revealed interactions between the MET receptor and the ERBB receptor family in the therapeutic resistance of several cancers. In this study, the relationship between MET expression/activity and the expression/activity of the ERBB receptor family in human breast cancer was interrogated. Importantly, a significant percentage of ERBB2(+) tumors coexpressing MET and ERBB2 were observed and displayed significant heterogeneity with subpopulations of cells that are MET(-)/ERBB2(+), MET(+)/ERBB2(-), and MET(+)/ERBB2(+). In a MET(+)/ERBB2(+) breast cancer cell line, MET depletion resulted in increased ERBB2 activation, and conversely, ERBB2 depletion resulted in increased MET activation. Neither EGFR nor ERBB3 compensated for MET or ERBB2 knockdown. The loss of either MET or ERBB2 led to a decrease in PI3K/AKT signaling and increased dependency on MAPK. These data show that a subset of ERBB2(+) breast cancers express MET and contain MET(+)/ERBB2(+) subpopulations. Moreover, analysis of RTK activation during ERBB2 knockdown indicated that MET signaling is a compensatory pathway of resistance. IMPLICATIONS: ERBB2(+) breast cancers with MET(+)/ERBB2(+) subpopulations may have an innate resistance to ERBB2 inhibition and may benefit from combined MET and ERBB2 inhibition.