“The story of cancer is the story of human ingenuity, resilience, and perseverance, but also of hubris, paternalism, and misperception” (Siddhartha Mukherjee). The present review discusses the evolution of early breast cancer (BC) treatment philosophy in the last 50 years and the shift from an emphasis on local therapy to an emphasis on systemic precision treatment options.
Purpose One-half of hormone receptor-positive (HR+) breast cancer (BC) patients have low expressions of HER2 (HER2-low) and may benefit from Trastuzumab Deruxtecan (TDxd). This study aimed to identify parameters associated with HER2 low levels in primary and metastatic tumors. We specifically sought to determine whether OncotypeDX and HER2 mRNA levels could identify patients that would otherwise be considered HER2 negative (HER2-) by immunohistochemistry (IHC). Methods This retrospective analysis of all consecutive HR+ patients who underwent OncotypeDX from January 2004 to December 2020 was conducted in a single medical center (n=1429). A HER2 positivity cutoff of >10% stained cells was applied. We divided HER2- cases into HER2-low (IHC=1 or 2 and non-amplified fluorescent situ hybridization) and HER2- (IHC=0). HER2-RT-PCR was evaluated from the OncotypeDX results. Results HER2-low cases reached higher HER2 RT-PCR scores (p=2.1e-9), expressed higher ER levels (p=0.0114) and were larger than the HER2- cases, (>2 cm; 36.6% versus 22.1%, respectively, p<0.00001). Primary tumors >2 cm are more likely to be HER2-low (OR=2.07, 95 % CI: 1.6317 to 2.6475, p< 0.0001). Of the 274 tumors with HER2-RT-PCR scores >10, 74% were classified as HER2-low. Metastatic BCs expressed higher HER2 IHC scores compared with primary BCs (Wilcoxon signed-rank, p=0.046). HER2 IHC scores were higher for low-risk vs. medium-risk OncotypeDX (p=0.0067). No other clinical or pathological parameters were associated with the increase of HER2 levels in the metastatic samples. Conclusion It might be beneficial using clinical data from the primary tumor, including the HER2-RT-PCR score, to determine a HER2-low status.
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