الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
BC is a considerable worldwide health concern, being the most commonly diagnosed cancer globally, and the most frequently diagnosed cancer among females in Egypt.
BC is no longer considered a single disease; each subtype has distinct clinical features and genetic drivers. The clinically relevant classification is based on HR and HER2 receptors status. Until recently, BC was either HER2 positive or negative based on whether the HER2 oncogene is amplified or not. This notion was challenged when a new HER2 targeting drug, TDX-d showed effectiveness among a subgroup of BC patients previously reported as HER2 negative, challenging the established classification.
HER2 low (IHC 1+ or IHC +2/ISH negative) require further study to understand their clinicopathological features and prognosis to determine whether they are indeed distinctly different from the HER2 negative subgroup.
This retrospective study of 1029 early BC patients diagnosed between 2014 and 2022 in Alexandria university hospitals. Tumors originally reported as HER2 negative were reclassified into HER2 0 and HER2 low and stratified based on HR status. Clinical and pathological features were compared, and rate of pCR, DFS, OS and TTR were calculated and compared for HER2 low, HER2 positive and HER2-0 groups.
HER2-low tumors were found to be positively associated with HR positive status compared to HER2-0 (p=0.019). The rate of HER2-low significantly increased as the level of ER expression increased (p<0.001), while HER2 positive tumors were more likely to be associated with negative HR status than HER2-0 (p<0.001).
No significant difference was observed between HER2-0 and HER2-low regarding clinicopathological features, apart from HER2 low being more likely of ductal histology (p=0.004), and having Ki67 level less than 20 (p=0.008), while HER2 positive tumors were more likely to be of high grade compared to HER-0 (p<0.001), Ki67 level was more likely to be 20 or more (p=0.011), and to present at a younger age (p=0.019).
Regarding disease outcome, HER2 low patients who received NACT had a trend toward lower rate of pCR compared to HER2-0, however this difference didn’t reach statistical significance. Conversely, HER2 positive patients who received anti-HER2 therapy in the neoadjuvant setting had higher rates of pCR compared to HER2-0 (p=0.01).
No significant difference in DFS or OS was observed between the HER2 low and HER2-0 groups, or the HER2 positive and HER2-0 groups, however TTR was significantly longer in HER2 low compared to HER2-0 (p=0.002).