The low mojo.

Top Line: HER2-low breast cancer is a thing now.

The Study: Now that we can give HER2-target drugs to most women, how should we think about the prognosis of women with low-level HER2 staining? A look at 5235 women treated at Dana Farber for historically HER2-negative breast cancer were retrospectively reclassified as either HER2-0 (no IHC staining, n=2318) or HER2-low (ICH 1-2+ and non-amplified on FISH, n=2917). The first distinction that emerged is that 91% of HER2-low tumors were also ER+ while only 82% of HER2-0 tumors were ER+. But more than that, since ER-positivity also occurs on a spectrum, it was noted that HER2-low was more and more common with increasingly-positive ER staining. So while at first look it appeared HER2-0 patients had a higher likelihood of achieving a pathologic complete response to neoadjuvant therapy, this was in fact due to the correlation with low ER-positivity. In other words, HER2-0 versus HER2-low status had no bearing on path responses or survival outcomes when separately analyzing ER-negative, ER-low and ER-high subgroups.

TBL: HER2-low expression is positively associated with ER expression and likewise is associated with better prognosis than HER2-0 tumors. | Tarantino, JAMA Oncol 2022

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