HER2 for lobular, too.
Top Line: Mutations in HER2 don’t necessarily mean amplification of HER2, and vice versa.
The Study: Importantly, when we talk about HER2(+) breast cancers we classically mean HER2 amplification. So what does that mean for HER2 non-amplified breast cancers with tumor profiling demonstrating a mutation in HER2? While HER2mutations are found in only a small minority of invasive ductal carcinomas, small series report an incidence approaching 30% in invasive lobular carcinomas (ILC). This case series from Cancer Treatment Centers of America reviews 17 women with metastatic ILC profiled with next generation sequencing. As expected, 16 had (16 different) CDH1 mutations, which some consider genetically pathognomic of ILC. Also as expected, 5 had (5 different) HER2 mutations, only one of which was also HER2 amplified. All five of these women received HER2-targeted therapy and...drum roll please...all five had marked clinical and/or biochemical responses.
Bottom Line: Tumor profiling may reveal targetable HER2 mutations in HER2 non-amplified invasive lobular carcinoma. | Citrin, JCO Precis Oncol 2018
The Study: Importantly, when we talk about HER2(+) breast cancers we classically mean HER2 amplification. So what does that mean for HER2 non-amplified breast cancers with tumor profiling demonstrating a mutation in HER2? While HER2mutations are found in only a small minority of invasive ductal carcinomas, small series report an incidence approaching 30% in invasive lobular carcinomas (ILC). This case series from Cancer Treatment Centers of America reviews 17 women with metastatic ILC profiled with next generation sequencing. As expected, 16 had (16 different) CDH1 mutations, which some consider genetically pathognomic of ILC. Also as expected, 5 had (5 different) HER2 mutations, only one of which was also HER2 amplified. All five of these women received HER2-targeted therapy and...drum roll please...all five had marked clinical and/or biochemical responses.
Bottom Line: Tumor profiling may reveal targetable HER2 mutations in HER2 non-amplified invasive lobular carcinoma. | Citrin, JCO Precis Oncol 2018
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