A positive spin.

Top Line: How much does hormone receptor (HR)-positivity matter in the setting of HER2+ metastatic breast cancer?

The Study: This large French cohort study suggests it matters a lot. The first interesting tidbit is that roughly two-thirds of all women with HER2+ disease (n=4145) were also HR+ (n=2696, 65%). What’s more, the majority with HR+ disease had significantly longer median progression-free (12 versus 10 months) and overall (4.6 versus 3.5 years) survival. Now onto therapies. Among women with HR+ tumors receiving standard chemo and HER2-targeted therapy, those who received the addition of maintenance endocrine therapy had significantly longer progression-free (HR 0.70) and overall (HR 0.47) survival. A more interesting hypothesis-generating findings was that it was actually chemo that was not carrying its weight.  Among 1723 women with HR+ tumors receiving HER2-targeted therapy, 203 (12%) received endocrine therapy without chemo. On multivariate analysis with and without propensity matching, there was no advantage detected with the addition of chemo. The elephant in the room here is that there was a reason these women didn’t receive chemo, one being that they were older but another that they tended to have fewer harbingers of bad biology such as (in addition to young age) higher grade disease and shorter interval from diagnosis to metastatic disease.

TBL: As you may have guessed, HR-positivity in the setting of HER2+ metastatic breast cancer may signal more favorable disease, and there may be a subset which does just as well with endocrine and HER2-targeted therapies sans cytotoxic chemo. | Carasu, JAMA Netw Open 2022