Breast cancer has, until recently, not been considered amenable to treatment with immunotherapy. However, recent studies have demonstrated the utility of PD-1 blockade for the treatment of triple-negative breast cancer,1,2 as well as the effectiveness of immunotherapy in patients with high tumor mutational burden (TMB) and/or high microsatellite instability (MSI-H), regardless of the tissue of origin.3–10 Although cancers in patients with Lynch syndrome have been shown to represent a specific group of patients with MSI who may respond to such treatment, there has been controversy as to whether breast cancer should be included among the cancers that are associated with this syndrome, and which Lynch syndrome genes might be associated with breast cancer.11–29
This report documents a remarkable response to a short course of pembrolizumab in a woman (self-reported female sex) with hormone receptor–positive, ERBB2-negative breast cancer, and provides data to suggest that the dysfunction of the c.1835 1837del variant of MLH1, whose pathogenicity has been uncertain, was the driver of the disease, rendering it susceptible to PD-1 blockade. This study received Providence St. Joseph Institutional Review Board approval (study 2021000589).
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