How would you manage a postmenopausal female with a history of early stage invasive ductal ER+/HER2- breast cancer s/p mastectomy who has a local recurrence of ER+/Her2 - lobular carcinoma while on letrozole?

I am sure most of us would offer local resection and radiation therapy along with staging work up without consideration for chemotherapy given CALOR data showing no benefit in ER positive cases. The final analysis of CALOR does not support the use of chemotherapy for ER-positive isolated loco-regional recurrence. The hazard ratio for disease-free survival (DFS) was 1.07 in the ER-positive ILRR cohorts.

She should be considered for alternate anti-estrogen therapy which could be tamoxifen or anothe...

I agree with treatment as per CALOR. However, since the CALOR, we now have increased understanding of primary and secondary endocrine resistance. In advanced breast cancer setting, we now have multiple preclinical and retrospective data sets that demonstrate that patients with ESR1 mutations have longer disease control with fulvestrant-based regimens than with AI (SoFea, JCO) and with newer SERDs which are in clinical trials. So, perhaps checking ESR1 mutation will be helpful.