How would you treat an elderly female with metastatic HR+,HER2- breast cancer on endocrine therapy who now has progressive bone only disease?

If it was minimal bone only progression, I would consider adding a CDK 4/6 to fulvestrant, albeit there is no data for doing so. I agree with checking for PI3K although I think this class of drugs is likely to be difficult to tolerate for someone described as elderly. Finally we still have the option of exemestane everolimus. Needless to say she should also be on either denosumab or zoledronic acid.

First, I would get a genomic profile looking for a PI3 kinase mutation, assuming she has good performance status and is a candidate for alpelisib. If she is truly endocrine resistant, then I would treat with capecitabine 2g/m2 on a one week one week off schedule. Finally, I would treat with zoledronic every 3 months after a dental screening exam and assuming she has adequate renal function.

There may also be a role for adding cdk 4/6 inhibitor therapy to current first line endocrine therapy. I agree with genetic profiling.