If a patient in this situation presented with asymptomatic metastases 3 years after adjuvant therapy, I would recommend changing the endocrine therapy to exemestane and combining it with everolimus. For me the decision is not so much whether to administer chemotherapy but whether the patient would benefit from endocrine therapy after 3 years. I believe it is reasonable that she would. I would also consider fulvestrant at the 500-mg dose as an option. I would be in favor of retesting ER expression to determine why she experienced relapse on endocrine therapy.

If the patient developed symptomatic disease recurrence 3 years after starting adjuvant treatment I would recommend exemestane and everolimus.

If a patient presented with metastases 3 years after adjuvant therapy, I’d be concerned about the possibility of acquired resistance. So I would consider an everolimus-based regimen with exemestane. My approach would be the same if this patient experienced symptomatic disease recurrence 3 years after adjuvant therapy.

If a patient presented 3 years after receiving adjuvant therapy, because she fared well on anastrozole for a long time, it is unlikely that I would add everolimus. I would recommend fulvestrant or tamoxifen alone in this scenario.

If the patient developed symptomatic metastases 3 years after adjuvant therapy, I’d administer chemotherapy followed by fulvestrant or tamoxifen. I would hold off on the exemestane/everolimus.

I would offer exemestane and everolimus if a patient presented after 3 years of adjuvant therapy. I would be a little more optimistic about hormone therapy being effective in this scenario than I would if the patient had presented after only 1 year of adjuvant therapy.

For a patient who was symptomatic 3 years after adjuvant therapy, I would lean toward everolimus/exemestane.

I would likely administer 500-mg fulvestrant to this asymptomatic patient if she presented 3 years after receiving adjuvant anastrozole. I tend to reserve everolimus/exemestane for patients with symptomatic disease given this regimen’s less favorable toxicity profile compared to hormonal therapy alone.

For a patient with symptomatic metastases 3 years after adjuvant therapy, I would suggest chemotherapy and, if she had a good response, follow that with fulvestrant. With a patient who is symptomatic, I would opt for chemotherapy because it has a significant chance of cytoreducing her cancer so that her symptoms improve. I prefer hormone therapy whenever possible because it is better tolerated than chemotherapy.

I would recommend 500-mg fulvestrant for a postmenopausal patient if she presented 3 years after receiving adjuvant anastrozole with asymptomatic disease because I think the toxicity profile of fulvestrant is favorable compared to that of everolimus.

I would also recommend fulvestrant for a patient who had symptomatic disease 3 years after adjuvant therapy.

If a patient experienced recurrence 3 years after adjuvant treatment on anastrozole, I would rebiopsy the tumor to confirm that it remains ER-positive, and then I would elect to administer exemestane and everolimus.

My recommendation for a patient who presented with symptomatic disease 3 years after adjuvant therapy would depend on where the disease is located and how symptomatic the patient is. Generally, if a patient is highly symptomatic, I will administer chemotherapy. I would use nanoparticle albumin-bound (nab) paclitaxel/capecitabine for this patient.

Because the patient has been receiving 3 years of adjuvant endocrine therapy, the tumor may have some degree of endocrine sensitivity. Most of the patients who benefited from exemestane/everolimus in the BOLERO-2 study had disease that was endocrine sensitive. However, I would like to give her the benefit of the doubt and treat with chemotherapy with the thought that I could administer exemestane and everolimus after chemotherapy.

For a patient who presented with asymptomatic metastases 3 years after adjuvant therapy, I would recommend everolimus and exemestane.

My recommendation for a patient who presented with symptomatic disease 3 years after adjuvant therapy would depend on whether the disease was visceral or nonvisceral. I would administer chemotherapy to a patient who has visceral disease and organ dysfunction to obtain a rapid response. If the metastases were limited to the bone, I might not opt for chemotherapy.