Duloxetine is the only agent for chemotherapy-induced peripheral neuropathy (CIPN) recommended by the American Society of Clinical Oncology. As a moderate inhibitor of cytochrome P450 isoenzyme 2D6, duloxetine is theorized to decrease the efficacy of tamoxifen, which may be used to treat estrogen receptor–positive breast cancer. A case prompted our team to review the literature to elucidate the risks and benefits of duloxetine use in patients with this cancer.

We present the case of a patient with estrogen receptor–positive breast cancer who was doing well on duloxetine for CIPN. Due to concern for the possible future need for tamoxifen, she was switched to multiple other agents, including venlafaxine, without success.

Ultimately, the patient was switched back to duloxetine due to persistent CIPN symptoms. The theoretical risk of tamoxifen interaction with duloxetine has not been demonstrated to be clinically significant in the literature.

While emerging evidence suggests venlafaxine may prove an effective alternative, duloxetine remains the agent with the strongest evidence of benefit in patients with CIPN and must remain an option in this patient population.