A call for reporting of tumor-specific outcomes in studies of DPYD genotyping

We read with great interest the findings published in your journal by Muldoon et al. of real-world implementation of DPYD and UGT1A1 pharmacogenetic testing in a community-based cancer center¹ and would like to share some comments regarding the need for specifically reporting outcomes by tumor type.

Most existing studies focus on preemptive DPYD genotyping for fluoropyrimidines in gastrointestinal cancers, rarely are outcomes reported for breast cancer. Previous studies evaluating the impact of DPYD on outcomes enrolled a small proportion of patients with breast cancer, including Muldoon, at 6%,¹ and another recent study at 12%.² Because of the small number of patients, the outcomes are not typically reported separately by tumor type, it is challenging to determine the true incidence of treatment-related toxicities experienced by DPYD variant carriers in this patient population.

Preemptive DPYD testing for patients treated with fluoropyrimidine is still controversial among US oncologists, and the hesitation is even greater in breast cancer clinicians due to limited data and a lack of endorsements from the NCCN and ASCO.³ To fill this gap in knowledge, we evaluated capecitabine-related toxicities in 62 patients with breast cancer that were enrolled in an institutional biobank.⁴ Serious treatment-related adverse events (TRAEs) were defined as chemotherapy-related events necessitating treatment in the hospital, emergency department, or oncology evaluation center (i.e., oncology urgent care).

One of the three variant carriers experienced severe diarrhea. This TRAE began during Week 1 of Cycle 1 of capecitabine initiation and resulted in 14 days of hospitalization. The patient was dose reduced from 2000 mg twice daily to 1000 mg in the morning and 1500 mg in the evening for cycle two. However, despite the dose reduction and loperamide administration, the patient still could not tolerate the treatment. The patient skipped several doses due to worsening diarrhea, which resulted in capecitabine being later discontinued.

Patients with breast cancer treated with capecitabine are classically monitored for reversible Hand-Foot Syndrome.⁵ However, other side effects such as diarrhea and mucositis still occur and can result in hospitalization or treatment discontinuation as demonstrated in this case study. It is critical to focus on bridging the current knowledge and practice gap around the use of DPYD genotyping and preemptive dose reduction in patients on capecitabine for breast cancer, thereby optimizing efficacy and minimizing harm in this population.

No funding was received for this work.

The authors declared no competing interests for this work.