New research suggests that patients with hormone receptor (HR)-positive/HER2-negative breast cancer who have BRCA1/2 pathogenic variants (PVs) are overtreated. 

The study suggests that these patients are twice as likely as patients without BRCA1/2 PVs to receive platinum chemotherapy. 

This finding “emphasizes the need to monitor how genetic testing results are managed in oncology practice,” the researchers wrote. They reported the finding in JNCI Cancer Spectrum.


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The researchers noted that, although germline genetic testing is widespread, it hasn’t been clear whether carriers of germline PVs in BRCA1/2 or other cancer susceptibility genes benefit from some chemotherapy drugs more than others.

To investigate this, the researchers analyzed a cohort of patients from Georgia and California who had stage I-III breast cancer and were diagnosed from 2013 to 2017. Data on patients’ chemotherapy regimens were obtained from SEER registries, and the patients’ germline genetic testing results were obtained from 4 clinical laboratories. 

Of the 2293 patients included, 1451 had HR-positive/HER2-negative disease, and 842 had triple-negative breast cancer (TNBC). For all patients, the most commonly used drug was cyclophosphamide, followed by taxanes, anthracyclines, platinum agents, and other agents.

Multivariable analysis showed that, among patients with HR-positive/HER2-negative disease, the use of platinum agents varied by genetic results. Specifically, platinum agents were used more frequently in patients with BRCA1/2 PVs (odds ratio [OR], 2.44; 95% CI, 1.36-4.38; P =.003). 

“Practice guidelines do not advise that platinum agents should be used for most patients with early-stage, HER2-negative breast cancer; thus, we were surprised to find 2-fold greater odds of platinum receipt by BRCA1/2 PV carriers versus non-carriers with HR-positive/HER2-negative disease,” the researchers wrote. 

Patients with HR-positive/HER2-negative disease were also more likely to receive intensive chemotherapy if they had a higher disease stage (OR, 9.56; P <.001). They were less likely to receive intensive chemotherapy if they were younger (OR, 0.49; P <.001) or had grade 3 vs grade 1 disease (OR, 0.56; P <.001). 

Among patients with TNBC, there was no significant difference in the use of more intensive chemotherapy between patients with and without BRCA1/2 PVs. However, higher-stage disease was associated with a greater likelihood of receiving a more intensive regimen (OR, 4.59; P <.001).

The researchers noted that the possible overtreatment of BRCA1/2 carriers with HR-positive/HER2-negative disease may expose patients to unnecessary toxicities. This includes neuropathy, cardiomyopathy, and secondary hematologic malignancies.

Reference

Kurian AW, Abrahamse P, Hamilton AS, et al. Chemotherapy regimens received by women with BRCA1/2 pathogenic variants for early-stage breast cancer treatment. JNCI Cancer Spectrum. Published online June 20, 2022. doi:10.1093/jncics/pkac045