Breast Cancer Coverage from Every Angle

One Drug or Two for Metastatic Breast Cancer? The Decision May Depend on Serum Enzymes

By: Hope Craig, MSPH
Posted: Tuesday, January 11, 2022

According to a prospective retrospective study published in Clinical Cancer Research, patients with metastatic hormone receptor–positive breast cancer who have low levels of serum thymidine kinase 1 (TK1) may have a more favorable prognosis than patients with high levels of the enzyme. Results of the study suggest that a blood test be used to identify patients with slow-growing disease that may be controlled with single-drug endocrine therapy, rather than combination treatment.

“Delaying CDK4/6 or mTOR inhibitors might be warranted [in patients with low baseline serum TK1], decreasing toxicity and cost of therapy…. Further evaluation of the predictive potential of serum TK1 in hormone receptor–positive metastatic breast cancer is warranted in prospective clinical trials,” said James M. Rae, PhD, of the University of Michigan Medical School, Ann Arbor, and colleagues.

Researchers collected serum samples from 432 patients who took part in the phase III S0226 clinical trial. Patients were postmenopausal women with previously untreated hormone receptor–positive metastatic breast cancer; they were randomly assigned to receive 1 mg of anastrozole orally daily or a combination of the endocrine therapies anastrozole and fulvestrant. Researchers measured the level of serum TK1 in a total of 1,726 samples from patients, including before the start of treatment and four times during treatment.

Results showed that patients with low activity levels of serum TK1 at the start of antiestrogen treatment had longer progression-free survival (17.3 months vs. 11.2 months; P < .0001) and longer overall survival (median 58 months vs. 30 months; P < .0001) than patients with high levels of serum TK1. Further, patients with low serum TK1 levels had comparable outcomes with anastrozole alone or combination endocrine therapy. However, overall survival was significantly improved for patients with high serum TK1 who had no prior adjuvant tamoxifen and received the combination endocrine therapy versus anastrozole alone (median 46 months vs. 21 months; P = .0087).

Disclosures: Full authors’ disclosures are available at

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