Patients with metastatic hormone receptor (HR)-positive breast cancer who have low activity levels of the enzyme serum thymidine kinase 1 (sTK1) in their blood serum at the start of anti-estrogen treatment have both a longer overall survival (OS) and longer progression-free survival (PFS) than patients with high sTK1 activity levels, according to a study conducted by the SWOG Cancer Research Network and published in Clinical Cancer Research. The investigators said these results suggest patients with low sTK1 activity levels have slow-growing disease, which can be initially controlled through single-drug endocrine therapy.
“SWOG researchers have demonstrated that a blood serum test can identify which of these patients have slow-growing disease that might be controlled with a simple aromatase inhibitor pill alone,” said Lajos Pusztai, MD, DPhil, professor of medicine (medical oncology) at Yale Cancer Center, in a press release.
The study evaluated serum samples from 432 patients with breast cancer who took part in the S0226 clinical trial conducted by the SWOG Cancer Research Network. The investigators found that most participants with metastatic HR-positive breast cancer who have not had previous treatment for metastatic breast cancer live longer if they are treated with a combination of the endocrine therapy drugs anastrozole and fulvestrant, compared to receiving anastrozole alone.
Not all patients benefit from this drug combination, however, and the single drug therapy is often just as effective. Having the ability to identify which patients would not derive added benefit from the combination could reduce the cost of treatment as well as reduce the number of adverse effects these patients experience.
The investigators measured the level of sTK1—considered a marker of cellular proliferation—in 1726 samples taken from study participants before treatment and at 4 points during treatment. They found that 40% of the patients observed had levels of sTK1 activity that were considered high.
The patients with higher sTK1 levels tended to have a significantly shorter period of PFS, with a median PFS of 11.2 months for those with high levels of the enzyme compared to 17.3 months for those with low levels at baseline. Further, patients with higher levels of sTK1 activity had a shorter life expectancy, with a median OS of 30 months compared to 58 months for those with lower levels of the enzyme.
Patients with low sTK1 levels had similar results from the anastrozole single-drug therapy compared to the combination therapy of anastrozole and fulvestrant. According to the investigators, this suggests sTK1 levels could act as an indicator of whether single-drug or combination therapy is appropriate for the patient in question.
“These results should serve as the basis for future clinical studies to distinguish patients with estrogen receptor metastatic breast cancer who might be best treated with endocrine therapy alone versus those who should receive endocrine therapy plus an ancillary treatment, such as CDK4/6, mTOR, or PIK3CA inhibitors,” said Daniel Hayes, MD, of the University of Michigan Rogel Cancer Center, in the release. “Each of these has been shown to complement endocrine therapy, but each is associated with additional side effects and costs.”
Blood enzyme activity level may indicate which breast cancers are slow growing [news release]. EurekAlert; September 14, 2021. Accessed September 16, 2021. https://www.eurekalert.org/news-releases/928274