Blood Enzyme Activity Predicts Chronic Disease Progression

SWOG Cancer Research Network researchers have discovered that blood enzyme activity levels could determine the chronic disease progression of breast cancer. 

The study indicated that patients with metastatic hormone receptor-positive breast cancer with low enzyme sTk1 activity levels in their blood serum at the start of anti-estrogen treatment could live and avoid disease progression longer than patients with high levels.

According to researchers, these results suggest that patients with low sTK1 active levels have slow-growing cancers that can be controlled through chronic disease management with single-drug endocrine therapy. However, it remains unknown if these patients could gain further benefit from adding a DK4/6 inhibitor to their endocrine therapy. 

The SWOG Cancer Research Network analyzed serum samples from 432 women with breast cancer who took part in the S0226 clinical trial.

“SWOG researchers have demonstrated that a blood serum test can identify which of these patients have a slow-growing disease that might be controlled with a simple aromatase inhibitor pill alone,” co-author and professor of medicine at Yale Cancer Center, Lajos Pusztai, MD, DPhil, said in a press release.

Study 20226 found that most women with metastatic hormone receptor-positive breast cancer who had not had previous treatment for their metastatic breast cancer lived longest when they received a combination of the endocrine therapy drugs anastrozole and fulvestrant versus anastrozole alone.

However, not all patients show extra benefits from the drug combination. Some do just as well on a single drug. Having a method of identifying which patients would not benefit from the combinations could save patients the necessary side effects and extra costs tied to taking two drugs rather than one.

The study was led by Costanza Paoletti, MD, then with the University of Michigan Rogel Cancer Center. Paoletti and her team measured the level of sTK1 in 1,726 samples taken from S0226 patients before their treatment and four times during the treatment.

The samples were evaluated using a commercially available test called the DiviTum assay, which measures levels of the enzymatic activity of sTK1. The researchers discovered high enzyme levels in samples from 171 (40%) of the patients. 

Patients who showed high sTK1 levels before or during the treatment tended to have a much shorter window of time before their disease advanced (progression-free survival time, or PFS). At the start of treatment, those with high levels had a median PFS of only 11.2 months compared to 17.3 months for patients with low levels.

Additionally, the high-sTK1 patients typically died sooner than patients with low levels of the biomarkers, with a median survival time of 30 months compared to 58 months.

Patients with low sTK1 levels also did just as well on the single drug anastrozole as on the combination. Researchers explained that a measurement of pretreatment sTK1 levels could potentially be used to determine which treatment to give a patient.

The team also recommended further investigation into whether low sTK1 levels could predict which patients could avoid having targeted therapy drugs added to their endocrine therapy.

“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, also of the University of Michigan Rogel Cancer Center and a co-author on the paper. “Each of these has been shown to complement endocrine therapy, but each is associated with additional side effects and costs.”