Sphingotec LLC, Cambridge, Mass, has recently announced publication of the results of two studies examining the association between pro-enkephalin (pro-ENK) and incident breast cancer. The results of the studies were published online in the Journal of Clinical Oncology.1

Conducted by researchers at Skåne University Hospital, Malmö, Sweden, the studies encompassed almost 3,500 subjects. Results demonstrated a strong association between low plasma concentration of the opioid precursor peptide pro-ENK and increased breast cancer risk among middle-aged and postmenopausal women, independent of other possible risk factors.

Although previous experimental studies have established that enkephalins and related opioid hormones can inhibit the growth of cancer cells, these are the first studies to investigate whether plasma concentration of pro-ENK can predict near-term breast cancer risk in healthy women.

“We hypothesized that plasma levels of ENKs are predictive of the long-term breast cancer risk,” write the authors. “Therefore, our objective was to measure pro-ENK A—a surrogate for mature ENK—and evaluate its predictive value for the development of breast cancer in a large population of middle-aged women and an independent study population.”

The strong association between concentrations of pro-ENK and incident breast cancer found during the studies indicates that pro-ENK is a viable tool for predicting breast cancer risk.

The study results represent a potential breakthrough in helping women without a known family history of breast cancer understand their own risk. Current tools such as the Gail risk score are helpful, but the parameters included in the score cannot be modified, have only weak prognostic power, and do not address an individual’s risk. And while mammography is effective at detecting early-stage breast cancer, there is ongoing concern about over-diagnosis and missed cases. There is a great need for biomarkers that can identify women at highest risk so that appropriate interventional measures can be taken to prevent clinical manifestation of life-threatening breast cancer.

Bergmann

Andreas Bergmann, PhD, Sphingotec.

Study sponsor Sphingotec is developing diagnostic methods for prediction, prevention, intervention strategies, and early treatment of diseases in the fields of cancer, cardiovascular diseases, and kidney function. The company provides biomarkers that indicate susceptibility for a specific disease, making it possible to monitor prevention and intervention strategies.

“Our goal is to prevent deaths related to breast cancer,” says Andreas Bergmann, PhD, founder and CEO of Sphingotec. “We have now identified two promising biomarkers to achieve this goal: proneurotensin (pro-NT) and proenkephalin, which have been demonstrated now in two independent cohorts to predict risk in healthy women.”1,2

To conduct the first study, the investigators measured pro-ENK in fasting plasma from 1,929 healthy women from the Malmö Diet and Cancer Study with a mean age of 59 years. They then used Cox proportional hazard models to relate pro-ENK to the incidence of breast cancer during 15 years of follow up.

In the second study, using a case-control design, the investigators sampled 1,569 women from the Malmö Preventive Project with a mean age of 70 years. They then used multivariate adjusted logistic regression models to relate pro-ENK to the risk of breast cancer during the observation period. Results of the study appear online in the Journal of Clinical Oncology.1

“The results of these studies imply great promise for the future of breast cancer prevention,” says Bergmann. “We believe these findings will aid in helping women better understand their breast cancer risk so they can take the appropriate measures for preventing this devastating disease.”

REFERENCES

1. Melander O, Orho-Melander M, Manjer J, et al. Stable peptide of the endogenous opioid enkephalin precursor and breast cancer risk. JCO. Published online before print, July 13, 2015; doi: 10.1200/jco.2014.59.7682.

2. Melander O, Maisel AS, Almgren P, et al. Plasma proneurotensin and incidence of diabetes, cardiovascular disease, breast cancer, and mortality. JAMA. 2012;308(14):1469–1475; doi: 10.1001/jama.2012.12998.