As a prognostic tool, the preoperative endocrine prognostic index (PEPI) has been developed as a way to identify estrogen-receptor positive (ER+) breast cancers that have a poor long-term outcome because of a failure to respond to tamoxifen or an aromatase inhibitor after three to four months of pre-surgical treatment.

The PEPI is based on pathological tumour size, nodal stage, ER status and a protein marker for proliferation - Ki67. A team at Washington University School of Medicine has now developed a faster way to identify patients with poor outcome disease by measuring tumour Ki67 early, just two to four weeks after starting neoadjuvant endocrine therapy. By assessing tumour response to endocrine therapy sooner, non-responding tumours can be triaged to neoadjuvant chemotherapy. This approach is currently undergoing prospective evaluation in the American College of Surgeons Z1031 trial.

"We’d like to identify poor prognosis ER+ disease earlier than three to four months," said Matthew Ellis, Ph.D., professor of medicine at Washington University School of Medicine and program leader for the Breast Cancer Research Program at Siteman Comprehensive Cancer Center. "That way, we don’t continue ineffective neoadjuvant endocrine treatment and can switch to a more intensive treatment approach."

Researchers measured Ki67 levels in tumors of 158 postmenopausal women in two independent trials with confirmed ER+ stage II and III breast cancers two to four weeks into endocrine therapy.

Tumour Ki67 measuring more than 10 percent accurately predicted higher rates of relapse, and the absence of a group of patients with such a low score suggested adjuvant chemotherapy is not likely to be of benefit.

"Through these trials, we are also obtaining high-quality tumour samples from patients for sophisticated molecular profiling, including whole genome sequencing," said Ellis.

"The investigations will determine the molecular basis for endocrine therapy resistance so we can intervene with new regimens that might be more effective than standard chemotherapy."

Source: www.sabcs.org