A new genomic test designed to measure endocrine sensitivity of estrogen receptor positive breast cancer has the potential to identify patients diagnosed with ER+ breast cancer who could benefit more from dose dense chemotherapy, a regimen in which chemotherapy is administered more frequently than normal, when compared to non-dose dense regimens, research by Dana-Farber shows.

The investigators found that women with ER+ breast cancer that scores low for a biomarker called SET2,3 (i.e., indicating endocrine resistance) benefited far more from dose-dense chemotherapy than patients with higher scores.

The results applied to pre- as well as postmenopausal women.           

If confirmed by future studies, the biomarker could be the basis for the first test for identifying which of these patients diagnosed with ER+ breast cancer stands to have the best responses to dose-dense chemotherapy, says study presenter Otto Metzger, MD, of Dana-Farber.        

The SET2,3 (sensitivity to endocrine therapy) index measures the activity of genes involved in estrogen and progesterone receptor signalling and excludes genes related to cell proliferation.

A high SET2,3 score – indicates higher endocrine sensitivity, potentially deriving greater benefits from adjuvant endocrine therapy.           

For the new study, researchers did SET2,3 testing on 682 tumour samples from women with ER+ breast cancer who participated in the CALGB 9471 clinical trial, which compared dose-dense chemotherapy schedules to conventional schedules. (Dose-dense treatment involves administering chemotherapy every two weeks rather than every three weeks.)           

They found that patients with highly endocrine-sensitive tumours – and high SET2,3 scores – lived longer before their disease returned, and lived longer overall, than patients with less-sensitive tumours.

They further found that SET2,3 was a far better indicator of patients’ prognosis than an often-used genomic test of tumour cell proliferation named PAM50.      

The investigators then explored whether SET2,3 could fill the need for a test to identify patients with ER+ breast cancer who are likely to derive a greater magnitude of benefit with dose-dense chemotherapy following surgery for operable breast cancer. 

The findings can be summarised as follows: SET2,3 identifies patients diagnosed with ER+ breast cancer with significantly lower chances of experiencing disease recurrence.

SET2,3 outperformed PAM50 in its ability to predict patient’s outcome and in its ability to identify a subset of patients experiencing greater benefits with dose-dense chemotherapy. 

Metzger says this highlights the importance of evaluating endocrine sensitivity to estimate prognosis and potentially tailor therapies for patients facing a breast cancer diagnosis.

Source: Dana-Farber Cancer Institute