New publication shows EndoPredict Breast Cancer Prognostic Test accurately identified premenopausal women with ER+, HER2- breast cancer who could safely avoid adjuvant chemotherapy, regardless of nodal status.

31st August 2022 Myriad Genetics’ EndoPredict Breast Cancer Prognostic Test significantly predicted distant recurrence in premenopausal women with ER+, HER2- early-stage breast cancer, according to a newly published study which represents the first clinical validation of EndoPredict in a purely premenopausal population.

First presented in an abstract at the 2021 ASCO Annual Meeting by Anastasia Constantinidou et al., these results provide important additional data of gene expression testing in premenopausal patients and support testing in women regardless of menopausal status to inform treatment decisions. The results were published in the August 2022 issue of the Clinical Cancer Research journal.¹

“We are excited to present new data on our EndoPredict test which demonstrates our ongoing commitment to advancing personalized medicine for patients with breast cancer,” said Dr. Ralf Kronenwett, Director of International Medical Affairs, Myriad Genetics.  “Importantly, this new study adds to the expanding body of evidence demonstrating how EndoPredict can be used also in premenopausal patients.”

In the Constantinidou et al. 2022 study, tumor samples from 385 premenopausal women with ER+, HER2- primary breast cancer (pT1-3, pN0-1) who were chemotherapy-naïve were tested with EndoPredict to produce its characteristic 12-gene molecular score and an integrated EPclin Risk Score, which includes clinicopathological factors like nodal status and tumor size.

After nearly 10 years, both the molecular score and EPclin Risk Score were significantly associated with risk of distant recurrence (hazard ratio = 1.33, p = 7.2×10^-6; hazard ratio = 3.58, p = 9.8×10^-8, respectively), even after adjusting for clinical factors.

Overall, 64.7% of patients had EPclin low-risk scores with significantly improved distant recurrence free survival (DRFS) compared to high-risk patients – at 10 years premenopausal women with EPclin low-risk scores had a 97% DRFS versus 76% for high-risk patients.

Notably, and in line with previous trials, EndoPredict identified low-risk premenopausal patients regardless of nodal status, with nearly 20% of patients with node positive disease able to safely avoid chemotherapy and continue onto endocrine therapy alone.

Another key result went some ways to address the topic of adjuvant ovarian suppression (OFS) in premenopausal breast cancer. An exploratory subgroup analysis comparing EPclin low-risk patients who did not and did receive OFS demonstrated similar DRFS, with less than 5% distant recurrence after 10 years in both groups. Contrary to trials such as RxPonder and TAILORx, which suggest menopausal status impacts test performance, the results from this study showed EndoPredict identifies low-risk women that can avoid chemotherapy, regardless of menopausal status.

In light of mounting clinical recommendations to de-escalate chemotherapy in breast cancer, the Constantinidou et al. 2022 results are particularly encouraging. With around a third of new breast cancer cases occurring in patients aged 54 or younger², use of EndoPredict among premenopausal women will provide important information to inform personalized treatment decisions for many patients and ensure the highest quality of life as possible.

“This important study shows that premenopausal patients with a low-risk EPclin score have a good long-term outcome without chemotherapy and may be considered for treatment with endocrine therapy only,” said Dr Anastasia Constantinidou, BoC Oncology Centre and Cyprus Cancer Research Institute, “These findings are relevant to better inform personalized treatment decisions for a large proportion of premenopausal women with ER+, HER2- early-stage breast cancer.”

Learn more about EndoPredict in premenopausal patients here.

About the study

The Clinical Validation of EndoPredict in Pre-Menopausal Women study tested tumor samples from 385 premenopausal women with ER+, HER2- primary breast cancer (pT1-3, pN0-1) who did not receive chemotherapy in addition to endocrine therapy. Associations of molecular and EPclin Risk Scores with 10-year distant recurrence free survival (DRFS) were evaluated by Cox proportional hazards models and Kaplan-Meier analysis.

All samples were retrospectively tested in one central laboratory blinded to clinical and outcome data with EndoPredict. The primary outcome was 10-year DRFS.

Besides EPclin and EP molecular score, clinical variables of interest included age at diagnosis, tumor size, tumor grade, nodal status, Ki 67 expression, and continuous estrogen receptor (ER) expression and progesterone receptor (PgR) expression.