Long-term distant recurrence in premenopausal receptor-positive early stage breast cancer: Prognostic impact of molecular subtypes, risk of recurrence score, and clinical-pathological factors

Background:

Gene-expression tests, like the PAM50-based Prosigna predicting 10-year risk of recurrence, are being increasingly integrated in clinical decision-making regarding treatment of early-stage, hormone-receptor (HR)-positive breast cancer (EBC). While Prosigna has been well validated in several retrospective studies in postmenopausal women, data for premenopausal women with potential fluctuations in hormone-levels due to their menstrual cycle is still scarce.

Methods:

Analyzing 50 different key genes determining intrinsic subtypes (Luminal A/B, HER2-enriched or Basal-like), the PAM50 Prosigna also estimates the risk of recurrence (ROR) score, using also nodal stage, tumor size, and proliferation rate. In this study, we will retrospectively analyze a cohort of 50 premenopausal patients with HR+ HER2- EBC diagnosed with and without distant recurrence after a long-term follow-up. Using a comprehensive breast custom code set (n = 745), we will be able to analyze not only PAM50 and ROR, but several pathways including immune-related genes. Results will be compared with clinical-pathological factors regarding their impact on patient outcome.

Hypothesis:

We expect ROR and PAM50 to have a prognostic impact on distant recurrence in premenopausal patients. Results will be compared with those in postmenopausal women in order to explore whether test results are influenced in premenopausal women by fluctuations in estrogen and progesterone levels based on the menstrual cycle. Results will be presented at the meeting.

Conclusion:

The estimation of relapse risk and potential benefit from adjuvant systemic therapy may also be improved in premenopausal women by including validated gene-expression tests, as already established for postmenopausal women.