Neoadjuvant Endocrine Therapy for Patients With Estrogen-Receptor-Positive Breast Cancer

Abstract

More than 70 % of patients with breast cancer have estrogen-receptor-positive tumors (ER+) and are considered hormone- sensitive. That is why a vast majority of patients with early operable tumors receive adjuvant endocrine therapy. Patients with metastatic ER+ breast cancer also receive hormone therapy as first-line treatment. Patients with ER+/PR+ locally advanced breast cancer including potentially operable cases (cT2N1, cT3N0M0) are still a subject to neoadjuvant chemotherapy in most of the oncology centers in Russia and worldwide. More than 10 years ago, several trials evaluating the efficacy of neoadjuvant endocrine therapy were conducted in the Petrov Research Institute of Oncology (aromatase inhibitors vs tamoxifen, neoadjuvant endocrine therapy vs neoadjuvant chemotherapy, etc.) The primary endpoint was the evaluation of pathologic complete/partial response to therapy and the frequency of breast-conserving surgeries following neoadjuvant treatment. We now represent 10-year long-term follow-up data on comparison of neoadjuvant chemotherapy with neoadjuvant endocrine therapy after retrospective determination of IHC- phenotypes of 239 patients with ER+ breast cancer. The study results show tendency to better 10-year disease-free survival in patients with luminal-A breast cancer who received endocrine therapy compared to neoadjuvant chemotherapy (72.8 % vs 53.9 %, respectively, p=0.062) There were no statistically significant differences in DFS rates among patients with the luminal B breast cancer subtype (41 % vs 40 %) The discovery of biomarkers of potential resistance to endocrine therapy (cycline-dependant kinase activity [cdk 4/6], estrogenreceptor mutation [ESR1], mTOR signaling pathway activity, co-expression of the ER and HER2neu [ER+/ HER2neu3+]) and ways to inhibit the activity of the resistance pathways (palbocyclib, everolimus, etc.) have expanded the armamentarium of endocrine-therapy for not only metastatic and locally-advanced but also operable cases of ER+ breast cancer.