First-line endocrine therapy for postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and meta-analysis

Abstract

Background In establishing the 2018 Breast Cancer Practice Guidelines of the Japan Breast Cancer Society, we explored the optimal first-line endocrine therapy for advanced postmenopausal hormone receptor-positive breast cancer. Methods We performed a systematic review of relevant reports from randomized-controlled studies published prior to November 2016 found using medical journal search engines. The main outcomes which we evaluated were progression-free survival (PFS), objective response rate (ORR), disease control rate (CBR), and toxicity. Results Four controlled trials comparing aromatase inhibitors (AI) and cyclin-dependent kinase (CDK)4/6 inhibitor combination therapy to AI monotherapy, and two controlled trials comparing anastrozole to fulvestrant 500 mg were analyzed. AI/CDK4/6 inhibitor combination therapy significantly improved PFS (Risk Ratio: 0.67, 95%CI 0.60-0.73), increased ORR (Risk Difference: 0.11, 95% CI 0.07-0.16), and increased CBR (Risk Difference: 0.11, 95% CI 0.07-0.15), compared with AI monotherapy. Patients who received this combination therapy had a higher grade ≥ 3 adverse event rate more than those who received AI monotherapy (Risk Difference: 43%, 95%CI: 0.39-0.47). Fulvestrant 500 mg alone significantly improved PFS (risk ratio: 0.85, 95%CI 0.72-0.98), but ORR and CBR were similar to those of anastrozole alone. Conclusion In the first-line treatment for advanced postmenopausal hormone receptor-positive breast cancer, a combination therapy of CDK4/6 inhibitors and AI showed significant improvement of PFS, ORR, and CBR but with significant increased toxicities compared with AI alone. Fulvestrant 500 mg monotherapy significantly prolonged PFS compared with AI monotherapy. We must wait for the results of the studies with longer follow-up period.

Endocrine Therapy-Based Strategies for Metastatic Breast Cancer with Different Endocrine Sensitivity Statuses: A Systematic Review and Network Meta-Analysis

“…This was also observed in a trial by Giuliano et al [ 71 ] where chemotherapy or hormone therapy regimen was non-inferior to palbociclib plus letrozole for improving PFS. Though CDK4/6i + Ful500 was a better regimen in pre-menopausal women and consistent with previous studies [ 10 , 72 ], the number of studies were insufficient to derive to a meaningful conclusion. Combination of targeted therapies with ETs also revealed interesting results.…”

Clinical Observation and Retrospective Analysis of the Effect of Comprehensive Treatment on Hepatic Hemangiomas in HR Positive Breast Cancer Patients

“…The exact pathogenesis of HH is currently unclear, and related theories suggest that it involves the congenital malformation of blood vessels, which may also be caused by the stimulation of hormones such as estrogen and progestogen [16] . Glannitrapani et al [7] proposed that estrogen is associated with the stimulation of hepatocyte proliferation and could be used as a liver tumor inducer. Breast cancer is a hormone-dependent malignant tumor, and estrone and estradiol are directly related to its incidence [17] .…”

“…Currently, there are no clinical observation data describing the effect of estrogeninhibiting therapy on HH. Endocrine therapy is the standard maintenance treatment option for hormone receptor positive (HR+) breast cancer patients [7] . HR+ breast cancer cases with HH show substantial changes in HH under different treatments after systematic anti-tumor therapy.…”

Cardiotoxicity from neoadjuvant targeted treatment for breast cancer prior to surgery

“…In recent years, CDK4/6 inhibitors have shown large benefits in HRpositive patients, and CDK4/6 inhibitor monotherapy combined with endocrine therapy has been used for the treatment of advanced BC. Since the U.S. Food and Drug Administration (FDA) approval of palbociclib in 2015, CDK4/6 inhibitors have been the first-line treatment option for patients with metastatic HR-positive/HER2-negative phenotypes (70). CDK4/6 inhibitors can block tumor cells in the first phase of the cell cycle (G1 phase) by binding to cell cycle proteins to promote the mid-phase transition, initiate DNA synthesis, and regulate cell transcription (71).…”