Strategies for Increasing the Effectiveness of Aromatase Inhibitors in Locally Advanced Breast Cancer: An Evidence-Based Review on Current Options

Abstract

Giulia Grizzi,1 Michele Ghidini,2 Andrea Botticelli,3,4 Gianluca Tomasello,5 Antonio Ghidini,6 Francesco Grossi,2 Nicola Fusco,7,8 Mary Cabiddu,9 Tommaso Savio,10 Fausto Petrelli9 1Oncology Unit, Oncology Department, ASST of Cremona, Cremona, Italy; 2Oncology Unit, Internal Medicine Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 3Medical Oncology Department, Sant’Andrea Hospital, Rome, Italy; 4Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, Rome, Italy; 5Oncology Unit, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; 6Medical Oncology Unit, Casa Di Cura Igea, Milan, Italy; 7Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 8Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; 9Oncology Unit, Medical Sciences Department, ASST of Bergamo Ovest, Treviglio, Italy; 10Breast Unit, ASST of Bergamo Ovest, Treviglio, ItalyCorrespondence: Fausto PetrelliOncology Unit, Medical Sciences Department, ASST of Bergamo Ovest, Piazzale Ospedale 1, Bergamo 24047, Treviglio, ItalyTel [phone]Fax [phone]Email [email protected]: Neoadjuvant hormonal therapy (NEO-HT) is a possible treatment option for breast cancer (BC) patient with estrogen receptor positive (ER+) and HER2 negative (HER2-) disease. The absence of solid data on the type of drugs to be used and duration of treatment as well as lack of clear evidence of effectiveness of NEO-HT compared to chemotherapy (CT) reserve its use for patients with old age or frail conditions. However, the low pathologic complete response rate (pCR) obtained with tamoxifen or aromatase inhibitors (AIs) alone does not make NEO-HT as a suitable option for the neoadjuvant treatment of HR+ HER2-. The use of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors palbociclib, ribociclib and abemaciclib of the mammalian target of rapamycin (mTOR) inhibitor everolimus and of the phosphoinositide 3 kinase (PI3K) inhibitor taselisib together with endocrine therapy (ET) has become a standard in advanced breast cancer, showing clinical effectiveness and significantly prolonging median progression-free survival compared to ET only. In the early phase disease, the use of ET together with CDK 4/6, mTOR and PI3K inhibitors is still investigational. Data from recent studies are promising even though less impressive than in metastatic setting. In this context, the use of genomic-transcriptomic tools (such as ONCOTYPE, PAM50) and the identification of novel biomarkers (ESR1, PI3Kca, PDGF-R) on tissue or with liquid biopsy could help to select patient prone to respond to endocrine-combined therapy and able to achieve pCR. With our review, we aimed at evaluating the current state of the art in the treatment of locally advanced breast cancer with NEO-HT.Keywords: neoadjuvant endocrine therapy, breast cancer, CDK 4/6 inhibitors, mTOR inhibitors, PI3K inhibitors, aromatase inhibitors

Keywords

• neoadjuvant endocrine therapy
• breast cancer
• cdk 4/6 inhibitors
• mtor inhibitors
• pi3k inhibitors
• aromatase inhibitors