title: Opportunities and challenges of long term anti-estrogenic adjuvant therapy: treatment forever or intermittently?
abstract: Extended adjuvant (5-10 years) therapy targeted to the estrogen receptor (ER) has significantly decreased mortality from breast cancer (BC). Areas covered: Translational research advanced clinical testing of extended adjuvant therapy with tamoxifen or aromatase inhibitors (AIs). Short term therapy or non-compliance increase recurrence, but surprisingly recurrence and death does not increase dramatically after 5 years of adjuvant therapy stops. Expert commentary: Compliance ensures optimal benefit from extended antihormone adjuvant therapy.Retarding acquired resistance using CDK4/6 or mTOR inhibitors is discussed. Preventing acquired resistance from mutations of ER could be achieved with Selective ER Downregulators (SERDs), eg fulvestrant. Fulvestrant is a depot injectable so oral SERDs are sought for extended use. In reality, a 'super SERD' which destroys ER but improves women's health like a Selective ER Modulator (SERM), would aid compliance to prevent recurrence and death. Estrogen-induced apoptosis occurs in 30% of BC with antihormone resistance. The 'one in three' rule that dictates that one in three unselected patients respond to either hormonal or antihormonal therapy in BC occurs with estrogen or antiestrogen therapy and must be improved. The goal is to maintain patients for their natural lives by blocking cancer cell survival through precision medicine using short cycles of estrogen apoptotic salvage therapy, and further extended antihormone maintenance.
authors.affiliation: a Department of Breast Medical Oncology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Poulomi
authors.initials: P
authors.lastname: Bhattacharya
authors.affiliation: a Department of Breast Medical Oncology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Balkees
authors.initials: B
authors.lastname: Abderrahman
authors.affiliation: a Department of Breast Medical Oncology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: V Craig
authors.initials: VC
authors.lastname: Jordan
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D055118:Medication Adherence; D009364:Neoplasm Recurrence, Local; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors; D057170:Translational Research, Biomedical / Q000458:organization & administration
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen
keywords: Adjuvant therapy; Breast Cancer; antiestrogen; aromatase inhibitors; estrogen-induced apoptosis; tamoxifen