title: Prognostic and Predictive Biomarkers of Endocrine Responsiveness for Estrogen Receptor Positive Breast Cancer.
abstract: The estrogen-dependent nature of breast cancer is the fundamental basis for endocrine therapy. The presence of estrogen receptor (ER), the therapeutic target of endocrine therapy, is a prerequisite for this therapeutic approach. However, estrogen-independent growth often exists de novo at diagnosis or develops during the course of endocrine therapy. Therefore ER alone is insufficient in predicting endocrine therapy efficacy. Several RNA-based multigene assays are now available in clinical practice to assess distant recurrence risk, with majority of these assays evaluated in patients treated with 5 years of adjuvant endocrine therapy. While MammaPrint and Oncotype Dx are most predictive of recurrence risk within the first 5 years of diagnosis, Prosigna, Breast Cancer Index (BCI), and EndoPredict Clin have also demonstrated utility in predicting late recurrence. In addition, PAM50, or Prosigna, provides further biological insights by classifying breast cancers into intrinsic molecular subtypes. Additional strategies are under investigation in prospective clinical trials to differentiate endocrine sensitive and resistant tumors and include on-treatment Ki-67 and Preoperative Endocrine Prognostic Index (PEPI) score in the setting of neoadjuvant endocrine therapy. These biomarkers have become important tools in clinical practice for the identification of low risk patients for whom chemotherapy could be avoided. However, there is much work ahead toward the development of a molecular classification that informs the biology and novel therapeutic targets in high-risk disease as chemotherapy has only modest benefit in this population. The recognition of somatic mutations and their relationship to endocrine therapy responsiveness opens important opportunities toward this goal.
authors.affiliation: Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, 63110, St Louis, MO, USA.
authors.forename: Cynthia X
authors.initials: CX
authors.lastname: Ma
authors.affiliation: Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, 63110, St Louis, MO, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Bose
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, 320A Cullen, MS 600, 77030, Houston, TX, USA. mjellis@bcm.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009154:Mutation; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen
keywords: BCI; EndoPredict; Endocrine therapy; Estrogen receptor positive breast cancer; MammaPrint; Multi-gene assay; Oncotype Dx; Prognostic markers; Prosigna; Risk of recurrence