Personalized Therapy for Breast Cancer: A Dream or a Reality?

Abstract

Breast cancer oncology represents one of the disciplines where personalized cancer medicine has been most actively pursued. The class-discovery studies conceptually advanced the field, underlining the molecular heterogeneity governing this common disease. The advent of high-throughput molecular profiling technologies holds great promise for the advance of all aspects of personalized cancer medicine, namely accurate prognostication, prediction of response to common systemic therapies and individualized monitoring of the disease. Moreover, an ever-expanding arsenal of targeted therapeutic compounds under clinical development, coupled with emerging powerful tools for comprehensive molecular and functional characterization, pose significant promise for improved clinical outcomes for breast cancer patients. Interrogation of the germline genetic variation offers further promise towards tailoring of breast cancer management. Well-conducted prospective validation studies are needed if breast cancer personalized therapy is to transform from a dream into a reality.

Small breast cancers: When and how to treat

“…Although the overall prognosis of this population is quite good, a subgroup of these patients recur and eventually succumb to their disease. In the era of personalized cancer medicine, the development of a genotype-phenotype based tailored treatment for BC would be able to accurately guide treatment decisions, targeting specific molecular pathways responsible for the cancer aggressiveness [63][64][65][66]. Additionally, emerging targeted agents for BC could represent potentially less toxic and more effective treatment options, if matched correctly to specific molecular subgroups of patients, a hypothesis still needing clinical proof [67].…”

The AURORA initiative for metastatic breast cancer

“…Detailed molecular profiling of breast cancer is deepening our understanding of the molecular biology underpinning this common disease, promising to lead to personalised cancer medicine (Zardavas et al , 2013b). Currently, there are multiple initiatives worldwide aiming to provide a detailed molecular characterisation of several types of cancer (Table 1).…”

Molecular fingerprinting catches responders to therapeutic agents

“…Application of integrated molecular datasets to develop clinically useful predictive gene signatures to guide precision medicine is currently under way [5]. However, there are three noteworthy studies that generated predictive multigene signatures.…”

“…One study used a multifactorial approach to identify a multi-gene classifier as predictive for response to anthracyclines. The resulting anthracycline-based score (A-score) could serve as a valuable tool for sparing a subset of breast cancer patients from chemotherapy [4,5,8]. Similarly, the amplification of chromosome 8q22 and/or overexpression of YWHAZ/LAPTM4B can be used as predictive biomarkers to anthracycline response [5].…”

“…The predictors are now clinically available (examples include PAM50®, Oncotype DX®, MammaPrint®, MapQuantDx®, Theros® and Endopredict®). These first-generation gene signatures can also be partially used as predictive gene signatures and have been instrumental in sparing a subgroup of ER-positive breast cancer patients from adjuvant cytotoxic chemotherapy [4,5]. However, there has been less success in the development of gene signatures to predict response to specific therapeutic agents, and as such no commercially available tests are currently available.…”