Current Breast Cancer Reports

Malik, Fayaz; Korkaya, Hasan; Clouthier, Shawn; Wicha, Max

2012 Current Breast Cancer Reports

doi: 10.1007/s12609-012-0093-5

Although the heterogeneity of breast cancer has long been recognized, the hierarchical organization and existence of tumor initiating subpopulation within breast tumors was not known until the last decade. These tumor initiating cells called cancer stem cells (CSCs) display features of stem cells such as unlimited ability to self-renew and lineage differentiation. Accumulating evidence now suggests that by virtue of their relative resistance to both radiation and chemotherapy, these cells contribute to resistance and relapse following therapy. Utilizing cell cultures and mouse xenograft models, we and others demonstrated that breast CSCs have far greater invasive and metastatic potential than differentiated tumor cells which comprise the tumor bulk. Altogether, these studies suggest that targeting and elimination of breast CSCs may be required to improve patient outcome. In this review, we will discuss recent developments in breast CSC research and advances in CSC specific targeted therapies that are in preclinical and clinical trials.

Bruin, Monique; Ford, James; Kurian, Allison

2012 Current Breast Cancer Reports

doi: 10.1007/s12609-012-0091-7

Genetic alterations are important drivers of breast cancer development. Rare, high penetrance mutations, including BRCA1 and BRCA2, account for a minority of breast cancer cases. Recent advances in genomic sequencing technologies have aided the search for additional genetic modifiers of breast cancer risk. An increasing number of risk-associated single nucleotide polymorphisms (SNPs) are being identified. These SNPs are relatively common in the studied populations, and while they generally confer a small increase in risk individually, they may act in combination to alter risk more substantially. This review synthesizes the current understanding of these genetic polymorphisms and breast cancer risk, and discusses experiences and challenges with implementing them into existing risk models and into clinical practice. As additional SNPs are discovered and risk estimates are refined, the aim will be to use this information to guide personalized decisions around managing risk, and to deepen our understanding of breast carcinogenesis.

Sikov, William

2012 Current Breast Cancer Reports

doi: 10.1007/s12609-012-0092-6

With the help of ever more powerful research tools triple-negative breast cancer (TNBC) is slowly yielding its secrets. The neoadjuvant setting gives us the best opportunity to address questions raised by the biologic heterogeneity of the disease, and eventually design individualized treatment plans for patients who are identified as likely to have a suboptimal response to chemotherapy. However, given a plethora of aberrantly activated pathways, exacerbated by its genomic instability, the challenge is to separate what drives the behavior of TNBC from the consequences of that behavior. This article reviews our current understanding of TNBC, including recent efforts to identify clinically relevant subsets of the disease, the role of treatments that exploit defects in DNA repair, including chemotherapeutic agents such as the platinum analogues, and biologic agents such as the poly ADP-ribose polymerases (PARP) inhibitors, and then discusses potential targeted approaches to its treatment, most of which are still early in development.

Oakman, Catherine; Tenori, Leonardo; Cappadona S, Silvia; Luchinat, Claudio; Bertini, Ivano; Leo, Angelo

2012 Current Breast Cancer Reports

doi: 10.1007/s12609-012-0090-8

Metabolomics is a science that provides a dynamic portrait of the metabolic status of a biological system. Down from genomics, transcriptomics, and proteomics, metabolomics assesses end product metabolites and small intermediate molecules. In oncology, identification and quantification of metabolites and correlation with critical metabolic pathways in carcinogenesis may provide insight into tumoral biology. In breast cancer, promising early work suggests that metabolomics might enhance current clinical practice by refining biological subclassification, improving prediction of recurrence, and aiding in treatment decisions.

Barginear, Myra; Poznak, Catherine

2012 Current Breast Cancer Reports

doi: 10.1007/s12609-012-0089-1

Bone is the most common site of breast cancer metastases. When breast cancer has metastasized to bone, it is considered an incurable disease. Osseous metastases are associated with significant morbidities including pain, pathological fractures, hypercalcemia of malignancy, and spinal cord compression. In this setting, the palliative goals of care include preventing skeletal related events, managing complications, reducing bone pain, and improving quality of life. Antiresorptive agents such as bisphosphonates have been the mainstay of bone-directed treatment, along with radiation therapy, and surgery. Most recently, RANKL-inhibitors have become another tool in the treatment of bone metastases. This review discusses bone-modifying agents and other targeted interventions in breast cancer patients with skeletal metastases.

Robertson, Fredika; Cristofanilli, Massimo

2012 Current Breast Cancer Reports

doi: 10.1007/s12609-012-0087-3

Inflammatory breast cancer (IBC) is the most lethal variant of locally advanced breast cancer. Although recognized as a distinct clinical entity, there have been few advances in the development of pre-clinical models of IBC, and a lack of IBC-specific therapeutic targets translated into clinical utility to increase overall survival, which is currently 40 % at three years. By use of newly developed pre-clinical models of IBC and patient tumor tissues, E-cadherin, anaplastic lymphoma kinase (ALK), and HSP90 have been identified as targets relevant to IBC that are matched by therapeutics that are either currently in clinical trials or will be tested in clinical trials within the next year. These exciting results illustrate the advances that have been made in recent years in defining the molecular basis of IBC as a distinct disease and the significant strides made in identifying more effective strategies for treatment of patients with IBC.

Yao, Song; Maghsoudlou, Daria; Ambrosone, Christine

2012 Current Breast Cancer Reports

doi: 10.1007/s12609-012-0088-2

Pharmacogenetic research has the potential to identify appropriate individualized therapeutic regimens based upon a patient’s genetic makeup. Numerous genetic variants that may modify the effects of drugs commonly used to treat breast cancer have been examined; however, current evidence is insufficient to support the clinical utility of any of these markers. Recent research in breast cancer pharmacogenetics has included genes in drug metabolism, oxidative stress, DNA repair, and other pathways, and outcome after breast cancer chemotherapy. Studies have also addressed the basis for taxane-induced neurotoxicity and aromatase inhibitor-induced musculoskeletal symptoms. For tamoxifen, despite promising results from previous studies for a role of CYP2D6 genotypes in predicting breast cancer recurrence, data from two prospective randomized trials have not supported these findings. Genome-wide approaches based on large prospective randomized trials have the potential to greatly elucidate the genomic basis for optimizing drug efficacy and reducing toxicity.