Pharmacogenomics of breast cancer therapy: An update

Abstract

Clinical and histopathologic characteristics of breast cancer have long played an important role in treatment decision-making. Well-recognized prognostic factors include tumor size, node status, presence or absence of metastases, tumor grade, and hormone receptor expression. High tumor grade, presence of hormone receptors, and HER2-positivity are a few predictive markers of response to chemotherapy, endocrine manipulations, and anti-HER2 agents, respectively. However, there is much heterogeneity of outcomes in patients with similar clinical and pathologic features despite equivalent treatment regimens. Some of the difference in response to specific therapies can be attributed to somatic tumor characteristics, such as degree of estrogen receptor expression and HER2 status. In recent years, there has been great interest in evaluating the role that pharmacogenetics/pharmacogenomics, or variations in germline DNA, play in alteration of drug metabolism and activity, thus leading to disparate outcomes among patients with similar tumor characteristics. The utility of these variations in treatment decision-making remains debated. Here we review the data available to date on genomic variants that may influence response to drugs commonly used to treat breast cancer. While none of the variants reported to date have demonstrated clinical utility, ongoing prospective studies and increasing understanding of pharmacogenetics will allow us to better predict risk of toxicity or likelihood of response to specific treatments and to provide a more personalized therapy.

Mitogen-Activated Protein Kinase Signal Transduction in Solid Tumors

“…Breast cancer is the leading cancer diagnosis in women aged 20-45 .Risk Factors of breast cancer include breast density (a highly heritable quantitative trait) (Boyd et al, 2010), age, family history, parity, and so on (Westbrook et al, 2013). To be more accurate, estrogen receptor (ER), progesterone receptor (PR) and HER2 expression are of great importance (Liu et al, 2013).…”

No Clinically Significant Association between CFH and ARMS2 Genotypes and Response to Nutritional Supplements

“…For example, in oncology, information on genetic variants that predict successful responses to therapy (or adverse events) has led to genetically-informed treatment strategies. 11,12 Numerous studies have evaluated the association of genetic testing and treatment with anti-vascular endothelial growth factor drugs for neovascular AMD with retrospective analyses. 13,14,15,16,17,18 These have been several studies with varying outcome variables and duration, resulting in no clear consensus about this association.…”

Community Education of Personalized Breast Cancer Therapy Utilizing Students of HealthCare Professions

“…There are many combinations of receptor types that a patient can have in breast cancer. One, patients can be hormone receptor positive (HR+/HER2-), though most seen in non-Hispanic white women [10], over 80% of breast cancers are ER+, and nearly 65% are PR+. [11] In 20% of breast cancers, cells make too much protein known as HER2, leading to a very aggressive and fast growing cancer [11].…”

“…HER2 positive (HR-/HER2+) patients are associated with decreased overall and relapse-free survival [6]. Lastly, though seen mostly in non-Hispanic black women, patients can be "triple negative" (ER-/PR-/HER2-), which leads to a poorer prognosis and higher recurrence rate [10]. Based on what type of somatic alterations and receptor markers are present, treatment can be tailored specifically to the patient.…”