Targeted therapy for breast cancer prevention.

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer

Association between the c.*229C>T polymorphism of the topoisomerase IIb binding protein 1 (TopBP1) gene and breast cancer

Topoisomerase IIb binding protein 1 (TopBP1) is involved in cell survival, DNA replication, DNA damage repair and cell cycle checkpoint control. The biological function of TopBP1 and its close relation with BRCA1 prompted us to investigate whether alterations in the TopBP1 gene can influence the risk of breast cancer. The aim of this study was to examine the association between five polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 30UTR region of the TopBP1 gene and breast cancer risk as well as allele-specific gene expression. Five hundred thirty-four breast cancer patients and 556 population controls were genotyped for these SNPs. Allele-specific Top- BP1 mRNA and protein expressions were determined by using real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with breast cancer. Compared to homozygous common allele carriers, heterozygous and homozygous for the T variant had significantly increased risk of breast cancer (adjusted odds ratio = 3.81, 95 % confidence interval: 1.63–8.34, p = 0.001). Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT or TT genotype. There was a significant association between the rs115160714 and tumor grade and stage. Most carriers of minor allele had a high grade (G3) tumors classified as T2-T4N1M0. Our study raises a possibility that a genetic variation of TopBP1 may be implicated in the etiology of breast cancer

A Decision Technology System To Advance the Diagnosis and Treatment of Breast Cancer

Geographical variations in cancer rates have been observed for decades. Described spatial patterns and trends have provided clues for generating hypotheses about the etiology of cancer. For breast cancer, investigators have demonstrated that some variation can be explained by differences in the population distribution of known breast cancer risk factors such as menstrual and reproductive variables (Laden, Spiegelman, and Neas, 1997; Robbins, Bescianini, and Kelsey, 1997; Sturgeon, Schairer, and Gail, 1995). However, regional patterns also may reflect the effects of Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer (1995): (a) environmental hazards (such as air and water pollution), (b) demographics and the lifestyle of a mobile population, (c) subgroup susceptibility, (d) changes and advances in medical practice and healthcare management, and (e) other factors. To accurately measure breast cancer risk in individuals and population groups, it is necessary to singly and jointly assess the association between such risk and the hypothesized factors. Various statistical models will be needed to determine the potential relationships between breast cancer development and estimated exposures to environmental contamination. To apply the models, data must be assembled from a variety of sources, converted into the statistical models’ parameters, and delivered effectively to researchers and policy makers. A Web-enabled decision technology system can be developed to provide the needed functionality. This chapter will present a conceptual architecture for such a decision technology system. First, there will be a brief overview of a typical geographical analysis. Next, the chapter will present the conceptual Web-based decision technology system and illustrate how the system can assist users in diagnosing and treating breast cancer. The chapter will conclude with an examination of the potential benefits from system use and the implications for breast cancer research and practice

Self-Reported Chemicals Exposure, Beliefs About Disease Causation, and Risk of Breast Cancer in the Cape Cod Breast Cancer and Environment Study: A Case-Control Study

BACKGROUND: Household cleaning and pesticide products may contribute to breast cancer because many contain endocrine disrupting chemicals or mammary gland carcinogens. This population-based case-control study investigated whether use of household cleaners and pesticides increases breast cancer risk. METHODS: Participants were 787 Cape Cod, Massachusetts, women diagnosed with breast cancer between 1988 and 1995 and 721 controls. Telephone interviews asked about product use, beliefs about breast cancer etiology, and established and suspected breast cancer risk factors. To evaluate potential recall bias, we stratified product-use odds ratios by beliefs about whether chemicals and pollutants contribute to breast cancer; we compared these results with odds ratios for family history (which are less subject to recall bias) stratified by beliefs about heredity. RESULTS: Breast cancer risk increased two-fold in the highest compared with lowest quartile of self-reported combined cleaning product use (Adjusted OR = 2.1, 95% CI: 1.4, 3.3) and combined air freshener use (Adjusted OR = 1.9, 95% CI: 1.2, 3.0). Little association was observed with pesticide use. In stratified analyses, cleaning products odds ratios were more elevated among participants who believed pollutants contribute "a lot" to breast cancer and moved towards the null among the other participants. In comparison, the odds ratio for breast cancer and family history was markedly higher among women who believed that heredity contributes "a lot" (OR = 2.6, 95% CI: 1.9, 3.6) and not elevated among others (OR = 0.7, 95% CI: 0.5, 1.1). CONCLUSIONS: Results of this study suggest that cleaning product use contributes to increased breast cancer risk. However, results also highlight the difficulty of distinguishing in retrospective self-report studies between valid associations and the influence of recall bias. Recall bias may influence higher odds ratios for product use among participants who believed that chemicals and pollutants contribute to breast cancer. Alternatively, the influence of experience on beliefs is another explanation, illustrated by the protective odds ratio for family history among women who do not believe heredity contributes "a lot." Because exposure to chemicals from household cleaning products is a biologically plausible cause of breast cancer and avoidable, associations reported here should be further examined prospectively.Massachusetts Legislature; Massachusetts Department of Public Health; Susan S. Bailis Breast Cancer Research Fund at Silent Spring Institute; United States Centers for Disease Control and Prevention (R01 DP000218-01, 1H75EH000377-01

CYP3A variation, premenopausal estrone levels, and breast cancer risk.

BACKGROUND: Epidemiological studies have provided strong evidence for a role of endogenous sex steroids in the etiology of breast cancer. Our aim was to identify common variants in genes involved in sex steroid synthesis or metabolism that are associated with hormone levels and the risk of breast cancer in premenopausal women. METHODS: We measured urinary levels of estrone glucuronide (E1G) using a protocol specifically developed to account for cyclic variation in hormone levels during the menstrual cycle in 729 healthy premenopausal women. We genotyped 642 single-nucleotide polymorphisms (SNPs) in these women; a single SNP, rs10273424, was further tested for association with the risk of breast cancer using data from 10 551 breast cancer case patients and 17 535 control subjects. All statistical tests were two-sided. RESULTS: rs10273424, which maps approximately 50 kb centromeric to the cytochrome P450 3A (CYP3A) gene cluster at chromosome 7q22.1, was associated with a 21.8% reduction in E1G levels (95% confidence interval [CI] = 27.8% to 15.3% reduction; P = 2.7 × 10(-9)) and a modest reduction in the risk of breast cancer in case patients who were diagnosed at or before age 50 years (odds ratio [OR] = 0.91, 95% CI = 0.83 to 0.99; P = .03) but not in those diagnosed after age 50 years (OR = 1.01, 95% CI = 0.93 to 1.10; P = .82). CONCLUSIONS: Genetic variation in noncoding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and is associated with the risk of breast cancer in younger patients. This association may have wider implications given that the most predominantly expressed CYP3A gene, CYP3A4, is responsible for metabolism of endogenous and exogenous hormones and hormonal agents used in the treatment of breast cancer

Breast Cancer

This chapter in Cancer Concepts: A Guidebook for the Non-Oncologist presents an overview of breast cancer, including etiology, screening, pathology, staging, and treatment.https://escholarship.umassmed.edu/cancer_concepts/1019/thumbnail.jp

Intrauterine environment, mammary gland mass and breast cancer risk

Two intimately linked hypotheses on breast cancer etiology are described. The main postulate of the first hypothesis is that higher levels of pregnancy estrogens and other hormones favor the generation of a higher number of susceptible stem cells with compromised genomic stability. The second hypothesis postulates that the mammary gland mass, as a correlate of the number of cells susceptible to transformation, is an important determinant of breast cancer risk. A simple integrated etiological model for breast cancer is presented and it is indicated that the model accommodates most epidemiological aspects of breast cancer occurrence and natural history

The role of diet and lifestyle in women with breast cancer: An update review of related research in the Middle East

© Zainab Taha and Sakina E. Eltom 2018. Breast cancer is the most common malignancy among Arab women in Eastern Mediterranean Region (EMR). The incidence of breast cancer has substantially increased in recent years among this women population, especially those younger than 50, and the incidence is expected to double by 2030. Considerable experimental evidence supports the potential role of dietary habits and lifestyle in cancer etiology and cancer prevention. In this review we examined the literature for evidence to link dietary choices and the rise in incidence and mortality of breast cancer among women in EMR. A literature search was conducted in PubMed and Ovid MEDLINE databases up to December 2017. The search terms used are breast cancer prevalence, breast cancer incidence worldwide, breast cancer and: nutrition, protein intake, Vitamin D intake, fat intake, phytoestrogens, EMR, Arab, Middle East, Gulf countries, the UAE Arab women, breast cancer risk, diet, and chemoprevention. We found evidence to suggest that there is an alarming epidemic of obesity among women in most of the EMR countries, especially Gulf Cooperation Council (GCC) countries. The rise in the new breast cancer cases among women could be attributed to excess body weight. Their dietary pattern, which correlates with obesity, can be an important factor in the etiology of cancer. Although very few studies were found to support a direct causal relationship between obesity and breast cancer in the EMR, circumstantial evidence clearly points to the possible role of the epidemic, obesity, in this population and the startling rise in cases of breast cancer. Well-designed and systematic studies are urgently needed to confirm these associations and to elucidate potential mechanisms. More urgently, calls to action are needed in many sectors and at all levels of society, to establish intensive strategies for reducing obesity and promoting an overall healthy diet. Continued and expanded research on diet, lifestyle, and breast cancer risk is urgently needed to build the foundation for future progress in evidence-based public health efforts