Breast Cancer In High-risk Populations Research Articles

Olufunmilayo Olopade—preventive oncologist using genetics to fight breast cancer in high-risk populations

Olufunmilayo Olopade—preventive oncologist using genetics to fight breast cancer in high-risk populations

Vitamin D and Calcium Supplement Use and High-Risk Breast Cancer: A Case-Control Study among BRCA1 and BRCA2 Mutation Carriers.

The role of vitamin D and calcium use in the development of breast cancer among women in the general population is not clear. Furthermore, whether vitamin D and calcium supplement use are associated with breast cancer in high-risk populations has not been evaluated. Thus, we evaluated the association between vitamin D and/or calcium supplement use and breast cancer among women with a pathogenic variant (mutation) in BRCA1 or BRCA2. BRCA mutation carriers enrolled in a longitudinal study were invited to complete a supplemental questionnaire on lifetime supplement use. Cases included women with a prevalent diagnosis of invasive breast cancer, and controls had no history of breast cancer. Vitamin D and calcium use were categorized as never/ever use, and as tertiles of supplement intake (total average daily supplement use). Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of breast cancer. This study included 134 breast cancer cases and 276 controls. Women who used vitamin D-containing supplements had 46% lower odds of having breast cancer compared to those who never used supplements (OR 0.54; 95% CI 0.31, 0.91; p = 0.02). Increasing vitamin D and calcium supplement intake was inversely associated with the odds of having breast cancer (p-trend = 0.04). Findings were suggestively stronger among BRCA1 mutation carriers; however, analyses were limited by small strata. These findings suggest a potential inverse association between vitamin D and calcium supplementation and BRCA breast cancer. Additional studies are warranted to confirm these findings and accurately inform clinical care guidelines.

The Clinical Application of Combined Ultrasound, Mammography, and Tumor Markers in Screening Breast Cancer among High-Risk Women.

In order to explore the clinical application value of color Doppler ultrasound (CDUS), mammography (MAM), and serum tumor marker carbohydrate antigen 153 (CA153) in screening breast cancer (BC) for high-risk women, a total of 38,241 women were surveyed by epidemiological questionnaire on BC high-risk factors. A total of 10,821 cases were screened, accounting for 28.30%. They were randomly divided into US, MAM, and CA153 and combined examination group which has no significant difference in high-risk factors. Breast cancer in high-risk population was screened by CDUS, MAM, and CA153 and combined examination. CA153 was detected by electroluminescence method. The positive detection rate of BC was 360.41/100,000 (39/10,821). The overall difference in the positive detection rate of BC among 10,821 cases in all age groups was statistically significant. The sensitivity and negative predictive value of combined examination were significantly improved compared with each single examination. Combined examination for BC screening can significantly improve the sensitivity of BC early diagnosis and reduce the missed diagnosis rate.

Tumor necrosis factor receptor signaling modulates carcinogenesis in a mouse model of breast cancer

Pro-inflammatory conditions have long been associated with mammary carcinogenesis and breast cancer progression. The underlying mechanisms are incompletely understood but signaling of pro-inflammatory cytokine TNFα through its receptors TNFR1 and TNFR2 is a major mediator of inflammation in both obesity and in the response of tissues to radiation, 2 known risk factors for the development of breast cancer. Here, we demonstrated the loss of one TNFR2 allele led to ductal hyperplasia in the mammary gland with increased numbers of mammary epithelial stem cell and terminal end buds. Furthermore, loss of one TNFR2 allele increased the incidence of breast cancer in MMTV-Wnt1 mice and resulted in tumors with a more aggressive phenotype and metastatic potential. The underlying mechanisms include a preferential activation of canonical NF-κB signaling pathway and autocrine production of TNFα. Analysis of the TCGA dataset indicated inferior overall survival for patients with down-regulated TNFR2 expression. These findings unravel the imbalances in TNFR signaling promote the development and progression of breast cancer, indicating that selective agonists of TNFR2 could potentially modulate the risk for breast cancer in high-risk populations.

Is Lipid Mapping an Effective Early Detection Tool for Breast Cancer in High-risk Populations?

Is Lipid Mapping an Effective Early Detection Tool for Breast Cancer in High-risk Populations?

Ultrasound for Breast Cancer Screening in High-Risk Women: Results From a Population-Based Cancer Screening Program in China.

Background: Ultrasound is an important modality for breast cancer screening. However, the evidence on the effectiveness of ultrasound screening in population-based cancer screening program in lacking. We aimed to evaluate the diagnostic yield of ultrasound screening in a population-based breast cancer screening in China.Methods: The analyses were conducted in the context of the Cancer Screening Program in Urban China, which recruited 1,938,996 eligible participants aged 40–69 years from 16 provinces in China from 2012 to 2016. We included 72,250 women assessed to be high-risk for breast cancer who undertook ultrasound screening per study protocol. Diagnostic yield according to the Breast Imaging Reporting and Data System (BI-RADS) was evaluated. Risk factors associated with the positive findings of ultrasound were also explored by univariate and multivariable logistic regression analyses.Results: Overall, there were 9,765 (13.51%) women had positive findings of ultrasound screening, including 8,487 (11.75%), 1,210 (1.67%), and 68 (0.09%) of BI-RADS categories of III, IV, and V, respectively. Younger ages, late age of 1st live birth and short-term breast feeding were found to be positively associated with positive findings under ultrasound in multivariate analyses stratified by menopause status and family history of breast cancer. Multivariable prediction models were constructed and yielded only modest prediction accuracy, with AUCs around 0.55.Conclusions: We found the diagnostic yield of ultrasound screening for breast cancer in high-risk population was satisfactory. Prediction models based on environmental risk factors had limited prediction accuracy and need to be improved in the future.

Use of Receiver Operating Characteristic (ROC) Curve Analysis for Tyrer-Cuzick and Gail in Breast Cancer Screening in Jiangxi Province, China.

BackgroundBreast cancer is a malignant tumor derived from breast gland epithelium. The screening and early diagnosis of breast cancer in high-risk populations can effectively suppress its threat to women’s health and improve treatment efficiency, and thus has critical importance. Using various evaluation models, the present study evaluated cancer risk in 35–69-year-old women, and the usefulness of models in breast cancer prevention was compared.Material/MethodsA total of 150 infiltrative breast cancer patients who were diagnosed with breast cancer at our hospital were recruited, along with 130 healthy women as the control group. A retrospective study was performed to collect information. The 5-year risk of breast cancer was evaluated using the Gail and Tyrer-Cuzick models. Diagnostic results were analyzed to plot ROC curves for comparing the value for screening between Gail and Tyrer-Cuzick models.ResultsThe Gail model has 53.33% sensitivity and 77.69% specificity, with 73.39% positive prediction value, 59.06% negative prediction value, 64.64% accuracy, and 0.31 Jordon index. The Tyrer-Cuzick model had 66.00% sensitivity, 86.92% specificity, 85.34% positive prediction value, 68.90% negative prediction value, 75.71% accuracy, and 0.53 Jordon index. The area under the curve (AUC) was 0.665 for the Gail model (95% CI: 0.629~0.701) and 0.786 for the Tyrer-Cuzick model (95% CI: 0.757~0.815).ConclusionsBoth Gail model and Tyrer-Cuzick models can be used to evaluate breast cancer risk. The Gail model has relatively lower accuracy in evaluating breast cancer risk in Jiangxi province of China and the Tyrer-Cuzick model had relatively higher accuracy.

Abstract IA19: Homologous recombination repair deficiency and breast cancer progression in high-risk populations

Abstract Analysis of cancer genomes has rapidly become an integral part of the practice of clinical oncology, with implications for diagnosis, prognosis, treatment, and prevention. Inherited and sporadic cancers often share common mutational events. When inherited mutations are identified, genetic counseling is an essential component of care. Pathogenic BRCA1 and BRCA2 mutations are the strongest predictors of breast cancer risk and may be the strongest predictors of other inherited forms of solid tumors and hematologic malignancies as well. Waiting to treat advanced breast cancer with targeted therapies is a failure of primary prevention, and population-based strategies for risk management in high-risk populations will be needed. Understanding breast cancer progression in genetic defined subgroups has the potential to accelerate progress in precision medicine. I will discuss ongoing research in our group, our recent findings in defining the genomic landscape of early-onset breast cancer, and future directions for the early detection, treatment, and prevention of breast cancer in high-risk populations. Citation Format: Olufunmilayo I. Olopade. Homologous recombination repair deficiency and breast cancer progression in high-risk populations [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA19.

Guest Editorial: Breast Cancer Epigenetics in the Era of Precision Medicine

The Precision Medicine Initiative (PMI) was officially unveiled on January 20, 2015 by President Obama during his State of the Union address. This initiative will transform healthcare by providing health professionals with new and improved strategies to identify individuals at risk for diseases like breast cancer and to determine which treatments and therapies are best suited for the patient. The term “precision medicine” which most researchers often refer to as “personalized or individualized medicine” considers the approach that one-size-does-not-fit-all [1]. The phrase “onesize-does-not-fit-all” refers to a treatment or drug that may work well for some individuals but not for others. A nice example is the anti-estrogen breast cancer drug tamoxifen (TAM) which is used to prevent breast cancer in high-risk populations and to treat postmenopausal estrogen receptor (ER) – positive breast cancers [2,3]. Breast cancer is the most common cancer and one of the leading causes of cancer death among women [4]. Close to one-third of postmenopausal breast cancer patients experience a relapse after adjuvant treatment with TAM [5,6]. It is unclear as to why some patients experience a more favorable response to certain drugs, such as TAM, while other patients with the same diagnosis experience multiple adverse side effects from taking TAM. Recent advances in the field of breast cancer pharmacogenomics provide strong evidence that acquired or inherited genetic differences in drug metabolic pathways can affect an individual’s response to TAM and other chemotherapeutic drugs [7-10]. In support of these observations, our pharmacogenetic study showed that a single nucleotide polymorphism in the promoter of the TAM metabolizing gene UDP-glucuronosyltransferase 1A4 (UGT1A4) significantly decreases how TAM and its derivatives are metabolized in the human liver [11]. These studies, along with countless other pharmacogenomic studies, demonstrate the influence of pharmacogenomics on policy implementation and efforts that guide the development of more effective medical treatments tailored to an individual’s genetic makeup. Currently, more than 100 pharmacogenomic biomarkers have been added to drug labels that may help clinicians take appropriate actions to manage their patient’s health based on their biomarker information [12]. Because the PMI has directed most of its efforts toward research that seeks to provide new knowledge about how an individual’s genetic makeup, environment, and behavior can impact disease risk and response to treatment, I expect that this initiative will require continuous and effective collaborations between clinicians, scientists, health professionals and policy makers.

Breast Tumor Detection Using Piezoelectric Fingers: First Clinical Report

Mammography is key to detection of breast cancer in high-risk populations. Currently, aside from palpation and risk-assessment questionnaires, there is no prescreening test that can improve the accuracy, safety, and cost effectiveness of screening low-risk populations. The piezoelectric finger (PEF) is a radiation-free, portable, and low-cost breast tumor detector we developed to be used as a prescreening tool. Patients presenting with breast abnormalities detected by palpation or imaging were enrolled in this IRB-approved study. The PEF testing was performed with the patient in supine position before undergoing biopsy or surgical excision. The locations of the lesions detected by PEF were compared with those confirmed on imaging or pathology. A total of 40 patients were enrolled and 46 lesions were confirmed by imaging or pathology. The PEF reported 55 lesions, with 9 false positives and 2 true positives not originally found on imaging or palpation. The overall sensitivity of the PEF test was 87% (40 of 46). In women 40 years old or younger, overall sensitivity was or 100% (19 of 19). In women who had a lesion visible on mammography, PEF had a sensitivity of 83% (24 of 29). Of these, in women aged 40 years or younger, PEF identified all 7 mammographically visible lesions, including 2 malignant lesions. When compared with ultrasound, PEF correctly identified 87% (34 of 39) in this group. Of these, in women aged 40 years or younger, PEF identified 100% (19 of 19) of all ultrasound-visible lesions. The PEF identified abnormalities in all 39 patients who presented with breast abnormalities and did not demonstrate any false negatives that would prevent the patients from additional evaluation, which makes it a good prescreening tool. In addition, PEF demonstrated 100% sensitivity in women aged 40 years or younger, a traditionally low-risk population.

Breast Cancer Onset in Twins and Women With Bilateral Disease

Little is known of the onset of breast cancer in high-risk populations. We investigated the risk of breast cancer in twin sisters and in the contralateral breast taking family history into consideration. We analyzed a Scandinavian population-based cohort of 2,499 female twin pairs, in which at least one had a diagnosis of breast cancer and estimated the risk of breast cancer in the sister. Using a total of 11 million individuals in Sweden with complete family links, we identified 93,448 women with breast cancer and estimated the risk of a bilateral breast cancer. The incidence of breast cancer in twin sisters of breast cancer patients was 0.64% per year and 0.42% per year in mono- and dizygotic twin sisters, respectively. In comparison, the risk of familial (affected first-degree relative) and nonfamilial bilateral breast cancer was 1.03% per year and 0.68% per year, respectively. Contrary to the risk of unilateral disease, the risk of cancer in the nonaffected twin and the opposite breast was not affected by age or time since first event. The relative risk of familial bilateral cancer was 52% higher (incidence rate ratio [IRR] = 1.52; 95% CI, 1.42 to 1.64) and the relative risk in the dizygotic twin sister was 25% lower (IRR = 0.75; 95% CI, 0.61 to 0.91) compared with the risk of nonfamilial bilateral cancer. The elevated risk of breast cancer in high-risk groups is little affected by age and time since diagnosis. Our findings suggest that susceptible groups of women might have already aggregated genetic prerequisites for breast cancer.

Screening for Recurrences in Patients Treated with Breast-Conserving Surgery: Is there a Role for MRI?

Although it has been shown that magnetic resonance imaging (MRI) is more sensitive than mammography in the detection of breast cancer in high-risk populations, there is little data on the use of MRI as a screening tool to detect recurrence after breast-conserving surgery. Our objective was to determine the potential role of MRI in the screening of breast cancer patients treated with breast-conserving surgery. Retrospective chart review of all patients undergoing margin-negative lumpectomy and adjuvant radiation therapy for infiltrating breast carcinoma between 1(st) January 1993 and 1(st) January 2004. Patients were followed for recurrence in the ipsilateral or contralateral breast by physical exam and mammography. Four hundred and seventy-six primary tumor excisions were performed. Patients were followed for a median of 5.4 years. Ipsilateral breast recurrences developed in eight patients (1.7%) with a mean diameter of 1.6 cm. All of these women are alive and free of metastases. Contralateral cancers developed in 11 patients (2.3%) with a mean diameter of 1.5 cm. Ten of these 11 women are alive and free of disease. In a contemporary patient population the risk of local recurrence after lumpectomy and radiation therapy is very low. If screening MRI had been a part of annual follow-up, a total of 2570 MRIs would have been performed. Given the small tumor size at detection and the excellent survival of those who recurred, annual screening MRI would have incurred significant cost and would have been unlikely to improve overall survival.

Quimioprevenção do câncer de mama

Chemoprevention is defined as the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenic progression of invasive cancer. Drugs that act as chemoprevention agents for breast cancer are divided into two major groups: drugs that prevent Estrogen Receptor (ER)-positive breast cancers [selective estrogen receptor modulators (SERM), aromatase inhibitors GnKH agonists and phytoestrogens] and drugs that prevent ER-negative breast cancers [cyclooxygenase-2 (COX-2) inhibitors, retinoids, statins, receptor tyrosine, kinase inhibitors, monoclonal antibody against HER-2 and telomerase inhibitors]. Results from the NSABP Study of Tamoxifen and Raloxifene (STAR), which compared the risk-reducing efficacy as well as toxicity of these two SERMs in a similar high-risk for breast cancer population, showed that Raloxifene is as effective as Tamoxifen in reducing the risk of non-invasive breast cancer (p=.83). It has a statistically significant lower risk of thromboembolic events and cataracts, however a non- statistically significant higher risk of noninvasive breast cancer. Based on promising data involving reduction of contralateral breast cancer risk in adjuvant studies, several aromatase inhibitors, including letrozole, anastrozole and exemestane, are being included in trials to evaluate their efficacy in breast cancer prevention in both case-control and cohort studies As such randomized studies to confirm this efficacy are needed. Positive results of several recent clinical trials for preventing breast cancer in high-risk populations suggest that chemoprevention is a rational and attractive strategy.

Genetic predisposition to cancer

Genetic predisposition to cancer - an introduction from families to chromosomes - genetic linkage and other methods of finding cancer-predisposing genes how to isolate cancer-predisposing genes retinoblastoma - the paradigm for a genetically inherited cancer syndrome neurofibromatosis - types I and II multiple endocrine neoplasia - types I and II Wilms' tumor and other genetic causes of renal cancer the Li-Fraumeni syndrome and cancers arising from germline p53 mutations ataxia telangiectasia and radiation sensitivity Fanconi's anemia Gorlin's syndrome xeroderma pigmentosum and related syndrome genetics and the common cancers familial breast cancer the breast/ovarian cancer syndrome and BrCA1 screening for breast cancer in high-risk populations. The management of women with a high risk of breast cancer: (1) prophylactic tamoxifen (2) the contraversy of prophylactic mastectomy. familial prostrate cancer and its management psychological effects of the high-risk breast cancer the genetics of familial colon cancer familial melanoma and its management the organization of a familial cancer clinic screening for known cancer-predisposition genes the ethics of testing for cancer predisposition genes.