Background. Improvements in screening techniques have made significant contributions to the early detection of breast cancer. Physicians thus face the task of providing appropriate screening schedules for their patients. One group for whom this is particularly important are those women with a family history of breast cancer.

Methods. In this report, data from the Cancer and Steroid Hormone Study, a population-based, case-control study conducted by the Centers for Disease Control, are used to provide age-specific risk estimates of breast cancer for women with a family history of breast cancer. The data set includes 4730 patients with histologically confirmed breast cancer age 20–54 years and 4688 control subjects who were frequency matched to patients by geographic region and 5-year age intervals. The data set also includes family histories of breast cancer in mothers and sisters of both patients and control subjects.

Results. Genetic models fit previously to these data by the authors have provided evidence for a rare autosomal dominant allele that results in increased susceptibility to breast cancer. In addition, these models predict that women who carry the allele are at greater risk of developing breast cancer at any age than are women who do not carry the allele. The increase in risk in carriers versus noncarriers does, however, decrease with increasing age. Based on the parameters of this model, age-specific risks for a woman with one or more relatives affected with breast cancer at various ages at onset are given.

Conclusions. These tables can be used for the purpose of counseling women at high risk of breast cancer development, that is, women with a family history of breast cancer.

Autosomal Dominant Inheritance of Early-Onset Breast Cancer: Implications for Risk Prediction

Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis

We evaluated whether a 76-locus polygenic risk score (PRS) and Breast Imaging Reporting and Data System (BI-RADS) breast density were independent risk factors within three studies (1643 case patients, 2397 control patients) using logistic regression models. We incorporated the PRS odds ratio (OR) into the Breast Cancer Surveillance Consortium (BCSC) risk-prediction model while accounting for its attributable risk and compared five-year absolute risk predictions between models using area under the curve (AUC) statistics. All statistical tests were two-sided. BI-RADS density and PRS were independent risk factors across all three studies (P interaction = .23). Relative to those with scattered fibroglandular densities and average PRS (2(nd) quartile), women with extreme density and highest quartile PRS had 2.7-fold (95% confidence interval [CI] = 1.74 to 4.12) increased risk, while those with low density and PRS had reduced risk (OR = 0.30, 95% CI = 0.18 to 0.51). PRS added independent information (P < .001) to the BCSC model and improved discriminatory accuracy from AUC = 0.66 to AUC = 0.69. Although the BCSC-PRS model was well calibrated in case-control data, independent cohort data are needed to test calibration in the general population.

/pdf/the-contributions-of-breast-density-and-common-genetic-4tf0tkv8bf.pdf

The Contributions of Breast Density and Common Genetic Variation to Breast Cancer Risk

The aim of this study is to determine breast cancer risk at mammographic screening episodes and integrate standard risk factors with mammographic density and genetic data to assess changing the screening interval based on risk and offer women at high risk preventive strategies. We report our experience of assessing breast cancer risk within the U.K. National Health Service Breast Screening Program using results from the first 10,000 women entered into the "Predicting Risk Of breast Cancer At Screening" study. Of the first 28,849 women attending for screening at fifteen sites in Manchester 10,000 (35%) consented to study entry and completed the questionnaire. The median 10-year Tyrer-Cuzick breast cancer risk was 2.65% (interquartile range, 2.10-3.45). A total of 107 women (1.07%) had 10-year risks 8% or higher (high breast cancer risk), with a further 8.20% having moderately increased risk (5%-8%). Mammographic density (percent dense area) was 60% or more in 8.3% of women. We collected saliva samples from 478 women for genetic analysis and will extend this to 18% of participants. At time of consent to the study, 95.0% of women indicated they wished to know their risk. Women with a 10-year risk of 8% or more or 5% to 8% and mammographic density of 60% or higher were invited to attend or be telephoned to receive risk counseling; 81.9% of those wishing to know their risk have received risk counseling and 85.7% of these were found to be eligible for a risk-reducing intervention. These results confirm the feasibility of determining breast cancer risk and acting on the information in the context of population-based mammographic screening.

https://cancerpreventionresearch.aacrjournals.org/content/canprevres/5/7/943.full.pdf

Assessing individual breast cancer risk within the U.K. national health service breast screening program : a new paradigm for cancer prevention

The information available about breast cancer risk factors has increased dramatically during the last 10 years. In particular, studies of low-penetrance genes and mammographic density have improved our understanding of breast cancer risk. In addition, initial steps have been taken in investigating interactions between genes and environmental factors. This review concerns with actual data on this topic. Several genome-wide association studies (GWASs) with a case–control design, as well as large-scale validation studies, have identified and validated more than a dozen single nucleotide polymorphisms (SNPs) associated with breast cancer risk. They are located not only in or close to genes known to be involved in cancer pathogenesis, but also in genes not previously associated with breast cancer pathogenesis, or may even not be related to any genes. SNPs have also been identified that alter the lifetime risk in BRCA mutation carriers. With regard to nongenetic
 risk factors, studies of postmenopausal hormone replacement therapy (HRT) have revealed important information on how to weigh up the risks and benefits of HRT. Mammographic density (MD) has become an accepted and important breast cancer risk factor. Lifestyle and nutritional considerations have become an integral part of most studies of breast cancer risk, and some improvements have been made in this field as well. More than 10 years after the publication of the first breast cancer prevention studies with tamoxifen, other substances such as raloxifene and aromatase inhibitors have been investigated and have also been shown to have preventive potential. Finally, mammographic screening systems have been implemented in most Western countries during the last decade. These may be developed further by including more individualized methods of predicting the patientʼs breast cancer risk.

https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0031-1280437.pdf

Breast Cancer Risk - Genes, Environment and Clinics.

It has been shown in several studies that antihormonal compounds can offer effective prophylactic treatment to prevent breast cancer. In view of the low participation rates in chemoprevention trials, the purpose of this study was to identify the characteristics of women taking part in a population-based mammography screening program who wished to obtain information about the risk of breast cancer and then participate in the the International Breast Cancer Intervention Study II (IBIS-II) trial, a randomized double-blind controlled chemoprevention trial comparing anastrozole with placebo. A paper-based survey was conducted in a population-based mammography screening program in Germany between 2007 and 2009. All women who met the criteria for the mammography screening program were invited to complete a questionnaire. A total of 2,524 women completed the questionnaire, and 17.7% (n = 446) met the eligibility criteria for the IBIS-II trial after risk assessment. The women who wished to receive further information about chemoprevention were significantly younger (P < 0.01) and had significantly more children (P = 0.03) and significantly more relatives with breast cancer (P < 0.001). There were no significant differences between the participants with regard to body mass index or hormone replacement therapy. Normal mammographic findings at screening were the main reason (42%) for declining to participate in the IBIS-II trial or attend risk counseling. The ultimate rate of recruitment to the IBIS-II trial was very low (three women). Offering chemoprevention to women within a mammography screening unit as part of a paper-based survey resulted in low participation rates for both, the survey and the final participation in the IBIS-II trial. More individualized approaches and communication of breast cancer risk at the time of the risk assessment might be helpful to increase the participation and the understanding of chemopreventive approaches.

/pdf/breast-cancer-risk-assessment-in-a-mammography-screening-2vzpclot3u.pdf

Breast cancer risk assessment in a mammography screening program and participation in the IBIS-II chemoprevention trial

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Breast cancer risk assessment in a mammography screening program and participation in the IBIS-II chemoprevention trial