Breast cancer risk assessment for possible tailored screening for Japanese women

Accurate risk assessment for individual women is essential for effective screening of breast cancer (BC) in Japan, because the incidence of BC is still lower than in Western countries. We investigated various new risk factors of BC by means of case control studies and found that serum estrone and adiponectine levels as well as mammographic breast density were significantly correlated to BC risk. Combining these new factors and conventional risk factors of BC may result in a new and useful risk assessment tool, may improve the cost-effectiveness of screening, and may enable us to reduce the BC mortality of Japanese women.     

Association Between Lifestyle Changes,Mammographic Breast Density,and Breast Cancer

In screening for breast cancer (BC), mammographic breast density (MBD) is a powerful risk factor that increases breast carcinogenesis and synergistically reduces the sensitivity of mammography. It also reduces specificity of lesion identification, leading to recalls, additional testing, and delayed and later-stage diagnoses, which result in increased health care costs. These findings provide the foundation for dense breast notification laws and lead to the increase in patient and provider interest in MBD. However, unlike other risk factors for BC, MBD is dynamic through a woman’s lifetime and is modifiable. Although MBD is known to change as a result of factors such as reproductive history and hormonal status, few conclusions have been reached for lifestyle factors such as alcohol, diet, physical activity, smoking, body mass index (BMI), and some commonly used medications. Our review examines the emerging evidence for the association of modifiable factors on MBD and the influence of MBD on BC risk. There are clear associations between alcohol use and menopausal hormone therapy and increased MBD. Physical activity and the Mediterranean diet lower the risk of BC without significant effect on MBD. Although high BMI and smoking are known risk factors for BC, they have been found to decrease MBD. The influence of several other factors, including caffeine intake, nonhormonal medications, and vitamins, on MBD is unclear. We recommend counseling patients on these modifiable risk factors and using this knowledge to help with informed decision making for tailored BC prevention strategies.     

A Review of Breast Density Implications and Breast Cancer Screening

Breast density is an independent risk factor for breast cancer and significantly decreases the sensitivity of mammography. Assessing a woman’s risk of developing breast cancer is becoming increasingly important for establishing individual screening recommendations and preventive strategies. This article reviews the factors influencing mammographic density (MD), the available methods of MD assessment, and its effect on breast cancer. Finally, we discuss the supplemental screening methods for women with dense breast tissue.     

Evidence of the effect of adjunct ultrasound screening in women with mammography-negative dense breasts: interval breast cancers at 1 year follow-up

Surveillance of interval cancers (IC) provides a measure of breast screening efficacy. Increased breast density is a predictor of breast cancer risk and of the risk of IC in screening. Improving screening sensitivity in women with dense breasts, through adjunct ultrasound (US), may potentially reduce IC; however this has not been proven. We report on first-year IC in a retrospective cohort of 8865 women who had 19,728 screening examinations (2001-2006): women with non-dense (D1-D2) breasts received mammography (M) screening, and women with dense (D3-D4) breasts also received ultrasound. Data linkage with both hospital discharge records and cancer registry databases was used to identify IC.Underlying cancer rates (cancers observed within 1-year from screening) were 6.3/1000 screens in the D1-D2 group and 8.3/1000 screens in the D3-D4 group. Cancer detection rate (CDR) was 5.98/1000 in all screening examinations; in D3-D4 breasts ultrasound had an additional CDR of 4.4/1000 screens. There were 21 first-year IC, an overall interval cancer rate (ICR) of 1.07/1000 negative screens: 0.95/1000 in women <50 years and 1.16/1000 screens in women ?50 years. ICR by breast density were 1.0/1000 negative screens in D1-D2, and 1.1/1000 negative screens in D3-D4. Interval cancers were early stage (in situ or small invasive) cancers, almost all were node-negative. Screening sensitivity was 83.5% for mammography alone in D1-D2 breasts relative to 86.7% for mammography with ultrasound in D3-D4 breasts.Our study shows that including ultrasound as adjunct screening in women with D3-D4 breasts brings the IC rate to similar levels as IC in non-dense breasts - this suggests that additional cancer detection by ultrasound is likely to improve screening benefit in dense breasts, and supports the implementation of a randomised trial of adjunct ultrasound in women with increased breast tissue density.     

Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study

Introduction

It is not clear whether high mammographic density (MD) is equally associated with all subtypes of breast cancer (BC). We investigated the association between MD and subsequent BC, considering invasiveness, means of detection, pathologic subtype, and the time elapsed since mammographic exploration and BC diagnosis.

Methods

BC cases occurring in the population of women who attended screening from 1997 through 2004 in Navarre, a Spanish region with a fully consolidated screening program, were identified via record linkage with the Navarre Cancer Registry (n = 1,172). Information was extracted from the records of their first attendance at screening in that period. For each case, we randomly selected four controls, matched by screening round, year of birth, and place of residence. Cases were classified according to invasiveness (ductal carcinoma in situ (DCIS) versus invasive tumors), pathologic subtype (considering hormonal receptors and HER2), and type of diagnosis (screen-detected versus interval cases). MD was evaluated by a single, experienced radiologist by using a semiquantitative scale. Data on BC risk factors were obtained by the screening program in the corresponding round. The association between MD and tumor subtype was assessed by using conditional logistic regression.

Results

MD was clearly associated with subsequent BC. The odds ratio (OR) for the highest MD category (MD >75%) compared with the reference category (MD <10%) was similar for DCIS (OR = 3.47; 95% CI = 1.46 to 8.27) and invasive tumors (OR = 2.95; 95% CI = 2.01 to 4.35). The excess risk was particularly high for interval cases (OR = 7.72; 95% CI = 4.02 to 14.81) in comparison with screened detected tumors (OR = 2.17; 95% CI = 1.40 to 3.36). Sensitivity analyses excluding interval cases diagnosed in the first year after MD assessment or immediately after an early recall to screening yielded similar results. No differences were seen regarding pathologic subtypes. The excess risk associated with MD persisted for at least 7 to 8 years after mammographic exploration.

Conclusions

Our results confirm that MD is an important risk factor for all types of breast cancer. High breast density strongly increases the risk of developing an interval tumor, and this excess risk is not completely explained by a possible masking effect.     

Mammographic density—a review on the current understanding of its association with breast cancer

There has been considerable recent interest in the genetic, biological and epidemiological basis of mammographic density (MD), and the search for causative links between MD and breast cancer (BC) risk. This report will critically review the current literature on MD and summarize the current evidence for its association with BC. Keywords ‘mammographic dens*’, ‘dense mammary tissue’ or ‘percent dens*’ were used to search the existing literature in English on PubMed and Medline. All reports were critically analyzed. The data were assigned to one of the following aspects of MD: general association with BC, its relationship with the breast hormonal milieu, the cellular basis of MD, the generic variations of MD, and its significance in the clinical setting. MD adjusted for age, and BMI is associated with increased risk of BC diagnosis, advanced tumour stage at diagnosis and increased risk of both local recurrence and second primary cancers. The MD measures that predict BC risk have high heritability, and to date several genetic markers associated with BC risk have been found to also be associated with these MD risk predictors. Change in MD could be a predictor of the extent of chemoprevention with tamoxifen. Although the biological and genetic pathways that determine and perhaps modulate MD remain largely unresolved, significant inroads are being made into the understanding of MD, which may lead to benefits in clinical screening, assessment and treatment strategies. This review provides a timely update on the current understanding of MD’s association with BC risk.     

Benign Breast Disease as a Breast Cancer Risk in Japanese Women

A hospital-based retrospective cohort study of benign breast disease (BBD) as a risk factor of future breast cancer (BC) development was conducted. Four hundred and twenty-eight patients with biopsied BBD were followed-up for a median period of 8 years, together with age-matched women with normal breasts (normal control) and BC patients (cancer control), at the ratio of 1:2:2. Twenty-one breast cancers developed, 7 in the cases, 4 in the normal controls, and 10 in the BC controls, showing the relative risk (RR) with 95% confidence intervals (CD to be 3.5 (1.03–11.9) in the cases with respect to the normal controls. The RR of the cases is not lower than that of contralateral breast cancer incidence. There were no significant differences in the risks of cancers in other organs among the groups. Pathological examination revealed that only atypical hyperplasia increased the RR of BC, as compared with the normal control breast group, or with non-proliferative disease. These results suggest that in a low-risk country, Japan, BBD is a definite risk factor for BC development as in high-risk countries.     

江西省10254例乳腺癌普查资料分析

目的调查江西省乳腺癌的发病率,乳腺癌发生的危险因素及普查对乳腺癌早期发现的作用。方法采用调查表、体检、乳腺钼靶X线、乳腺多普勒超对江西省10254名妇女进行乳腺癌普查,比较普查发现乳腺癌与门诊发现的乳腺癌的临床病理特点。结果体检、乳腺钼靶X线和多普勒超声联合方法进行乳腺癌普查具有较高的准确性,普查组发现13例乳腺癌（检出率为126.8/10万）,好发年龄段为40～49岁,乳腺癌的高危因素还包括乳腺癌家族史、未生育、月经初潮小于12岁、未哺乳、高脂饮食、饮酒、乳腺疾病史。普查发现的乳腺癌早期比率显著高于门诊组。结论体检、乳腺钼靶X线和多普勒超声联合方法是乳腺癌普查的有效手段,普查可以发现更多的早期乳腺癌,对高危因素进行干预可能减少乳腺癌发生。     

Circulating Sex Hormones and Mammographic Breast Density among Postmenopausal Women

The use of breast density as an intermediate or predictive marker of breast cancer risk is limited by an incomplete understanding of the etiology of breast density. High blood levels of endogenous estrogens and androgens are associated with increased risk of breast cancer among postmenopausal women. We sought to examine whether these hormones are also associated with breast density. The Wisconsin Breast Density Study enrolled 257 postmenopausal women, ages 55-70 years, with no history of postmenopausal hormone use, from mammography clinics in Madison, Wisconsin. Subjects provided a blood sample for sex hormone analysis, and breast density was measured from subjects' screening mammograms using a computer-assisted thresholding method. Numerous sex hormones were associated with breast density in age-adjusted analyses. However, further adjustment for body mass index and other potentially confounding factors substantially attenuated or eliminated these associations. In the fully adjusted model, there remained a positive association between percent breast density and serum progesterone (P=0.03), with percent density rising from 11.9% (95% CI: 9.8, 14.1%) among women in the lowest quartile of serum progesterone to 15.4% (12.9, 18.2%) among women in the highest quartile. There was also a positive association between sex hormone binding globulin and percent breast density (P=0.06). In contrast, there were no independent associations between percent breast density and estradiol (total, free, or bioavailable), estrone, estrone sulfate, or testosterone (total, free, or bioavailable). These results suggest that breast density has a hormonal etiology; however, it may differ in important ways from that of breast cancer risk.     

Breast Density and the Importance of Supplemental Screening

Purpose of Review

Mammographically dense breast tissue raises the risk of developing breast cancer and makes detection of breast cancer more difficult using standard of care mammography. This paper seeks to outline the evidence behind these risks and highlight the importance of informing patients, and their clinicians, of their density status. Solutions are also offered for improved detection in cancer screening in this population.

Recent Findings

Many states now require density information be conveyed to the patient. When performed in addition to screening mammography, supplemental screening methods (including tomosynthesis, ultrasound, and especially MRI) have demonstrated markedly improved rates of cancer detection in the dense screening population. However, only six states mandate insurance coverage for supplemental screening.

Summary

Increased breast density inherently raises the risk of breast cancer and reduces mammographic sensitivity. It is essential that women with dense breasts are notified of these hazards and provided with additional screening methods to aid in early detection.

     

Perceived Barriers to Breast Cancer Screening among Saudi Women at Primary Care Setting

Introduction: Screening for breast cancer (BC) is of low rate in Saudi Arabia; although it is provided in the country free of charge to the population. This cross-sectional study aimed at investigating the perceived barriers towards BC screening in Al Hassa, Saudi Arabia. Participants and Methods: A total of 816 adult Saudi women aged ≥ 30 years attending for routine primary health services or accompanying patients at the selected primary health care centers (PHCs) were randomly selected from 12 PHCs (8 urban and four rural) using multi-stage sampling method. Participants were invited to personal interview using semi-structured data collection instrument including inquiries about socio-demographics, reproductive history, previous histories of diagnosed breast lesions and breast cancer. The perceived individual barriers towards screening, their attitudes, the reasons for not attending previously held screening campaigns in Al Hassa, were also included. Results: Low utilization of BC screening has being significantly associated with woman’s age (OR=2.55; 95% CI= 1.71-3.83), higher educational status (OR=2.98; 95% CI=2.05-4.34), higher family income (OR=1.96; 95% CI=1.31-2.93), using hormonal contraception (OR=1.46; 95% CI=0.99-2.13) and positive history of previous breast (OR=12.16; 95% CI=6.89-21.46), as shown by the results of the logistic regression model. Exploratory factor analysis showed that personal fears (especially fear of doctors/examiners, fear of hospitals and health facilities and fear of consequences/results) were the major factors that hinder women from utilizing the free of charge BC screening with high loading eigenvalue of 3.335, explaining 30.4% of the barriers. Conclusion: Educational interventions aim at improving breast cancer knowledge and addressing barriers should be incorporated as core component of the screening program in Saudi Arabia.     

Risk Factors for Screen-Detected Breast cancer a case-control study

Risk factors for breast cancer (BC) detected in mammography screening were sought using a questionnaire among 31 927 women aged from 40 to 74 years who attended screening. Data from 204 women with screen-detected BC were compared with those of 612 controls who did not have EC in screening. Mothers of women with BC had more often BC than those of the controls (8% vs. 3%, odds ratio, OR, 3.18, 95% CI 1.59-6.35). Women with screen-detected BC were older at their first, childbirth (25.7 years vs. 24.7 years, OR 1.61, 1.14-2.33), and younger at menarche (13.6 years vs. 13.8 years, OR 1.38, 1.00-1.91), but there was no significant difference in the body mass index, number of pregnancies, breast size, smoking, or in the use of contraceptive pills between the cases and the controls. In multivariate logistic regression analyses, late age at the first childbirth, BC in the mother, and early age at menarche were independent risk factors for screen-detected BC but they appear to be of limited value in targeting screening in the female population aged from 40 to 74 in order to improve its cost-effectiveness.     

MRI and breast cancer: role in detection, diagnosis, and staging

Increasing experience with magnetic resonance imaging (MRI) has raised important questions about how it should be used in breast cancer screening, and for presurgical evaluation and posttherapy follow-up of women with this disease. Overall, the availability of MRI as an adjunct to mammography and ultrasound offers clear clinical benefit to women at increased risk of breast cancer development due to BRCA1 and BRCA2 mutations, and to women presenting with axillary adenopathy and an occult primary breast tumor. In contrast, its benefit for routine selection of breast conservation or further assessment of lobular carcinoma in women of average risk has not been demonstrated. This article reviews the use of MRI in these settings, with an emphasis on the clinical outcomes that have been observed to date.     

Breast density and outcome of mammography screening: a cohort study

The purpose of this study was to investigate the effect of breast density on breast cancer (BC) mortality in a mammography screening programme. The cohort included 48 052 women participating in mammography screening in Copenhagen, Denmark, where biennial screening is offered to women aged 50–69 years. We collected information for the years 1991–2001 on screening outcome, incident BCs (screen-, interval-, and later detected), and BC deaths. Breast density was dichotomised into fatty (F) and mixed/dense (M/D) breasts. Screening sensitivity was measured as the odds ratio of interval versus screen-detected cancer for dense versus F breasts. Poisson regression was used to estimate the ratios for BC incidence, case fatality, and mortality between women with M/D and F breasts. For women with M/D breasts, the odds ratio of an interval cancer was 1.62 (95% confidence interval, CI, 1.14–2.30), and the age-adjusted rate ratios were 2.45 (95% CI 2.14–2.81) for BC incidence, 0.60 (95% CI 0.43–0.84) for case fatality, and 1.78 (95% CI 1.17–2.72) for BC mortality. The study shows that BC in women with M/D breasts is more frequent, but on average less severe, than in women with F breasts.     

Clinical and epidemiological issues in mammographic density

High mammographic density is associated with an increased risk of breast cancer, and of all known breast cancer risk factors has the greatest attributable fraction. Mammographic density is estimated to account for 16% of all breast cancers, but can be altered by endogenous and exogenous hormonal factors, and generally declines with age. Confounding factors such as age, parity, menopausal status and BMI make the interpretation of mammographic density particularly challenging. Furthermore, none of the established means of measuring mammographic density are entirely satisfactory because they are time consuming or subjective. It is hoped that by adding information regarding mammographic density to existing models of breast cancer risk assessment, the accuracy of individual risk assessments can be improved. Although mammographic density has clearly been shown to be a powerful factor for predicting the risk of developing breast cancer, its potential role in assessing hormonal preventive regimens and helping to tailor screening algorithms cannot be fully realized until we have more-precise, simple and reproducible density measures.     

Self administered screening for hereditary cancers in conjunction with mammography and ultrasound

We evaluated the feasibility of an automated tablet computer application providing a family and personal history based cancer risk assessment for hereditary breast, ovarian, endometrial and colorectal cancers. 1,002 women presenting for screening mammography and 1,000 presenting for ultrasound were offered screening. The application calculated the risk of BRCA mutations using BRCAPRO, Myriad and Tyrer–Cuzick risk assessment models. Lifetime risk of breast and ovarian cancer was assessed with the BRCAPRO, Claus and Tyrer–Cuzick models. Colorectal and endometrial cancer risk was calculated via the MMRpro model. Patients were identified as high-risk based on thresholds 10 % or greater risk for carrying genetic mutations or 20 % or greater lifetime risk of breast or ovarian cancer. The percent of women found to be high-risk by a single risk assessment tool ranged from 0.5 to 5.3 %. Combining assessment tools found 9.3 % of women to be high-risk. The risk assessments performed similarly for the mammography and ultrasound cohorts with yields (combining assessment tools) of 9.2 and 9.4 % respectively. The average ages of all the high-risk women were 45.8 and 39.6 years for the mammography and ultrasound cohorts respectively. Difficulties encountered included a need for software upgrade, wireless network unreliability and hardware theft. Automated family history screening can identify women probably at high-risk for hereditary cancers efficiently. The number of women identified is increased by employing multiple risk assessment models simultaneously. Surveying women in conjunction with ultrasound identified women at increased risk as effectively and at a younger age than with screening mammography.     

Breast cancer risk in ataxia telangiectasia (AT) heterozygotes: haplotype study in French AT families.

Epidemiological studies in ataxia telangiectasia (AT) families have suggested that AT heterozygotes could have an increased cancer risk, especially breast cancer (BC) in women. It has also been suggested that an increased sensibility of AT heterozygotes to the effect of ionizing radiation could be responsible for the increased BC risk. BC relative risk (RR) estimation in AT heterozygotes within families ascertained through AT children is presented here. Family data collected included demographic characteristics, occurrence of cancers, past radiation exposures and blood samples. DNA samples were studied using seven ATM linked microsatellites markers allowing AT haplotypes reconstitution. The relative risk of BC was assessed using French estimated incidence rates. A significant increase risk of BC is found among obligate ATM heterozygotes with a point estimate of 3.32 (P = 0.002). BC relative risk calculated according to age is significantly increased among the obligate ATM heterozygotes female relatives with an age < or = 44 years (RR = 4.55, P = 0.005). The BC relative risk is statistically borderline among the obligate ATM heterozygote female relatives with an age > or = 45 years (RR = 2.48, P = 0.08). The estimated BC relative risk among ATM heterozygotes is consistent with previously published data. However, the increased risk is only a little higher than classical reproductive risk factors and similar to the risk associated with a first-degree relative affected by BC.     

Early detection of breast cancer: benefits and risks of supplemental breast ultrasound in asymptomatic women with mammographically dense breast tissue. A systematic review

Background  

Mammographic screening alone will miss a certain fraction of malignancies, as evidenced by retrospective reviews of mammograms following a subsequent screening. Mammographic breast density is a marker for increased breast cancer risk and is associated with a higher risk of interval breast cancer, i.e. cancer detected between screening tests. The purpose of this review is to estimate risks and benefits of supplemental breast ultrasound in women with negative mammographic screening with dense breast tissue.     

Association of Empirically Derived Food-Based Inflammatory Potential of the Diet and Breast Cancer: A Hospital-Based Case-Control Study

BackgroundDiet may be a modifiable factor in the prevention of breast cancer (BC) by modulating inflammation. We used a food-based empirical dietary inflammatory index (FDII) to evaluate the association between FDII and odds of breast cancer in Iranian women.MethodsThe present case-control study carried out on 150 age-matched women with newly diagnosed breast cancer and controls. Data for dietary intake and anthropometric measures were collected. FDII score was developed according to participants dietary intakes of 27 pre-defined food groups. Multivariate odds ratios (OR) with 95% confidence intervals (CI) were used to investigate the association of empirically derived food-based inflammatory potential of the diet and breast cancer.ResultsThe odds ratios of BC according to quartiles of FDII score by multivariate logistic regression models indicated the FDII score was significantly associated with BC risk (OR: 2.38; 95% CI: 1.23-4.59, P _trend = .04). After controlling confounders, multivariate logistic regressions remained significant which revealed in participants at the fourth quartile of FDII score chance of breast cancer was 2.8 times higher than participants in the first quartile.ConclusionsThe results of our study suggested that more pro-inflammatory diet (higher FDII scores) was associated with increased BC risk. These findings suggest that developing an effective dietary modification based on FDII may reduce risk of BC.