Comparing the diagnostic accuracy, reading time, and inter-rater agreement of breast MRI abbreviated and full protocols: a multi-reader study.

BACKGROUND: Earlier studies have shown that abbreviated protocol magnetic resonance imaging (AB-MRI) has similar diagnostic accuracy as the full protocol (Full MRI). PURPOSE: To compare the diagnostic accuracy, reading time, and inter-rater agreement of AB-MRI to Full MRI among women without known increased familial risk of breast cancer or prior biopsy. MATERIAL AND METHODS: In total, 395 MRI examinations were included in this study. Three readers were blinded to all patient information. The AB-MRI and Full MRI were read separately and in a different random order for each of the readers. Scores 1-2 were considered test negative while scores 3-5 were test positive. A positive reference test was the diagnosis of malignancy; a negative reference test was the absence of a diagnosis of breast cancer within a two-year follow-up. We used a generalized estimating equations approach to compare sensitivity and specificity between the two protocols. We used t-tests to compare the average reading time and Krippendorff's alpha to compare inter-rater agreement. RESULTS: MRI examinations of 395 women (median age=56 years) were evaluated. For AB-MRI and Full MRI, respectively, the sensitivity was 93.0% (95% CI=90.6-95.0) vs. 92.0% (95% CI=89.4-94.1), the specificity was 91.7% (95% CI=90.3-92.9) vs. 94.3% (95% CI=93.2-95.3), average reading time was 67 vs. 126 s, and the inter-rater agreement 0.79 vs. 0.83. The difference in sensitivity was not statistically significant (P=0.840), but the difference in specificity was significant (P=0.003). CONCLUSION: AB-MRI has similar sensitivity, but somewhat lower specificity. The average reading time for the abbreviated protocol is lower, as is inter-rater agreement.

Early detection of breast cancer rectifies inequality of breast cancer outcomes.

OBJECTIVES: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome. METHODS: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression. RESULTS: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range. CONCLUSIONS: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.

Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women.

BACKGROUND: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death. METHODS: Among 549,091 women, covering approximately 30% of the Swedish screening-eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression. RESULTS: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51-0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66-0.84 [P < .001]). CONCLUSIONS: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.

The association between breast cancer risk factors and background parenchymal enhancement at dynamic contrast-enhanced breast MRI.

BACKGROUND: Background parenchymal enhancement (BPE) of normal tissue at breast magnetic resonance imaging is suggested to be an independent risk factor for breast cancer. Its association with established risk factors for breast cancer is not fully investigated. PURPOSE: To study the association between BPE and risk factors for breast cancer in a healthy, non-high-risk screening population. MATERIAL AND METHODS: We measured BPE and mammographic density and used data from self-reported questionnaires in 214 healthy women aged 43-74 years. We estimated odds ratios for the univariable association between BPE and risk factors. We then fitted an adjusted model using logistic regression to evaluate associations between BPE (high vs. low) and risk factors, including mammographic breast density. RESULTS: The majority of women had low BPE (84%). In a multivariable model, we found statistically significant associations between BPE and age (P = 0.002) and BMI (P = 0.03). We did find a significant association between systemic progesterone medication and BPE, but due to small numbers, the results should be interpreted with caution. The adjusted odds ratio for high BPE was 3.1 among women with density D (compared to B) and 2.1 for density C (compared to B). However, the association between high BPE and density was not statistically significant. We did not find statistically significant associations with any other risk factors. CONCLUSION: Our study confirmed the known association of BPE with age and BMI. Although our results show a higher likelihood for high BPE with increasing levels of mammographic density, the association was not statistically significant.

Does three-dimensional functional infrared imaging improve breast cancer detection based on digital mammography in women with dense breasts?

PURPOSE: We aimed to estimate the incremental cancer detection rate achieved by adding three-dimensional functional infrared imaging (3DIRI) to digital mammography in women with dense breasts. MATERIALS AND METHODS: In this prospective study conducted between December 2014 and April 2016, 1727 women (median age 56) with percentage volumetric breast density > 6% were recruited at routine screening mammography to undergo additional 3DIRI. The 3DIRI findings were classified as negative or positive. Women with a negative mammography but positive 3DIRI were referred to dynamic contrast-enhanced MRI, whereas all other women underwent routine follow-up based on the mammography finding. Diagnosis of breast cancer was verified by histopathologic examination. The number of women diagnosed with a malignancy formed the basis of our statistical analysis. RESULTS: Mammography detected 7 cancers in 7 women. Of 1692 women with negative mammography, 222 women (13%) had a positive 3DIRI of which 219 underwent MRI. An additional 6 cancers were identified in 5 women, increasing the diagnostic yield from 7 of 1727 (0.41%) to 12 of 1727 (0.69%). The incremental cancer detection rate associated with using 3DIRI to select women for MRI was 5 of 222 (22.5 additional cancers per 1000). CONCLUSION: The use of 3DIRI to select women for an additional MRI can result in the detection of additional cancers in women with dense breasts, but at the expense of additional false positives and considerably lower positive predictive value of the combined examinations. Additional studies are necessary to evaluate the role of 3DIRI as an adjunct to mammography. KEY POINTS: • Use of three-dimensional functional infrared imaging to select women for an MRI in addition to screening mammography has the potential to improve breast cancer detection in women with dense breasts.

Prospective blinded surveillance screening of Swedish women with increased hereditary risk of breast cancer.

PURPOSE: To evaluate the sensitivity and specificity of different screening modalities in women with a family history of breast cancer. METHODS: Our blinded, prospective, comparative cohort analysis included three types of screening, mammography, ultrasound, and clinical breast examination once per year for 6 years. Eligible patients for this study were healthy women with ≥ 17% lifetime risk of breast cancer or with a mutation in BRCA1 or BRCA2. RESULTS: A total of 632 women were screened between 2002 and 2012 (each for 6 years). During the study, 30 women were diagnosed with breast cancer, with 10 of these diagnoses occurring between screening visits, and six of the 10 diagnosed women were gene carriers. The clinical presentation for the women diagnosed with breast cancer was followed until 2017. No consistent patterns for the diagnostic capacity of the different screening modalities were found, although mammography showed low sensitivity, whereas ultrasound showed better sensitivity in three of the six rounds. The specificity was high in mammography and improved in ultrasound over time. Most importantly, clinical breast examination provided no additional information toward the diagnosis of breast cancer. CONCLUSION: Neither mammography nor ultrasound performed yearly were sensitive enough as standalone modalities, although high specificity was confirmed. Our findings indicate that high risk (> 29% life time risk) individuals and gene carriers can be screened biannually, using the same protocol as used in mutation carriers. Our results also suggest that low-risk groups (< 20%) may continue to be referred to population mammography screening program, while clinical breast examination may be omitted in all risk groups, and could be optional in gene carriers.

Automated measurement of volumetric mammographic density: a tool for widespread breast cancer risk assessment.

INTRODUCTION: Mammographic density is a strong risk factor for breast cancer and an important determinant of screening sensitivity, but its clinical utility is hampered due to the lack of objective and automated measures. We evaluated the performance of a fully automated volumetric method (Volpara). METHODS: A prospective cohort study included 41,102 women attending mammography screening, of whom 206 were diagnosed with breast cancer after a median follow-up of 15.2 months. Percent and absolute dense volumes were estimated from raw digital mammograms. Genotyping was performed in a subset of the cohort (N = 2,122). We examined the agreement by side and view and compared density distributions across different mammography systems. We also studied associations with established density determinants and breast cancer risk. RESULTS: The method showed good agreement by side and view, and distributions of percent and absolute dense volume were similar across mammography systems. Volumetric density was positively associated with nulliparity, age at first birth, hormone use, benign breast disease, and family history of breast cancer, and negatively with age and postmenopausal status. Associations were also observed with rs10995190 in the ZNF365 gene (P < 1.0 × 10(-6)) and breast cancer risk [HR for the highest vs. lowest quartile, 2.93; 95% confidence interval, 1.73-4.96 and 1.63 (1.10-2.42) for percent and absolute dense volume, respectively]. CONCLUSIONS: In a high-throughput setting, Volpara performs well and in accordance with the behavior of established density measures. IMPACT: Automated measurement of volumetric mammographic density is a promising tool for widespread breast cancer risk assessment.

High-throughput mammographic-density measurement: a tool for risk prediction of breast cancer.

INTRODUCTION: Mammographic density (MD) is a strong, independent risk factor for breast cancer, but measuring MD is time consuming and reader dependent. Objective MD measurement in a high-throughput fashion would enable its wider use as a biomarker for breast cancer. We use a public domain image-processing software for the fully automated analysis of MD and penalized regression to construct a measure that mimics a well-established semiautomated measure (Cumulus). We also describe measures that incorporate additional features of mammographic images for improving the risk associations of MD and breast cancer risk. METHODS: We randomly partitioned our dataset into a training set for model building (733 cases, 748 controls) and a test set for model assessment (765 cases, 747 controls). The Pearson product-moment correlation coefficient (r) was used to compare the MD measurements by Cumulus and our automated measure, which mimics Cumulus. The likelihood ratio test was used to validate the performance of logistic regression models for breast cancer risk, which included our measure capturing additional information in mammographic images. RESULTS: We observed a high correlation between the Cumulus measure and our measure mimicking Cumulus (r = 0.884; 95% CI, 0.872 to 0.894) in an external test set. Adding a variable, which includes extra information to percentage density, significantly improved the fit of the logistic regression model of breast cancer risk (P = 0.0002). CONCLUSIONS: Our results demonstrate the potential to facilitate the integration of mammographic density measurements into large-scale research studies and subsequently into clinical practice.

Measuring walking speed in COPD: test-retest reliability of the 30-metre walk test and comparison with the 6-minute walk test.

AIMS: To examine test-retest reliability of the 30-metre walk test (30mWT) in patients with chronic obstructive pulmonary disease (COPD) and to compare the 30mWT with the 6-minute walk test (6MWT). METHODS: Forty-nine subjects with stable COPD were included. The 30mWT consists of walking at different walking intensities over a distance of 30 metres - self-selected speed (ss-30mWT) and maximal speed (ms-30mWT). The test was conducted twice and the time to walk 30 metres was recorded. The 6MWT was performed in duplicate on the same day. RESULTS: Test-retest reliability was high: intraclass correlation coefficient (ICC(2.1)) = 0.93 (95% CI 0.87 to 0.97) for maximal walking speed and 0.87 (95% CI 0.78 to 0.93) for self-selected walking speed. Both maximal and self-selected speed had a standard error of measurement (SEM) of 0.07 m/s and SEM% was 4.4 for maximal speed and 5.9 for self-selected speed. The correlation, criterion validity, between ms-30mWT and the 6MWT was r=0.78 (p<0.001). Heart rate, dyspnoea, exertion and oxygen saturation were more affected after the 6MWT than after the 30mWT (p<0.001). CONCLUSIONS: The 30mWT is a reliable submaximal test that is easy to perform and can be used to measure physical function (walking ability) in patients with COPD. It may be well suited for primary care settings.

The impact of organized mammography service screening on breast carcinoma mortality in seven Swedish counties.

BACKGROUND: The evaluation of organized mammographic service screening programs is a major challenge in public health. In particular, there is a need to evaluate the effect of the screening program on the mortality of breast carcinoma, uncontaminated in the screening epoch by mortality from 1) cases diagnosed in the prescreening period and 2) cases diagnosed among unscreened women (i.e., nonattenders) after the initiation of organized screening. METHODS: In the current study, the authors ascertained breast carcinoma deaths in the prescreening and screening epochs in 7 Swedish counties from tumors diagnosed in these epochs and in the age group 40-69 years in 6 counties and 50-69 years in 1 county. Data regarding deaths were obtained from the Uppsala Regional Oncologic Center in conjunction with the National Cause of Death Register. The total number of women in the eligible age range living in each county was obtained from the annual population data of Statistics Sweden. Detailed screening data were provided by the screening centers in the seven counties, including the number of invited, the number attended, and whether each individual breast carcinoma case was exposed (screen-detected and interval cases combined) or unexposed (not-invited or nonattenders) to mammographic screening. There were 2044 breast carcinoma deaths from 14,092 incident tumors diagnosed in the prescreening and screening epochs, and the total number of person-years was 7.5 million. Data were analyzed using Poisson regression with corrections for self-selection bias and lead-time bias when appropriate. RESULTS: The mortality reduction for breast carcinoma in all 7 counties combined for women actually exposed to screening compared with the prescreening period was 44% (relative risk [RR] = 0.56; 95% confidence interval [95% CI], 0.50-0.62). When all incident tumors were considered, both those exposed and those unexposed to screening combined, counties with > 10 years of screening were found to demonstrate a significant 32% mortality reduction (RR = 0.68; 95% CI, 0.60-0.77) and counties with < or = 10 years of screening showed a significant 18% reduction in breast carcinoma mortality (RR = 0.82; 95% CI, 0.72-0.94) for the screening epoch compared with the prescreening epoch. Within the screening epoch, after adjustment for self-selection bias, a 39% mortality reduction (RR = 0.61; 95%CI, 0.55-0.68) was observed in association with invitation to screening. CONCLUSIONS: Organized service screening in 7 Swedish counties, covering approximately 33% of the population of Sweden, resulted in a 40-45% reduction in breast carcinoma mortality among women actually screened. The policy of offering screening is associated with a mortality reduction in breast carcinoma of 30% in the invited population, exposed and unexposed combined. The results of the current study indicate that the majority of the breast carcinoma mortality reduction is indeed due to the screening.