Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Development of an online authentic radiology viewing and reporting platform to test the skills of radiology trainees in Low- and Middle-Income Countries.

BACKGROUND: Diagnostic radiology residents in low- and middle-income countries (LMICs) may have to provide significant contributions to the clinical workload before the completion of their residency training. Because of time constraints inherent to the delivery of acute care, some of the most clinically impactful diagnostic radiology errors arise from the use of Computed Tomography (CT) in the management of acutely ill patients. As a result, it is paramount to ensure that radiology trainees reach adequate skill levels prior to assuming independent on-call responsibilities. We partnered with the radiology residency program at the Aga Khan University Hospital in Nairobi (Kenya) to evaluate a novel cloud-based testing method that provides an authentic radiology viewing and interpretation environment. It is based on Lifetrack, a unique Google Chrome-based Picture Archiving and Communication System, that enables a complete viewing environment for any scan, and provides a novel report generation tool based on Active Templates which are a patented structured reporting method. We applied it to evaluate the skills of AKUHN trainees on entire CT scans representing the spectrum of acute non-trauma abdominal pathology encountered in a typical on-call setting. We aimed to demonstrate the feasibility of remotely testing the authentic practice of radiology and to show that important observations can be made from such a Lifetrack-based testing approach regarding the radiology skills of an individual practitioner or of a cohort of trainees. METHODS: A total of 13 anonymized trainees with experience from 12 months to over 4 years took part in the study. Individually accessing the Lifetrack tool they were tested on 37 abdominal CT scans (including one normal scan) over six 2-hour sessions on consecutive days. All cases carried the same clinical history of acute abdominal pain. During each session the trainees accessed the corresponding Lifetrack test set using clinical workstations, reviewed the CT scans, and formulated an opinion for the acute diagnosis, any secondary pathology, and incidental findings on the scan. Their scan interpretations were composed using the Lifetrack report generation system based on active templates in which segments of text can be selected to assemble a detailed report. All reports generated by the trainees were scored on four different interpretive components: (a) acute diagnosis, (b) unrelated secondary diagnosis, (c) number of missed incidental findings, and (d) number of overcalls. A 3-score aggregate was defined from the first three interpretive elements. A cumulative score modified the 3-score aggregate for the negative effect of interpretive overcalls. RESULTS: A total of 436 scan interpretations and scores were available from 13 trainees tested on 37 cases. The acute diagnosis score ranged from 0 to 1 with a mean of 0.68 ± 0.36 and median of 0.78 (IQR: 0.5-1), and there were 436 scores. An unrelated secondary diagnosis was present in 11 cases, resulting in 130 secondary diagnosis scores. The unrelated secondary diagnosis score ranged from 0 to 1, with mean score of 0.48 ± 0.46 and median of 0.5 (IQR: 0-1). There were 32 cases with incidental findings, yielding 390 scores for incidental findings. The number of missed incidental findings ranged from 0 to 5 with a median at 1 (IQR: 1-2). The incidental findings score ranged from 0 to 1 with a mean of 0.4 ± 0.38 and median of 0.33 (IQR: 0- 0.66). The number of overcalls ranged from 0 to 3 with a median at 0 (IQR: 0-1) and a mean of 0.36 ± 0.63. The 3-score aggregate ranged from 0 to 100 with a mean of 65.5 ± 32.5 and median of 77.3 (IQR: 45.0, 92.5). The cumulative score ranged from - 30 to 100 with a mean of 61.9 ± 35.5 and median of 71.4 (IQR: 37.4, 92.0). The mean acute diagnosis scores and SD by training period were 0.62 ± 0.03, 0.80 ± 0.05, 0.71 ± 0.05, 0.58 ± 0.07, and 0.66 ± 0.05 for trainees with ≤ 12 months, 12-24 months, 24-36 months, 36-48 months and > 48 months respectively. The mean acute diagnosis score of 12-24 months training was the only statistically significant greater score when compared to ≤ 12 months by the ANOVA with Tukey testing (p = 0.0002). We found a similar trend with distribution of 3-score aggregates and cumulative scores. There were no significant associations when the training period was categorized as less than and more than 2 years. We looked at the distribution of the 3-score aggregate versus the number of overcalls by trainee, and we found that the 3-score aggregate was inversely related to the number of overcalls. Heatmaps and raincloud plots provided an illustrative means to visualize the relative performance of trainees across cases. CONCLUSION: We demonstrated the feasibility of remotely testing the authentic practice of radiology and showed that important observations can be made from our Lifetrack-based testing approach regarding radiology skills of an individual or a cohort. From observed weaknesses areas for targeted teaching can be implemented, and retesting could reveal their impact. This methodology can be customized to different LMIC environments and expanded to board certification examinations.

The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide.

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

Mammographic density assessed on paired raw and processed digital images and on paired screen-film and digital images across three mammography systems.

BACKGROUND: Inter-women and intra-women comparisons of mammographic density (MD) are needed in research, clinical and screening applications; however, MD measurements are influenced by mammography modality (screen film/digital) and digital image format (raw/processed). We aimed to examine differences in MD assessed on these image types. METHODS: We obtained 1294 pairs of images saved in both raw and processed formats from Hologic and General Electric (GE) direct digital systems and a Fuji computed radiography (CR) system, and 128 screen-film and processed CR-digital pairs from consecutive screening rounds. Four readers performed Cumulus-based MD measurements (n = 3441), with each image pair read by the same reader. Multi-level models of square-root percent MD were fitted, with a random intercept for woman, to estimate processed-raw MD differences. RESULTS: Breast area did not differ in processed images compared with that in raw images, but the percent MD was higher, due to a larger dense area (median 28.5 and 25.4 cm2 respectively, mean √dense area difference 0.44 cm (95% CI: 0.36, 0.52)). This difference in √dense area was significant for direct digital systems (Hologic 0.50 cm (95% CI: 0.39, 0.61), GE 0.56 cm (95% CI: 0.42, 0.69)) but not for Fuji CR (0.06 cm (95% CI: -0.10, 0.23)). Additionally, within each system, reader-specific differences varied in magnitude and direction (p < 0.001). Conversion equations revealed differences converged to zero with increasing dense area. MD differences between screen-film and processed digital on the subsequent screening round were consistent with expected time-related MD declines. CONCLUSIONS: MD was slightly higher when measured on processed than on raw direct digital mammograms. Comparisons of MD on these image formats should ideally control for this non-constant and reader-specific difference.

Breast Camps for Awareness and Early Diagnosis of Breast Cancer in Countries With Limited Resources: A Multidisciplinary Model From Kenya.

BACKGROUND: Breast cancer is the most common cancer of women in Kenya. There are no national breast cancer early diagnosis programs in Kenya. OBJECTIVE: The objective was to conduct a pilot breast cancer awareness and diagnosis program at three different types of facilities in Kenya. METHODS: This program was conducted at a not-for-profit private hospital, a faith-based public hospital, and a government public referral hospital. Women aged 15 years and older were invited. Demographic, risk factor, knowledge, attitudes, and screening practice data were collected. Breast health information was delivered, and clinical breast examinations (CBEs) were performed. When appropriate, ultrasound imaging, fine-needle aspirate (FNA) diagnoses, core biopsies, and onward referrals were provided. RESULTS: A total of 1,094 women were enrolled in the three breast camps. Of those, 56% knew the symptoms and signs of breast cancer, 44% knew how breast cancer was diagnosed, 37% performed regular breast self-exams, and 7% had a mammogram or breast ultrasound in the past year. Of the 1,094 women enrolled, 246 (23%) had previously noticed a lump in their breast. A total of 157 participants (14%) had abnormal CBEs, of whom 111 had ultrasound exams, 65 had FNAs, and 18 had core biopsies. A total of 14 invasive breast cancers and 1 malignant phyllodes tumor were diagnosed CONCLUSION: Conducting a multidisciplinary breast camp awareness and early diagnosis program is feasible in different types of health facilities within a low- and middle-income country setting. This can be a model for breast cancer awareness and point-of-care diagnosis in countries with limited resources like Kenya. IMPLICATIONS FOR PRACTICE: This work describes a novel breast cancer awareness and early diagnosis demonstration program in a low- and middle-income country within a limited resource setting. The program includes breast self-awareness and breast cancer education, clinical exams, and point-of-care diagnostics for women in three different types of health facilities in Kenya. This pilot program has the potential of being replicated on a national scale to create awareness about breast cancer and downstage its presentation.

Mammographic Breast Density and Breast Cancer Molecular Subtypes: The Kenyan-African Aspect.

INTRODUCTION: Data examining mammographic breast density (MBD) among patients in Sub-Saharan Africa are sparse. We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography. METHODS: This cross-sectional study included women with pathologically confirmed breast cancers (n = 123). Pretreatment mammograms of the unaffected breast were assessed to estimate absolute dense area (cm2), nondense area (cm2), and percent density (PD). Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance. RESULTS: Median PD and dense area were 24.9% and 85.3 cm2. Higher PD and dense area were observed in younger women (P < 0.01). Higher dense and nondense areas were observed in obese women (P-trend < 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients (P ≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area (P ≤ 0.01) compared with non-TNBCs. No associations were observed between MBD and tumor size and grade. CONCLUSIONS: Our findings show discordant relationships between MBD and molecular tumor subtypes to those previously observed in Western populations. The relatively low breast density observed at diagnosis may have important implications for cancer prevention initiatives in Kenya. Subsequent larger studies are needed to confirm these findings.

International Consortium on Mammographic Density: Methodology and population diversity captured across 22 countries.

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses.