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.

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.

Body mass index, breast density, and the risk of breast cancer development in relation to the menopausal status; results from a population-based screening program in a native African-Arab country.

Background: Risk factors are traits or behaviors that have an influence on the development of breast cancer (BC). Awareness of the prevalent risk factors can guide in developing prevention interventions. Purpose: To evaluate the correlation between the breast density, body mass index, and the risk of breast cancer development in relation to the menopausal status in a native African-Arab population. Material and methods: The study included 30,443 screened females who were classified into cancer and non-cancer groups and each group was further sub-classified into pre- and postmenopausal groups. The breast density (BD) was reported and subjectively classified according to the 2013 ACR BI-RADS breast density classification. The weight and height were measured, and the body mass index (BMI) was calculated and classified according to the WHO BMI classification. Results: A statistically significant difference was calculated between the mean BMI in the cancer and non-cancer groups (p: .027) as well as between the pre- and postmenopausal groups (p < .001). A positive statistically insignificant correlation was calculated between the breast density and the risk of breast cancer in the premenopausal group (OR: 1.062, p: .919) and a negative highly significant correlation was calculated in the postmenopausal group (OR: 0.234, p < .001). Conclusion: BMI and BD are inversely associated with each other. The current studied population presented unique ethnic characteristics, where a decreased BD and an increased BMI were found to be independent risk factors for developing breast cancer.

Classification of inflammatory breast disorders and step by step diagnosis.

In this study, the authors proposed a classification of inflammatory breast disorders based on which a practical systematic scheme in diagnosis was applied aiming to differentiate simple forms of mastitis from more complicated and malignant forms. The study population included 197 female patients who were clinically or pathologically diagnosed as having mastitis. All patients underwent Ultrasound examination. Mammography was performed for 133/197 cases. Cases of simple mastitis and periductal mastitis were followed up to ensure complete resolution. Abscess cavities and postoperative collections were drained. Other cases were biopsied to confirm diagnosis and were managed accordingly by their treating physicians. Statistical analysis was performed by the Statistical Package for Social Science. Nominal Data were expressed as frequency and relative frequencies (percentage). Ultrasound and Mammography categorical results were compared using the Pearson Chi Square and Fisher's exact test. Patients were classified into three groups; infectious, noninfectious and malignant mastitis. Simple and malignant forms of mastitis showed many signs in common. The presence of ill defined collections and abscess cavities on ultrasound favored simple over malignant forms of mastitis while extensive skin thickening and infiltrated malignant nodes favored malignant forms. Interstitial edema, edematous fat lobules, abscess cavities, skin thickening seen on ultrasound examination were significantly lower in noninfectious than simple and malignant mastitis. Mammography signs were less discriminating. Diffuse skin thickening and increased density favored malignant mastitis while dilated retro areolar ducts and characteristic calcification patterns favored noninfectious forms. Simple mastitis showed nonspecific signs. Ultrasound examination in mastitis cases shows more specific signs in differentiating between the three forms of mastitis and is useful in monitoring treatment, excluding complications and guide for interventional procedures. Mammography should be performed whenever complicated, malignant and uncommon forms of mastitis are suspected.

The impact of contrast-enhanced spectral mammogram (CESM) and three-dimensional breast ultrasound (3DUS) on the characterization of the disease extend in cancer patients.

OBJECTIVE: The main importance of imaging breast cancer is to guide conservative surgeries. In this study, we evaluated the role of contrast-enhanced spectral mammogram (CESM) in correlation with three-dimensional (3D) breast ultrasound in characterizing the extension of the intramammary cancer in view of the: (i) the size of the main tumor, (ii) the multiplicity of the breast cancer, and (iii) the peri-tumoral stromal involvement (i.e. free or intraductal extension of the cancer). METHODS: The study is a prospective analysis that included 300 breast masses proved to be malignant. The masses were evaluated for their size, multiplicity and surrounding stromal involvement. Contrast-based mammography performed with low (22-33 kVp) and high (44-49 kVp) energy exposures that were taken after i.v. injection of contrast agent and followed by bilateral 3D breast ultrasound. Operative data were the gold standard reference. RESULTS: There was no significant difference between the sizes of the included cancers as measured by CESM and 3D ultrasound and that measured at the pathological analysis. CESM showed higher accuracy (32.7%, n = 98) than 3D ultrasound (24.7%, n = 74) in the size agreement within 5% range. CESM was the most accurate modality (94%, n = 282) in detecting tumor multiplicity, followed by traditional sonomammogram (88%, n = 264), then 3D breast ultrasound (84%, n = 252). Intraductal extension of the breast cancer was best evaluated by the 3D ultrasound with an accuracy value of 98% (n = 294) compared to only 60% (n = 180) by CESM. CONCLUSION: CESM is a recommended investigation in breast cancer to increase the accuracy of size measurement and the detection of multiple tumors. The addition of 3D ultrasound can enhance the detection of intraductal extension. Advances in knowledge: Choice of conservative breast surgery vs mastectomy is still a debate. We used an advanced, contrast-based, application of the mammogram: CESM and a non-invasive 3D breast ultrasound in the assessment of the local extension of the breast cancer regarding size, perifocal stromal infiltration and multiplicity to guide the selection of proper management in proved cases of breast cancer.

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.

Breast imaging in the young: the role of magnetic resonance imaging in breast cancer screening, diagnosis and follow-up.

Diagnosis of breast cancer in young individuals (younger than 40 years old) poses a real challenge to breast radiologists because their breast tissue is often denser than the breast tissue of older women. Magnetic Resonance Imaging (MRI) may be particularly helpful in such situations. The American Cancer Society (ACS) recommended breast MRI screening as an adjunct to mammography for: BRCA mutation carriers and their first-degree relatives; women with a lifetime breast cancer risk ≥20% to 25%; women with a history of chest radiation between ages of 10 and 30 years; and women with predisposing genetic syndromes. Currently, breast MRI demonstrates a high sensitivity in the range of 93-100%. As many benign lesions also show enhancement or other atypical features on MRI, the primary weakness of contrast enhanced MRI remains in its low specificity, reported to be in the range of 37-97%. Breast MRI is helpful in demonstrating the true tumor size initially, as well as identifying residual tumor following the completion of neo-adjuvant therapy. In general, sensitivities ranging from 61% to 86% for detecting residual disease have been reported. The absence of enhancement virtually excludes a recurrence and the presence of enhancement is very specific for tumor even in the radiated breast. MRI is also the preferred modality for assessment of the breast after re- constructive surgery. The role of Magnetic Resonance Imaging (MRI) in breast diagnosis will continue to evolve as technology improves and clinical experience with new techniques expands.

Assessment of bone mineral density by dual x-ray absorptiometry in dermatological patients treated by corticosteroids.

BACKGROUND: Corticosteroids are mainstay of dermatological therapy and they are also a well known cause of osteoporosis. The objective of the present study was to find out the influence of the systemic intake of corticosteroids, either by the oral route or by IV pulse administration, on bone mineral density in dermatological patients using dual X-ray absorptiometry (DXA). MATERIALS AND METHODS: This study was carried on 100 patients and 55 controls. The first group of patients included 55 patients undergoing long-term oral corticosteroid therapy daily and the second group included 45 patients who received IV dexamethasone pulse therapy. DXA was measured once for both the controls and patients in group 1. DXA was measured twice for patients in group 2, before starting pulse therapy (baseline DXA) and six months after regular treatment with pulse therapy (follow-up DXA). RESULTS: The results show that significant reduction in BMD occurs in both groups, however, oral corticosteroids produce significantly more reduction in BMD in the lumbar spine. BMD was not found to be affected by the cumulative doses of corticosteroids, the duration of daily oral corticosteroid intake, or the number of IV dexamethasone pulses. CONCLUSION: Corticosteroid treatment causes significant BMD loss in patients treated by either route. Prophylactic treatment against osteoporosis is mandatory in patients receiving either form of corticosteroids.

Modification and implementation of NCCN guidelines on breast cancer in the Middle East and North Africa region.

Published data from the Middle East and North Africa (MENA) region indicate suboptimal quality of cancer care, while the World Health Organization predicts an increase in cancer cases in developing countries. Major advances in breast cancer management mandate the development of guidelines to improve the quality and efficacy of oncology practice in the MENA region. A Breast Cancer Regional Guidelines Committee was organized and activated, comprising experts from various regional cancer institutions. The multidisciplinary team included 12 medical oncologists, 3 radiation oncologists, 2 radiologists, 2 surgeons, and 1 pathologist. The committee members agreed on adapting the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Breast Cancer for use in the MENA region to achieve common practice standards for treating patients. The members suggested several modifications to the guidelines, especially those related to risk factor profiles. United States-based NCCN experts reviewed these recommendations before final approval. The MENA-NCCN Breast Cancer Guidelines modification process was the first initiative in the development of common practice guidelines in the region. This project may serve as a foundation for the development of evidence-based practice standards, and improve collaborative projects and initiatives.

Women Health Outreach Program; a New Experience for all Egyptian Women.

UNLABELLED: The global health community faces a challenge with breast cancer being the most common cause of cancer related death among women around the globe. Since breast cancer's pathogenesis is poorly understood, primary prevention is still a distant goal. Thus secondary prevention through early detection is the only feasible approach at present. With this strong conviction, the launching of the first Egyptian national screening program "Women Health Outreach Program" (WHOP), was announced on October 30th 2007. This project is a government- funded program that offers free breast screening for all Egyptian women above the age of 45 years. In addition to free mammograms, the program gives the participants a chance to be screened for diabetes, hypertension and obesity as well. Positively detected cases are also offered the option of free management. During the period from October 30th, 2007, up to February 9th, 2009, 20, 098 women in Cairo, Alexandria and Suez governorates were screened for breast cancer, diabetes, hypertension and obesity through the program. In this article we will represent the achievements, challenges and services delivered by WHOP. KEY WORDS: Breast cancer - Breast screening - Early detection - Breast biopsy.