Reproductive Factors Related to Childbearing and a Novel Automated Mammographic Measure, V.

BACKGROUND: We investigated the associations between several reproductive factors related to childbearing and the variation (V) measure (a novel, objective, single summary measure of breast image intensity) by menopausal status. METHODS: Our study included 3,814 cancer-free women within the Nurses' Health Study (NHS) and NHSII cohorts. The data on reproductive variables and covariates were obtained from biennial questionnaires closest to the mammogram date. V-measures were obtained from mammographic images using a previously developed algorithm capturing the standard deviation of pixel values. We used multivariate linear regression to examine the associations of parity, age at first birth, time between menarche and first birth, time since last pregnancy, and lifetime breastfeeding duration with V-measure, adjusting for breast cancer risk factors, including the percentage of mammographic density (PMD). We further examined whether these associations were statistically accounted for (mediated) by PMD. RESULTS: Among premenopausal women, none of the reproductive factors were associated with V. Among postmenopausal women, inverse associations of parity and positive associations of age at first birth with V were mediated by PMD (percent mediated: nulliparity: 66.7%, P < 0.0001; parity: 50.5%, P < 0.01; age at first birth 76.1%, P < 0.001) and were no longer significant in PMD-adjusted models. Lifetime duration of breastfeeding was positively associated with V [>36 vs. 0 ≤1 months ß = 0.29; 95% confidence interval (CI) 0.07; 0.52, Ptrend < 0.01], independent of PMD. CONCLUSIONS: Parity, age at first birth, and breastfeeding were associated with postmenopausal V. IMPACT: This study highlights associations of reproductive factors with mammographic image intensity.

Family History of Breast Cancer and Mammographic Breast Density in Premenopausal Women.

Importance: Family history of breast cancer (FHBC) and mammographic breast density are independent risk factors for breast cancer, but the association of FHBC and mammographic breast density in premenopausal women is not well understood. Objectives: To investigate the association of FHBC and mammographic breast density in premenopausal women using both quantitative and qualitative measurements. Design, Setting, and Participants: This single-center cohort study examined 2 retrospective cohorts: a discovery set of 375 premenopausal women and a validation set of 14 040 premenopausal women. Data from women in the discovery set was collected between December 2015 and October 2016, whereas data from women in the validation set was collected between June 2010 and December 2015. Data analysis was performed between June 2018 and June 2020. Exposures: Family history of breast cancer (FHBC). Main Outcomes and Measures: The primary outcomes were mammographic breast density measured quantitatively as volumetric percent density using Volpara (discovery set) and qualitatively using BI-RADS (Breast Imaging Reporting and Data System) breast density (validation set). Multivariable regressions were performed using a log-transformed normal distribution for the discovery set and a logistic distribution for the validation set. Results: Of 14 415 premenopausal women included in the study, the discovery set and validation set had similar characteristics (discovery set with FHBC: mean [SD] age, 47.1 [5.6] years; 15 [17.2%] were Black or African American women and 64 [73.6%] were non-Hispanic White women; discovery set with no FHBC: mean [SD] age, 47.7 [4.5] years; 87 [31.6%] were Black or African American women and 178 [64.7%] were non-Hispanic White women; validation set with FHBC: mean [SD] age, 46.8 [7.3] years; 720 [33.4%] were Black or African American women and 1378 [64.0%] were non-Hispanic White women]; validation set with no FHBC: mean [SD] age, 47.5 [6.1] years; 4572 [38.5%] were Black or African American women and 6632 [55.8%] were non-Hispanic White women]). In the discovery set, participants who had FHBC were more likely to have a higher mean volumetric percent density compared with participants with no FHBC (11.1% vs 9.0%). In the multivariable-adjusted model, volumetric percent density was 25% higher (odds ratio [OR], 1.25 ;95% CI, 1.12-1.41) in women with FHBC compared with women without FHBC; and 24% higher (OR, 1.24; 95% CI, 1.10-1.40) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.40; 95% CI, 0.95-2.07) compared with women with no relatives affected. In the validation set, women with a positive FHBC were more likely to have dense breasts (BI-RADS 3-4) compared with women with no FHBC (BI-RADS 3: 41.1% vs 38.8%; BI-RADS 4: 10.5% vs 7.7%). In the multivariable-adjusted model, the odds of having dense breasts (BI-RADS 3-4) were 30% higher (OR, 1.30; 95% CI, 1.17-1.45) in women with FHBC compared with women without FHBC; and 29% higher (OR, 1.29; 95% CI, 1.14-1.45) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.38; 95% CI, 0.85-2.23) compared with women with no relatives affected. Conclusions and Relevance: In this cohort study, having an FHBC was positively associated with mammographic breast density in premenopausal women. Our findings highlight the heritable component of mammographic breast density and underscore the need to begin annual screening early in premenopausal women with a family history of breast cancer.

Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?

Regions of high mammographic density (MD) in the breast are characterised by a proteoglycan (PG)-rich fibrous stroma, where PGs mediate aligned collagen fibrils to control tissue stiffness and hence the response to mechanical forces. Literature is accumulating to support the notion that mechanical stiffness may drive PG synthesis in the breast contributing to MD. We review emerging patterns in MD and other biological settings, of a positive feedback cycle of force promoting PG synthesis, such as in articular cartilage, due to increased pressure on weight bearing joints. Furthermore, we present evidence to suggest a pro-tumorigenic effect of increased mechanical force on epithelial cells in contexts where PG-mediated, aligned collagen fibrous tissue abounds, with implications for breast cancer development attributable to high MD. Finally, we summarise means through which this positive feedback mechanism of PG synthesis may be intercepted to reduce mechanical force within tissues and thus reduce disease burden.

Association between skeletal muscle mass and mammographic breast density.

Mammographic density (MD) of the breast and body mass index (BMI) are inversely associated with each other, but have inconsistent associations with respect to the risk of breast cancer. Skeletal muscle mass index (SMI) has been considered to reflect a relatively accurate fat and muscle percentage in the body. So, we evaluated the relation between SMI and MD. A cross-sectional study was performed in 143,456 women who underwent comprehensive examinations from 2012 to 2016. BMI was adjusted to analyze whether SMI is an independent factor predicting dense breast. After adjustment for confounding factors including BMI, the odds ratios for MD for the dense breasts was between the highest and lowest quartiles of SMI at 2.65 for premenopausal women and at 2.39 for postmenopausal women. SMI was a significant predictor for MD, which could be due to the similar growth mechanism of the skeletal muscle and breast parenchymal tissue. Further studies are needed to understand the causal link between muscularity, MD and breast cancer risk.

Biomarkers of mammographic density in premenopausal women.

BACKGROUND: While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density. METHODS: A total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers' Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors. RESULTS: Sphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components. CONCLUSIONS: We identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer.

Influential factors and prediction model of mammographic density among Chinese women.

ABSTRACT: To evaluate the characteristics and influential factors of breast density and establish a new model for predicting breast density in Chinese women, so as to provide a basis for breast cancer screening techniques and duration.A total of 9412 women who were selected from screening and intervention techniques for Breast and Cervical Cancer Project between April 2018 and June 2019 were enrolled in this study. Selected women were randomly assigned to training and validation sets in a ratio of 1:1. Univariable and multivariable analyzes were performed by Logistic regression model. Nomogram was generated according to the results of multivariate analysis. Calibration, area under curve (AUC) and akaike information criterion (AIC) were used for measuring accuracy of prediction model.There were 377 (4.0%) women in breast imaging reporting and data system (BI-RADS) A category, 2164 (23.0%) in B category, 5749 (61.1%) in C category and 1122 (11.9%) in D category. Age duration, educational attainment, history of benign diseases, breastfeeding history, menopausal status, and body mass index (BMI) were imputed as independent influential factors for breast density in multivariable analysis. The AUC and AIC of training and validation set were 0.7158, 0.7139, and 4915.378, 4998.665, respectively.This study indicated that age, educational attainment, history of benign breast disease, breastfeeding history, menopausal status and BMI were independent influential factors of breast density. Nomogram generated on the basis of these factors could relatively predict breast density, which in turn could be used for recommendations of breast cancer screening techniques.

Adolescent and early adulthood inflammation-associated dietary patterns in relation to premenopausal mammographic density.

BACKGROUND: Adolescence and early adulthood has been identified as a critical time window for establishing breast cancer risk. Mammographic density is an independent risk factor for breast cancer that may be influenced by diet, but there has been limited research conducted on the impact of diet on mammographic density. Thus, we sought to examine the association between adolescent and early adulthood inflammatory dietary patterns, which have previously been associated with breast cancer risk, and premenopausal mammographic density among women in the Nurses' Health Study II (NHSII). METHODS: This study included control participants with premenopausal mammograms from an existing breast cancer case-control study nested within the NHSII who completed a Food Frequency Questionnaire in 1998 about their diet during high school (HS-FFQ) (n = 685) and/or a Food Frequency Questionnaire in 1991 (Adult-FFQ) when they were 27-44 years old (n = 1068). Digitized analog film mammograms were used to calculate the percent density, absolute dense, and non-dense areas. Generalized linear models were fit to evaluate the associations of a pro-inflammatory dietary pattern and the Alternative Healthy Eating Index (AHEI, an anti-inflammatory dietary pattern) with each breast density measure. RESULTS: Significant associations were observed between an adolescent pro-inflammatory dietary pattern and mammographic density in some age-adjusted models; however, these associations did not remain after adjustment for BMI and other breast cancer risk factors. No associations were observed with the pro-inflammatory pattern or with the AHEI pattern in adolescence or early adulthood in fully adjusted models. CONCLUSIONS: To our knowledge, this is the first study to evaluate the dietary patterns during adolescence and early adulthood in relation to mammographic density phenotypes. Our findings do not support an association between adolescent and early adulthood diet and breast density in mid-adulthood that is independent of BMI or other breast cancer risk factors.

Outcomes of Return to Routine Screening for BI-RADS 3 Lesions Detected at Supplemental Automated Whole-Breast Ultrasound in Women With Dense Breasts: A Prospective Study.

BACKGROUND. Supplemental screening breast ultrasound (US) detects additional cancers in women with dense breasts but identifies many BI-RADS 3 lesions that result in short-term follow-up and biopsies. OBJECTIVE. The purpose of this study was to evaluate outcomes in patients recommended for return to routine screening for lesions assessed as BI-RADS 3 on supplemental automated whole-breast US. METHODS. This prospective study invited patients with BI-RADS 1 or 2 on screening mammography and breast density C or D to undergo supplemental automated breast US (ABUS). ABUS was interpreted as BI-RADS 1, 2, 3, or 0. Return to routine screening was recommended for ABUS BI-RADS 1, 2, or 3. ABUS BI-RADS 0 lesions underwent targeted handheld US. Remaining patients were followed for 2 years. Malignancy rates were compared using Fisher exact tests. RESULTS. A total of 2257 women (mean age, 58.0 ± 11.2 [SD] years) were included. Supplemental ABUS was scored as BI-RADS 1 in 1186 (52.5%) women, BI-RADS 2 in 591 (26.2%), BI-RADS 3 in 395 (17.5%), and BI-RADS 0 in 85 (3.8%). A total of 394 patients with ABUS BI-RADS 3 had 2-year follow-up, during which no cancer (0%; 95% CI, 0.0-0.9%) was diagnosed in the quadrant of the lesion. Among patients with 2-year follow-up, breast cancer was diagnosed in 4/1117 (0.4%) with ABUS BI-RADS 1, 2/556 (0.4%) with ABUS BI-RADS 2, and 2/394 (0.5%) with ABUS BI-RADS 3 (cancer in other quadrant than the lesion). Malignancy rates were not different between ABUS BI-RADS 1, 2, and 3 (p = .28). The ABUS recall rate was 3.8% (85/2257; 95% CI, 3.6-4.0%). If short-term follow-up had been recommended for ABUS BI-RADS 3, the ABUS recall rate would have been 21.3% (480/2257, 95% CI 19.6-23.0%). The biopsy rate was 0.5% (12/2257; 95% CI, 0.3-0.9%); the positive biopsy rate was 58.3% (7/12). One of seven cancers diagnosed by initial supplemental ABUS and none of eight cancers diagnosed during subsequent follow-up were node-positive cancer. CONCLUSION. Return to routine screening for ABUS BI-RADS 3 lesions results in a substantial decrease in recall rate and is unlikely to result in an adverse outcome. CLINICAL IMPACT. This prospective study supports a recommendation for routine annual follow-up for BI-RADS 3 lesions at supplemental ABUS. TRIAL REGISTRATION. ClinicalTrials.gov NCT02650778.

Breast density in dedicated breast computed tomography: Proposal of a classification system and interreader reliability.

ABSTRACT: The aim of this study was to develop a new breast density classification system for dedicated breast computed tomography (BCT) based on lesion detectability analogous to the ACR BI-RADS breast density scale for mammography, and to evaluate its interrater reliability.In this retrospective study, 1454 BCT examinations without contrast media were screened for suitability. Excluding datasets without additional ultrasound and exams without any detected lesions resulted in 114 BCT examinations. Based on lesion detectability, an atlas-based BCT density (BCTD) classification system of breast parenchyma was defined using 4 categories. Interrater reliability was examined in 40 BCT datasets between 3 experienced radiologists.Among the included lesions were 63 cysts (55%), 18 fibroadenomas (16%), 7 lesions of fatty necrosis (6%), and 6 breast cancers (5%) with a median diameter of 11 mm. X-ray absorption was identical between lesions and breast tissue; therefore, the lack of fatty septae was identified as the most important criteria for the presence of lesions in glandular tissue. Applying a lesion diameter of 10 mm as desired cut-off for the recommendation of an additional ultrasound, an atlas of 4 BCTD categories was defined resulting in a distribution of 17.5% for density A, 39.5% (B), 31.6% (C), and 11.4% (D) with an intraclass correlation coefficient (ICC) among 3 readers of 0.85 to 0.87.We propose a dedicated atlas-based BCTD classification system, which is calibrated to lesion detectability. The new classification system exhibits a high interrater reliability and may be used for the decision whether additional ultrasound is recommended.

Benign breast disease and changes in mammographic breast density.

BACKGROUND: Mammographic breast density (MBD) and benign breast disease (BBD) are two of the strongest risk factors for breast cancer. Understanding trends in MBD by age and parity in women with BBD is essential to the clinical management and prevention of breast cancer. METHODS: Using data from the Early Determinants of Mammographic Density (EDMD) study, a prospective follow-up study of women born in 1959-1967, we evaluated MBD in 676 women. We used linear regression with generalized estimating equations to examine associations between self-reported BBD and MBD (percent density, dense area, and non-dense area), assessed through a computer-assisted method. RESULTS: A prior BBD diagnosis (median age at diagnosis 32 years) was reported by 18% of our cohort. The median time from BBD diagnosis to first available study mammogram was 9.4 years (range 1.1-27.6 years). Women with BBD had a 3.44% higher percent MBD (standard error (SE) = 1.56, p-value = 0.03) on their first available mammogram than women without BBD. Compared with parous women without BBD, nulliparous women with BBD and women with a BBD diagnosis prior to first birth had 7-8% higher percent MBD (ß = 7.25, SE = 2.43, p-value< 0.01 and ß = 7.84, SE = 2.98, p-value = 0.01, respectively), while there was no difference in MBD in women with a BBD diagnosis after the first birth (ß = -0.22, SE = 2.40, p-value = 0.93). CONCLUSION: Women with self-reported BBD had higher mammographic breast density than women without BBD; the association was limited to women with BBD diagnosed before their first birth.

Mammographic breast density and characteristics of invasive breast cancer.

INTRODUCTION: Inconclusive data exist on the association between breast density and breast cancer characteristics. MATERIALS AND METHODS: We conducted a case-only study on 667 invasive breast cancers, using data from the Piedmont Cancer Registry. We applied a multivariate logistic regression model to estimate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of high breast density (Breast Imaging Reporting and Data System, BI-RADS 3-4) versus low (BI-RADS 1-2) in relation to histologic grade, pathological tumour size and lymph node status, histotype, estrogen and progesterone receptor, HER2 and Ki67 status. Histopathological data were assessed according to the American Joint Committee on Cancer (AJCC) Staging Manual guidelines. The model includes terms for age at diagnosis, education level, body mass index, reproductive factors, family history of breast cancer, smoking and diabetes. RESULTS: As regards histologic grade, compared to well differentiated tumours, the OR of high (versus low) breast density cases was 0.61 (95% CI 0.38-0.98) for moderately-poorly differentiated tumours. No other associations with hormonal and histopathological characteristics were observed. DISCUSSION: Our results indicate that low breast density is associated with moderately-poorly differentiated breast tumours.

Pubertal mammary gland development is a key determinant of adult mammographic density.

Mammographic density refers to the radiological appearance of fibroglandular and adipose tissue on a mammogram of the breast. Women with relatively high mammographic density for their age and body mass index are at significantly higher risk for breast cancer. The association between mammographic density and breast cancer risk is well-established, however the molecular and cellular events that lead to the development of high mammographic density are yet to be elucidated. Puberty is a critical time for breast development, where endocrine and paracrine signalling drive development of the mammary gland epithelium, stroma, and adipose tissue. As the relative abundance of these cell types determines the radiological appearance of the adult breast, puberty should be considered as a key developmental stage in the establishment of mammographic density. Epidemiological studies have pointed to the significance of pubertal adipose tissue deposition, as well as timing of menarche and thelarche, on adult mammographic density and breast cancer risk. Activation of hypothalamic-pituitary axes during puberty combined with genetic and epigenetic molecular determinants, together with stromal fibroblasts, extracellular matrix, and immune signalling factors in the mammary gland, act in concert to drive breast development and the relative abundance of different cell types in the adult breast. Here, we discuss the key cellular and molecular mechanisms through which pubertal mammary gland development may affect adult mammographic density and cancer risk.

Comparison of sonoelastographic values of breast tissue with mammographically and ultrasonically assessed density: a cross-sectional study.

AIM: To determine the relationship between breast stiffness assessed with sonoelastography (elasticity) and breast tissue density assessed with mammography (MG) and ultrasound (US). METHODS: This cross-sectional study involved 100 women who underwent MG, gray-scale US, and shear-wave sonoelastography during 2013. Mammographic density was categorized into four groups and sonographic density into three groups according to Breast Imaging-Reporting and Data System criteria. The stiffness of breast parenchymal and adipose tissue in all breast quadrants was quantified by shear-wave sonoelastography. Mean elastographic estimates were compared with MG- and US-derived density estimates. RESULTS: Parenchymal and adipose tissue elasticity positively correlated with MG- and US-derived breast density (for parenchyma: for MG Kendall's tau b 0.522; Jonckheere-Terpstra test P<0.001 and for US Kendall's tau b 0.533; Jonckheere-Terpstra test P<0.001); the higher was the breast density on MG and US, the higher was the elastographic stiffness. CONCLUSION: Sonoelastographic breast stiffness strongly positively correlated with breast density. Thus, sonoelastography may have a potential for estimating the breast cancer risk, which allows a novel application of this technique in routine clinical practice.

Screening Performance of Digital Breast Tomosynthesis vs Digital Mammography in Community Practice by Patient Age, Screening Round, and Breast Density.

Importance: Digital mammography (DM) and digital breast tomosynthesis (DBT) are used for routine breast cancer screening. There is minimal evidence on performance outcomes by age, screening round, and breast density in community practice. Objective: To compare DM vs DBT performance by age, baseline vs subsequent screening round, and breast density category. Design, Setting, and Participants: This comparative effectiveness study assessed 1 584 079 screening examinations of women aged 40 to 79 years without prior history of breast cancer, mastectomy, or breast augmentation undergoing screening mammography at 46 participating Breast Cancer Surveillance Consortium facilities from January 2010 to April 2018. Exposures: Age, Breast Imaging Reporting and Data System breast density category, screening round, and modality. Main Outcomes and Measures: Absolute rates and relative risks (RRs) of screening recall and cancer detection. Results: Of 1 273 492 DM and 310 587 DBT examinations analyzed, 1 028 891 examinations (65.0%) were of white non-Hispanic women; 399 952 women (25.2%) were younger than 50 years; and 671 136 women (42.4%) had heterogeneously dense or extremely dense breasts. Adjusted differences in DM vs DBT performance were largest on baseline examinations: for example, per 1000 baseline examinations in women ages 50 to 59, recall rates decreased from 241 examinations for DM to 204 examinations for DBT (RR, 0.84; 95% CI, 0.73-0.98), and cancer detection rates increased from 5.9 with DM to 8.8 with DBT (RR, 1.50; 95% CI, 1.10-2.08). On subsequent examinations, women aged 40 to 79 years with heterogeneously dense breasts had improved recall rates and improved cancer detection with DBT. For example, per 1000 examinations in women aged 50 to 59 years, the number of recall examinations decreased from 102 with DM to 93 with DBT (RR, 0.91; 95% CI, 0.84-0.98), and cancer detection increased from 3.7 with DM to 5.3 with DBT (RR, 1.42; 95% CI, 1.23-1.64). Women aged 50 to 79 years with scattered fibroglandular density also had improved recall and cancer detection rates with DBT. Women aged 40 to 49 years with scattered fibroglandular density and women aged 50 to 79 years with almost entirely fatty breasts benefited from improved recall rates without change in cancer detection rates. No improvements in recall or cancer detection rates were observed in women with extremely dense breasts on subsequent examinations for any age group. Conclusions and Relevance: This study found that improvements in recall and cancer detection rates with DBT were greatest on baseline mammograms. On subsequent screening mammograms, the benefits of DBT varied by age and breast density. Women with extremely dense breasts did not benefit from improved recall or cancer detection with DBT on subsequent screening rounds.

Breast Cancer Population Attributable Risk Proportions Associated with Body Mass Index and Breast Density by Race/Ethnicity and Menopausal Status.

BACKGROUND: Overweight/obesity and dense breasts are strong breast cancer risk factors whose prevalences vary by race/ethnicity. The breast cancer population attributable risk proportions (PARP) explained by these factors across racial/ethnic groups are unknown. METHODS: We analyzed data collected from 3,786,802 mammography examinations (1,071,653 women) in the Breast Cancer Surveillance Consortium, associated with 21,253 invasive breast cancers during a median of 5.2 years follow-up. HRs for body mass index (BMI) and breast density, adjusted for age and registry were estimated using separate Cox regression models by race/ethnicity (White, Black, Hispanic, Asian) and menopausal status. HRs were combined with observed risk-factor proportions to calculate PARPs for shifting overweight/obese to normal BMI and shifting heterogeneously/extremely dense to scattered fibroglandular densities. RESULTS: The prevalences and HRs for overweight/obesity and heterogeneously/extremely dense breasts varied across races/ethnicities and menopausal status. BMI PARPs were larger for postmenopausal versus premenopausal women (12.0%-28.3% vs. 1.0%-9.9%) and nearly double among postmenopausal Black women (28.3%) than other races/ethnicities (12.0%-15.4%). Breast density PARPs were larger for premenopausal versus postmenopausal women (23.9%-35.0% vs. 13.0%-16.7%) and lower among premenopausal Black women (23.9%) than other races/ethnicities (30.4%-35.0%). Postmenopausal density PARPs were similar across races/ethnicities (13.0%-16.7%). CONCLUSIONS: Overweight/obesity and dense breasts account for large proportions of breast cancers in White, Black, Hispanic, and Asian women despite large differences in risk-factor distributions. IMPACT: Risk prediction models should consider how race/ethnicity interacts with BMI and breast density. Efforts to reduce BMI could have a large impact on breast cancer risk reduction, particularly among postmenopausal Black women.

Optimal Screening in Breast Cancer Survivors With Dense Breasts on Mammography.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

Serum Phospholipid Fatty Acids and Mammographic Density in Premenopausal Women.

BACKGROUND: The role of fatty acids (FAs) on mammographic density (MD) is unclear, and available studies are based on self-reported dietary intake. OBJECTIVES: This study assessed the association between specific serum phospholipid fatty acids (PLFAs) and MD in premenopausal women. METHODS: The cross-sectional study DDM-Madrid recruited 1392 Spanish premenopausal women, aged 39-50 y, who attended a screening in a breast radiodiagnosis unit of Madrid City Council. Women completed lifestyle questionnaires and FFQs. Percentage MD was estimated using a validated computer tool (DM-Scan), and serum PLFA percentages were measured by GC-MS. Multivariable linear regression models were used to quantify the association of FA tertiles with MD. Models were adjusted for age, education, BMI, waist circumference, parity, oral contraceptive use, previous breast biopsies, and energy intake, and they were corrected for multiple testing. RESULTS: Women in the third tertile of SFAs showed significantly higher MD compared with those in the first tertile (ßT3vsT1 = 7.53; 95% CI: 5.44, 9.61). Elevated relative concentrations of palmitoleic (ßT3vsT1 = 3.12; 95% CI: 0.99, 5.25) and gondoic (ßT3vsT1 = 2.67; 95% CI: 0.57, 4.77) MUFAs, as well as high relative concentrations of palmitelaidic (ßT3vsT1 = 5.22; 95% CI: 3.15, 7.29) and elaidic (ßT3vsT1 = 2.69; 95% CI: 0.59, 4.79) trans FAs, were also associated with higher MD. On the contrary, women with elevated relative concentrations of n-6 (ω-6) linoleic (ßT3vsT1 = -5.49; 95% CI; -7.62, -3.35) and arachidonic (ßT3vsT1 = -4.68; 95% CI: -6.79, -2.58) PUFAs showed lower MD. Regarding desaturation indices, an elevated palmitoleic to palmitic ratio and a low ratio of oleic to steric and arachidonic to dihomo-γ-linolenic acids were associated with higher MD. CONCLUSIONS: Spanish premenopausal women with high relative concentrations of most SFAs and some MUFAs and trans FAs showed an increased MD, whereas those with high relative concentrations of some n-6 PUFAs presented lower density. These results, which should be confirmed in further studies, underscore the importance of analyzing serum FAs individually.

Effect of excessive gestational weight on daughters' breast density at the end of puberty onset.

The effect of excessive gestational weight gain (EGWG) is related to adverse health outcomes in the offspring; however, its effect on the daughters' breast density is unclear. We aimed to assess the association between EGWG and daughters' breast composition (% of fibroglandular volume (%FGV) and absolute fibroglandular volume (AFGV)) at Tanner stage 4 (Tanner B4)). We included 341 girls and their mothers from an ongoing cohort of low-income Chilean girls born from 2002-2003. Maternal gestational weight gain was self-reported in 2007, and breast density by digital mammography was measured in 2010. Weight, height and breast composition by dual X-ray absorptiometry (DXA) were measured in daughters at Tanner B4. Logistic regression models were run to assess the association between EGWG and the 80th percentile of %FGV and AFGV. Mean gestational weight gain was 13.7 kg (SD = 6.9 kg). Women with pregestational overweight or obesity exceeded the recommended gestational weight gain (58.8% vs. 31.8%, respectively). Daughters of women who had EGWG had higher levels of AFGV (OR: 2.02; 95%CI 1.16-3.53) at Tanner B4, which could be explained by metabolic and hormonal exposure in utero. However, we did not observe an association with %FGV.

Race May Not Impact Endocrine Therapy-Related Changes in Breast Density.

BACKGROUND: Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD). METHODS: This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor-positive invasive breast cancer treated with ET. VBD, the ratio of fibroglandular volume (FGV) to breast volume (BV), was measured using Volpara software. Changes in measurements were evaluated using a multivariable linear mixed effects model. RESULTS: Compared with white women (n = 191), black women (n = 107) had higher rates of obesity [mean ± SD body mass index (BMI) 34.5 ± 9.1 kg/m2 vs. 30.6 ± 7.0 kg/m2, P < 0.001] and premenopausal status (32.7% vs. 16.7%, P = 0.002). Age- and BMI-adjusted baseline FGV, BV, and VBD were similar between groups. Modeled longitudinal changes were also similar: During a follow-up of 30.7 ± 15.0 months (mean ± SD), FGV decreased over time in premenopausal women (slope = -0.323 cm3; SE = 0.093; P = 0.001), BV increased overall (slope = 2.475 cm3; SE = 0.483; P < 0.0001), and VBD decreased (premenopausal slope = -0.063%, SE = 0.011; postmenopausal slope = -0.016%, SE = 0.004; P < 0.0001). Race was not significantly associated with these longitudinal changes, nor did race modify the effect of time on these changes. Higher BMI was associated with lower baseline VBD (P < 0.0001). Among premenopausal women, VBD declined more steeply for women with lower BMI (time × BMI, P = 0.0098). CONCLUSIONS: Race does not appear to impact ET-related longitudinal changes in VBD. IMPACT: Racial disparities in estrogen receptor-positive breast cancer recurrence and mortality may not be explained by differential declines in breast density due to ET.

Outcomes of solitary dilated breast ducts in symptomatic and asymptomatic patients.

OBJECTIVE: The purpose of this study is to assess the outcomes of symptomatic and asymptomatic solitary dilated ducts detected on mammography, ultrasound, and MRI. METHODS: All cases of isolated solitary dilated ducts between January 1, 2009 and December 31, 2016 in non-lactating females were reviewed. Clinical data, including patient's age, breast cancer history, and pathology results were collected. Imaging was reviewed, and indication for the exam, breast density, maximum diameter of the dilated duct on ultrasound, presence of an intraductal mass, presence of intraductal vascularity, presence of intraductal echogenicity, and subareolar or peripheral location of the dilated duct were recorded. RESULTS: 87 cases of solitary dilated ducts were assessed in this study, of which 3 were malignant, resulting in a positive predictive value of 3.5% (3/87). No malignancy was identified in asymptomatic screening patients. The three malignant cases were seen in patients presenting with a palpable lump (n = 1) or bloody nipple discharge (n = 2). There was a statistically significant association observed between the dilated duct diameter (p = 0.049) and presence of intraductal vascularity (p = 0.0005) with presence of malignancy. CONCLUSION: Rate of malignancy is low in solitary dilated ducts, especially among asymptomatic patients. Patient's presenting with clinical symptoms, larger dilated duct diameters, and/or intraductal vascularity may require additional evaluation including biopsy to exclude malignancy. ADVANCES IN KNOWLEDGE: Clinical and imaging factors can assist in better identifying patients with solitary dilated ducts who should undergo biopsy.