Low Breast Density Research Articles

Low breast density is associated with epicardial adipose tissue volume and coronary artery disease

Low breast density is associated with epicardial adipose tissue volume and coronary artery disease

Combined mammographic breast density and breast arterial calcification is incrementally predictive of coronary artery disease beyond traditional risk factors

Abstract Background Coronary artery disease (CAD) risk is underestimated in women using current risk stratification tools. The mammographic finding of breast arterial calcification (BAC) associates with CAD. Furthermore, breast adipose tissue, measured through breast density (BD) on mammography (low breast density indicates high adiposity) has shown potential to act as a pro-inflammatory, pro-atherogenic fat deposit. Given its uptake in screening programs, mammography may therefore represent a novel risk stratification tool for cardiovascular disease in women. Purpose To evaluate the association between the combined mammographic features of BD and BAC, with CAD. Methods Single-centre, retrospective, cross-sectional study, including 153 women, mean age 62±10, who had both clinically indicated mammography, and coronary computed tomography angiogram (CCTA) for suspected CAD. CAD risk was identified by the CAD Consortium Score, with a 15% threshold for low and high risk. BD was visually assessed and categorised by 4-level BI-RADS grade with grade A-B representing low density, and C-D representing high density (Figure 1). BAC was visually assessed and categorised as present/absent (Figure 1). CAD was categorised as presence/absence of coronary artery plaque on CCTA. Logistic regression was performed with results presented as Odds Ratio (OR) and [95% Confidence Intervals]. Receiver operator characteristic area under the curve (AUC) was used for model discrimination. Results Low BD (n=103 (67%)) was associated with CAD (OR 3.20 [1.58-6.53], p=0.001, as was BAC presence (n=37 (24%), OR 4.36 [1.58-12], p=0.004). There were 51 (33%) with elevated CAD risk. Participants were categorised into 4 subgroups based on low/high BD and presence/absence of BAC: 29 (19%) had low BD and BAC, 74 (48%) had low BD and no BAC, 8 (5%) had high BD and BAC and 42 (27%) had high BD and no BAC. Significantly higher proportions of CAD were noted with low BD and BAC alone, as well as combined low BD and BAC (Figure 2). Compared with high BD/BAC negative, the presence of low BD and BAC independently associated with CAD (OR 5.27 [1.19-23.3], p=0.03). Significant incremental benefit was seen after adding BD/BAC status to CAD Consortium Score (AUC 0.65 vs. 0.72, p=0.004). Conclusions Combined, and individual mammographic features of low BD and BAC presence are associated with CAD and improve risk prediction beyond standard coronary risk probabilities. Standardised reporting of these features to inform risk identification may be of further benefit and should be tested in prospective screening studies.

The association between mammographic breast density, epicardial adipose tissue volume and coronary artery disease

Abstract Background Dysfunctional adipose tissue is strongly linked to cardiometabolic disease. Epicardial adipose tissue (EAT) which is measurable on cardiac computed tomography (CT) is well correlated with cardiovascular disease (CVD), however it is not reported clinically. Breast mammography mandates reporting of breast density (BD), which is also a marker of breast adipose tissue quantity with less dense breasts indicating greater adipose tissue volume. Given the widespread use of screening mammography, this presents an opportunity to employ BD as a possible surrogate for CVD risk. Purpose To evaluate the correlation between BD, EAT and coronary artery disease (CAD). Methods Single-centre, retrospective, cross-sectional study, including women who had both clinically indicated coronary computed tomography angiogram (CCTA) and mammography. Epicardial adipose tissue volume (EATv) was quantified using semi-automated software (QFAT 2.0). BD was visually assessed by standard 4-level Breast Imaging-Reporting and Data System (BI-RADS) grade with grade A-B representing low density, and C-D representing high density. CAD was categorised as presence/absence of any coronary artery plaque, and CAD severity was quantified using the Coronary Artery Disease Reporting and Data Systems (CAD-RADS) score, with CAD-RADS 1-2 representing mild disease, CAD-RADS 3 moderate disease and CAD-RADS 4 severe disease. CAD analyses were adjusted for modifiable (hypertension, dyslipidaemia, diabetes, body mass index) and non-modifiable (age, past smoking, family history, breast cancer) risk factors. Logistic regression was performed with results presented as Odds Ratio (OR) and [95% Confidence Intervals]. Results Among 153 patients (mean age 62±10), 103 (67.3%) had low BD (high breast adiposity). Compared with high BD, low BD patients were older, had greater rates of hypertension, had significantly higher mean EAT (106.6 ± 43.0 vs 81.0 ± 31.6ml, p<0.001) (Figure 1), and body mass index (30.5 ± 6.3 vs 26.4 ± 5.4kg/m², p<0.001). Adjusted for age and hypertension, EATv remained independently predictive of low BD (OR:1.02 [1.01-1.03], p=0.006). Low BD made up a higher proportion of mild (76.5%), moderate (73.9%) and severe (80.0%) disease. Low BD was strongly associated with presence of CAD (prevalence 75% vs 48%, OR 3.21 [1.58-6.53], p=0.001) independent of EATv (p=0.25), and independent of modifiable (OR: 2.69 [1.24-5.92], p=0.012) and non-modifiable (OR: 2.42 [1.04-5.85], p=0.047) risk factors (Figure 2). Conclusions Low breast density is associated with higher EATv and independently associated with CAD presence beyond EATv and other risk factors. Consequently, mammographic breast density may act as an early risk identification tool for CAD in women.

Radiological features of screening-detected and interval breast cancers and subsequent survival in Eastern Finnish women.

Interval breast cancers are diagnosed between scheduled screenings and differ in many respects from screening-detected cancers. Studies comparing the survival of patients with interval and screening-detected cancers have reported differing results. The aim of this study was to investigate the radiological and histopathological features and growth rates of screening-detected and interval breast cancers and subsequent survival. This retrospective study included 942 female patients aged 50-69years with breast cancers treated and followed-up at Kuopio University Hospital between January 2010 and December 2016. The screening-detected and interval cancers were classified as true, minimal-signs, missed, or occult. The radiological features were assessed on mammograms by one of two specialist breast radiologists with over 15years of experience. A χ2 test was used to examine the association between radiological and pathological variables; an unpaired t test was used to compare the growth rates of missed and minimal-signs cancers; and the Kaplan-Meier estimator was used to examine survival after screening-detected and interval cancers. Sixty occult cancers were excluded, so a total of 882 women (mean age 60.4 ± 5.5years) were included, in whom 581 had screening-detected cancers and 301 interval cancers. Disease-specific survival, overall survival and disease-free survival were all worse after interval cancer than after screening-detected cancer (p < 0.001), with a mean follow-up period of 8.2years. There were no statistically significant differences in survival between the subgroups of screening-detected or interval cancers. Missed interval cancers had faster growth rates (0.47% ± 0.77%/day) than missed screening-detected cancers (0.21% ± 0.11%/day). Most cancers (77.2%) occurred in low-density breasts (< 25%). The most common lesion types were masses (73.9%) and calcifications (13.4%), whereas distortions (1.8%) and asymmetries (1.7%) were the least common. Survival was worse after interval cancers than after screening-detected cancers, attributed to their more-aggressive histopathological characteristics, more nodal and distant metastases, and faster growth rates.

Imaging for local recurrence of breast cancer

PurposeIsolated locoregional recurrence of breast cancer (ILRR) and contralateral breast cancer (CBC) affect up to 20% of all breast cancer (BC) patients in the first 20 years after primary diagnosis. Treatment options comprise surgical interventions and further systemic therapies depending on the histological subtype. Patients with hereditary breast or ovarian cancer (HBOC) undergo MRI, mammography, and ultrasound in the aftercare of BC, while non-HBOC (nHBOC) patients do not regularly receive MRI. Since early detection is crucial for morbidity and mortality, the evaluation and constant improvement of imaging methods of the breast is necessary.MethodsWe retrospectively analyzed the data of 1499 former BC patients that received imaging of the breast at a tertiary-care university hospital between 2015 and 2020. The analysis comprised various patient characteristics, such as breast density, age, tumor size and subtype, and their influence on BC detection rates by the different imaging methods.ResultsWithin the patient sample, 176 individuals (11.7% of former BC patients) were diagnosed with either ILRR or CBC. CBC was observed in 32.4% of patients, while both ILRR and secondary breast cancer occurred in 20.5% and 23.9% of all patients. Sensitivity of MRI, mammography, and ultrasound for recurrent malignancy was 97.9%, 66.3%, and 67.8%, respectively. ILRR and CBC detection rates were similar for patients with and without HBOC history. Lower breast density and larger tumor size increased the detection rates of all imaging modalities.ConclusionIn breast cancer survivors, MRI might improve the early detection of ILRR and CBC in both HBOC and nHBOC patients.

The Relationship Between Breast Density and Breast Cancer Surgical Outcomes: A Systematic Review.

This study aims to investigate the relationship between mammographic breast density and the surgical outcomes of breast cancer. PubMed, SCOPUS, Web of Science, Science Direct, and the Wiley Library were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process. Our results included ten studies with a total of 5017 women diagnosed with breast cancer. The follow-up duration ranged from 1 year to 15.1 years. Eight out of the twelve included studies reported that low mammographic breast density was significantly associated with no local recurrence, metachronous contralateral breast cancer, and fewer challenges in the preoperative and intraoperative phases. On the other hand, four studies reported that mammographic breast density is not linked to disease recurrence, survival, re-excision, or an incomplete clinical and pathological response. There is a significant association between low mammographic breast density and reduced challenges in the preoperative and intraoperative phases, as well as no local recurrence and fewer mastectomy cases. However, the link between mammographic breast density and disease recurrence, survival, re-excision, and incomplete clinical and pathological response is less clear, with some studies reporting no significant association. The findings suggest that mammographic breast density may play a role in certain aspects of breast cancer outcomes, but further research is needed to fully understand its impact.

The Relationship Between Breast Cancer Risk Factors and Mammographic Density

Background: Mammography is the most important evaluation technique for breast cancer screening. The importance of understanding mammographic density becomes evident when considering its relationship with breast cancer risk. There exists a positive correlation between high mammographic density and an increased susceptibility to breast cancer. Therefore, knowing the prevalence of breast density and its associated factors helps consider possible interventions and medical management to alter the density and properly follow up with the patients. Methods: A total of 350 women in Azerbaijan enrolled in this cross-sectional study. Patient’s questionnaires included demographic data such as age, weight, height, education, menarche age, menopause status and age, oophorectomy history, marital status, number of successful deliveries, age of first delivery, number of breast-feeding times, duration of breastfeeding, oral contraceptives/ hormone replacement therapy (HRT) usage, menstrual status, familial history of cancer, history of benign breast lesion biopsy, and alcohol/smoking status. The evaluation of breast density was done according to the American College of Radiology grading A to D. Results: The average age of the studied patients was 45.68±6.96 years with a median of 44.5 years. The population of women with breast density above 50% was higher compared to those with low breast density (51.4% versus 48.6%). In women without a history of breastfeeding, the frequency of breast density above 50% was observed in 76.4% of women. Significantly, lower densities were observed during menopause, and higher densities were observed during nonmenopause (P=0.001). Furthermore, no relationship was observed between breast composition and nulliparity, history of oophorectomy, duration of breastfeeding, marital status, menstrual status, and oral contraceptive pill (OCP) consumption. Conclusion: The main risk factors of high breast density include young age, menstrual status (non-menopausal patients), lack of breastfeeding after childbirth, older age of first delivery, and lower body mass index

Increased matrix stiffness enhances pro-tumorigenic traits in a physiologically relevant breast tissue- monocyte 3D model

High mammographic density, associated with increased tissue stiffness, is a strong risk factor for breast cancer per se. In postmenopausal women there is no differences in the occurrence of ductal carcinoma in situ (DCIS) depending on breast density. Preliminary data suggest that dense breast tissue is associated with a pro-inflammatory microenvironment including infiltrating monocytes. However, the underlying mechanism(s) remains largely unknown. A major roadblock to understanding this risk factor is the lack of relevant in vitro models. A biologically relevant 3D model with tunable stiffness was developed by cross-linking hyaluronic acid. Breast cancer cells were cultured with and without freshly isolated human monocytes. In a unique clinical setting, extracellular proteins were sampled using microdialysis in situ from women with various breast densities. We show that tissue stiffness resembling high mammographic density increases the attachment of monocytes to the cancer cells, increase the expression of adhesion molecules and epithelia-mesenchymal-transition proteins in estrogen receptor (ER) positive breast cancer. Increased tissue stiffness results in increased secretion of similar pro-tumorigenic proteins as those found in human dense breast tissue including inflammatory cytokines, proteases, and growth factors. ER negative breast cancer cells were mostly unaffected suggesting that diverse cancer cell phenotypes may respond differently to tissue stiffness. We introduce a biological relevant model with tunable stiffness that resembles the densities found in normal breast tissue in women. The model will be key for further mechanistic studies. Additionally, our data revealed several pro-tumorigenic pathways that may be exploited for prevention and therapy against breast cancer. Statement of significanceWomen with mammographic high-density breasts have a 4–6-fold higher risk of breast cancer than low-density breasts. Biological mechanisms behind this increase are not fully understood and no preventive therapeutics are available. One major reason being a lack of suitable experimental models. Having such models available would greatly enhance the discovery of relevant targets for breast cancer prevention. We present a biologically relevant 3D-model for studies of human dense breasts, providing a platform for investigating both biophysical and biochemical properties that may affect cancer progression. This model will have a major scientific impact on studies for identification of novel targets for breast cancer prevention.

Low breast density and peritumoral edema on MR predict worse overall survival of breast cancer patients after neoadjuvant chemotherapy

ObjectivesTo investigate the relationship of pre-treatment MR image features (including breast density) and clinical-pathologic characteristics with overall survival (OS) in breast cancer patients receiving neoadjuvant chemotherapy (NAC). MethodsThis retrospective study obtained an approval of the institutional review board and the written informed consents of patients were waived. From October 2013 to April 2019, 130 patients (mean age, 47.6 ± 9.4 years) were included. The univariable and multivariable Cox proportional hazards regression models were applied to analyze factors associated with OS, including MR image parameters and clinical-pathologic characteristics. ResultsAmong the 130 included patients, 11 (8.5%) patients (mean age, 48.4 ± 11.8 years) died of breast cancer recurrence or distant metastasis. The median follow-up length was 70 months (interquartile range of 60–85 months). According to the Cox regression analysis, older age (hazard ratio [HR] = 1.769, 95% confidence interval [CI]): 1.330, 2.535), higher T stage (HR = 2.490, 95%CI:2.047, 3.029), higher N stage (HR = 1.869, 95%CI:1.507, 2.317), low breast density (HR = 1.693, 95%CI:1.391, 2.060), peritumoral edema (HR = 1.408, 95%CI:1.078, 1.840), axillary lymph nodes invasion (HR = 3.118, 95%CI:2.505, 3.881) on MR were associated with worse OS (all p < 0.05). ConclusionsPre-treatment MR features and clinical-pathologic parameters are valuable for predicting long-time OS of breast cancer patients after NAC followed by surgery. Low breast density, peritumoral edema and axillary lymph nodes invasion on pre-treatment MR images were associated with worse prognosis.

Abstract C118: Racial disparities in insurance coverage for supplemental breast cancer screening

Abstract Introduction and Purpose: Women with dense breasts have increased risk both for developing breast cancer and false-negative mammograms. Supplemental screening with breast MRI has been shown to shown to significantly increase cancer detection among women with dense breasts. In May 2023, Pennsylvania (PA) mandated insurance coverage of one supplemental screening study (breast MRI or ultrasound ) annually for women with dense breasts. Prior research suggests that Black women have lower breast density on average than white women based on subjective grading from the American College of Radiology Breast Imaging and Reporting Data System (BI-RADS), partially due to larger average breast size and higher body mass index (BMI) than white women. The purpose of this study was to estimate the potential impact of this supplemental screening law on different patient populations in a large health system. Methods: Women without prior breast cancer or known BRCA1/2 mutations who underwent mammographic screening at a large PA health system from April 2015-December 2017and completed a risk factor questionnaire were included (N=83,579). Under PA law, women must have either heterogeneously dense breasts plus &amp;gt;20% lifetime risk of breast cancer or extremely dense breasts to be eligible for insurance coverage for supplemental screening, both of which involve subjectively graded breast measurements. Breast cancer risk for each patient was estimated using the Gail model. The cancer detection rate (CDR) for mammographic screening was calculated as the number of cancers diagnosed within one year of a positive mammographic screen; the interval cancer rate was calculated as the number of cancers diagnosed within one year of a non-actionable screening mammogram per 1000 women. Logistic regression was used to calculate the odds of eligibility adjusted for age and BMI. Results: Black women were less likely to have extremely or heterogeneously dense breasts than white women (23.7% vs. 45.0%, p&amp;lt;0.001). Under PA law, 2.5% of Black women and 9.9% of white women would qualify for insurance coverage for supplemental screening (p&amp;lt;0.001). Only 0.2% of Black women and 2.3% of white women had heterogeneously dense breasts and &amp;gt;20% lifetime risk. Black women were more likely to have triple-negative breast cancer (TNBC) than white women (p&amp;lt;0.001). After adjusting for age and BMI, Black women remained 54% less likely to be eligible for supplemental screening than white women (OR=0.46, 95% 0.42-0.51, p&amp;lt;0.001).Conclusions: Black women are less likely to qualify for insurance coverage for supplemental breast cancer screening than white women under PA law. Given that Black women have lower prevalence of subjectively graded dense breasts and higher prevalence of TNBC, the new supplemental screening law is unlikely to meaningfully reduce racial disparities in breast cancer mortality. Methods to better assess breast cancer risk among Black women, particularly the risk of TNBC, are urgently needed to identify Black women that may benefit from supplemental screening. Citation Format: Mattia A. Mahmoud, Sarah Ehsan, Oluwadamilola M. Fayanju, Susan M. Domchek, Katherine L. Nathanson, Despina Kontos, Emily F. Conant, Anne Marie McCarthy. Racial disparities in insurance coverage for supplemental breast cancer screening [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C118.

Comparison of mammography and ultrasound findings in the follow-up of patients with breast cancer treated with segmental mastectomy followed by intraoperative electron radiotherapy versus external whole breast radiotherapy

This study aims to describe imaging findings in patients treated with intraoperative electron radiotherapy and compare them with those detected in patients treated with external whole breast radiotherapy (WBRT). The study population consisted of 25 patients who received intraoperative radiotherapy [IORT (21 Gy)] as single-dose radiotherapy and a control group of 25 patients who received WBRT at the same institution. Mammography and ultrasound (US) findings were divided into three groups: minor, intermediate, and advanced. On mammography, mass lesions were considered advanced, and asymmetries or architectural distortions were considered intermediate. Oil cysts, linear scars, and the increase in parenchymal density were considered minor findings. On US, irregular non-mass lesions were considered advanced, and circumscribed hypoechoic lesions or planar irregular scars with shadowing were considered intermediate. Oil cysts, fluid collections, or linear scars were considered minor findings. On mammography, skin thickening (P = 0.001), edema (P < 0.001), increased parenchymal density (P < 0.001), dystrophic calcifications (P = 0.045), and scar/distortion (P = 0.005) were significantly more common in the WBRT group. On US, irregular non-mass lesions, which made interpretation considerably difficult, were significantly more common in the IORT group (P = 0.004). Dominant US findings were fluid collections and postoperative linear or planar scars in the WBRT group. Minor findings were more common in low-density breasts, and major findings (intermediate and advanced) were more common in high-density breasts on both mammographies (P = 0.011) and US (P = 0.027) in the IORT group. Ill-defined non-mass lesions detected on US in the IORT group have not been defined previously. Radiologists should be aware of these lesions because they can be confusing, especially in early follow-up studies. This study has found that minor findings are seen more frequently in low-density breasts, while major findings are more common in high-density breasts in the IORT group. This has not been reported before, and further studies with more cases are needed to verify these results.

Variations of image interpretations of radiologists from different populations in mammography and tomosynthesis with different levels of breast density.

This study aims to investigate the diagnostic performances of Australian and Shanghai-based Chinese radiologists in reading full-field digital mammogram (FFDM) and digital breast tomosynthesis (DBT) with different levels of breast density. Eighty-two Australian radiologists interpreted a 60-case FFDM set, and 29 radiologists also reported a 35-case DBT set. Sixty Shanghai radiologists read the same FFDM set, and 32 radiologists read the DBT set. The diagnostic performances of Australian and Shanghai radiologists were assessed using truth data (cancer cases were biopsy proven) and compared overall in specificity, case sensitivity, lesion sensitivity, receiver operating characteristics (ROC) area under the curve, and jack-knife free-response receiver operating characteristics (JAFROC) figure of merit, and they were stratified by case characteristics using the Mann-Whitney U test. The Spearman rank test was used to explore the association between radiologists' performances and their work experience in mammogram interpretation. There were significantly higher performances of Australian radiologists compared with Shanghai radiologists in low breast density for case sensitivity, lesion sensitivity, ROC, and JAFROC in the FFDM set ( ); in high breast density, Shanghai radiologists' performances in lesion sensitivity and JAFROC were also lower than Australian radiologists ( ). In the DBT test set, Australian radiologists performed better than Shanghai radiologists in cancer detection in both low and high breast density. The work experience of Australian radiologists was positively linked to their diagnostic performances, whereas this association was not statistically significant in Shanghai radiologists. There were significant variations in reading performances between Australian and Shanghai radiologists in FFDM and DBT across different levels of breast density, lesion types, and lesion sizes. An effective training initiative tailored to suit local readers is essential to enhancing the diagnostic accuracy of Shanghai radiologists.

Abstract PD16-02: Factors Associated with Receipt of Digital Breast Tomosynthesis Among Racially/Ethnically Diverse Women Undergoing Screening Mammography

Abstract Introduction: Digital breast tomosynthesis (DBT) is increasingly utilized in breast cancer screening, including among women at high risk for breast cancer. While there is a lack of rigorous data from randomized controlled trials demonstrating superior efficacy compared to two-dimensional (2D) digital mammography, observational studies suggest that DBT might have lower rates of false-positive results and increased detection of invasive cancer than 2D mammography. However, uptake of DBT might be lower among racial/ethnic minorities, which could contribute to breast cancer disparities. We evaluated whether sociodemographic and breast cancer risk factors were associated with receipt of DBT vs. 2D mammography among a racially/ethnically diverse population of women undergoing screening mammography. Methods: We conducted a respective cohort study among women, age 40-74 years, who underwent screening mammography at Columbia University Irving Medical Center (CUIMC) in New York, NY, from February 2020 to January 2022. We extracted data from the electronic health record (EHR) on age, race/ethnicity, first-degree family history of breast cancer (yes/no), prior breast biopsies (yes/no), and mammographic breast density (high vs. low), and calculated individual 5-year risks of invasive breast cancer according to the Breast Cancer Surveillance Consortium (BCSC) model. High risk was defined as a 5-year invasive breast cancer risk 1.67%. Our primary outcome was receipt of at least one DBT screening examination from 2020-2022 (yes/no). We conducted multivariable logistic regression analyses to assess the association between demographic/clinical factors and receipt of DBT. Results: Among 5617 evaluable women, mean age was 55.4 years (SD, 9.5 years) and 56% identified as non-Hispanic White, 10% as non-Hispanic Black, 17% as Hispanic, 8% as Asian, and 9% other/unknown. Over 60% of women had high breast density, and 34% met high-risk criteria. Seventy percent of women had at least one DBT from 2020-2022. In multivariable analyses (Table 1), women with high vs. low breast density were 2.5 times more likely to receive DBT (odds ratio [OR]=2.51, 95% confidence interval [CI]=2.19-2.88), while first-degree family history of breast cancer, prior breast biopsy, and age were inversely associated with DBT. Racial/ethnic minorities were less than half as likely to undergo DBT compared to non-Hispanic Whites; for example, Hispanic women were over 85% less likely to receive DBT (OR=0.14, 95% CI=0.11-0.16). Overall, there was no association between breast cancer risk status (high vs. low/average) and receipt of DBT (OR=1.00, 95% CI 0.92-1.08). Conclusion: We observed that the majority of women undergoing screening mammography at CUIMC from 2020-2022 received DBT for breast cancer screening. However, racial/ethnic minorities, including non-Hispanic Blacks and Hispanics, were significantly less likely than non-Hispanic Whites to have received DBT. Breast cancer risk according the BCSC model was also not associated with receipt of DBT. Future studies should determine which subsets of women are more likely to benefit from DBT. Citation Format: Julia E. McGuinness, Gargi Patel, Jacquelyn N. Amenta, Rita Kukafka, Katherine D. Crew. Factors Associated with Receipt of Digital Breast Tomosynthesis Among Racially/Ethnically Diverse Women Undergoing Screening Mammography [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD16-02.

Abstract P4-03-10: BREAST DENSITY AND RISK OF BREAST CANCER

Abstract Background: Early studies reported a 4-6-fold risk of breast cancer between women with extremely dense and fatty breasts. As most early studies were case-control studies, we took advantage of a population-based screening program to study density and breast cancer incidence in a cohort design. Methods: In the Capital Region, Denmark, woman aged 50-69 are invited to screening biennially. Women screened November 2012 - December 2017 were included, and classified by BI-RADS density code, version 4, at first screen after recruitment. Women were followed up for incident breast cancer, including ductal carcinoma in situ (DCIS), to 2020 in nationwide pathology data. Rate ratios (RR) and 95% confidence intervals (CI) were compared across density groups using Poisson-regression. Results: We included 189,609 women; 1,067,293 person-years; and 4110 incident breast cancers/DCIS. Thirty-three percent of women had BI-RADS density code 1; 38% code 2; 24% code 3; 4.7% code 4; and missing 0.3%. Using women with BI-RADS density code 1 as baseline; women with code 2 had RR 1.69 (95% CI 1.56-1.84); women with code 3, RR 2.06 (95% CI 1.89-2.25); and women with code 4, RR 2.37 (95% CI 1.05-2.74). Results differed between observations accumulated during screening and above screening age. Conclusions: This cohort study showed a 2.37-fold difference in breast cancer risk between women with highest and lowest breast density. Translated into absolute risk of breast cancer after age 50, this was a 6.2% risk for the one-third of women with lowest density, and 14.7% for the five percent of women highest density. Citation Format: Elsebeth Lynge, Ilse Vejborg, Martin Lillholm, Mads Nielsen, George Napolitano, My von Euler-Chelpin. BREAST DENSITY AND RISK OF BREAST CANCER [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-10.

Cosmetics Use and Mammographic Breast Density (MBD) in Iranian Women: A Cross-Sectional Study

Background: Since breast cancer is increasing worldwide and previous risk factors cannot justify such an increasing trend, investigating new environmental factors is necessary for each population. Mammographic breast density (MBD) is a strong risk factor for breast cancer as well as a biomarker for the effect of chemicals on breast tissue. Objective: Given limited data about the association between breast density and cosmetic products containing endocrine-disrupting chemicals (EDCs), the purpose of this study was to evaluate the effects of cosmetic products on MBD in Iranian women. Methods: In this cross-sectional study, women who attended two university hospitals for breast screening mammography and who had been living in the capital city of Iran for the last 3 years or more were recruited. We asked women to fill out a questionnaire containing two parts; the first part was about the women's characteristics and medical history and the second part consisted of cosmetic use. The frequency of cosmetic use was measured using the Likert scale in four scales. One expert radiologist in each center reported the MBD on a four-category scale. Results: The mean age of 813 participants was 50.16 ± 7.65. Three hundred-seven (37.8%) women had low breast density and 506 (62.2%) had high breast density. Based on our results, heavy use of moisturizers, sunscreen, nail polish, eye products, makeup products, and lipstick was associated with increased breast density. In multivariable analysis after adjusting for menopause, excessive use of nail polish, sunscreen, and moisturizing cream was associated with increased MBD. Conclusion: Our study shows a probability of an increased MBD with the excessive use of cosmetic products. Since a small increase in the risk of breast cancer may lead to a considerable public health impact, thus further studies are needed to find new prevention strategies.

High-resolution synthesis of high-density breast mammograms: Application to improved fairness in deep learning based mass detection.

Computer-aided detection systems based on deep learning have shown good performance in breast cancer detection. However, high-density breasts show poorer detection performance since dense tissues can mask or even simulate masses. Therefore, the sensitivity of mammography for breast cancer detection can be reduced by more than 20% in dense breasts. Additionally, extremely dense cases reported an increased risk of cancer compared to low-density breasts. This study aims to improve the mass detection performance in high-density breasts using synthetic high-density full-field digital mammograms (FFDM) as data augmentation during breast mass detection model training. To this end, a total of five cycle-consistent GAN (CycleGAN) models using three FFDM datasets were trained for low-to-high-density image translation in high-resolution mammograms. The training images were split by breast density BI-RADS categories, being BI-RADS A almost entirely fatty and BI-RADS D extremely dense breasts. Our results showed that the proposed data augmentation technique improved the sensitivity and precision of mass detection in models trained with small datasets and improved the domain generalization of the models trained with large databases. In addition, the clinical realism of the synthetic images was evaluated in a reader study involving two expert radiologists and one surgical oncologist.

Correlation of mammographic density and breast cancer characteristics

Background and objective: Mammographic density is regarded as one of the most prevalent risk factors for developing breast cancer. However, there is limited data on its relationship with tumor characteristics. Therefore, this study has been conducted to evaluate the association between mammographic density and breast cancer subtypes as well as tumor characteristics. Methods: This retrospective cross-sectional study was performed on 105 women with pathologically proved breast cancer. Mammographic breast density was scored according to Breast Imaging Reporting and Data System classification before receiving treatment, followed by correlation with some risk factors and tumor characteristics. Results: From the 105 enrolled cases, about 70% had low mammographic density, and 30% had high mammographic density. Mammographic breast density was significantly associated with age and menopausal status, where high density was more prevalent among age group &lt;45 years (58%) and among premenopausal women (71%). No significant association was found between density and Body Mass Index. Overall, estrogen positive, progesterone positive and luminal B were more prevalent in both low and high breast density cases; however, these findings were not significant. No significant relationship between mammography density and tumor grade, stage, size or lymph node involvement was observed. Conclusion: Mammographic breast density is positively associated with age and menopausal status but not associated with Body Mass Index or tumor characteristics.

In vivo assignment of methylmalonic acid in breast tissue using 2D MRS and relationship with breast density, menopausal status and cancer risk.

Methylmalonic acid (MMA) is linked to progression and aggressiveness of tumours. A recent study showed that high levels of circulatory MMA directed genetic programs promoting cancer progression. To evaluate in vivo two-dimensional correlated spectroscopy (2D COSY) data from women at elevated risk of breast cancer to determine if resonances consistent with MMA are present, and if so to correlate levels with breast density, menopausal status and risk categories. With institutional review board approval, 106 women at elevated risk (mean age 47), including 46 participants at medium risk, 43 at high risk with no known mutation and 17 BRCA-mutation carriers, were recruited. Breast density was assessed using a T2 sequence. A T1 sequence was used to place the voxel for the 2D COSY data. Peak volumes were normalized to the methylene peak at (1.30, 1.30)ppm. Chi-squared and Mann-Whitney tests were used. Two resonances are assigned on the diagonal at 3.15 ppm and 3.19 ppm consistent with and denoted MMA1 and MMA2 respectively. MMA1 and MMA2 increased in parallel with increased risk. BRCA-mutation carriers recorded an increase in mean MMA1 of 120% (p = 0.033) and MMA2 of 127% (p = 0.020) in comparison with participants with no known mutation. BRCA-mutation carriers with dense breasts recorded a significant increase in mean MMA1 of 137% (p = 0.002) and in mean MMA2 of 143% (p = 0.004) compared with BRCA-mutation participants with low-density breast tissue. MMA1 and MMA2 were higher in premenopausal women with dense breasts compared with those with low-density tissue. The highest values of MMA were recorded in BRCA-mutation carriers. Two tentative assignments are made for MMA in breast tissue of women at elevated risk for cancer. BRCA-mutation carriers exhibited higher values of MMA than those with no known mutation. Premenopausal women with BRCA mutation and dense breasts recorded the highest levels of MMA compared with other categories.

Effect of cell density on the malignant biological behavior of breast cancer by altering the subcellular localization of ANXA2 and its clinical implications.

To investigate the subcellular localization of ANXA2 in breast cancer of different cell densities in humans and its relationship with the clinicopathological features of patients. To investigate the differences in ANXA2 subcellular localization in MDA-MB-231 cells of different cell densities. To compare the proliferation, invasion, and migration ability of MDA-MB-231 cells under different ANXA2 subcellular localization. Immunohistochemistry was applied to detect the subcellular localization of ANXA2 in tissue sections of 60 breast cancer patients, and the association with ANXA2 subcellular localization was verified in conjunction with cell density. To investigate the relationship between cell density and clinicopathological data of breast cancer patients. To establish high- and low-density models of MDA-MB-231 breast cancer cell lines and verify the subcellular localization of ANXA2 using immunofluorescence and observation under confocal microscopy. The proliferation, migration, and invasion ability of MDA-MB-231 cells under different subcellular localization of ANXA2 were detected and compared using CCK-8 assay and Transwell assay. After changing the subcellular localization of ANXA2 in high-density MDA-MB-231 cells with PY-60, changes in biological behaviors of the compared MDA-MB-231 cells were observed. Two different 4T1 cell lines with high and low densities were implanted subcutaneously in nude mice to observe the effects of different cell densities on tumor growth in nude mice. The clinical data showed that breast cancer with high cell density had higher T stage and higher TNM stage, and the cell density was positively correlated with breast cancer mass size. ANXA2 was mainly localized to the cell membrane when the cell density of breast cancer cells was high and to the cytoplasm when the cell density was low. The CCK-8 assay showed that the proliferation rate of MDA-MB-231 cells increased (P < 0.05) after shifting the subcellular localization of ANXA2 from the cell membrane to the cytoplasm. Transwell invasion assay and Transwell migration assay showed that the invasion and migration ability of MDA-MB-231 cells increased significantly after the subcellular localization of ANXA2 was transferred from the cell membrane to the cytoplasm (P < 0.05). The animal experiments showed that high-density breast cancer cells could promote the growth of subcutaneous tumors in nude mice relative to low-density breast cancer cells. Cell density can regulate the subcellular localization of ANXA2, and changes in the subcellular localization of ANXA2 are accompanied by the changes in the biological behavior of breast cancer.

Modern interpretation of risk factors in breast cancer of women

Breast cancer is a major public health problem, being the most common cancer diagnosed in women and accounting for more than 1 in 10 new diagnoses of cancer each year. It is the most common neoplasm of women under the age of 40 and the second leading cause of cancer death in this age group, with more frequent detection of pathogenic mutations in breast cancer susceptibility genes. Women with BRCA1 and BRCA2 mutations are about 70% more likely to develop breast cancer. The incidence is rising in most countries and it is expected to have a growing trend in the next 20 years, despite the current efforts to prevent the disease. In order to improve the survival rate, it is necessary to make a diagnosis as early as possible and to initiate the appropriate therapeutic management as soon as possible. Therefore, in order to detect breast formations, mammography screening is very important, breast density being an important factor in predicting the risk of breast cancer. Thus, the presence of high breast density represents a 4-6 times higher risk of developing breast cancer compared to women with low breast density. Aging and menopause are also risk factors for breast cancer. Hormone replacement therapy for postmenopausal women has the benefit of relieving symptoms such as hot flashes, depression or sleep disturbances, but it increases the risk of developing breast cancer.