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Background: Mammographic density has been associated with breast cancer risk, and is modulated by established breast cancer risk factors, such as reproductive and hormonal history, as well as lifestyle. Recent epidemiological and biological findings underscore the recognized benefits of breastfeeding in reducing breast cancer risk, especially for aggressive subtypes. Current research exploring the association among mammographic density, breastfeeding, and breast cancer is sparse. Main findings: Changes occur in the breasts during pregnancy in preparation for lactation, characterized by the proliferation of mammary gland tissues and the development of mammary alveoli. During lactation, the alveoli fill with milk, and subsequent weaning triggers the involution and remodeling of these tissues. Breastfeeding influences the breast microenvironment, potentially altering mammographic density. When breastfeeding is not initiated after birth, or is abruptly discontinued shortly after, the breast tissue undergoes forced and abrupt involution. Conversely, when breastfeeding is sustained over an extended period and concludes gradually, the breast tissue undergoes slow remodeling process known as gradual involution. Breast tissue undergoing abrupt involution displays denser stroma, altered collagen composition, heightened inflammation and proliferation, along with increased expression of estrogen receptor α (ERα) and progesterone receptor. Furthermore, elevated levels of pregnancy-associated plasma protein-A (PAPP-A) surpass those of its inhibitors during abrupt involution, enhancing insulin-like growth factor (IGF) signaling and collagen deposition. Prolactin and small molecules in breast milk may also modulate DNA methylation levels. Drawing insights from contemporary epidemiological and molecular biology studies, our review sheds light on how breastfeeding impacts mammographic density and explores its role in influencing breast cancer. Conclusion: This review highlights a clear protective link between breastfeeding and reduced breast cancer risk via changes in mammographic density. Future research should investigate the effects of breastfeeding on mammographic density and breast cancer risk among various ethnic groups and elucidate the molecular mechanisms underlying these associations. Such comprehensive research will enhance our understanding and facilitate the development of targeted breast cancer prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Methods of modelling the female torso during physical activity often neglect the position and movement of the breast. This novel investigation compares three female torso modelling approaches that differ in complexity (integrated breast, fixed breast, dynamic breast) to determine the effect on spinal joint moments during running and jumping. The commonly used integrated breast model distributed breast mass within the torso, the fixed breast model attached the mass of the breasts to fixed positions on the anterior of the torso, and a new dynamic breast model enabled relative motion between the breasts and anterior torso. Key findings demonstrated minimal differences in lumbar spine moments (<0.05 Nm/kg; 4%) between integrated breast and fixed breast models but greater differences, up to 0.86 Nm/kg (68%) during running and 0.89 Nm/kg (82%) during jumping, when breast motion was included. Thoracic spine moments revealed similar patterns with minimal differences (<0.05 Nm/kg; 11%) between integrated breast and fixed breast models and greater differences, up to 0.48 Nm/kg (92%) during running and 0.63 Nm/kg (66%) during jumping, with the dynamic breast model. Future female musculoskeletal models should consider including breast mass and motion to avoid mis-representing spinal loading in females during running and jumping. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common cancer worldwide and a leading cause of cancer-related deaths in women. Mammographic breast density, the relative amount of fibroglandular tissue as seen on a mammogram, is one of the strongest predictors of breast cancer risk, with higher breast density associated with greater risk. Breasts undergo extensive fibroglandular tissue proliferation in early life, making this a potential window of vulnerability for carcinogen exposures. Early-life growth (e.g., height and weight) is also associated with breast cancer risk. Research into the 'developmental origins of health and disease' paradigms investigate the pathways of risk for disease in later life from early-life exposures across developmental phases. However, little is known about the association between early-life growth and breast density. Further investigation into these risk pathways could increase knowledge of disease etiology and help identify women at increased risk at an earlier age and inform potential mediation of breast cancer risk. Breast density is a strong intermediate endpoint to investigate the association between early-life exposures and breast cancer risk. This study investigates the association between early-life growth and breast density in young adult women measured using Optical Breast Spectroscopy (OBS) and Dual X-ray Absorptiometry (DXA). OBS measurements were obtained for 536 female Raine Cohort Study participants at ages 27–28, with 268 completing DXA measurements. Participants with three or more height and weight measurements from ages 8 to 22 were used to generate linear growth curves for height, weight and body mass index (BMI) using SITAR modelling. Three growth parameters (size, velocity and timing) were examined for association with breast density measures, adjusting for potential confounders. Women who reached their peak height rapidly (velocity) and later in adolescence (timing) had lower OBS-breast density. Overall, women who were taller (size) had higher OBS-breast density. For weight, women who grew quickly (velocity) and later in adolescence (timing) had higher absolute DXA-breast density. Overall, weight (size) was also inversely associated with absolute DXA-breast density, as was BMI. These findings provide new evidence that adolescent growth is associated with breast density measures in young adult women, suggesting potential mediation pathways for breast cancer risk in later life. [ABSTRACT FROM AUTHOR]

Background High mammographic density increases breast cancer risk and reduces mammographic sensitivity. We reviewed evidence on accuracy of supplemental MRI for women with dense breasts at average or increased risk. Methods PubMed and Embase were searched 1995-2022. Articles were included if women received breast MRI following 2D or tomosynthesis mammography. Risk of bias was assessed using QUADAS-2. Analysis used independent studies from the articles. Fixed-effect meta-analytic summaries were estimated for predefined groups (PROSPERO: 230277). Results Eighteen primary research articles (24 studies) were identified in women aged 19-87 years. Breast density was heterogeneously or extremely dense (BI-RADS C/D) in 15/18 articles and extremely dense (BI-RADS D) in 3/18 articles. Twelve of 18 articles reported on increased-risk populations. Following 21 440 negative mammographic examinations, 288/320 cancers were detected by MRI. Substantial variation was observed between studies in MRI cancer detection rate, partly associated with prevalent vs incident MRI exams (prevalent: 16.6/1000 exams, 12 studies; incident: 6.8/1000 exams, 7 studies). MRI had high sensitivity for mammographically occult cancer (20 studies with at least 1-year follow-up). In 5/18 articles with sufficient data to estimate relative MRI detection rate, approximately 2 in 3 cancers were detected by MRI (66.3%, 95% CI, 56.3%-75.5%) but not mammography. Positive predictive value was higher for more recent studies. Risk of bias was low in most studies. Conclusion Supplemental breast MRI following negative mammography in women with dense breasts has breast cancer detection rates of ~16.6/1000 at prevalent and ~6.8/1000 at incident MRI exams, considering both high and average risk settings. [ABSTRACT FROM AUTHOR]

Breast diseases are on the rise throughout the world. It is essential to learn correct technique of "clinical breast examination" to ascertain the appropriate diagnostic workup in the most efficient manner. The ABCD rule is proposed by three highly skilled clinicians in the field of breast care trained in the famous Cardiff Breast Unit of Prof LE Hughes, Prof David JT Webster and Prof Robert E Mansel. The ABCD rule will allow early detection of breast cancer and other diseases with timely management of patients. It will help both the medical and nursing students as well as the field health workers in learning about diagnosis of breast diseases and in screening for breast cancer. [ABSTRACT FROM AUTHOR]

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Purpose: Preoperative breast MRI has been recommended at our center since 2016 for invasive lobular carcinoma and cancers in dense breasts. This study examined how preoperative breast MRI impacted surgical timing and outcomes for patients with newly diagnosed breast cancer. Methods: Retrospective single-center study of consecutive women diagnosed with new breast cancer between June 1, 2019, and March 1, 2021, in whom preoperative breast MRI was recommended. MRI, tumour histology, breast density, post-MRI biopsy, positive predictive value of biopsy (PPV3), surgery, and margin status were recorded. Time from diagnosis to surgery was compared using t -tests. Results: There were 1054 patients reviewed, and 356 were included (mean age 60.9). Of these, 44.4% (158/356) underwent preoperative breast MRI, and 55.6% (198/356) did not. MRI referral was more likely for invasive lobular carcinoma, multifocal disease, and younger patients. Following preoperative MRI, 29.1% (46/158) patients required additional breast biopsies before surgery, for a PPV3 of 37% (17/46). The time between biopsy and surgery was 55.8 ± 21.4 days for patients with the MRI, compared to 42.8 ± 20.3 days for those without (P <.00001). MRI was not associated with the type of surgery (mastectomy vs breastconserving surgery) (P =.44) or rate of positive surgical margins (P =.52). Conclusion: Among patients who underwent preoperative breast MRI, we observed significant delays to surgery by almost 2 weeks. When preoperative MRI is requested, efforts should be made to mitigate associated delays. [ABSTRACT FROM AUTHOR]

Objective We investigated patient experience with screening contrast-enhanced mammography (CEM) to determine whether a general population of women with dense breasts would accept CEM in a screening setting. Methods In this institutional review board–approved prospective study, patients with heterogeneous and extremely dense breasts on their mammogram were invited to undergo screening CEM and complete pre-CEM and post-CEM surveys. On the pre-CEM survey, patients were asked about their attitudes regarding supplemental screening in general. On the post-CEM survey, patients were asked about their experience undergoing screening CEM, including causes and severity of any discomfort and whether they would consider undergoing screening CEM again in the future or recommend it to a friend. Results One hundred sixty-three women were surveyed before and after screening CEM. Most patients, 97.5% (159/163), reported minimal or no unpleasantness associated with undergoing screening CEM. In addition, 91.4% (149/163) said they would probably or very likely undergo screening CEM in the future if it cost the same as a traditional screening mammogram, and 95.1% (155/163) said they would probably or very likely recommend screening CEM to a friend. Patients in this study, who were all willing to undergo CEM, more frequently reported a family history of breast cancer than a comparison cohort of women with dense breasts (58.2% vs 47.1%, P = .027). Conclusion Patients from a general population of women with dense breasts reported a positive experience undergoing screening CEM, suggesting screening CEM might be well received by this patient population, particularly if the cost was comparable with traditional screening mammography. [ABSTRACT FROM AUTHOR]

Background of the Study: Mammograms are sometimes met with issues of overdiagnosis and underdiagnosis; therefore, they are less reliable in identifying cancer in women with dense breasts. As a result, it is critical to be aware of other sensitive screening techniques for the early diagnosis of breast cancer. Aim: The ultimate objective of this study was to assess the knowledge of nursing undergraduates regarding non-invasive biomarkers, such as volatile organic compounds in breath, nipple aspirate fluid, sweat, urine, and tears, for the early detection of breast cancer to help improve patient care, determine the risk factors, and encourage practice of breast self-examination. Methods: Cross-sectional research was done in the Department of Nursing at Farasan campus using a self-structured questionnaire as the study tool. A total of 260 students willingly participated. The study tool had evaluation questions focused on the non-invasive biomarkers of breast cancer, risk factors, and breast self-examination practices to collect data. The data were subjected to descriptive and inferential statistics. The statistical significance was calculated at P <.05. Data analyses were done using Microsoft Excel (2013). Results: A s ignificant knowledge gap existed among the study participants about the non-invasive biomarkers of breast cancer. A lesser percentage of students (25%) stated that they do breast self-examination on a monthly basis. The most common reasons for not doing the breast self-examination were "not knowing how to do the breast self-examination" (77.3%), fear of a positive diagnosis (53.9%), thinking that they are not at risk as all were in their teens and hence not required (44.7%), and lack of time (48.7%). Age and frequency of breast self-examination were significantly associated (P <.05) as those few students (22.7%) who were doing breast self-examination practices every 2–4 months belonged to a higher study year. Furthermore, knowledge regarding incidence rates and health care expenditure by the government on breast cancer was also significantly low (P <.05). Conclusions: Outcomes would help prioritize actions to help future nurses better understand breast cancer, allowing them to extend patient care in the best way possible. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer affects women in every country in the world and is the type of cancer that causes the most deaths among women. The disease is, nevertheless, one of the very few where it is women with higher education and a higher socio-economic status who are primarily affected. Most of those affected live in developed countries in Europe and North America. The purpose of this study was to gain more knowledge about what could be said with certainty to be the causes of breast cancer in women. Could it, for example, be something to do with the way women in these countries live their lives? Unfortunately, an extensive literature review did not give us very good answers. We still know little about the causes of breast cancer in women. Breast cancer affected more than 2.3 million women in 2022 and is the most diagnosed cancer among women worldwide. The incidence rates are greater in developed regions and are significantly higher among women with higher education and socioeconomic status. Therefore, it is reasonable to assume that the way women live their lives may impact their risk of being diagnosed with breast cancer. This systematic review aimed to identify what is known about the causes and risk factors of breast cancer, excluding genetic causes. A comprehensive systematic search identified 2387 systematic reviews, 122 were included and six overall themes identified. In our "top list" with the 36 most important findings, a study of breast density had the highest effect size for increasing the risk of breast cancer, and a high sex-hormone-binding globulin level was the most protective factor. Many of the included studies investigating the same topics had conflicting results. The conclusion from this evidence synthesis reveals a lack of consensus of factors associated with the causes and risk of breast cancer. These findings suggest that recommendations about lifestyle and breast cancer should be made with caution. [ABSTRACT FROM AUTHOR]

Background: Breast cancer survivors who underwent breast conserving therapy (BCT) are still 10% more likely to develop a second breast cancer at follow-up, Digital mammography (DM) was advised in every practical guideline for follow-up after BCT; however, it was difficult to distinguish between actual recurrence and scar development at DM. Our research objective is to assess the value of Digital Breast Tomosynthesis (DBT) on the final Breast Imaging Reporting and Data System lexicon (BI-RADS) assessment categories compared to diagnostic digital mammography (DM) of breast cancer patients treated with breast conservation therapy (BCT), and to determine the additive value of DBT to DM or the use of DBT with synthetic 2D images in the diagnostic workup following BCT. Results: Four hundred and seventeen breast cancer patients who underwent breast-conserving therapy (BCT) and received diagnostic assessments, including digital mammography (DM), digital breast tomosynthesis (DBT), and reconstructed synthetic 2D images, were enrolled in the study. There is a significant reduction in the proportion of studies classified as probably benign BI-RADS 3 in synthetic 2D + DBT and DM + DBT compared with those in DM alone, and this was demonstrated by the two readers and at double reading (all P = 0.01). There is a significant increase in the PPV of malignancy in synthetic 2D + DBT and DM + DBT compared with those in DM alone for reader 2 (P = 0.01) and at double reading (P < 0.04) without a significant difference in the proportion of studies classified as BI-RADS category 4 or 5 for both readers and at double reading (p > 0.3). Regarding the mammographic abnormalities, we noted a significant reduction in asymmetry and a significant increase in architectural distortion in synthetic 2D + DBT and DM + DBT compared with those in DM alone, and this was demonstrated by the two readers and at double reading (all P = 0.01). Conclusions: The addition of digital breast tomosynthesis (DBT) into the diagnostic process after breast-conserving therapy (BCT), either in conjunction with digital mammography (DM) or with synthetic 2D images in the diagnostic workup following BCT, significantly decreases the proportion of studies classified as probably benign, significantly increases the rate of studies classified as normal or benign, and significantly increase in the positive predictive value (PPV) of malignancy without significant difference in the patients classified as BI-RADS category 4 or 5. Moreover it improved diagnostic confidence in biopsy recommendations, regardless of mammographic density. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast density is an independent risk factor for breast cancer and can impede detection of cancer by mammography. There is growing awareness of breast density in Australia and globally, but it is unclear whether this awareness is increasing knowledge of what breast density is and what it means to have dense breasts. This study was conducted to investigate South Australian women's knowledge of the common facts and misconceptions about breast density. This study reports that women who had previously heard the term breast density had increased knowledge compared to those who had not, suggesting that current efforts to raise awareness are leading to better knowledge. Despite this, the study shows that there are widespread misconceptions that must be actively dispelled, including the misunderstanding that breast density can be determined by touch. Background: There is growing awareness of breast density in women attending breast cancer screening; however, it is unclear whether this awareness is associated with increased knowledge. This study aims to evaluate breast density knowledge among Australian women attending breast cancer screening. Method: This cross-sectional study was conducted on women undergoing breast cancer screening at The Queen Elizabeth Hospital Breast/Endocrine outpatient department. Participants were provided with a questionnaire to assess knowledge, awareness, and desire to know their own breast density. Result: Of the 350 women who participated, 61% were familiar with 'breast density' and 57% had 'some knowledge'. Prior breast density notification (OR = 4.99, 95% CI = 2.76, 9.03; p = 0.004), awareness (OR = 4.05, 95% CI = 2.57, 6.39; p = 0.004), younger age (OR = 0.97, 95% CI = 0.96, 0.99; p = 0.02), and English as the language spoken at home (OR = 3.29, 95% CI = 1.23, 8.77; p = 0.02) were independent predictors of 'some knowledge' of breast density. A significant proportion of participants (82%) expressed desire to ascertain their individual breast density. Conclusions: While knowledge of breast density in this Australian cohort is generally quite low, we have identified factors associated with increased knowledge. Further research is required to determine optimal interventions to increase breast density knowledge. [ABSTRACT FROM AUTHOR]

Objective To determine breast radiologists' confidence in detecting invasive lobular carcinoma (ILC) on mammography and the perceived need for additional imaging in screening and preoperative settings. Methods A 16-item anonymized survey was developed, and IRB exemption obtained, by the Society of Breast Imaging (SBI) Patient Care and Delivery Committee and the Lobular Breast Cancer Alliance. The survey was emailed to 2946 radiologist SBI members on February 15, 2023. The survey recorded demographics, perceived modality-specific sensitivity for ILC to the nearest decile, and opinions on diagnosing ILC in screening and staging imaging. Five-point Likert scales were used (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = strongly agree). Results Response rate was 12.4% (366/2946). Perceived median (interquartile range) modality-specific sensitivities for ILC were MRI 90% (80–90), contrast-enhanced mammography 80% (70–90), molecular breast imaging 80% (60–90), digital breast tomosynthesis 70% (60–80), US 60% (50–80), and 2D mammography 50% (30–60). Only 25% (85/340) respondents were confident in detecting ILC on screening mammography in dense breasts, while 67% (229/343) were confident if breasts were nondense. Most agreed that supplemental screening is needed to detect ILC in women with dense breasts (272/344, 79%) or a personal history of ILC (248/341, 73%), with 34% (118/334) indicating that supplemental screening would also benefit women with nondense breasts. Most agreed that additional imaging is needed to evaluate extent of disease in women with newly diagnosed ILC, regardless of breast density (dense 320/329, 97%; nondense 263/329, 80%). Conclusion Most breast radiologists felt that additional imaging beyond mammography is needed to more confidently screen for and stage ILC. [ABSTRACT FROM AUTHOR]

Background The evaluation of tumor-infiltrating lymphocytes (TILs) for breast cancer prognosis is now established. However, the clinical value for their spatial distributions of specific immune subsets, namely CD103+ tissue-resident memory T cells FoxP3+ regulatory T ells, have not been thoroughly examined. Method Representative whole sections of breast cancers were subjected to CD103 and FoxP3 double staining. Their density, ratio, and spatial features were analyzed in tumor area and tumor-stromal interface. Their associations with clinicopathological parameters and patient's prognosis were analyzed. Results CD103 TILs were closer to tumor nests than FoxP3 TILs in the tumor-stromal interface. Their densities were associated with high-grade disease, TNBC, and stromal TILs. High stromal FoxP3 (sFoxP3) TILs and close proximity of sCD103 TILs to tumor were independently associated with better survival at multivariate analysis. Subgroup analysis showed the high FoxP3 TILs density associated better survival was seen in HER2-OE and TNBC subtypes while the proximity of CD103 TILs to tumor nests associated better survival was seen in luminal cancers. Conclusion The prognostic impact of CD103 and FoxP3 TILs in breast cancer depends on their spatial localization. High sFoxP3 TIL density and the lower distance of CD103 TILs from the tumor nests had independent favorable prognostic values. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer, a prevalent global concern, continuously motivates the research and development of new technologies for its quick detection and diagnosis. Dielectric spectroscopy is a technique previously used for material characterization but with limitations in accuracy for breast cancer diagnosis due to a lack of control over the material to be characterized. For the first time, and thanks to the assistance of 70 volunteer patients, accurate tissue characterization of breast tumors, benign or malignant (ductal carcinoma, lobular carcinoma, mucinous carcinoma and fibroadenoma), was achieved with dielectric spectroscopy. The results obtained in both relative permittivity and loss tangent show, for the first time, notable differences between the four types of tumors, which can help in making an instantaneous diagnosis of the excised tumor and accelerating subsequent treatment. Early analysis and diagnosis of breast tumors is essential for either quickly launching a treatment or for seeing the evolution of patients who, for instance, have already undergone chemotherapy treatment. Once tissues are excised, histological analysis is the most frequent tool used to characterize benign or malignant tumors. Dielectric microwave spectroscopy makes use of an open-ended coaxial probe in the 1–8 GHz frequency range to quickly identify the type of tumor (ductal carcinoma, lobular carcinoma, mucinous carcinoma and fibroadenoma). The experiment was undertaken with data from 70 patients who had already undergone chemotherapy treatment, which helped to electrically map the histological tissues with their electric permittivity. Thus, the variations in the permittivity of different types of tumors reveal distinctive patterns: benign tumors have permittivity values lower than 35, while malignant ones range between 40 and 60. For example, at a frequency of 2 GHz, the measured permittivity was 45.6 for ductal carcinoma, 33.1 for lobular carcinoma, 59.5 for mucinous carcinoma, and 27.6 for benign tumors. This differentiation remains consistent in a frequency range of 1 to 4.5 GHz. These results highlight the effectiveness of these measurements in the classification of breast tumors, providing a valuable tool for quick and accurate diagnosis and effective treatment. [ABSTRACT FROM AUTHOR]

Breast cancer survival has increased significantly over the last few decades due to more effective strategies for prevention and risk modification, advancements in imaging detection, screening, and multimodal treatment algorithms. However, many have observed disparities in benefits derived from such improvements across populations and demographic groups. This review summarizes published works that contextualize modern disparities in breast cancer prevention, diagnosis, and treatment and presents potential strategies for reducing disparities. We conducted searches for studies that directly investigated and/or reported disparities in breast cancer prevention, detection, or treatment. Demographic factors, social determinants of health, and inequitable healthcare delivery may impede the ability of individuals and communities to employ risk-mitigating behaviors and prevention strategies. The disparate access to quality screening and timely diagnosis experienced by various groups poses significant hurdles to optimal care and survival. Finally, barriers to access and inequitable healthcare delivery patterns reinforce inequitable application of standards of care. Cumulatively, these disparities underlie notable differences in the incidence, severity, and survival of breast cancers. Efforts toward mitigation will require collaborative approaches and partnerships between communities, governments, and healthcare organizations, which must be considered equal stakeholders in the fight for equity in breast cancer care and outcomes. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent form of malignancy among women worldwide. Breast cancer can emerge on the skin in two ways: directly, as skin metastases or a direct extension of the tumor; or indirectly, as a paraneoplastic disease. Breast cancer imaging is an essential part of breast cancer screening, diagnosis, preoperative/treatment assessment, and follow-up. The selection of optimal imaging modalities should be contingent upon the patient's risk factors and breast density since breast cancer imaging necessitates a personalized approach rather than a universal solution. There are a lot of different skin conditions that point to breast cancer, either as a sign of recurring disease, undiagnosed breast cancer, or a condition that puts you at a higher risk of getting it. Even though reconstruction has been shown to improve quality of life for many women, there are still a lot of complicated factors that affect morbidity and results. [ABSTRACT FROM AUTHOR]

Background: Interval cancers might be divided into true negative interval cancer where a new lesion is detected that no sign of disease could be detected on previous screening mammogram. For false-negative interval cancers, those missed for overt symptoms and those missed for mild or undetectable ones, this includes interpretive error as benign interval cancer (benign mimics), subtle changes, masked carcinoma or slowly growing or patient factors, such as the dense breast parenchyma. Technical failure interval cancer hampered the reader to discover the abnormality. The aim of this study was to relate the risk factors for the development of the interval breast cancer such as breast density, positive family history of breast cancer in Egyptian population. Highlight the causes of missed breast cancer in order to overcome it in the future radiological interpretation. Methods: A total of 74,546 screening mammographic examinations were performed in the radiology department at specialized breast cancer center in the period between 2015 and 2021 with about 844 pathologically proved malignant cases. Out of the 844 pathologically proven breast cancer cases, 185 breast cancer patients were interval breast cancer having reported normal examination in the previous year, 88 were true interval breast cancer and 97 were missed on mammography and detected later on. The cases were subjected to full-field digital mammogram (FFDM), complementary ultrasound, contrast-enhanced digital mammography (CEDM) and magnetic resonance imaging (MRI) in some cases, and all cases were histopathologically proven by either fine needle aspiration, core needle biopsy (CNB) or open biopsy. Results: The mean age of the patients was 53.5 years (range 36–83 years). The overall breast cancer detection rate was 11 per 1000 women. The 185 interval cancers were present at a rate of 3.8 per 1000 women. True negative interval breast cancers where 88 cancers were not present in retrospect on screening mammograms, 17 cases present with benign findings (benign mimics mass or calcifications) and 80 cancers were missed cancers. Analysis of the cause of missed carcinoma revealed patient-related, tumor-related, or provider-related factors. Tumor factors were the most commonly encountered, accounting for 49.5% (48 cases), then provider factors in 25.8% (25 cases) while the patient factors were the least commonly encountered in 24.7% (24 cases). Recorded positive family history found in about 35% (31cases) of the true interval breast cancers. Conclusions: Although mammography is the standard for detecting early breast cancer, some cancers can be missed due to various causes. Mammographic interpretation must meet high standards to reduce missed cancers. Radiologists should carefully assess screening views and order additional imaging if needed. Palpable lesions and clinical data should be further examined with ultrasound and contrast imaging if necessary. Always compare current images with previous examinations to check for any changes in lesion size. When one pathology is found, search for additional lesions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Advanced nodal disease is associated with poor prognosis. However, modern neoadjuvant systemic therapy (NST) regimens have resulted in higher pathologic complete response (pCR) rates, which are associated with improved survival. We sought to assess contemporary outcomes in patients with advanced nodal involvement and response to NST. STUDY DESIGN: We conducted a single-institution, retrospective study of 521 patients with cN2--3 primary nonmetastatic breast cancer treated with NST followed by surgery and radiation from 2012 to 2018. Descriptive statistics, multivariate Cox regression, and Kaplan--Meier analyses were performed. RESULTS: The mean age was 50.5 years, and median follow-up was 61 (4.7 to 197) months. The majority of patients had hormone receptor--positive (HR+)/HER2-negative tumors (HER2-; n = 242, 47.8%). Most were cT2 (n = 243; 46.6%) or cT3 (n = 139; 26.7%) and 73.3% (n = 382) had cN3 disease. Rate of axillary pCR was 34.2%, and breast and axillary pCR was 19.4% (n = 101). Event-free survival (EFS) at 5 years was 75.1% (95% CI, 0.71 to 0.79). Rate of locoregional recurrence was 6.7%; distant metastatic rate was 29.4%. Axillary pCR with or without breast pCR was significantly associated with longer EFS (p = 0.001). Achieving breast/axillary pCR was an independent predictor of improved EFS (hazard ratio 0.22, p < 0.0001). Having triple-negative disease was associated with worse EFS (hazard ratio 1.74, p = 0.008). CONCLUSIONS: In a high-risk cohort of patients with cN2--3 disease, trimodality therapy was effective in achieving durable EFS. Approximately one-third of patients achieved axillary pCR, which was associated with improved survival. Further studies are needed to accurately determine axillary response in cN2--3 breast cancer after NST in order to develop de-escalation strategies to reduce morbidity associated with axillary surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Vacuum-assisted breast biopsy (VABB) represents one of the best instruments for radiologists to obtain a histological diagnosis of suspicious lesions on imaging. The advent of digital breast tomosynthesis (DBT)-guided VABB has increased the accuracy of diagnosis in the most complex lesions, particularly those without ultrasound correlation or those visible only on DBT. In this paper, we retrospectively analyzed our experience with VABB. Starting from a review of the literature, we evaluated the challenges arising from clinical practice to provide useful indications for the implementation of this technique. We identified 37 breast cancers at an early stage with a low complication rate and high histopathological concordance between VABB and surgery. Compared to the literature, our results confirmed the fundamental role of DBT-VABB in achieving a timely diagnosis for nonpalpable lesions, offering a safe and minimally invasive approach when the technique is executed correctly. Vacuum-assisted breast biopsy (VABB) guided by digital breast tomosynthesis (DBT) represents one of the best instruments to obtain a histological diagnosis of suspicious lesions with no ultrasound correlation or those which are visible only on DBT. After a review of the literature, we retrospectively analyzed the DBT-guided VABBs performed from 2019 to 2022 at our department. Descriptive statistics, Pearson's correlation and χ2 test were used to compare distributions of age, breast density (BD) and early performance measures including histopathology. We used kappa statistics to evaluate the agreement between histological assessment and diagnosis. Finally, we compared our experience to the literature to provide indications for clinical practice. We included 85 women aged 41–84 years old. We identified 37 breast cancers (BC), 26 stage 0 and 11 stage IA. 67.5% of BC was diagnosed in women with high BD. The agreement between VABB and surgery was 0.92 (k value, 95% CI: 0.76–1.08). We found a statistically significant inverse correlation between age and BD. The post-procedural clip was correctly positioned in 88.2%. The post-procedural hematoma rate was 14.1%. No infection or hemorrhage were recorded. When executed correctly, DBT-guided VABB represents a safe and minimally invasive technique with high histopathological concordance, for detecting nonpalpable lesions without ultrasound correlation. [ABSTRACT FROM AUTHOR]

Response rates vary among breast cancer patients treated with neoadjuvant systemic therapy (NAST). Thus, there is a need for reliable treatment predictors. Evidence suggests tumor-infiltrating lymphocytes (TILs) predict NAST response. Still, TILs are seldom used clinically as a treatment determinant. Mammographic density (MD) is another potential marker for NAST benefit and its relationship with TILs is unknown. Our aims were to investigate TILs and MD as predictors of NAST response and to study the unexplored relationship between TILs and MD. We studied 315 invasive breast carcinomas treated with NAST between 2013 and 2020. Clinicopathological data were retrieved from medical records. The endpoint was defined as pathological complete response (pCR) in the breast. TILs were evaluated in pre-treatment core biopsies and categorized as high (≥10%) or low (<10%). MD was scored (a–d) according to the breast imaging reporting and data system (BI-RADS) fifth edition. Binary logistic regression and Spearman's test of correlation were performed using SPSS. Out of 315 carcinomas, 136 achieved pCR. 94 carcinomas had high TILs and 215 had low TILs. Six carcinomas had no available TIL data. The number of carcinomas in each BI-RADS category were 37, 122, 112, and 44 for a, b, c, and d, respectively. High TILs were independently associated with pCR (OR: 2.95; 95% CI: 1.59–5.46) compared to low TILs. In the univariable analysis, MD (BI-RADS d vs. a) showed a tendency of higher likelihood for pCR (OR: 2.43; 95% CI: 0.99–5.98). However, the association was non-significant, which is consistent with the result of the multivariable analysis (OR: 2.51; 95% CI: 0.78–8.04). We found no correlation between TILs and MD (0.02; p =.80). TILs significantly predicted NAST response. We could not define MD as a significant predictor of NAST response. These findings should be further replicated. [ABSTRACT FROM AUTHOR]

Background: Human hindmilk contains higher concentrations of fat than foremilk and is more desirable for growth in preterm infants who can tolerate limited volumes of breastmilk. There is currently no clear demarcation between foremilk and hindmilk. This study characterized the change in breastmilk's fat content from the start to end of milk flow and defined this demarcation. Methods: Mothers of infants born at ≤ 32 weeks gestational age and ≥ 14 days after childbirth in a University hospital in Bangkok, Thailand between July, 2011, and April, 2012 were included in this cross-sectional study. Breastmilk samples were sequentially collected from the start to end of milk flow in 5-mL aliquots using breast pumps. The fat content of each aliquot from each breast was determined through creamatocrit. The average creamatocrit of foremilk and hindmilk were compared in predefined foremilk to hindmilk ratios of 20:80, 25:75, 33:67, and 50:50. Creamatocrit of the first and last aliquots were compared for mothers who expressed low- (≤ 25-mL per breast) and high-volumes (> 25-mL per breast) of breastmilk. Results: Of the 25 mothers enrolled, one was excluded due to unsuccessful creamatocrit measurement. The last aliquot of breastmilk had a significantly higher creamatocrit than the first from the same breast (median [interquartile range] of 12.7% [8.9%, 15.3%] vs. 5.6% [4.3%, 7.7%]; test statistic 1128, p < 0.001). Mean creamatocrit in hindmilk portions (9.23%, 9.35%, 9.81%, and 10.62%, respectively) was significantly higher than foremilk portions (6.28%, 6.33%, 6.72%, and 7.17%, respectively) at all predefined ratios. Creamatocrit increased by 1% for every 10% incremental increase in expressed breastmilk volume until the breast was emptied. Low-volume mothers had a significantly higher creamatocrit in the first aliquot compared with high-volume mothers (U = 437, p = 0.002). No significant difference in breastmilk volume was observed between mothers with and without breastfeeding experience. Conclusions: Fat content in breastmilk increased on an incremental basis. More fluid definitions of foremilk and hindmilk should be adopted. Mothers should prepare their breastmilk into aliquots based on the required feeding volume of their infant. Hindmilk aliquots can be prioritized over foremilk aliquots to ensure infants obtain optimal caloric intake. [ABSTRACT FROM AUTHOR]

Background: Despite suggesting many genetic risk markers as the outcome of Genome-wide association studies (GWAS) for breast cancer, replicating the results in different populations has remained the main issue. In this regard, this study assessed the association of two variations in Zinc Finger 365 (ZNF365) in an Iranian population. Methods: In a case-control study conducted at Mashhad University of Medical Sciences, Mashhad, Iran, between 2017 and 2020, ZNF365-rs10822013 and rsl0995190 were genotyped using Allele-Specific PCR (AS-PCR). Breast density was assessed using mammography images. PHASE software module version 2 and SPSS version 16.0 were used for haplotype and statistical analyses. Quantitative and qualitative variables were compared between groups using independent t tests and Chi square tests, respectively. Binary logistic regression analysis was performed to calculate odds ratios. Multivariate analysis was then undertaken for the baseline variables, with a P<0.05 in the univariate analysis. The survival analysis was performed using the Kaplan-Meier method and the log-rank test. Results: In this survey, 732 females, including 342 breast cancer patients and 390 healthy subjects, were enrolled. rs10822013-T allele (P=0.014), rs10995190-G allele (P=0.003), and TG haplotype (P=0.002) were significantly associated with the increased risk of breast cancer. Moreover, rs10995190-GG genotype (P=0.042) and C-G haplotype (P=0.019) revealed a significant association with better overall survival. However, considered polymorphisms and their haplotypes indicated no association with breast density and clinical features of breast cancer. Conclusion: ZNF365 variants might be a potential risk marker of breast cancer in the Iranian population. The interaction between alleles in haplotypes may modulate the amount of the risk conferred by these variants. Further studies on different ethnic groups can validate these results. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to build machine learning models to predict surgical upstaging risk of ductal carcinoma in situ (DCIS) to invasive cancer and to compare model performance to eligibility criteria used by the Comparison of Operative versus Monitoring and Endocrine Therapy (COMET) active surveillance trial. Methods: Medical records were retrospectively reviewed of all women with DCIS at core-needle biopsy who underwent surgery from 2007 to 2016 at an academic medical center. Multivariable regression and machine learning models were developed to evaluate upstaging-related features and their performance was compared with that achieved using the COMET trial eligibility criteria. Results: Of 1387 women (mean age, 57 years; range, 27-89 years), the upstaging rate of DCIS was 17% (235/1387). On multivariable analysis, upstaging-associated features were presentation of DCIS as a palpable area of concern, imaging finding of a mass, and nuclear grades 2 or 3 at biopsy (P < 0.05). If COMET trial eligibility criteria were applied to our study cohort, then 496 women (42%, 496/1175) would have been eligible for the trial, with an upstaging rate of 12% (61/496). Of the machine learning models, none had a significantly lower upstaging rate than 12%. However, if using the models to determine eligibility, then a significantly larger proportion of women (56%--87%) would have been eligible for active surveillance. Conclusion: Use of machine learning models to determine eligibility for the COMET trial identified a larger proportion of women eligible for surveillance compared with current eligibility criteria while maintaining similar upstaging rates. [ABSTRACT FROM AUTHOR]

Thirty-eight states and the District of Columbia (DC) have dense breast notification laws that mandate varying levels of patient notification about breast density after a mammogram, and these cover over 90% of American women. On March 10, 2023, the Food and Drug Administration issued a final rule amending regulations under the Mammography Quality Standards Act for a national dense breast reporting standard for both patient results letters and mammogram reports. Effective September 10, 2024, letters will be required to tell a woman her breasts are "dense" or "not dense," that dense tissue makes it harder to find cancers on a mammogram, and that it increases the risk of developing cancer. Women with dense breasts will also be told that other imaging tests in addition to a mammogram may help find cancers. The specific density category can be added (eg, if mandated by a state "inform" law). Reports to providers must include the Breast Imaging Reporting and Data System density category. Implementing appropriate supplemental screening should be based on patient risk for missed breast cancer on mammography; such assessment should include consideration of breast density and other risk factors. This article discusses strategies for implementation. Currently 21 states and DC have varying insurance laws for supplemental breast imaging; in addition, Oklahoma requires coverage for diagnostic breast imaging. A federal insurance bill, the Find It Early Act, has been introduced that would ensure no-cost screening and diagnostic imaging for women with dense breasts or at increased risk and close loopholes in state laws. [ABSTRACT FROM AUTHOR]

Background: One of the top four malignancies affecting women worldwide is breast cancer. Breast density is a risk factor for breast cancer on its own and also a limiting factor for the sensitivity of screening mammography. Tools of artificial intelligence (AI) can help radiologists to make decisions, potentially reducing perceptual and interpretation errors, or as a way to prioritize exams based on the likelihood of malignancy. Objectives: The purpose of this study was to assess the impact of breast density on the performance of AI in mammography (MG) for the diagnosis of breast malignancy. Methods: In total, 110 patients with pathologically proven breast cancer participated in this retrospective study. These patients had full field digital mammography, and the mammogram pictures were exported to the AI software system. Heat maps displaying the location of discovered lesions then highlighted the affected area or areas and also provided abnormality scores indicating the probability of malignancy (POM). The results of the histopathological analysis were correlated with the breast density and AI category. Results: The artificial intelligence software gave a breast density score to each patient as well as POM scoring. Both the software and the radiologist agreed on the breast density in 80.00% (N = 88) of the patients. Upon correlation of AI results to the BI-RADS given by radiologist, demonstrated statistically very significant correlation (P value 0.001), indicating that the likelihood of error is less than one in a thousand. Upon correlating the pathology results with the AI abnormality score, the AI showed sensitivity of 93.64% as it detected 103 true positive lesions. AI showed 100% sensitivity in both ACR A and ACR B, and 94.74%, 76.47% in ACR C, ACR D, respectively. False negative results represented 5.26% in ACR C group and the highest with 23.53% in ACR D group of patients. The P value was found less than 0.001. Pearson correlation coefficient was calculated (R = 0.27) which was interpreted as a weak correlation between the decrease in sensitivity of AI and the breast density. Conclusions: Our study showed that there is a slight link between increasing breast density and a relative decline in AI's ability to detect malignant lesions, suggesting that AI can detect breast cancer effectively in breasts of different parenchymal densities, with its effectiveness being highest in breasts with lower parenchymal density. [ABSTRACT FROM AUTHOR]

Background. Breast density is an important risk factor for breast cancer and is known to be associated with characteristics such as age, race, and hormone levels; however, it is unclear what factors contribute to changes in breast density in postmenopausal women over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and facilitate potential strategies for prevention. Methods. This study investigated potential associations between personal factors and changes in mammographic density in a cohort of 3,392 postmenopausal women with no personal history of breast cancer between 2011 and 2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and breast imaging reporting and database system (BI-RADS) mammographic density scores were obtained from electronic medical records. Factors associated with a longitudinal increase or decrease in mammographic density were identified using Fisher's exact test and multivariate conditional logistic regression. Results. 7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were correlated with age, race/ethnicity, and age at menopause in the univariate analysis. In the multivariate analysis, Asian women were more likely to exhibit a longitudinal increase in mammographic density and less likely to exhibit a decrease compared to White women. On the other hand, obese women were less likely to exhibit an increase and more likely to exhibit a decrease compared to normal weight women. Women who underwent menopause at age 55 years or older were less likely to exhibit a decrease in mammographic density compared to women who underwent menopause at a younger age. Besides obesity, lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density. Conclusions. The associations we observed between Asian race/obesity and longitudinal changes in BI-RADS density in postmenopausal women are paradoxical in that breast cancer risk is lower in Asian women and higher in obese women. However, the association between later age at menopause and a decreased likelihood of decreasing in BI-RADS density over time is consistent with later age at menopause being a risk factor for breast cancer and suggests a potential relationship between greater cumulative lifetime estrogen exposure and relative stability in breast density after menopause. Our findings support the complexity of the relationships between breast density, BMI, hormone exposure, and breast cancer risk. [ABSTRACT FROM AUTHOR]

Healthcare providers often are uncertain about how best to assess and manage breast cancer risk. Women at average risk wonder when to start mammography and how often to go. Women at increased risk might inquire about genetic testing, MRI screening, and preventive measures. Patients who carry gene mutations face higher stakes and more complex risk management choices, but only some are aware of their status. This article helps clinicians stratify breast cancer risk and discusses a newer genomic test, the polygenic risk score, that may enable more personalized risk management and decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: The study aimed to develop and validate a prediction model that can be used to classify women for tailored breast cancer screening based on their individual risk. The model included data on age, mammographic density, family history of breast cancer, body mass index, age at menarche, alcohol consumption, exercise, pregnancy, hormone replacement therapy, and benign breast disease for 57,411 women screened in BreastScreen Norway 2007–2019. The 4-year predicted risk of breast cancer ranged between 0.2% and 7.3%, with 95% of the population having a risk of 0.6–2.3%. The differences in the predicted risk favor personalized screening for breast cancer. Background: We aimed to develop and validate a model predicting breast cancer risk for women targeted by breast cancer screening. Method: This retrospective cohort study included 57,411 women screened at least once in BreastScreen Norway during the period from 2007 to 2019. The prediction model included information about age, mammographic density, family history of breast cancer, body mass index, age at menarche, alcohol consumption, exercise, pregnancy, hormone replacement therapy, and benign breast disease. We calculated a 4-year absolute breast cancer risk estimates for women and in risk groups by quartiles. The Bootstrap resampling method was used for internal validation of the model (E/O ratio). The area under the curve (AUC) was estimated with a 95% confidence interval (CI). Results: The 4-year predicted risk of breast cancer ranged from 0.22–7.33%, while 95% of the population had a risk of 0.55–2.31%. The thresholds for the quartiles of the risk groups, with 25% of the population in each group, were 0.82%, 1.10%, and 1.47%. Overall, the model slightly overestimated the risk with an E/O ratio of 1.10 (95% CI: 1.09–1.11) and the AUC was 62.6% (95% CI: 60.5–65.0%). Conclusions: This 4-year risk prediction model showed differences in the risk of breast cancer, supporting personalized screening for breast cancer in women aged 50–69 years. [ABSTRACT FROM AUTHOR]

Objectives: As the hormonal status of women does influence both mammographic breast density and atherosclerosis, the aim of the study was to evaluate the association between breast density on mammography and carotid intima-media thickness (CIMT). Methods: Two-hundred premenopausal women with mammographic breast density of one (n=100) or four (n=100) were selected for this cross-sectional study. CIMT was measured according to the guidelines of Mannheim Consensus. The correlation between mammographic breast density and CIMT was assessed. Results: Mean age was 45.9±3.4 years and 45.8±3.2 years in the groups with mammographic density of 1 and 4, respectively, which showed no significant difference. CIMT correlated with age with a Pearson Correlation Coefficient of 0.470 (p<0.001). CIMT was significantly higher in women with ACR-mammographic density of 1 (p<0.001). Conclusion: Women with mammographic breast density of 1 revealed a higher CIMT. Further studies evaluating breast density and CIMT in pre- and postmenopausal women and assessing simultaneously the serum hormone level could give more information about the cause and effect of this correlation. [ABSTRACT FROM AUTHOR]

Breast density information aims to increase awareness of breast density and its risks and to foster more informed future breast screening decisions among women with dense breasts. We explored associations between such information and outcomes including anxiety, confusion, or feeling informed, and whether they varied by race/ethnicity or literacy, or differentially affected future mammography plans. A national telephone survey of a diverse sample of women previously informed of personal breast density (N = 1,322) assessed reactions to receipt of breast density information and future mammography plans. Most women (86%) felt informed after receiving personal breast density information; however, some felt anxious (15%) or confused (11%). Reactions varied significantly by sociodemographics; non-Hispanic Black, Asian, and Hispanic women and women with low literacy were nearly two to three times more likely to report anxiety than non-Hispanic White women (all p s <.05). Asian women and those with low literacy less often felt informed and more often felt confused. Non-Hispanic Black and Asian women were nearly twice as likely to report that knowing their breast density made them more likely to have future mammograms. Women with low literacy were more likely to change mammography plans, with some being more likely and others less likely to plan to have future mammograms. Greater anxiety and confusion were associated with higher likelihood of planning future mammograms; those feeling informed were less likely to plan future mammography. Differential reactions to breast density information are concerning if associated with disparate future screening plans. Future breast density education efforts should ensure that such information is readily accessible and understandable to all women in order to lead to desired effects. [ABSTRACT FROM AUTHOR]

Controversy surrounding recommendations for supplemental screening (ultrasound and magnetic resonance screening) in women with dense breasts exists, as the long-term benefits from these additional modalities may not outweigh the harms. This study aimed to examine factors associated with supplemental screening intentions following a hypothetical breast density notification in a population of women who have not been routinely notified. Australian women of breast screening age participated in an online randomised experimental study where they were presented with one of two breast density notifications (with or without health literacy-sensitive information) and asked their screening intentions. After adjusting for covariates in multivariable analyses, women in both groups (n = 940) who indicated higher levels of breast cancer worry, had private health insurance, had a family history of breast cancer, and had a greater number of times previously attending mammography screening had higher intentions for supplemental screening. Understanding women's supplemental screening intentions following notification of dense breasts has important implications for health systems with breast screening considering the impacts of widespread notification. Personal, clinical and psychological factors should be considered when discussing both the benefits and harms of supplemental screening with women with dense breasts. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the second most commonly diagnosed cancer among women. Novel breast cancer screening techniques are necessary to improve early detection and increase the chances of successful treatment. This study investigates the presence of specific volatile organic compounds in the sweat of breast cancer patients, which could serve as biomarkers for non-invasive screening. Sweat samples were collected from 21 breast cancer patients before and after tumor removal surgery and analyzed using thermal desorption coupled with gas chromatography and mass spectrometry. This work demonstrates that volatile organic compounds in sweat differ between pre-and post-surgery status in breast cancer patients, suggesting the possibility to use these compounds as novel breast cancer biomarkers and opening the way to new screening tools. Breast cancer (BC) remains one of the most commonly diagnosed malignancies in women. There is increasing interest in the development of non-invasive screening methods. Volatile organic compounds (VOCs) emitted through the metabolism of cancer cells are possible novel cancer biomarkers. This study aims to identify the existence of BC-specific VOCs in the sweat of BC patients. Sweat samples from the breast and hand area were collected from 21 BC participants before and after breast tumor ablation. Thermal desorption coupled with two-dimensional gas chromatography and mass spectrometry was used to analyze VOCs. A total of 761 volatiles from a homemade human odor library were screened on each chromatogram. From those 761 VOCs, a minimum of 77 VOCs were detected within the BC samples. Principal component analysis showed that VOCs differ between the pre- and post-surgery status of the BC patients. The Tree-based Pipeline Optimization Tool identified logistic regression as the best-performing machine learning model. Logistic regression modeling identified VOCs that distinguish the pre-and post-surgery state in BC patients on both the breast and hand area with sensitivities close to 1. Further, Shapley additive explanations and the probe variable method identified the most important and pertinent VOCs distinguishing pre- and post-operative status which are mostly of distinct origin for the hand and breast region. Results suggest the possibility to identify endogenous metabolites linked to BC, hence proposing this innovative pipeline as a stepstone to discovering potential BC biomarkers. Large-scale studies in a multi-centered VOC analysis setting must be carried out to validate obtained findings. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to identify nurses' understanding of dense breast and their perception of breast cancer risk based on their status of dense breast notification. Methods: Data were collected between September 13 and November 2, 2021, using self-report questionnaires from 220 female nurses in their 40s or 50s who are currently working at hospitals and have had mammogram experiences. Results: Only 44.5% (n=98) of participants reported receiving dense breast notification; the remaining participants either did not receive the notification (n=106, 48.2%) or did not remember receiving it (n=16, 7.3%). Nurses' status of dense breast notification was significantly associated with their understanding of dense breast, but not with their perception of breast cancer risk. Conclusion: Future studies should focus on improving the notification process since nurses play a key role in educating clients about breast cancer prevention in relation to dense breast. [ABSTRACT FROM AUTHOR]

Simple Summary: In the US, Black women are disproportionately affected by higher breast cancer mortality rates and later-stage tumor diagnoses compared with White women. Breast density, the ratio of dense fibroglandular breast tissue to overall breast tissue area, has previously been identified as an important breast cancer risk factor. Most current genome-wide association studies for breast density have been performed in participants of European ancestry, which have yielded important insights into genetic etiology of breast density. However, little is known about the influence of common genetic variants on breast density in African ancestry populations. Our study aimed to determine genetic factors associated with breast density in African ancestry populations using a Genome-Wide Association Study (GWAS) and post-GWAS analyses on a cohort of genomic data available through the Penn Medicine BioBank. Results of this study elucidate potential genetic mechanisms associated with breast density, and thus cancer risk, among women of African ancestry. Breast density, the amount of fibroglandular versus fatty tissue in the breast, is a strong breast cancer risk factor. Understanding genetic factors associated with breast density may help in clarifying mechanisms by which breast density increases cancer risk. To date, 50 genetic loci have been associated with breast density, however, these studies were performed among predominantly European ancestry populations. We utilized a cohort of women aged 40–85 years who underwent screening mammography and had genetic information available from the Penn Medicine BioBank to conduct a Genome-Wide Association Study (GWAS) of breast density among 1323 women of African ancestry. For each mammogram, the publicly available "LIBRA" software was used to quantify dense area and area percent density. We identified 34 significant loci associated with dense area and area percent density, with the strongest signals in GACAT3, CTNNA3, HSD17B6, UGDH, TAAR8, ARHGAP10, BOD1L2, and NR3C2. There was significant overlap between previously identified breast cancer SNPs and SNPs identified as associated with breast density. Our results highlight the importance of breast density GWAS among diverse populations, including African ancestry populations. They may provide novel insights into genetic factors associated with breast density and help in elucidating mechanisms by which density increases breast cancer risk. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD), including coronary artery disease (CAD), continue to be the leading cause of global mortality among women. While traditional CVD/CAD prevention tools play a significant role in reducing morbidity and mortality among both men and women, current tools for preventing CVD/CAD rely on traditional risk factor-based algorithms that often underestimate CVD/CAD risk in women compared with men. In recent years, some studies have suggested that breast arterial calcifications (BAC), which are benign calcifications seen in mammograms, may be linked to CVD/CAD. Considering that millions of women older than 40 years undergo annual screening mammography for breast cancer as a regular activity, innovative risk prediction factors for CVD/CAD involving mammographic data could offer a gender-specific and convenient solution. Such factors that may be independent of, or complementary to, current risk models without extra cost or radiation exposure are worthy of detailed investigation. This review aims to discuss relevant studies examining the association between BAC and CVD/CAD and highlights some of the issues related to previous studies' design such as sample size, population types, method of assessing BAC and CVD/CAD, definition of cardiovascular events, and other confounding factors. The work may also offer insights for future CVD risk prediction research directions using routine mammograms and radiomic features other than BAC such as breast density and macrocalcifications. [ABSTRACT FROM AUTHOR]

Simple Summary: Screening mammography reduces mortality from breast malignancy. However, breast cancer screening is, unfortunately, hindered due to the poor sensitivity of mammography in dense breasts: up to 15–30% of all cancers may be missed. Given the rapid development of Contrast-Enhanced Mammography (CEM) and its potential for diagnostic use, even in an asymptomatic population, it seems very important to correctly assess the Average Glandular Dose (AGD) for a single CEM examination. Few studies have compared the AGD of CEM versus Digital Mammography (DM) and protocols, including Digital Breast Tomosynthesis (DBT) plus DM, in the same group of patients. The additional role of tomosynthesis versus digital mammography in asymptomatic patients with dense breasts in screening examinations has been well investigated with encouraging results. In this study, we intend to compare the AGD and the diagnostic performance of CEM versus DM, and of CEM versus DM + DBT, performed in the same group of patients over the same period of time in a screening setting. This study aims to evaluate the Average Glandular Dose (AGD) and diagnostic performance of CEM versus Digital Mammography (DM) as well as versus DM plus one-view Digital Breast Tomosynthesis (DBT), which were performed in the same patients at short intervals of time. A preventive screening examination in high-risk asymptomatic patients between 2020 and 2022 was performed with two-view Digital Mammography (DM) projections (Cranio Caudal and Medio Lateral) plus one Digital Breast Tomosynthesis (DBT) projection (mediolateral oblique, MLO) in a single session examination. For all patients in whom we found a suspicious lesion by using DM + DBT, we performed (within two weeks) a CEM examination. AGD and compression force were compared between the diagnostic methods. All lesions identified by DM + DBT were biopsied; then, we assessed whether lesions found by DBT were also highlighted by DM alone and/or by CEM. We enrolled 49 patients with 49 lesions in the study. The median AGD was lower for DM alone than for CEM (3.41 mGy vs. 4.24 mGy, p = 0.015). The AGD for CEM was significantly lower than for the DM plus one single projection DBT protocol (4.24 mGy vs. 5.55 mGy, p < 0.001). We did not find a statistically significant difference in the median compression force between the CEM and DM + DBT. DM + DBT allows the identification of one more invasive neoplasm one in situ lesion and two high-risk lesions, compared to DM alone. The CEM, compared to DM + DBT, failed to identify only one of the high-risk lesions. According to these results, CEM could be used in the screening of asymptomatic high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Adipocytokines are signaling molecules secreted by adipose tissue contributing to the control of body fat, energy expenditure and secretion of insulin and cytokines. They have been related to the development of obesity, type-2 diabetes, cardiovascular diseases and cancer. Diet and physical activity (PA) may have beneficial effects on their level. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of adipocytokines as a secondary analysis in the DAMA (Diet, physical Activity and Mammography) trial. Methods: The 234 study participants (healthy postmenopausal women with high breast density, 50–69 years, non-smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Leptin, resistin and adiponectin were measured at baseline and at the end of the intervention. Analyses were performed using Tobit regression. Results: After 24 months, women randomised to PA intervention (arms #2 + #3) showed significant lower level of leptin (37.5% lower) and resistin (65.6% lower) compared to the control group (arms #1 + #4). No significant differences emerged in adiponectin levels. No significant differences in leptin, resistin and adiponectin levels at follow-up emerged in women randomised to the dietary intervention (arms #1 + #3) in comparison with controls (arms #2 + #4). Conclusion: This study supports the effectiveness of PA, even at moderate intensity, in improving the leptin and resistin profile in postmenopausal women. Trial registration number: ISRCTN28492718, date of trial registration 17/05/2012. [ABSTRACT FROM AUTHOR]

Simple Summary: Mammographic breast density is a strong independent risk factor for breast cancer. We investigated the association between volumetric mammographic breast density measures, their changes over time, and breast cancer risk in a cohort of women participating in the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) study. For the 6148 study women (262 breast cancer cases, average 7.8 years of follow-up), repeated measures of mammographic breast density from full-field digital mammograms and repeated information on lifestyle habits, reproductive history, and anthropometry were available. The association between mammographic breast density measures (modeled as time-dependent covariates), their relative annual changes, and breast cancer risk was evaluated by adjusted Cox models. Higher values of volumetric percent density and dense volume were positively associated with increased breast cancer risk, while an inverse association was evident for increasing non-dense volume. No clear effect of annual changes in mammographic breast density emerged. Mammographic breast density (MBD) is a strong independent risk factor for breast cancer (BC). We investigated the association between volumetric MBD measures, their changes over time, and BC risk in a cohort of women participating in the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) study. The study was carried out among 6148 women with repeated MBD measures from full-field digital mammograms and repeated information on lifestyle habits, reproductive history, and anthropometry. The association between MBD measures (modeled as time-dependent covariates), their relative annual changes, and BC risk were evaluated by adjusted Cox models. During an average of 7.8 years of follow-up, 262 BC cases were identified. BC risk was directly associated with standard deviation increments of volumetric percent density (VPD, HR 1.37, 95%CI 1.22–1.54) and dense volume (DV, HR 1.29, 95%CI 1.18–1.41). An inverse association emerged with non-dense volume (NDV, HR 0.82, 95%CI 0.69–0.98). No significant associations emerged between annual changes in VPD, DV, NDV, and BC risk. Higher values of MBD measures, modeled as time-dependent covariates, were positively associated with increased BC risk, while an inverse association was evident for increasing NDV. No effect of annual changes in MBD emerged. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphedema affecting the breast can develop after breast cancer treatment. Currently breast lymphedema isn't well recognised nor techniques to measure lymphedema affecting the breast as well studied. This paper explores the validity and reliability of measures which can be used to determine the presence of breast lymphedema. Women with and without breast lymphedema were included in this study to enable comparisons to be made. Improving the assessment of breast lymphedema will advance clinical practice and enable the outcome of treatment to be reported. Ultrasound and tissue dielectric constant were found to be able to reliably distinguish between edema and non edematous breast tissue. In addition certain patient characteristics and breast caner treatments were found to associated with the development of breast lymphedema. Lymphedema can develop after treatment for breast cancer (BCRL). Lymphedema of the breast is not well studied. Currently, the main techniques used to diagnose and monitor the effectiveness of treatment are subjective clinician assessment and patient reports. Eighty-nine women who had undergone breast cancer treatment were recruited with and without breast lymphedema. Blinded clinical assessment determined the presence or absence of breast lymphedema. Measurement of skin thickness by ultrasound scanning, local tissue water by tissue dielectric constant (TDC) and tissue indentation by tonometry was recorded. Breast cancer treatment and demographic details were documented. Descriptive statistics were undertaken to compare sample characteristics, including the Chi-squared test, Odds Ratio (OR) and Relative Risks (RR) calculated. Increased body mass index (BMI), larger bra size, increased number of positive lymph nodes, axillary surgery, chemotherapy and increased Nottingham Prognostic Index (NPI) were all associated with breast lymphedema (p < 0.05). Ultrasound and TDC measurements were significantly higher in the lymphedema group (p < 0.05). Receiver Operator Characteristic (ROC) curves demonstrated that ultrasound and TDC measurements could distinguish between edematous and non-edematous breasts. Threshold levels were produced, which demonstrated good levels of sensitivity and specificity. These findings have the potential to improve the diagnosis of breast lymphedema. [ABSTRACT FROM AUTHOR]

Objective: Evaluate lesion visibility and radiologist confidence during contrast-enhanced mammography (CEM)-guided biopsy. Methods: Women with BI-RADS >4A enhancing breast lesions were prospectively recruited for 9-g vacuum-assisted CEM-guided biopsy. Breast density, background parenchymal enhancement (BPE), lesion characteristics (enhancement and conspicuity), radiologist confidence (scale 1-5), and acquisition times were collected. Signal intensities in specimens were analyzed. Patient surveys were collected. Results: A cohort of 28 women aged 40-81 years (average 57) had 28 enhancing lesions (7/28, 25% malignant). Breast tissue was scattered (10/28, 36%) or heterogeneously dense (18/28, 64%) with minimal (12/28, 43%), mild (7/28, 25%), or moderate (9/28, 32%) BPE on CEM. Twelve non-mass enhancements, 11 masses, 3 architectural distortions, and 2 calcification groups demonstrated weak (12/28, 43%), moderate (14/28, 50%), or strong (2/28, 7%) enhancement. Specimen radiography demonstrated lesion enhancement in 27/28 (96%). Radiologists reported complete lesion removal on specimen radiography in 8/28 (29%). Average time from contrast injection to specimen radiography was 18 minutes (SD = 5) and, to post-procedure mammogram (PPM), 34 minutes (SD = 10). Contrast-enhanced mammography PPM was performed in 27/28 cases; 13/19 (68%) of incompletely removed lesions on specimen radiography showed residual enhancement; 6/19 (32%) did not. Across all time points, average confidence was 2.2 (SD = 1.2). Signal intensities of enhancing lesions were similar to iodine. Patients had an overall positive assessment. Conclusion: Lesion enhancement persisted through PPM and was visible on low energy specimen radiography, with an average "confident" score. Contrast-enhanced mammography-guided breast biopsy is easily implemented clinically. Its availability will encourage adoption of CEM. [ABSTRACT FROM AUTHOR]

Objective: We sought to identify patient factors associated with patient-reported screening behaviors in women with dense breasts. Methods: An IRB-approved survey study of women with dense breasts presenting for annual screening mammography at an outpatient imaging center was previously conducted from March 2017 to February 2018. The survey included questions regarding mammographic screening frequency and recent participation in supplemental screening. These survey data were combined post hoc with clinical and demographic data and socioeconomic data imputed from census data. Logistic regression was used to identify patient factors associated with reported screening behaviors. Results: Surveys were completed by 508 women (median age, 59.0 years; range, 31.0-86.0 years) with dense breasts. Multivariable analysis demonstrated an independent association of undergoing mammographic screening annually with a history of discussing breast density with a doctor (adjusted odds ratio [AOR], 2.60; P = 0.019). Undergoing supplemental screening in the previous three years was independently associated with younger age (AOR, 1.59; P = 0.004), strong family history of breast cancer (AOR, 3.84; P = 0.027), higher perceived personal risk for breast cancer (AOR, 3.47; P = 0.004), and increased concern about radiation associated with screening examinations (AOR, 3.31; P = 0.006). Conclusion: Women with dense breasts who had discussed breast density with a doctor were more likely to report undergoing annual screening mammography, while younger women and women with a strong family history of breast cancer, higher perceived personal risk for breast cancer, or greater concern about radiation were more likely to report recently undergoing supplemental screening. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored the diagnostic efficacy of radiologists when reading screening mammograms in the absence of previous images (NP), and with prior images obtained from the same (SP) and different vendors (DP). There were 612 radiologists reading 9 mammogram test sets (361-normal and 179-cancer) with 245 cases having prior images from the same vendor and 129 from different vendors. Radiologists obtained 12.8% and 10.3% higher sensitivity in NP and DP than SP. The ROC AUC for NP and DP were also significantly higher than SP. The odds ratio of true positive for NP and DP was 1.6 and 1.5, respectively, relative to SP cases. Radiologists were more likely to detect architectural distortion (OR = 3.2) and calcifications (OR = 2.85) in DP than SP. The findings suggest exploring a mixed reading strategy in viewing cases with prior mammograms acquired from the same and different manufacturers to enhance the diagnostic accuracy in the digital era. Background: This study aims to investigate the diagnostic efficacy of radiologists when reading screening mammograms in the absence of previous images, and with the presence of prior images from the same and different vendors. Methods: 612 radiologists' readings across 9 test sets, consisting of 540 screening mammograms (361-normal and 179-cancer) with 245 cases having prior images obtained from same vendor as current images, 129 from a different vendor and 166 cases having no prior images, were retrospectively analysed. True positive (sensitivity), true negative (specificity) and area under ROC curve (AUC) values of radiologists were calculated for three groups of cases (without prior images (NP), with prior images from same vendor (SP), and with prior images from different vendor (DP)). Logistic regression was used to estimate the odds ratio (OR) of true positive, true negative and true cancer localization among case groups with different levels of breast density and lesion characteristics. Results: Radiologists obtained 12.8% and 10.3% higher sensitivity in NP and DP than SP (0.803-and-0.785 vs. 0.712; p < 0.0001). Specificity in NP and DP cases were 4.8% and 2.0% lower than SP cases (0.749 and 0.771 vs. 0.787). The AUC values for NP and DP were significantly higher than SP cases across different levels of breast density (0.814-and-0.820 vs. 0.782; p < 0.0001). The odds ratio (OR) of true positive for NP relative to SP was 1.6 (p < 0.0001) and DP relative to SP was 1.5 (p < 0.0001). Radiologists were more like to detect architectural distortion in DP than SP cases (OR = 3.2; p < 0.0001), whilst the OR for abnormal calcifications was 2.85 (p < 0.0001). Conclusions: Cases without previous mammograms or with prior mammograms obtained from different vendors were more likely to benefit radiologists in cancer detection, whilst prior mammograms undertaken from the same vendor were more useful for radiologists in evaluating normal cases. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effectiveness of the low-potency laser, local and systemic, for the healing and reduction of pain caused by nipple trauma. Methods: Clinical, randomized and controlled trial carried out with 54 lactating women assisted in a Human Milk Bank, from December 2017 to June 2018. The lactating women, which totaled 101 lesions, received guidance on the clinical management of their breasts and breasts designated in: Control Group (CG), Local Laser Group (GLL), which received laser directly on the injured nipple, and Intravascular Blood Laser Irradiation Group (GILIB), which received systemic laser therapy. Data were analyzed using the SPSS to assess the homogeneity of the groups (Kruskal-Wallis) and the linear regression to identify the effect of the intervention on the size of breast lesions and the intensity of pain. Results: The three analysis groups were homogeneous before the experiment (p=0.191). After the intervention, the healing of the lesions in the three groups was significantly higher in GLL and GILIB (p<0.050). As for the pain, there is a reduction of up to 4.0 points in GLL and GILIB (p=0.002). Conclusion: The administration of local and systemic laser therapy was more effective for the cure of nipple trauma and pain reduction, in comparison with the control group. [ABSTRACT FROM AUTHOR]

Microcalcifications (MCs) are the main signs of precancerous cells. The development of aided-system for their detection has become a challenge for researchers in this field. In this paper, we propose a system for MCs detection based on the multifractal approach that classifies mammographic ROIs into normal (healthy) or abnormal ROIs containing MCs. The proposed method is divided into four main steps: a mammogram pre-processing step based on breast selection, breast density reduction using haze removal algorithm and contrast enhancement using multifractal measures. The second step consists of extracting the normal and abnormal ROIs and calculating the multifractal spectrum of each ROI. The next step represents the extraction of the multifractal features from the multifractal spectrum and the GLCM characteristics of each ROI. The last step is the classification of ROIs where three classifiers are tested (KNN, DT, and SVM). The system is evaluated on images from the INbreast database (308 images) with a total of 2688 extracted ROIs (1344 normal, 1344 with MC) from different BI-RADS classes. In this study, the SVM classifier gave the best classification results with a sensitivity, specificity, and precision of 98.66%, 97.77%, and 98.20% respectively. These results are very satisfactory and remarkable compared to the literature. [ABSTRACT FROM AUTHOR]

Objective: Little is known about women's confidence in their breast cancer screening. We sought to characterize breast cancer screening confidence by imaging modality and clinically assessed breast density. Materials and Methods: We undertook a cross-sectional survey of women ages 40–74 years who received digital mammography (DM), digital breast tomosynthesis (DBT), and/or breast magnetic resonance imaging (MRI) with a normal screening exam in the prior year. The main outcome was women's confidence (Very, Somewhat, A little, Not at all) in their breast cancer screening detecting any cancer. Multivariable logistic regression identified correlates of being very confident in breast cancer screening by screening modality group: Group 1) DM vs. DBT and Group 2) DM or DBT alone vs. with supplemental MRI. Results: Overall, 2329 of 7439 (31.3%) invitees participated, with 30%–61% being very confident in their screening across modality and density subgroups. Having dense versus nondense breasts was associated with lower odds of being very confident (Group 1: odds ratio [OR]: 0.58; 95% confidence interval [CI]: 0.46–0.79; Group 2: OR: 0.56; 95% CI: 0.40–0.79). There were no differences by modality within Group 1, but for Group 2, women undergoing MRI had higher odds of being very confident (OR: 1.69; 95% CI: 1.21–2.37). Other correlates of greater screening confidence were as follows: Group 1—being offered a screening test choice and cost not influencing modality received, and Group 2—decision satisfaction and worry. Conclusions: Women with dense breasts had lower screening confidence regardless of screening modality and those undergoing MRI had higher confidence regardless of density. The importance of informing women about screening options is underscored by observed associations between screening choice, decision satisfaction, and screening confidence. ClinicalTrials.gov : NCT02980848 [ABSTRACT FROM AUTHOR]

Objective: Establish a radiologist-run consultation clinic to review breast density and supplemental screening exams (SSEs) directly with patients in response to breast density reporting laws. Methods: Breast radiologists opened and staffed a clinic for formal patient consultations regarding breast density and SSEs. An IRB-approved questionnaire assessed patient knowledge of breast density, SSEs, and encounter satisfaction. Comparative statistical analyses were performed on knowledge-based questions. Results: From February 2019 to February 2021, 294 reimbursable consultations were performed with 215 patients completing pre- and post-consultation questionnaires (survey response rate, 73%). Median patient age was 58 years (range, 34-86 years) and 9% (19/210) had a personal history of breast cancer. An increase in patient knowledge of breast density and SSEs was observed as follows: breast density categories (9% correct pre-consultation (20/215), 86% correct postconsultation (185/215), P < 0.001), dense breast effects on cancer risk (39% correct pre-consultation (83/215), 84% post-consultation (180/215)), mammogram sensitivity (90% correct pre-consultation (193/215), 94% post-consultation (201/215)), and increased cancer detection with SSEs (82% correct pre-consultation (177/215), 95% post-consultation (205/215)) (P < 0.001). Post-consultation, 96% (200/209) were satisfied with the usefulness of information, 89% (186/209) strongly agreed they had sufficient knowledge of SSEs, and 81% (167/205) agreed they would like future opportunities to meet with a breast radiologist. Conclusion: A consultation clinic staffed by breast radiologists focused on breast density and supplemental breast cancer screening can provide personalized patient counseling, engage patients in shared decision making, assist referring clinicians, and support high quality patient-centered care. [ABSTRACT FROM AUTHOR]

Breast density continues to be a prevailing topic in the field of breast imaging, with continued complexities contributing to overall confusion and controversy among patients and the medical community. In this article, we explore the current status of breast cancer screening in women with dense breasts including breast density legislation. Risk-based approaches to supplemental screening may be more financially cost-effective. While all advanced imaging modalities detect additional primarily invasive, node-negative cancers, the degree to which this occurs can vary by density category. Future directions include expanding the use of density-inclusive risk models with appropriate risk stratification and imaging utilization. Further research is needed, however, to better understand how to optimize population-based screening programs with knowledge of patients' individualized risk, including breast density assessment, to improve the benefit-to-harm ratio of breast cancer screening. [ABSTRACT FROM AUTHOR]