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Introduction: Breast cancer is the most common cancer in women and a leading cause of mortality. This systematic review and meta-analysis aims to evaluate the correlation between breast density measurements obtained from various software and visual assessments by radiologists using full-field digital mammography (FFDM)., Methods: Following the PRISMA 2020 guidelines, five databases (Pubmed, Google Scholar, Science Direct, Cochrane Library, and MEDLINE) were searched for studies correlating volumetric breast density with breast cancer risk. The Newcastle-Ottawa Scale and the Joanna Briggs Institute Checklist were used to assess the quality of the included studies. Meta-analysis of correlation was applied to aggregate correlation coefficients using a random-effects model using MedCalc Statistical Software version 19.2.6., Results: The review included 22 studies with a total of 58,491 women. The pooled correlation coefficient for volumetric breast density amongst Volpara™ and Quantra™ was found to be 0.755 (95% CI 0.496-0.890, p < 0.001), indicating a high positive correlation, albeit with a significant heterogeneity (I 2  = 99.89%, p < 0.0001). Subgroup analyses based on study origin, quality, and methodology were performed but did not reveal the heterogeneity cause. Egger's and Begg's tests showed no significant publication bias., Conclusion: Volumetric breast density is strongly correlated with breast cancer risk, underscoring the importance of accurate breast density assessment in screening programs. Automated volumetric measurement tools like Volpara™ and Quantra™ provide reliable assessments, potentially improving breast cancer risk prediction and management., Implications for Practice: Implementing fully automated breast density assessment tools could enhance consistency in clinical practice, minimizing observer variability and improving screening accuracy. These tools should be further validated against standardized criteria to ensure reliability in diverse clinical settings., (Copyright © 2024 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

Introduction: Needle aspiration of breast abscesses during lactation are currently recommended as an alternative to surgery only for moderate forms. In case of breast abscess, many patients stop breastfeeding on the advice of a health professional. We reviewed our experience of treatment of lactating breast abscesses by ultrasound-guided aspiration and suggest an algorithm of their management. We also analyzed the continuation of breastfeeding of these patients after advices from trained teams., Materiel and Methods: We conducted a retrospective study from April 2016 to April 2017, including 28 patients referred for a breast abscess during lactation at the Duroc Breast Imaging Center. A management by ultrasound-guided aspiration was proposed to each patient. We collected data about the breastfeeding between October 2018 and January 2019., Results: A single aspiration was sufficient in 64.3% of cases. The delay between the occurrence of the abscess and the indication for drainage was significantly higher for patients who have needed finally surgical drainage (p = 0,0031). There were no difference of size of abscesses between patients receiving needle aspiration alone and those who have undergone surgery (p = 0,97). All patients who had been managed by needle aspiration continued breastfeeding after the treatment and 40% of the patients were still breastfeeding at 6 months., Conclusion: The management of lactating breast abscess by ultrasound-guided needle aspiration is an effective alternative to surgery. It appears to be effective regardless of the size of the abscess and is compatible with the continuation of breastfeeding. Our study has indeed shown that if they are well advised, the majority of patients continue breastfeeding so that it is essential that health professionals be better trained regarding the management of breastfeeding complications., (Copyright © 2021. Published by Elsevier Masson SAS.)

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

Background: Patients undergoing breast reduction mammoplasty for symptomatic macromastia have a significantly improved quality of life postoperatively. However, there are no data that examine the effect of reduction mammoplasty on quality of life as a function of the weight of tissue removed. Because the process by which insurance providers consider patients' candidacy for this breast reduction mammoplasty is most often based on the proposed weight of tissue to be removed, this gap in our understanding is particularly glaring. We therefore designed a prospective trial with the intent of investigating the correlation between breast reduction specimen weight and postoperative pain and quality of life., Methods: After obtaining institutional review board (IRB) approval, patients presenting for breast reduction mammoplasty at a single academic medical center between January 2016 and September 2019 were prospectively enrolled in the study. Study participants completed the Numerical Pain Rating Scale (NPRS), the short-form McGill Pain Questionnaire (SF-MPQ), and the BREAST-Q at set time points (preoperatively, 1 week/1 month/3 months/6 months postoperatively). Patients were divided into three cohorts based on breast reduction specimen weights: small (<500 g reduction), intermediate (500-1000 g reduction), and large (>1000 g reduction). The surveys were then analyzed while controlling for demographic factors and complications., Results: A total of 85 women were enrolled in the study and completed pre- and postoperative surveys (small reduction n = 21 (25%), intermediate n = 45 (53%), and large n = 19 (22%)). Regardless of reduction specimen weight, patients reported decreased overall pain and increased satisfaction with their breasts, as well as improved psychosocial, sexual, and physical well-being at each postoperative visit. Preoperative SF-MPQ pain scores were significantly lower in the small specimen weight group compared with either the intermediate or the large group (p = 0.001). Postoperatively, both the intermediate and large groups reported significant improvement in pain at each time point. The small specimen weight group did not report significant pain improvement until 3 months postoperatively., Conclusions: Patients undergoing breast reduction mammoplasty experience decreased pain and improved quality of life regardless of reduction specimen weight. Improvement in these parameters manifests as early as 1 week postoperatively and maintained at 3 months postoperatively. These data suggest that many patients who are denied coverage for reduction mammoplasty on the basis of low projected reduction specimen weight would derive significant benefit from the procedure., (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Regions of high mammographic density (MD) in the breast are characterised by a proteoglycan (PG)-rich fibrous stroma, where PGs mediate aligned collagen fibrils to control tissue stiffness and hence the response to mechanical forces. Literature is accumulating to support the notion that mechanical stiffness may drive PG synthesis in the breast contributing to MD. We review emerging patterns in MD and other biological settings, of a positive feedback cycle of force promoting PG synthesis, such as in articular cartilage, due to increased pressure on weight bearing joints. Furthermore, we present evidence to suggest a pro-tumorigenic effect of increased mechanical force on epithelial cells in contexts where PG-mediated, aligned collagen fibrous tissue abounds, with implications for breast cancer development attributable to high MD. Finally, we summarise means through which this positive feedback mechanism of PG synthesis may be intercepted to reduce mechanical force within tissues and thus reduce disease burden., (© 2021. The Author(s).)

Obesity and poor diet often go hand-in-hand, altering metabolic signaling and thereby impacting breast cancer risk and outcomes. We have recently demonstrated that dietary patterns modulate mammary microbiota populations. An important and largely open question is whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer. To address this, we performed fecal transplants between mice on control or high-fat diets (HFD) and recorded mammary tumor outcomes in a chemical carcinogenesis model. HFD induced protumorigenic effects, which could be mimicked in animals fed a control diet by transplanting HFD-derived microbiota. Fecal transplants altered both the gut and mammary tumor microbiota populations, suggesting a link between the gut and breast microbiomes. HFD increased serum levels of bacterial lipopolysaccharide (LPS), and control diet-derived fecal transplant reduced LPS bioavailability in HFD-fed animals. In vitro models of the normal breast epithelium showed that LPS disrupts tight junctions (TJ) and compromises epithelial permeability. In mice, HFD or fecal transplant from animals on HFD reduced expression of TJ-associated genes in the gut and mammary gland. Furthermore, infecting breast cancer cells with an HFD-derived microbiome increased proliferation, implicating tumor-associated bacteria in cancer signaling. In a double-blind placebo-controlled clinical trial of patients with breast cancer administered fish oil supplements before primary tumor resection, dietary intervention modulated the microbiota in tumors and normal breast tissue. This study demonstrates a link between the gut and breast that mediates the effect of diet on cancer. SIGNIFICANCE: This study demonstrates that diet shifts the microbiome in the gut and the breast tumor microenvironment to affect tumorigenesis, and oral dietary interventions can modulate the tumor microbiota in patients with breast cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/14/3890/F1.large.jpg., (©2021 American Association for Cancer Research.)

Abstract: The aim of this study was to develop a new breast density classification system for dedicated breast computed tomography (BCT) based on lesion detectability analogous to the ACR BI-RADS breast density scale for mammography, and to evaluate its interrater reliability.In this retrospective study, 1454 BCT examinations without contrast media were screened for suitability. Excluding datasets without additional ultrasound and exams without any detected lesions resulted in 114 BCT examinations. Based on lesion detectability, an atlas-based BCT density (BCTD) classification system of breast parenchyma was defined using 4 categories. Interrater reliability was examined in 40 BCT datasets between 3 experienced radiologists.Among the included lesions were 63 cysts (55%), 18 fibroadenomas (16%), 7 lesions of fatty necrosis (6%), and 6 breast cancers (5%) with a median diameter of 11 mm. X-ray absorption was identical between lesions and breast tissue; therefore, the lack of fatty septae was identified as the most important criteria for the presence of lesions in glandular tissue. Applying a lesion diameter of 10 mm as desired cut-off for the recommendation of an additional ultrasound, an atlas of 4 BCTD categories was defined resulting in a distribution of 17.5% for density A, 39.5% (B), 31.6% (C), and 11.4% (D) with an intraclass correlation coefficient (ICC) among 3 readers of 0.85 to 0.87.We propose a dedicated atlas-based BCTD classification system, which is calibrated to lesion detectability. The new classification system exhibits a high interrater reliability and may be used for the decision whether additional ultrasound is recommended., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Free nipple grafting indications in breast reduction surgery are outdated. Safety of inferior pedicle technique for large resections and long pedicles has not been clearly defined. We evaluated patients who underwent inferior pedicle reduction mammoplasty to define the safety constraints of the inferior pedicle., Methods: A retrospective review of patients who underwent inferior pedicle reduction mammoplasty due to symptomatic macromastia at Mayo Clinic over a six-year period was conducted. Patients with prior breast surgeries were excluded. Demographics, breast measurements, and surgical outcomes were collected. Univariate and multivariate analyses were performed to assess for predictors of necrosis., Results: Overall, 288 patients (576 breasts) underwent inferior pedicle breast reduction from 2014 to 2019. The mean sternal notch-to-nipple (SNN) distance was 31.5 cm (standard deviation[SD]:4.2; range[r]:16-48), and the mean nipple-to-inframammary fold (N-IMF) distance was 14.8 cm (SD:4.0; r:7.5-27). The mean resection weight was 699.6 g (SD:310.4; r:125-2,385). The median follow-up was 3.9 months (interquartile range[IQR]:2.8-9.0). The overall skin or nipple areolar complex necrosis rate was 2.1%; the overall complication rate was 14.8%. On multivariate analysis, overall necrosis was not found to be associated with the N-IMF distance (adjusted odds ratio[aOR]:1.05, 95%-CI 0.88-1.16). Resection weight was statistically associated with an increased risk of overall necrosis (aOR:1.003, 95%-CI 1.001-1.005), adjusting for N-IMF and SNN distances., Conclusion: Inferior pedicle breast reduction offers low risk of necrosis and can be safely performed in patients regardless of the N-IMF distance. No association was found between N-IMF distance and overall necrosis in our cohort, including lengths >15 cm. However, large resections could increase the risk of necrosis., Competing Interests: Declaration of Competing Interest All authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Breast cancer is the most prevalent cancer in women worldwide. In the United Kingdom, approximately 5% of all breast cancers are already metastatic at the time of diagnosis. An abundance of literature shows that exercise can have beneficial effects on the outcome and prognosis of breast cancer patients, yet the molecular mechanisms remain poorly understood. There are several in vitro models that aim to recapitulate the response of breast cancer to exercise in vivo; this systematic review and meta-analysis summarizes the existing literature. The following search terms were used to conduct a systematic literature search using a collection of databases (last search performed May 2020): "in vitro," "exercise," and "breast cancer." Only studies that investigated the effects of exercise on breast cancer in vitro were included. Standardized mean differences (SMD) were calculated to determine pooled effect sizes. This meta-analysis has successfully demonstrated that various identified exercise interventions on breast cancer cells in vitro significantly reduced breast cancer cell viability, proliferation, and tumorigenic potential (SMD = -1.76, P = 0.004, SMD = -2.85, P = 0.003, and SMD = -3.15, P = 0.0008, respectively). A clear direction of effect was found with exercise on breast cancer cell migration in vitro, however this effect was not significant (SMD = -0.62, P = 0.317). To our knowledge, this is the first meta-analysis and systematic review investigating and summarizing literature on exercise and breast cancer in vitro, highlighting models used and priority areas for future research focus.

Background: The earliest onset of puberty had shifted downward, which may be due to the role of early growth and development factors in childhood., Methods: All of 1575 Kindergarten Two (K2) children from Anhui province, China were followed up to elementary school. Girls (n = 342) with available data on AR and breast development were included for this analysis. Polygenic risk score (PRS) was computed based on 17 single nucleotide polymorphisms for early puberty. Accelerate failure time (AFT) model was used to describe thelarche timing by early AR among girls with different polygenic susceptibility., Results: After adjustment for perinatal anthropometric, household income, parental education and prepuberty BMI-Z score, puberty started 4.12-month earlier in early AR girls compared with normal AR girls (TR: 0.96; 95% CI: 0.95, 0.98, p < 0.001). Furthermore, this puberty-accelerating effect was observed among girls with high (6.06-month earlier, TR: 0.94; 95% CI: 0.90, 0.99) and moderate PRS (4.20-month earlier, TR: 0.96; 95% CI: 0.93, 0.98). No similar results were observed in the low PRS groups (TR: 1.00; 95% CI: 0.96, 1.04)., Conclusions: Girls with early AR displayed younger age at thelarche; however, this accelerating effect was only observed among those with genetic susceptibility to early puberty., Impact: Early AR plays a more important role in predicting earlier thelarche among girls with high and moderate PRS. This study combined with the hot topics of pubertal-related polygenic risk score (PRS) for pubertal timing to examine the longitudinal association between early AR with accelerated pubertal onset. Our results mean that accelerating growth in the early childhood years after birth might forecast early puberty only among girls with genetic predisposition to early puberty. Prevention strategies and management options should be emphasized to target early childhood to address secular trend for early puberty observed in the past decades in China.

Background: Obesity fosters worse clinical outcomes in both premenopausal and postmenopausal women with breast cancer. Emerging evidence suggests that an android body fat distribution in particular is deleterious for breast cancer prognosis. The extent of adipose tissue dysfunction, especially how it relates to breast cancer prognostic factors and anthropometric measurements, has not been fully investigated., Objective: Our objective was to examine if markers of adipose tissue dysfunction, such as hypertrophy and macrophage accumulation, are relevant for the pathophysiology of breast cancer and its associated prognostic factors in a well-characterised cohort of women with breast cancer who did not receive treatment before surgery., Methods: A consecutive series of 164 women with breast cancer provided breast adipose tissue sample. Multivariate generalised linear models were used to test associations of anthropometric indices and prognostic factors with markers of adipose tissue dysfunction., Results: We found associations of breast adipocyte size and macrophage infiltration (number of CD68+ cells/100 adipocytes) with adiposity, particularly a strong association between breast adipocyte size and central obesity, independent of total adiposity, age and menopausal status (β adj  = 0.87; p = 0.0001). We also identified relationships of adipocyte hypertrophy and macrophage infiltration with prognostic factors, such as cancer stage and tumour grade (p < 0.05). RNA expression of pro-inflammatory cytokines (IL6, TNF) and leptin was also increased as a function of adipocyte size and CD86+/CD11c+ macrophage number/100 adipocytes (p < 0.05)., Conclusions: Our findings support the model of dysfunctional adipose tissue in obesity-associated breast cancer.

Higher proportions of early-onset and estrogen receptor (ER) negative cancers are observed in women of African ancestry than in women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status may explain this disparity. We analyzed data from 1,126 cases (aged 18-74 years) with invasive breast cancer and 2,106 controls recruited from a population-based case-control study in Ghana. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. Among controls, medians for age at menarche, parity, age at first birth, and breastfeeding/pregnancy were 15 years, 4 births, 20 years and 18 months, respectively. For women ≥50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0.40 (95% CI 0.20-0.83) and 0.71 (95% CI 0.51-0.98) for ≥19 vs. <13 breastfeeding months/pregnancy, which did not differ by ER. In contrast, for earlier onset cases (<50 years) parity was associated with increased risk for ER-negative tumors (p-heterogeneity by ER = 0.02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relationships were observed with ages at menarche and first birth. Reproductive risk factor distributions are different from European populations but exhibited etiologic heterogeneity by age at diagnosis and ER status similar to other populations. Differences in reproductive patterns and subtype heterogeneity are consistent with racial disparities in subtype distributions., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Insulin-like growth factor (IGF) signaling and control of local bioavailability of free IGF by the IGF binding proteins (IGFBP) are important regulators of both mammary development and breast cancer. A recent genome-wide association study (GWAS) identified small nucleotide polymorphisms that reduce the expression of IGFBP-5 as a risk factor of developing breast cancer. This observation suggests that genetic alterations leading to a decreased level of IGFBP-5 may also contribute to breast cancer. In the current review, we focus on Pregnancy-Associated Plasma Protein A (PAPP-A), a protease involved in the degradation of IGFBP-5. PAPP-A is overexpressed in the majority of breast cancers but its role in cancer has only begun to be explored. More specifically, this review aims at highlighting the role of post-partum involution in the oncogenic function of PAPP-A. Notably, we summarize recent studies indicating that PAPP-A plays a role not only in the degradation of IGFBP-5 but also in the deposition of collagen and activation of the collagen receptor discoidin 2 (DDR2) during post-partum involution. Finally, considering the immunosuppressive microenvironment of post-partum involution, we also discuss the unexpected finding made in Ewing Sarcoma that PAPP-A plays a role in immune evasion. While the immunosuppressive role of PAPP-A in breast cancer remains to be determined, collectively these studies highlight the multifaced role of PAPP-A in cancer that extends well beyond its effect on IGF-signaling.

A 35-year-old woman presented to the surgery outpatient department with a lump in her right breast for 2 months and pain for 1 month. After clinical examination and relevant investigations, we kept a working diagnosis of antibioma. The lump was excised under local anaesthesia and biopsy was sent. However, histopathological examination reported multiple non-caseating granulomas without acid-fast bacilli. Two months later, she developed a sinus with serous discharge at the scar site. At the same time, she developed pain in the left upper breast, which subsequently progressed to an abscess. Incision and drainage of the abscess was done, but the wound did not heal, and a discharging sinus appeared at the site. Finally, a diagnosis of idiopathic granulomatous mastitis was made, after excluding all other causes, and the patient was prescribed oral steroids. She recovered fully after 8 months and there is no recurrence till date., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

This study sought to evaluate the association of breast arterial calcification (BAC) on breast screening mammography with the Coronary Artery Disease-Reporting and Data System (CAD-RADS) based on Deep Learning-coronary computed tomography angiography (CCTA). This prospective single institution study included asymptomatic women over 40 who underwent CCTA and breast cancer screening mammography between July 2018 and April 2019. CAD-RADS was scored based on Deep Learning (DL). Mammograms were assessed visually for the presence of BAC. A total of 213 patients were included in the analysis. In comparison to the low CAD-RADS (CAD-RADS < 3) group, the high CAD-RADS (CAD-RADS ≥ 3) group, more often had a history of hypertension (P = 0.036), diabetes (P = 0.017), and chronic kidney disease (P = 0.006). They also had a significantly higher level of LDL-C (P = 0.024), while HDL-C was lower than in the low CAD-RADS group (P = 0.003). BAC was also significantly higher in the high CAD-RADS group (P = 0.002). In multivariate analysis, the presence of BAC [odd ratio (OR) 10.22, 95% CI 2.86-36.49, P < 0.001] maintained a significant associations with CAD-RADS after adjustment by meaningful variable. The same tendency was also found after adjustment by all covariates. There was a significant correlation between the severities of CAD detected by DL based CCTA and BAC in women undergoing breast screening mammography. BAC may be used as an additional diagnostic tool to predict the severity of CAD in this population.

Background and Objective: Automatic segmentation of breast lesion from ultrasound images is a crucial module for the computer aided diagnostic systems in clinical practice. Large-scale breast ultrasound (BUS) images remain unannotated and need to be effectively explored to improve the segmentation quality. To address this, a semi-supervised segmentation network is proposed based on generative adversarial networks (GAN)., Methods: In this paper, a semi-supervised learning model, denoted as BUS-GAN, consisting of a segmentation base network-BUS-S and an evaluation base network-BUS-E, is proposed. The BUS-S network can densely extract multi-scale features in order to accommodate the individual variance of breast lesion, thereby enhancing the robustness of segmentation. Besides, the BUS-E network adopts a dual-attentive-fusion block having two independent spatial attention paths on the predicted segmentation map and leverages the corresponding original image to distill geometrical-level and intensity-level information, respectively, so that to enlarge the difference between lesion region and background, thus improving the discriminative ability of the BUS-E network. Then, through adversarial training, the BUS-GAN model can achieve higher segmentation quality because the BUS-E network guides the BUS-S network to generate more accurate segmentation maps with more similar distribution as ground truth., Results: The counterpart semi-supervised segmentation methods and the proposed BUS-GAN model were trained with 2000 in-house images, including 100 annotated images and 1900 unannotated images, and tested on two different sites, including 800 in-house images and 163 public images. The results validate that the proposed BUS-GAN model can achieve higher segmentation accuracy on both the in-house testing dataset and the public dataset than state-of-the-art semi-supervised segmentation methods., Conclusions: The developed BUS-GAN model can effectively utilize the unannotated breast ultrasound images to improve the segmentation quality. In the future, the proposed segmentation method can be a potential module for the automatic breast ultrasound diagnose system, thus relieving the burden of a tedious image annotation process and alleviating the subjective influence of physicians' experiences in clinical practice. Our code will be made available on https://github.com/fiy2W/BUS-GAN., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier B.V.)

Background: Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD)., Methods: This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor-positive invasive breast cancer treated with ET. VBD, the ratio of fibroglandular volume (FGV) to breast volume (BV), was measured using Volpara software. Changes in measurements were evaluated using a multivariable linear mixed effects model., Results: Compared with white women ( n = 191), black women ( n = 107) had higher rates of obesity [mean ± SD body mass index (BMI) 34.5 ± 9.1 kg/m 2 vs. 30.6 ± 7.0 kg/m 2 , P < 0.001] and premenopausal status (32.7% vs. 16.7%, P = 0.002). Age- and BMI-adjusted baseline FGV, BV, and VBD were similar between groups. Modeled longitudinal changes were also similar: During a follow-up of 30.7 ± 15.0 months (mean ± SD), FGV decreased over time in premenopausal women (slope = -0.323 cm 3 ; SE = 0.093; P = 0.001), BV increased overall (slope = 2.475 cm 3 ; SE = 0.483; P < 0.0001), and VBD decreased (premenopausal slope = -0.063%, SE = 0.011; postmenopausal slope = -0.016%, SE = 0.004; P < 0.0001). Race was not significantly associated with these longitudinal changes, nor did race modify the effect of time on these changes. Higher BMI was associated with lower baseline VBD ( P < 0.0001). Among premenopausal women, VBD declined more steeply for women with lower BMI (time × BMI, P = 0.0098)., Conclusions: Race does not appear to impact ET-related longitudinal changes in VBD., Impact: Racial disparities in estrogen receptor-positive breast cancer recurrence and mortality may not be explained by differential declines in breast density due to ET., (©2020 American Association for Cancer Research.)

Introduction: During the postpartum period, breast engorgement in preparation for lactation may trigger the onset of vulvar labial nodules that present with pain and discomfort. These labial nodules may originate from ectopic breast tissue and can rarely present in women during the postpartum period in the labia majora., Main Issue: A 37-year-old African American female, gravida 1 para 1, presented to the Loma Linda University Medical Center with complaints of new onset labial swelling worsening 6 days following her full term spontaneous vaginal delivery. Additionally, our respondent complained of difficulty breastfeeding due to intermittent lack of milk production. She reported bilateral breast engorgement with tenderness, despite frequent attempts at breastfeeding. The respondent's presentation did not meet the criteria for other common differentials due to the physical characteristics of the nodules. The location of the nodules along the milk line led physicians to believe that the respondent was presenting with engorged extra-mammary breast tissue in the labia majora., Management: The participant was told to observe her course over the next few days as she began to have milk production and ejection. The respondent was seen in clinic for her 6-week postpartum visit, and was no longer complaining of difficulty with breastfeeding. The labial nodules had resolved spontaneously., Conclusion: A literature search yielded no case reports that described a case of an extra-mammary vulvar mass that self-resolved with resolution of breast engorgement. The infrequent presentation of extra-mammary vulvar tissue makes it difficult to conclude a guideline for diagnosis and management.

Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads. Most disease-causing variants identified to date are putative loss-of-function alleles, although 15-20% of cases are attributed to missense variants. We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature. These individuals also lack the typical dysmorphic facial features found in Kabuki syndrome. Two of the four patients had severe interstitial lung disease. All of these variants cluster within a 40-amino-acid region of the protein that is located just N-terminal of an annotated coiled coil domain. These findings significantly expand the phenotypic spectrum of features associated with variants in KMT2D beyond those seen in Kabuki syndrome and suggest a possible new underlying disease mechanism for these patients., (© 2020 Wiley Periodicals, Inc.)

Background: Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively. Alcohol and tobacco use have been associated with increased breast cancer risk. However, their effects on mammographic density (MD) phenotypes are poorly understood., Methods: We examined associations of alcohol and tobacco use with PD, DA, and NDA in a population-based cohort of 23,456 women screened using full-field digital mammography machines manufactured by Hologic or General Electric. MD was measured using Cumulus. Machine-specific effects were estimated using linear regression, and combined using random effects meta-analysis., Results: Alcohol use was positively associated with PD ( P trend = 0.01), unassociated with DA ( P trend = 0.23), and inversely associated with NDA ( P trend = 0.02) adjusting for age, body mass index, reproductive factors, physical activity, and family history of breast cancer. In contrast, tobacco use was inversely associated with PD ( P trend = 0.0008), unassociated with DA ( P trend = 0.93), and positively associated with NDA ( P trend <0.0001). These trends were stronger in normal and overweight women than in obese women., Conclusions: These findings suggest that associations of alcohol and tobacco use with PD result more from their associations with NDA than DA., Impact: PD and NDA may mediate the association of alcohol drinking, but not tobacco smoking, with increased breast cancer risk. Further studies are needed to elucidate the modifiable lifestyle factors that influence breast tissue composition, and the important role of the fatty tissues on breast health., (©2020 American Association for Cancer Research.)

Knowledge about established breast carcinogens can support improved and modernized toxicological testing methods by identifying key mechanistic events. Ionizing radiation (IR) increases the risk of breast cancer, especially for women and for exposure at younger ages, and evidence overall supports a linear dose-response relationship. We used the Adverse Outcome Pathway (AOP) framework to outline and evaluate the evidence linking ionizing radiation with breast cancer from molecular initiating events to the adverse outcome through intermediate key events, creating a qualitative AOP. We identified key events based on review articles, searched PubMed for recent literature on key events and IR, and identified additional papers using references. We manually curated publications and evaluated data quality. Ionizing radiation directly and indirectly causes DNA damage and increases production of reactive oxygen and nitrogen species (RONS). RONS lead to DNA damage and epigenetic changes leading to mutations and genomic instability (GI). Proliferation amplifies the effects of DNA damage and mutations leading to the AO of breast cancer. Separately, RONS and DNA damage also increase inflammation. Inflammation contributes to direct and indirect effects (effects in cells not directly reached by IR) via positive feedback to RONS and DNA damage, and separately increases proliferation and breast cancer through pro-carcinogenic effects on cells and tissue. For example, gene expression changes alter inflammatory mediators, resulting in improved survival and growth of cancer cells and a more hospitable tissue environment. All of these events overlap at multiple points with events characteristic of "background" induction of breast carcinogenesis, including hormone-responsive proliferation, oxidative activity, and DNA damage. These overlaps make the breast particularly susceptible to ionizing radiation and reinforce that these biological activities are important characteristics of carcinogens. Agents that increase these biological processes should be considered potential breast carcinogens, and predictive methods are needed to identify chemicals that increase these processes. Techniques are available to measure RONS, DNA damage and mutation, cell proliferation, and some inflammatory proteins or processes. Improved assays are needed to measure GI and chronic inflammation, as well as the interaction with hormonally driven development and proliferation. Several methods measure diverse epigenetic changes, but it is not clear which changes are relevant to breast cancer. In addition, most toxicological assays are not conducted in mammary tissue, and so it is a priority to evaluate if results from other tissues are generalizable to breast, or to conduct assays in breast tissue. Developing and applying these assays to identify exposures of concern will facilitate efforts to reduce subsequent breast cancer risk.

Aim: Acute post-operative pain following modified radical mastectomy (MRM) in patients with breast cancer is challenging for anesthesiologists. This study aimed to prospectively compare the quality outcome of interfascial plane blocks performed with ultrasound guidance, and evaluate the consequences of sharing tasks with the breast surgeon., Patients and Methods: The study involved 255 patients scheduled for unilateral MRM, who were divided into two groups: Pecs group: General anesthesia plus ultrasound-guided modified pectoral nerves blocks type I and II, including serratus and parasternal infiltration according to surgical requirements; and Control group: general anesthesia only. Quality was evaluated based on perioperative opioid consumption, reported pain intensity, rescue analgesic requirement, side-effects and length of hospital stay. Moreover, a breast surgeon with expertise in ultrasound-guided breast biopsy was trained to perform the blocks. The patient benefits from regional anesthesia delivered by a non-anesthesiologist were assessed., Results: Significant reductions were noted in all of the following: Intraoperative opioid consumption (p<0.001), Numerating Rating Scale pain scores taken 0 and 24 h after surgery (p<0.001), post-operative analgesic administration (p<0.001), nausea and vomiting at 0, 6, and 12-h intervals (p<0.05), and hospital stay (p<0.001) were observed in the Pecs group compared with the control group. Furthermore, data obtained from patients receiving the block from the surgeon showed comparable benefits with no complications., Conclusion: Interfascial plane blocks may be an important alternative protocol in MRM, enhancing patient safety and cost benefits. Improvements in cross-disciplinary expertise through flexibility in the training of professionals with other backgrounds may provide effective analgesia and favorable outcomes., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Animation deformity is an undesirable outcome of subpectoral breast reconstruction that results in abnormal breast contraction with activity, breast pain, and increased implant visibility. Surgical correction requires implant removal and conversion of the reconstruction to a prepectoral plane. The authors present their institutional experience with their preferred surgical technique to treat this challenging problem and outline solutions for increased success in these patients., Methods: A retrospective review was performed of all patients undergoing conversion of their subpectoral breast reconstruction to a prepectoral plane at the authors' institution. Patient demographics and surgical details were analyzed, and postoperative outcomes and morbidity were assessed. The effects of changing operative strategies on enhanced success are also reported., Results: A total of 80 breast conversions were performed over a 2.5-year period. All patients demonstrated resolution of animation deformity at a mean follow-up of 15.2 months. Two reconstructions (2.5 percent) required an unplanned return to the operating room, and 11 reconstructions (13.8 percent) were treated for infection. Preconversion fat grafting and the use of acellular dermal matrix were both associated with a reduced incidence of postoperative asymmetry and capsular contracture (p < 0.05). There were no reconstructive failures associated with conversion to a prepectoral pocket., Conclusions: Treatment of animation deformity in the reconstructed patient can be safely performed by surgical conversion to a prepectoral plane. The use of acellular dermal matrix, and preconversion fat grafting, in appropriate patients can improve results. The authors promote this operative algorithm for all reconstructive patients experiencing symptomatic animation deformity with subpectoral breast reconstruction., Clinical Question/level of Evidence: Therapeutic, IV.

Extraskeletal osteosarcoma are rare malignant mesenchymal neoplasms of soft tissues representing around 1% of all soft tissue. The exact mechanism of tumorigenesis of primary breast osteosarcoma is still unclear. However, most of the cases develop without a recognized etiologic factor. Primary osteosarcoma of the breast is often initially misdiagnosed as breast fibroadenoma. Different imaging modalities and pathology play important role in differentiating breast osteosarcoma from other benign and malignant lesions of the breast resulting in dramatic change in the management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: As the stronger association of obesity with postmenopausal breast cancer in Asian than white women may be due to body fat distribution, we examined the relation of adiposity measures with percent mammographic density (PMD), a strong predictor of breast cancer incidence., Methods: A total of 938 women from five ethnic groups (69.1 ± 2.7 years) in the Adiposity Phenotype Study (APS) underwent DXA and MRI imaging. PMD was assessed in routine mammograms using a computer-assisted method. Spearman correlation coefficients were computed and general linear models were applied to estimate regression coefficients (β) for PMD per 0.5 SD units of adiposity measures while adjusting for known confounders, including DXA total body fat., Results: For 701 (75%) of the participants (69.1 ± 2.7 years), valid mammograms were obtained. Whereas total body fat, the trunk-to-periphery fat ratio (TPFR), visceral fat (VAT), and subcutaneous fat (SAT) were inversely correlated with PMD ( P < 0.0001), the VAT/SAT ratio correlated positively ( r spearman = 0.10; P = 0.01). In fully adjusted models, PMD remained inversely related to TPFR and SAT and disappeared for VAT, while it was strengthened for VAT/SAT (β = 0.51; P = 0.009). This relation was stronger in Japanese Americans than other ethnic groups., Conclusions: This is the first study to show an association of a high VAT/SAT ratio with greater PMD, a marker of breast cancer risk after taking into account total body fat., Impact: The results indicate a link between the propensity to accumulate VAT and the amount of fat in the breast (1-PMD), which may influence the relation of obesity with breast cancer incidence., (©2019 American Association for Cancer Research.)

Background: Breast cancer is the most common cancer in women. While mammography is the standard for early detection in women older than 50 years of age, there is no standard for younger women. The aim of this prospective pilot study was to assess liquid crystal contact thermography, using the Braster device, as a means for the early detection of breast cancer. The device is intended to be used as a complementary tool to standard of care (sonography, mammography, etc). Patients and Methods: A total of 274 consecutive women presenting at Polish breast centers for prophylactic breast examination were enrolled to receive thermography; 19 were excluded for errors in thermographic image acquisition. The women were divided according to age (n = 135, <50 years; n = 120, ≥50 years). A control population was included (n = 40, <50 years; n = 23, ≥50 years). The primary endpoint, stratified by age group, was the C -statistic for discrimination between breast cancer and noncancer. Results: In women with abnormal breast ultrasound (n = 95, <50 years; n = 87, ≥50 years), the C -statistic was 0.85 and 0.75, respectively ( P = .20), for discrimination between breast cancer and noncancer. Sensitivity did not differ ( P = .79) between the younger (82%) and older women (78%), while specificity was lower in the older women (60% vs 87%, P = .025). The false-positive rate was similar in women with normal and abnormal breast ultrasound. Positive thermographic result in women with Breast Imaging Reporting and Data System (BIRADS) 4A on ultrasound increased the probability of breast cancer by over 2-fold. Conversely, a negative thermographic result decreased the probability of cancer more than 3-fold. Breast size and structure did not affect the thermography performance. No adverse events were observed. Conclusions: Thermography performed well in women <50 years of age, while its specificity in women ≥50 years was inadequate. These promising findings suggest that the Braster device deserves further investigation as a supporting tool for the early detection of breast cancer in women younger than 50 years of age.

Excess breast volume can lead to changes in the postural pattern that may result in pain. This causes women to seek reduction mammaplasty, a surgical procedure that reduces breast volume and may provide relief from symptoms. The objective of this study was to evaluate whether reduction mammaplasty can influence the posture of women. The postures of women with breast hypertrophy were evaluated using postural assessment software and photographic recording performed on the day of surgery and 3 months after the procedure. After surgical breast reduction, the patients had statistically significant changes in their postural patterns related to the horizontal alignment of the anterosuperior iliac spines and the angle of the acromion and anterior superior iliac spines. The analysis of the results showed statistically significant data on postural changes in the patients 3 months after the surgical procedure.

Background: Expressing human milk using commercially available pumps has increased. Most women use mechanical means to transfer their milk at some point during lactation. Yet, there is very little quantification of any breast tissue changes that occur when using mechanical devices to facilitate milk transfer. Objective: Women comfortable with breastfeeding were recruited to participate in a study to measure physical changes of the breast with a variety of human milk transfer modalities under close observation. Materials and Methods: Direct breastfeeding with their infant, hand expression, and mechanical milk transfer using two commonly available breast pumps were utilized over four milk transfer sessions with each participant. Each participant directly breastfed on the first milk transfer session and the remaining modalities were randomized. Measurements were taken before and after each modality using digital calipers. Participants completed a modified pain scale after each observation. Measurements taken after breastfeeding were used as the control for data interpretation for each participant. After a 20-minute rest period, breast tissue was again examined, and tissue appearance was recorded. Within-subject modality differences were calculated, and paired analysis mean difference and standard error of the mean are presented. Results: Fifty eligible women were approached with 92% participating. The "before" measurements were not significant for all the modalities. The "after" measurements were significantly different at p  < 0.003 for breast pumps but not for breastfeeding or hand expressing. Many participants indicated pain with pumping. Conclusion: Mechanical pump use correlated with significantly increased length and diameter of the nipple compared with the post-breastfeeding and hand expressing dimensions. Pump use correlated with significant pain scores and resulted in localized inflammatory changes. Understanding how pumps affect breast tissue is helpful in improving experiences with breast pumps and may improve breastfeeding outcomes. Additional research is needed to better understand ramifications of long-term use of breast pumps.

Background: Gynecomastia (GM) is a benign proliferation of the glandular tissue of the breast in men. It is a frequent condition with a reported prevalence of 32-65%, depending on the age and the criteria used for definition. GM of infancy and puberty are common, benign conditions resolving spontaneously in the majority of cases. GM of adulthood is more prevalent among the elderly and proper investigation may reveal an underlying pathology in 45-50% of cases., Objectives: The aim was to provide clinical practice guidelines for the evaluation and management of GM., Materials and Methods: A literature search of articles in English for the term 'gynecomastia' was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system., Results: A set of five statements and fifteen clinical recommendations was formulated., Conclusions: The purpose of GM assessment should be the detection of underlying pathological conditions, reversible causes (administration/abuse of aggravating substances), and the discrimination from other breast lumps, particularly breast cancer. Assessment should comprise a thorough medical history and physical examination of the breast and genitalia (including testicular ultrasound). A set of laboratory investigations may integrate the evaluation: testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin, human chorionic gonadotropin (hCG), alpha-fetal protein (AFP), liver and renal function tests. Breast imaging may be used whenever the clinical examination is equivocal. In suspicious lesions, core needle biopsy should be sought directly instead. Watchful waiting is recommended after treatment of underlying pathology or discontinuation of substances associated with GM. T treatment should be offered to men with proven T deficiency. The use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and non-aromatizable androgens is not justified in general. Surgical treatment is the therapy of choice for patients with long-lasting GM., Summary of Statements (s) and Recommendations (r): S1. Gynecomastia (GM) is a benign proliferation of glandular tissue of the breast in males. S2. GM of infancy is a common condition that usually resolves spontaneously, typically within the first year of life. S3. GM of puberty is a common condition, affecting approximately 50% of mid-pubertal boys; in more than 90% of cases, it resolves spontaneously within 24 months. S4. The prevalence of GM in adulthood increases with increasing age; proper investigation may reveal an underlying pathology in approximately 45-50% of the cases. S5. Male breast cancer is rare; GM should not be considered a premalignant condition. The following recommendations are divided into 'strong', denoted by the number 1 and associated with the terminology 'we recommend', and 'weak' denoted by the number 2 and associated with the phrase 'we suggest'. The grading of the quality of evidence is denoted as follows: ⊕○○○ for very low-quality evidence; ⊕⊕○○ for low quality; ⊕⊕⊕○ for moderate quality; and ⊕⊕⊕⊕ for high quality. R1. The presence of an underlying pathology should be considered in GM of adulthood. We recommend that the identification of an apparent reason for GM in adulthood, including the use of medication known to be associated with GM, should not preclude a detailed investigation (1 ⊕⊕⊕○). R2. We suggest that the initial screening to rule out lipomastia, obvious breast cancer, or testicular cancer might be performed by a general practitioner or another non-specialist (2 ⊕○○○). R3. We recommend that in those cases where a thorough diagnostic workup is warranted, it should be performed by a specialist (1 ⊕○○○). R4. We recommend that the medical history should include information on the onset and duration of GM, sexual development and function, and administration or abuse of substances associated with GM (1 ⊕⊕⊕○). R5. We recommend that the physical examination should detect signs of under-virilization or systemic disease (1 ⊕⊕⊕⊕). R6. We recommend that breast examination should confirm the presence of palpable glandular tissue to discriminate GM from lipomastia (pseudo-gynecomastia) and rule out the suspicion of malignant breast tumor (1 ⊕⊕⊕⊕). R7. We recommend that the physical examination should include the examination of the genitalia to rule out the presence of a palpable testicular tumor and to detect testicular atrophy (1 ⊕⊕⊕⊕). R8. We recommend that genitalia examination is aided by a testicular ultrasound, as the detection of a testicular tumor by palpation has low sensitivity (1 ⊕⊕○○). R9. We suggest that a set of evaluations may include T, E 2 , SHBG, LH, FSH, TSH, prolactin, hCG, AFP, and liver and renal function tests (2 ⊕⊕○○). R10. We suggest that breast imaging may offer assistance, where the clinical examination is equivocal (2 ⊕⊕○○). R11. We suggest that, if the clinical picture is suspicious for a malignant lesion, core needle biopsy should be performed (2 ⊕⊕○○). R12. We recommend watchful waiting after treatment of underlying pathology or discontinuation of the administration/abuse of substances associated with GM (1 ⊕⊕○○). R13. We recommend that T treatment should be offered only to men with proven testosterone deficiency (1 ⊕⊕⊕○). R14. We do not recommend the use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or non-aromatizable androgens in the treatment of GM in general (1 ⊕⊕○○). R15. We suggest surgical treatment only for patients with long-lasting GM, which does not regress spontaneously or following medical therapy. The extent and type of surgery depend on the size of breast enlargement, and the amount of adipose tissue (2 ⊕⊕○○)., (© 2019 American Society of Andrology and European Academy of Andrology.)

Context: Previous case reports associated prepubertal gynecomastia with lavender-containing fragrances, but there appear to be no reports of premature thelarche., Objective: To add to a case series about lavender-fragranced product use and breast growth in children and to measure endocrine-disrupting chemical activity of essential oil components., Design, Setting, and Patients: Patients experiencing premature thelarche or prepubertal gynecomastia with continuous exposure to lavender-fragranced products were evaluated in the pediatric endocrinology departments of two institutions. Mechanistic in vitro experiments using eight components of lavender and other essential oils were performed at National Institute of Environmental Health Sciences., Main Outcome Measures: Case reports and in vitro estrogen and androgen receptor gene expression activities in human cell lines with essential oils., Results: Three prepubertal girls and one boy with clinical evidence of estrogenic action and a history of continuous exposure to lavender-containing fragrances were studied. Breast growth dissipated in all patients with discontinuation of the fragranced products. Some of the components tested elicited estrogenic and antiandrogenic properties of varying degrees., Conclusion: We report cases of premature thelarche that resolved upon cessation of lavender-containing fragrance exposure commonly used in Hispanic communities. The precise developmental basis for such conditions could be multifactorial. In vitro demonstration of estrogenic and antiandrogenic properties of essential oil components suggests essential oils in these cases could be considered a possible source and supports a possible link with idiopathic prepubertal breast development. Whether the level of lavender oil estrogenic potency is sufficient to cause these effects is unknown., (Copyright © 2019 Endocrine Society.)

Purpose: Elevated mammographic density (MD) is an independent risk factor for breast cancer (BC) as well as a source of masking in X-ray mammography. High-frequency longitudinal monitoring of MD could also be beneficial in hormonal BC prevention, where early MD changes herald the treatment's success. We present a novel approach to quantification of MD in breast tissue using single-sided portable NMR. Its development was motivated by the low cost of portable-NMR instrumentation, the suitability for measurements in vivo, and the absence of ionizing radiation., Methods: Five breast slices were obtained from three patients undergoing prophylactic mastectomy or breast reduction surgery. Carr-Purcell-Meiboom-Gill (CPMG) relaxation curves were measured from (1) regions of high and low MD (HMD and LMD, respectively) in the full breast slices; (2) the same regions excised from the full slices; and (3) excised samples after H 2 O-D 2 O replacement. T 2 distributions were reconstructed from the CPMG decays using inverse Laplace transform., Results: Two major peaks, identified as fat and water, were consistently observed in the T 2 distributions of HMD regions. The LMD T 2 distributions were dominated by the fat peak. The relative areas of the two peaks exhibited statistically significant (P < .005) differences between HMD and LMD regions, enabling their classification as HMD or LMD. The relative-area distributions exhibited no statistically significant differences between full slices and excised samples., Conclusion: T 2 -based portable-NMR analysis is a novel approach to MD quantification. The ability to quantify tissue composition, combined with the low cost of instrumentation, make this approach promising for clinical applications., (© 2019 International Society for Magnetic Resonance in Medicine.)

Background: Adolescent reduction mammaplasty remains controversial because of concerns of postoperative breast growth, complications, and the effect on well-being. The authors sought to prospectively quantify early and late complications following reduction mammaplasty in adolescents and young women, and examine the intersection of surgical complications and postoperative health-related quality of life., Methods: From 2008 to 2017, female patients aged 12 to 21 years undergoing reduction mammaplasty were asked to complete the 36-Item Short-Form Health Survey (version 2), the Rosenberg Self-Esteem Scale, the Breast-Related Symptoms Questionnaire, and the Eating-Attitudes Test-26 preoperatively and postoperatively at 6 months and 1, 3, 5, and 7 years. Clinical evaluations using standardized forms assessed baseline and postoperative symptomatology, complications, and surgical outcomes., Results: In the authors' sample of 512 participants, the most common complications included hypertrophic scarring (20.0 percent) and altered sensation of the nipple (8.4 percent) or breast (7.8 percent). Patient age, body mass index category, and amount of tissue resected did not significantly increase the odds of developing a complication. Significant postoperative improvements on the Rosenberg Self-Esteem Scale, the Breast-Related Symptoms Questionnaire, the Eating-Attitudes Test-26, and in all 36-Item Short-Form Health Survey domains (i.e., physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) were largely seen irrespective of whether complications occurred., Conclusions: Although complications following reduction mammaplasty were common, the vast majority were minor. Patients had significant postoperative improvements in their physical and psychosocial well-being regardless of whether they experienced a complication. Concerns for potential complication, especially in younger and overweight or obese patients, should not preclude otherwise healthy adolescents and young women from the benefits of reduction mammaplasty., Clinical Question/level of Evidence: Therapeutic, IV.

Purpose: To characterize reproducibility of patient breath-hold positioning and compare tracking system performance for Deep Inspiration Breath Hold (DIBH) gated left breast radiotherapy., Methods: 29 consecutive left breast DIBH patients (655 fractions) were treated under the guidance of Calypso surface beacons with audio-feedback and 35 consecutive patients (631 fractions) were treated using C-RAD Catalyst HD surface imaging with audiovisual feedback. The Calypso system tracks a centroid determined by two radio-frequency transponders, with a manually enforced institutional tolerance, while the surface image based CatalystHD system utilizes real-time biometric feedback to track a pre-selected point with an institutional tolerance enforced by the Elekta Response gating interface. DIBH motion data from Calypso was extracted to obtain the displacement of breath hold marker in ant/post direction from a set-zero reference point. Ant/post point displacement data from CatalystHD was interpreted by computing the difference between raw tracking points and the center of individual gating windows. Mean overall errors were compared using Welsh's unequal variance t-test. Wilcoxon rank sum test were used for statistical analysis with P < 0.05 considered significant., Results: Mean overall error for Calypso and CatalystHD were 0.33 ± 1.17 mm and 0.22 ± 0.43 mm, respectively, with t-test comparison P-value < 0.034. Absolute errors for Calypso and CatalystHD were 0.95 ± 0.75 mm and 0.38 ± 0.30 mm, respectively, with Wilcoxon rank sum test P-value <2×10 -16 . Average standard deviation per fraction was found to be 0.74 ± 0.44 mm for Calypso patients versus 0.54 ± 0.22 mm for CatalystHD., Conclusion: Reduced error distribution widths in overall positioning, deviation of position, and per fraction deviation suggest that the use of functionalities available in CatalystHD such as audiovisual biofeedback and patient surface matching improves accuracy and stability during DIBH gated left breast radiotherapy., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background: Research has shown that women with large and hypertrophic breast sizes report an increased prevalence and severity of musculoskeletal pain in the upper torso. Despite this evidence, factors contributing to the development of musculoskeletal pain among these women are poorly understood, and the threshold at which breast size becomes problematic in terms of musculoskeletal pain is currently unknown., Methods: Three hundred Australian women (aged 18 to 82 years) who volunteered as participants were divided into four breast size groups (small, breast volume <350 ml; medium, breast volume 350 to 700 ml; large, breast volume 701 to 1200 ml; and hypertrophic, breast volume >1200 ml). The thoracic flexion torque, thoracic kyphosis angle, total upper torso musculoskeletal pain score, and regional upper torso musculoskeletal pain scores derived for participants in the four groups were compared using an analysis of covariance design, controlling for age and body mass index., Results: Thoracic flexion torque significantly increased as breast size group increased. Women with hypertrophic breasts reported significantly higher total upper torso musculoskeletal pain scores compared with women who had small, medium, and large breasts, and this was significant for the upper back, shoulders, neck, and breasts. No significant difference was found in thoracic kyphosis angle among the four groups., Conclusions: Musculoskeletal pain became most pronounced in women with hypertrophic breasts who had the greatest breast volume and displayed the greatest thoracic flexion torque. Clinical and/or surgical treatment for symptomatic relief should aim to either counteract thoracic flexion torque or reduce breast volume., Clinical Question/level of Evidence: Risk, I.

Background: There is no general consensus regarding the best and most accurate method for assessing the size of implant required for achieving the best symmetry in oncoplastic reconstruction., Materials and Methods: Breast weight, volume and size of implant were recorded prospectively on patients undergoing immediate reconstruction over a 3-year period. Cases with specimen size greater than 2,000 g were excluded. The primary endpoint was size of implant used in relation to specimen weight and volume. Secondary endpoints were the influence of age and histology on specimen weight, volume and breast density., Results: A total of 278 mastectomies were performed. Correlation of implant size with volume was marginally stronger than that with weight (r=81%, p<0.001 vs. r=78.9%, p<0.001 respectively). Women aged 50 years and above had lower breast weight for the same breast volume than women under 50 years. The difference was merely 4%, but was statistically significant (p=0.001). Histology had no statistically significant influence on breast density., Conclusion: Specimen weight and volume were found to be closely correlated. Weight can be measured more accurately and easily with reproducible readings compared to volume., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: The aim of this work was to investigate the prevalence of premature thelarche (PT) in 18-month-old girls, and the incidence of clinically evaluated PT for girls aged 18-36 months., Methods: In the prevalence substudy, a prospective population-based cohort of 3,140 girls born at Northern Älvsborg county hospital (NÄL) in Trollhättan, Sweden, was followed for 2 years. Girls with breast development at the 18-month health check were referred to one pediatric center in NÄL for evaluation. All girls with PT were included and followed for clinical outcome and 17β-estradiol. The prospective incidence substudy covered 8 years in a 10-year period and included all girls aged 18-36 months born at NÄL who were clinically evaluated for PT., Results: The prevalence of PT at 18 months in our cohort was 1.6/1,000. The 5 girls with PT no longer showed symptoms at the follow-up 3-6 months later. The incidence was 1.1/1,000 for girls aged 18-36 months and 1.0/1,000 for girls aged 18-30 months who were clinically evaluated for their PT., Conclusion: This is the first prospective population-based study of PT and it shows a prevalence of PT at age 18 months of 1.6/1,000. The incidence of clinically evaluated PT was 1.1/1,000. Our result is in line with other studies reporting the incidence of PT from medical records (0.4-40/1,000). The outcome of PT in our study, as in the other studies, is that the great majority of girls show only benign symptoms., (© 2019 S. Karger AG, Basel.)

Background: Exercise has been shown to reduce adverse outcomes related to breast cancer. However, the rate of adherence to physical exercise is very low among breast cancer survivors (BCS). This study investigated the effects of high supervision ratio resistance training (RT), once a week for 8 weeks, on changes in body composition and muscular strength in BCS. Methods: Twenty-five female BCS undergoing hormone therapy were randomized into resistance training group (TG, n = 12) or control (CG, n = 13) group. The TG performed 8 weeks of supervised RT, with 1 trainer per volunteer, once a week. Body composition was evaluated by dual-energy X-ray absorptiometry, and muscle strength was evaluated by 10 repetition maximum (10 RM) for leg press (45°) and bench press exercises. A 1-way analysis of variance was used to compare within-group effects at pre- and post-intervention. An analysis of covariance test was used to compare post-intervention values, using pre-intervention measures as covariates. The effect size (ES) was calculated by Cohen's d . Results: The TG improved muscle strength in 10 RM leg press (45°; Δ 33.75 ± 11.51 kg, P = .02; ES = 0.96) and bench press (Δ 4.08 ± 1.83 kg, P = .01; ES = 1.15). Adherence to training was more than 99%. Changes in body composition were not detected. There were no changes in the CG for any assessment. Conclusion: Once-weekly supervised RT could be an alternative to increase the adherence to exercise and improve muscular strength in BCS.

Background: Clinical Breast Examination (CBE) is the examination of a women's breasts by a healthcare professional, such as a breast surgeon, family physician or breast-care nurse who is trained to recognise many different types of abnormalities and warning signs in the breast [1]. CBE is particularly important in rural areas and developing countries who have limited access to technology such as mammography. CBE needs to be taught to health professionals like any other clinical skill used by medical professionals in the workplace. CBE in part involves palpation of the breast, that is, determining by touch which breast lumps are normal and which are suspicious in feeling. The gold standard for assessing tactile skills in CBE is seeing whether students can accurately identify and discriminate between different breast lumps also known as masses (IDBM) on actual patients in a clinical setting. However, this is not practical in a medical education setting. Usually the testing methods 'go through the motions' of feeling the breast as part of CBE. So the students' technique is examined either using unrealistic simulation models or using an intimate examination associate (IEA), an actor/volunteer who permits students to examine their intimate body parts such as breast or genitals for teaching purposes. These volunteers do not have any abnormalities so this teaching does not include the actual detection of suspicious lumps. We undertook a study of clinical skill with 10 medical students to examine different methods of assessing novice student clinical skills after a brief training in CBE., Objectives: This study aims to evaluate the effectiveness of current training and assessment of novice students in CBE and their capacity to identify and discriminate breast masses (IDBM) on actual patients., Methods: We assessed each student's IDBM ability in an actual clinical situation, a breast clinic with a mixture of eight IEAs and one real patient with a large, easily palpable, putative breast cancer. We recruited 10 clinically inexperienced medical students, who were trained for 30 minutes by two breast surgeons using an IEA. Students were tested in a simulated clinical setting, a breast clinic where each examined 4 IEAs and one patient. The students were blind to who was the real patient and who was an IEA. Patients were examined by a breast surgeon in private prior to the commencement in the study. The breast surgeon recorded any clinical finding on the patients during the initial examination. The surgeon coached each patient on how to mark the students and showed the patient their results so the patients had a benchmark. After each examination was finished the students had four different assessments: 1) patients marked each student, 2) students were independently proctored - that is, marked by an expert, 3) students recorded their clinical findings and 4) students recorded how confident they were that they had the correct findings. Results from different kinds of student assessments were compared.RESULTSA chi-square test for independence between true positive or negative masses versus student-assessed positive or negative masses was not significant at alpha = .05. This means that there was no statistical association in the indication of positive or negative presence of masses versus whether such masses were actually present or absent. By comparison, experts (breast surgeons) were able to detect normal and abnormal breast masses by palpation alone 100% of the time and rate their confidence level as 'certain'. Unlike the experts, student self-reported confidence was unrelated to their competence score (CS). Proctoring was inversely related to the students' CS.CONCLUSIONSThe main conclusion is that novice students do not seem to be able to accurately detect breast masses in a clinical setting even after training. On the basis of these results, we believe that a comprehension component in the current CBE testing is needed in addition to the current methods of testing.

Purpose: Our aim is to search diagnostic value of diffusion tensor parameters in the breast cancer., Materials and Methods: We included 46 patients with contrast enhanced magnetic resonance imaging of the breast between the dates of July 2015 and December 2016. We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), relative anisotropy (RA) and volume ratio (VR) values of the malignant mass, ipsilateral and contralateral healthy breast parenchyma in each patient., Results: ADC and VR values of the malignant lesions were significantly lower than normal parenchyma (P < 0.01). FA values were statistically higher in masses than normal breast parenchyma (P < 0.05). RA values were statistically higher in the mass than ipsilateral breast parenchyma (P < 0.01) but not significantly different from in contralateral breast parenchyma (P > 0.05). Only ADC values were statistically lower in contralateral side than ipsilateral breast parenchyma (P < 0.05) other parameters showed no statistical significance between parenchymas., Conclusion: DTI findings, such as FA, ADC, RA and VR, provide significant contribution in differentiating cancer from healthy breast tissue., Competing Interests: There are no conflicts of interest.

We present an automated method for acquiring images and contrast parameters based on mechanical properties of breast lesions and surrounding tissue at load frequencies less than 1 Hz. The method called sub-Hertz analysis of viscoelasticity (SAVE) uses a compression device integrated with ultrasound imaging to perform in vivo ramp-and-hold uniaxial creep-like test on human breast in vivo. It models the internal deformations of tissues under constant surface stress as a linear viscoelastic response. We first discuss different aspects of our unique measurement approach and the expected variability of the viscoelastic parameters estimated based on a simplified one-dimensional reconstruction model. Finite-element numerical analysis is used to justify the advantages of using imaging contrast over viscoelasticity values. We then present the results of SAVE applied to a group of patients with breast masses undergoing biopsy.

Purpose: Mindfulness-based programs can reduce stress and help practitioners to have positive attitudes in their daily lives. This randomized controlled trial evaluated the impact of brief Mindfulness interventions on quantitative and qualitative stress parameters in patients undergoing imaging-guided breast biopsies., Methods: Eighty-two women undergoing percutaneous imaging-guided breast biopsy were randomized into two groups: MBI group or standard care group. One week before the biopsy procedure, on the waiting room and during the biopsy procedure, the MBI group was exposed to mindfulness techniques and the standard care group received supportive dialogue from the biopsy team. Participants completed questionnaires measuring depression, anxiety and stress, demographics, and medical history, besides evaluating their pain experience through a visual analogue scale for pain and had their systolic and diastolic blood pressure, initial and final temperate, heart rate, oxygen saturation, and salivary cortisol measured., Results: Participation in the mindfulness intervention group was associated with reduced levels of perceived stress, blood pressure, heart rate, and oxygen saturation compared to participation in the standard care group (P values < 0.05). No difference was observed regarding salivary cortisol levels, peripheral temperature, and pain perception between the two studied groups., Conclusion: Results indicate that an extremely brief mindfulness intervention is a feasible intervention, suggesting that Mindfulness-based programs may be beneficial to reduce discomfort in acutely stressful settings.

Although mammography (MG) has been widely used for breast cancer screening in the western world, over-diagnosis remains controversial. Milestone studies showed that ultrasound (US) was an effective primary screening test for breast cancer both in the western world and in China. US improves the sensitivity of screening in Chinese women who have denser breasts and develop breast cancer earlier than Caucasian counterparts, and is used as the primary imaging test in the hospital-based opportunistic screening among asymptomatic self-referred women. Our previous work showed that US result might further differentiate the MG-detected breast cancers into low risk (US+) and ultra-low risk (US-). Indeed, most of the MG+/US- breast cancers would be ultra-low risk cancers and almost always present as MG micro-calcifications. Furthermore, majority of the commonest MG+/US- abnormal finding of micro-calcification is usually benign. Biopsy of benign breast disease increases not only the risk of breast cancer, but the expenses of screening and healthcare. Our hypothesis proposes that mammography-positive ultrasound-negative (MG+/US-) asymptomatic micro-calcifications might not need immediate invasive procedures and be safe to observe until the micro-calcifications increase significantly or become US-positive. If this hypothesis is proved, US would serve as the primary imaging test for breast cancer screening in China, with MG as the selective screening test and diagnostic tool for surgical plan. Unnecessary biopsy or surgery might be avoided with screening expenses considerably decrease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Phytoestrogens, a class of plant-derived compounds that are structural mimics of estrogen, can bind to estrogen receptors, acting as either agonists or antagonists. They have been implicated in estrogen-mediated physiology, which makes them interesting targets of study, especially for biomedical applications in woman's health. The 1998 Women's Health Initiative sparked considerable interest in natural alternatives to hormone replacement therapy, thereby triggering many additional studies on phytoestrogens. In this review, key advancements in dietary phytoestrogens are addressed, emphasizing their relation to breast pathophysiology. Recent developments such as clinical trials, precise bioassays for screening and selection of potential phytoestrogens, drug delivery systems to enhance bioavailability of therapeutically favorable phytoestrogens, regulatory guidelines on phytoestrogen-based supplements, and avenues that need further improvement are also discussed., (Copyright © 2018 John Wiley & Sons, Ltd.)

The aim of this work is to study the radiation doses delivered to a group of patients that underwent a stereotactic breast biopsy (SBB) procedure. Mean glandular doses (MGD) were estimated from the air-kerma measured at the breast surface entrance multiplying by specific conversion coefficients (DgN) that were estimated using Monte Carlo simulations. DgN were calculated for the 0° and  ±15° projections used in SBB and for the particular beam quality. Data on 61 patients were collected showing that a typical SBB procedure is composed by ten images. MGD was on average (4  ±  2) mGy with (0.38  ±  0.06) mGy per image. The use of specific conversion coefficients instead of typical DgN for mammography/tomosynthesis yields to obtain MGD values for SBB that are around a 65% lower on average.

Background: In over 20% of breast conserving operations, postoperative pathological assessment of the excised tissue reveals positive margins, requiring additional surgery. Current techniques for intra-operative assessment of tumor margins are insufficient in accuracy or resolution to reliably detect small tumors. There is a distinct need for a fast technique to accurately identify tumors smaller than 1 mm 2 in large tissue surfaces within 30 min., Methods: Multi-modal spectral histopathology (MSH), a multimodal imaging technique combining tissue auto-fluorescence and Raman spectroscopy was used to detect microscopic residual tumor at the surface of the excised breast tissue. New algorithms were developed to optimally utilize auto-fluorescence images to guide Raman measurements and achieve the required detection accuracy over large tissue surfaces (up to 4 × 6.5 cm 2 ). Algorithms were trained on 91 breast tissue samples from 65 patients., Results: Independent tests on 121 samples from 107 patients - including 51 fresh, whole excision specimens - detected breast carcinoma on the tissue surface with 95% sensitivity and 82% specificity. One surface of each uncut excision specimen was measured in 12-24 min. The combination of high spatial-resolution auto-fluorescence with specific diagnosis by Raman spectroscopy allows reliable detection even for invasive carcinoma or ductal carcinoma in situ smaller than 1 mm 2 ., Conclusions: This study provides evidence that this multimodal approach could provide an objective tool for intra-operative assessment of breast conserving surgery margins, reducing the risk for unnecessary second operations.