Microcalcifications in breast cancer: From pathophysiology to diagnosis and prognosis.

The implementation of mammographic screening programmes in many countries has been linked to a marked increase in early detection and improved prognosis for breast cancer patients. Breast tumours can be detected by assessing several features in mammographic images but one of the most common are the presence of small deposits of calcium known as microcalcifications, which in many cases may be the only detectable sign of a breast tumour. In addition to their efficacy in the detection of breast cancer, the presence of microcalcifications within a breast tumour may also convey useful prognostic information. Breast tumours with associated calcifications display an increased rate of HER2 overexpression as well as decreased survival, increased risk of recurrence, high tumour grade and increased likelihood of spread to the lymph nodes. Clearly, the presence of microcalcifications in a tumour is a clinically significant finding, suggesting that a detailed understanding of their formation may improve our knowledge of the early stages of breast tumourigenesis, yet there are no reports which attempt to bring together recent basic science research findings and current knowledge of the clinical significance of microcalcifications. This review will summarise the most current understanding of the formation of calcifications within breast tissue and explore their associated clinical features and prognostic value.

Mycoplasma bovis subverts autophagy to promote intracellular replication in bovine mammary epithelial cells cultured in vitro.

Mycoplasma species are the smallest prokaryotes capable of self-replication. To investigate Mycoplasma induced autophagy in mammalian cells, Mycoplasma bovis (M. bovis) and bovine mammary epithelial cells (bMEC) were used in an in vitro infection model. Initially, intracellular M. bovis was enclosed within a membrane-like structure in bMEC, as viewed with transmission electron microscopy. In infected bMEC, increased LC3II was verified by Western blotting, RT-PCR and laser confocal microscopy, confirming autophagy at 1, 3 and 6 h post-infection (hpi), with a peak at 6 hpi. However, the M. bovis-induced autophagy flux was subsequently blocked. P62 degradation in infected bMEC was inhibited at 3, 6, 12 and 24 hpi, based on Western blotting and RT-PCR. Beclin1 expression decreased at 12 and 24 hpi. Furthermore, autophagosome maturation was subverted by M. bovis. Autophagosome acidification was inhibited by M. bovis infection, based on detection of mCherry-GFP-LC3 labeled autophagosomes; the decreases in protein levels of Lamp-2a indicate that the lysosomes were impaired by infection. In contrast, activation of autophagy (with rapamycin or HBSS) overcame the M. bovis-induced blockade in phagosome maturation by increasing delivery of M. bovis to the lysosome, with a concurrent decrease in intracellular M. bovis replication. In conclusion, although M. bovis infection induced autophagy in bMEC, the autophagy flux was subsequently impaired by inhibiting autophagosome maturation. Therefore, we conclude that M. bovis subverted autophagy to promote its intracellular replication in bMEC. These findings are the impetus for future studies to further characterize interactions between M. bovis and mammalian host cells.

LsrR, the effector of AI-2 quorum sensing, is vital for the H2O2 stress response in mammary pathogenic Escherichia coli.

Mammary pathogenic Escherichia coli (MPEC) is an important causative agent of mastitis in dairy cows that results in reduced milk quality and production, and is responsible for severe economic losses in the dairy industry worldwide. Oxidative stress, as an imbalance between reactive oxygen species (ROS) and antioxidants, is a stress factor that is common in most bacterial habitats. The presence of ROS can damage cellular sites, including iron-sulfur clusters, cysteine and methionine protein residues, and DNA, and may cause bacterial cell death. Previous studies have reported that Autoinducer 2 (AI-2) can regulate E. coli antibiotic resistance and pathogenicity by mediating the intracellular receptor protein LsrR. This study explored the regulatory mechanism of LsrR on the H2O2 stress response in MPEC, showing that the transcript levels of lsrR significantly decreased under H2O2 stress conditions. The survival cell count of lsrR mutant XW10/pSTV28 was increased about 3080-fold when compared with that of the wild-type WT/pSTV28 in the presence of H2O2 and overexpression of lsrR (XW10/pUClsrR) resulted in a decrease in bacterial survival rates under these conditions. The ß-galactosidase reporter assays showed that mutation of lsrR led to a remarkable increase in expression of the promoters of ahpCF, katG and oxyR, while lsrR-overexpressing significantly reduced the expression of ahpCF and katG. The electrophoretic mobility shift assays confirmed that LsrR could directly bind to the promoter regions of ahpCF and katG. These results revealed the important role played by LsrR in the oxidative stress response of MPEC.

Breast tuberculosis in East London: A 13-year retrospective observational study.

SETTING: Breast tuberculosis (TB) is rare in Western Europe, and its diagnosis may be delayed through lack of awareness of presenting features. Our institution serves a large East London population with a high incidence of TB. OBJECTIVE: To characterize presenting features and avoidable diagnostic delay in breast TB patients. DESIGN: We conducted a 13-year retrospective study of breast TB patients treated at our institution including demographic, clinical, microbiology, and pathology data. RESULTS: Forty-seven cases were included; 44 (94%) were female, with a median age of 33 years (IQR 28.5-39.5). The main presenting feature was a breast lump in 41 cases (87%); which were predominantly solitary unilateral lesions (25, 61%) and frequently located in the upper outer quadrant (28, 68%). Where performed, Mycobacterium tuberculosis was cultured in 15/36 (42%) cases. Granulomata were present on biopsy or aspirate in 21 (47%) and 17 (36%) cases, respectively. The median duration between symptom onset and treatment was 20 weeks (IQR 15-30). Forty-six (98%) completed treatment successfully and one relapsed. CONCLUSION: A high index of suspicion for TB is required for individuals presenting with breast symptoms from countries where TB is endemic. Development of standardized pathways may improve detection and management of breast TB may reduce diagnostic delay.

Clinical Presentations of Breast Disorders in Pregnancy and Lactation.

The breast tissue undergoes significant physiological change during pregnancy and lactation. These changes can give rise to some unique disorders during pregnancy , puerperium and lactation or exaggerate pre-existing conditions. Clinical examination becomes less reliable due to textural change and density of breast tissue as a result of hormonal changes. The main symptoms during pregnancy and lactation are breast pain, mastitis, lactational abscess, breast lump, and blood- stained nipple discharge.Lactational mastitis/ abscess must be treated without delay. Open incision and drainage of lactational abscess is rarely required, any lactational abscess should be treated with appropriate antibiotics and ultrasound guided aspiration of the pus.Any breast lump during pregnancy and lactation should be investigated with triple assessment. Pregnancy associated breast cancer (PABC ) must be ruled out. The choice of investigations and treatment needs careful consideration. While ultrasound is the investigation of choice, mammography can be performed with abdominal shielding if malignancy is suspected. Core biopsy is necessary for evaluation of any breast pathology but it comes with risk of infection, bleeding, hematoma and even milk fistula.The treating clinical specialist must be aware of certain unusual unique clinical conditions in pregnancy and lactation including accessory axillary breast tissue, gigantomastia and Raynaud's phenomenon.

The female adolescent breast: disorders of development.

PURPOSE OF REVIEW: This article will provide an overview on female breast development and focus on common abnormalities of growth, the emerging role of breast self-awareness, and discuss trends in the evaluation and treatment of the breast masses and disorders most often encountered in the female adolescent population. RECENT FINDINGS: Although the embryology of breast development is unchanged, data are emerging on the role of environmental factors on the timing of puberty and thelarche. As breast development occurs, the role of breast self-awareness is also a new trend that allows teens to be cognizant of changes in their own breast and to become more comfortable with their own anatomy. Finally, when breast treatments are needed or desired, the timing of breast treatments is a subject that must be individualized. SUMMARY: There are numerous conditions that can result from disruption of normal breast development. These resultant breast disorders are generally benign but can still cause emotional distress to both the patient and family. It is thus imperative that healthcare providers be educated on breast development, the common breast masses that occur in the adolescent population and be prepared to discuss breast self-awareness and shared decision-making in this population.

Nipple hypersensitivty-An unusual symptom of duct ectasia.

Mammary duct ectasia (MDE) is a benign and often troublesome breast condition. The usual presentation includes colored nipple discharge and mastalgia. Nipple hypersensitivity has never before been described as a presenting complaint for MDE. This case report looks into such an unusual case.

Body composition patterns and breast cancer risk in Chinese women with breast diseases: A latent class analysis.

AIMS: To identify unobserved body composition patterns among Chinese women with breast diseases using latent class analysis (LCA) and to examine the relationship between body composition patterns and breast cancer (BC) risk. DESIGN: A descriptive, cross-sectional study. METHODS: Female patients (N = 1816) with breast diseases were included in the study from April 2016 - March 2017. Body composition measures were done by the bioelectrical impedance analysis. The LCA models were estimated using Mplus 8.1. RESULTS: Four latent classes were identified based on water, protein, minerals and body fat mass: Class 1 - Low Muscle Mass class; Class 2 - High Body Composition class; Class 3 - High Fat class; and Class 4 - Normal Body Composition Class. Classes 2 and 3 are higher risk classes for developing BC compared with the other two classes (p < 0.05). Overall, age is positively associated with the odds of BC development (p < 0.001). However, age effect depends on the body composition patterns. Age effect on the odds of BC was statistically significant only for women who had least body fat mass (Class 1, OR = 1.110, 95% C.I.: 1.084-1.136) or had normal body composition (Class 4, OR = 1.090, 95% C.I.: 1.036-1.147). The effect of age was not statistically significant if women had higher risk body composition (e.g., in Classes 2 or 3). CONCLUSION: Latent Class Analysis is a useful person-centred analytical approach for identification of unobserved patterns of body composition and it could be used to predict the risk of BC and develop personalized interventions for body composition studies.

Breast pain in lactating mothers.

INTRODUCTION: The number of new mothers who breastfeed has increased dramatically over the last three decades. There is a concern that the present related medical service may be inadequate. Breast pain is the most common complaint among lactating mothers who seek medical help. This study aimed to investigate this problem. METHODS: Medical records of women who presented with breast pain to a private clinic run by a doctor who was trained as an International Lactation Consultant were reviewed over a period of 6 months in 2015. Most patients were self-referred after chatting online. Assessment included characteristics and duration of pain, treatment prior to consultation, feeding practices, mother's diet, and breast examination. Any site of blockage was identified and relieved. Those with persistent pain were given antibiotics. When there were signs of abscess or abscess that could not be drained, they were referred to a breast surgeon. RESULTS: A total of 69 patients were seen of whom 45 had been breastfeeding for more than 1 month. Pain was experienced for longer than 7 days in 22 women. Antifungal or antibacterial treatment had been unsuccessful in 31 women prior to consultation. The diagnoses were engorgement in five women, blocked duct in 35, mastitis in 13, breast abscess in six, poor positioning and latch in seven, nipple cracks in two, and skin infection in one. Oral antibiotics were prescribed to 21 patients and local antifungal treatment was given to one patient only. CONCLUSION: Blocked duct was the most common cause of breast pain in lactating mothers. Without prompt relief it is possible that it will progress to mastitis/breast abscess or the mother may discontinue breastfeeding. This may be a suitable time for Hong Kong to set up one or more public full-time breastfeeding clinics to provide a better service to lactating mothers and to facilitate professional training and research.

A RARE CASE OF HYDATID CYST DISEASE OF THE BREAST: A CASE REPORT AND REVIEW OF LITERATURE.

Hydatid cyst of the breast is extremely rare even in endemic areas and it only accounts for 0.27% of all hydatid cyst disease cases. It can either be a primary site or part of a disseminated hydatidosis. Surgery remains to be a treatment of choice. Only few reports are published in the literatures and most of the reported cases have been diagnosed postoperatively as it is not easy to reach at a definitive diagnosis with clinical examination and radiological investigations only. This is a case of an isolated hydatid cyst of breast in an 18-year old woman from the Amhara region, Ethiopia. She presented with left breast painless lump of 5 years duration and a correct pre-operative diagnosed was made by fine needle aspiration cytology, then confirmed after surgery. We believe this disease should be included in the differential diagnosis of benign breast lumps especially in endemic areas.

Biomagnetic activity and non linear analysis in obstetrics and gynecology in a Greek population.

This article reports the application of non-linear analysis to biomagnetic signals recorded from fetal growth restriction, fetal brain activity, ovarian lesions, breast lesions, umbilical arteries, uterine myomas, and uterine arteries in a Greek population. The results were correlated with clinical findings. The biomagnetic measurements and the application of non-linear analysis are promising procedures in Obstetrics and Gynecology.

Stiffness of the surrounding tissue of breast lesions evaluated by ultrasound elastography.

OBJECTIVE: To evaluate the stiffness of the surrounding tissue of breast lesions using the strain ratio assessment method by ultrasound (US) elastography. METHODS: This was an institutional ethics committee approved prospective study. A total of 127 breast lesions in 118 women (mean age 48.23 ± 14.32, range 20-90) were examined with conventional and elastographic US. The strain ratio assessment method was utilized to semi-quantitatively evaluate the stiffness of the breast lesions and the surrounding tissue. RESULTS: Fifty-five lesions were malignant and 72 were benign. The strain ratio of the surrounding tissue was significantly higher in malignant cases (1.49 ± 0.67) than in benign ones (1.17 ± 0.44) (P = 0.001), and yielded an Az value of 0.669 in the diagnosis of breast lesions. There was a significant high positive correlation between the strain ratio of the lesion and the strain ratio of the surrounding tissue in the malignant group (r = 0.740, P < 0.001), and a significant moderate positive correlation in the benign group (r = 0.595, P < 0.001). CONCLUSION: The stiffness of the surrounding tissue of malignant breast lesions was higher than that of benign lesions. The strain ratio of the surrounding tissue and the lesions was significantly correlated, and has potential for breast lesion diagnosis. KEY POINTS: • Stiffness of the surrounding tissue of malignant breast lesions was increased. • Stiffness of the surrounding tissue correlated with stiffness of breast lesions. • Stiffness of the surrounding tissue has potential use in diagnosis of breast lesions.

Association of breast vascular calcifications with low bone mass in postmenopausal women.

BACKGROUND: In developing countries, there is a deficiency of densitometers with which to screen the population for osteoporosis. Thus, strategies with which to select patients for a bone density test are desirable. OBJECTIVE: To determine whether breast vascular calcifications (BVCs) may be employed to identify postmenopausal women with osteoporosis/osteopenia. METHODS: This was a cross-sectional study of postmenopausal women subjected to bilateral mammography and bone densitometry (DXA) of the spine and hip. A medical interview registered possible confounding factors, such as age, length of menopause, previous use of postmenopausal hormone therapy, family history of osteoporosis, smoking, alcoholism, hypertension, diabetes, cardiovascular diseases, and medication use. RESULTS: The study included 211 postmenopausal women aged 62.1 ± 9.3 years, 38 of whom (18.0%) exhibited BVC. Osteoporosis was detected in 36 (17.1%), and a T-score < 21.0 for any site was found in 164 (77.7%). No statistically significant difference was found between the groups without BVC (n = 173) and with BVC (n = 38) for the prevalence of 'osteoporosis' or 'moderate/severe osteopenia or osteoporosis' at the spine or at any other site. There was a difference between the groups in terms of age (59.0 ± 7.8 vs. 71.9 ± 8.9 years, respectively; p < 0.001), sedentary lifestyle (57.8% vs. 84.2%, respectively; p = 0.002), smoking (27.7% vs. 7.9%, respectively; p = 0.009), and high blood pressure (65.3% vs. 92.1%, respectively; p = 0.001). Logistic regression analysis confirmed the lack of statistical significance for BVC as a predictor of an osteoporosis diagnosis. Sensitivity values of BVCs to detect osteoporosis or osteopenia ranged from 17.9% to 25.0%. CONCLUSION: BVCs have been shown to be inadequate to identify postmenopausal women with osteoporosis or osteopenia.

The prevalence, severity, and impact of breast pain in the general population.

Breast pain has been investigated in clinical populations; however we have yet to understand the prevalence and severity of this condition in the general population to determine whether more should be done to minimize the impact of this condition on women's quality of life. Therefore, this study investigated the prevalence, severity, and impact of breast pain on quality of life and factors associated with breast pain in a normal population sample. 1,659 females (34.1 ± 13.2 years) completed the Breast Pain Questionnaire online, providing information on demographics, duration, frequency, and severity of breast pain, its association with the menstrual cycle, relieving, and aggravating factors and the impact on quality of life. Over half the sample (51.5%) experienced breast pain, with a severity similar to that reported in clinical populations. There was a higher prevalence of breast pain in older participants, larger breasted participants and those who were less fit and active. Of symptomatic participants, 41% and 35% reported breast pain affecting quality of life measures of sex and sleep and 10% of symptomatic participants had sufferer for over half their lives. The results of this study suggest that breast pain is a significant issue within the general population and yet this is the first study to investigate it. It is concluded that this condition warrants increased investigation, awareness, and treatment. The reported relationship between breast pain and fitness/activity levels may offer an alternative treatment in the form of exercise intervention strategies to reduce breast pain.

No Increase in Female Breast Size or Fat Redistribution to the Upper Body After Liposuction: A Prospective Controlled Photometric Study.

BACKGROUND: Some studies have indicated that liposuction may cause breast enlargement. Fat redistribution to the upper body as a compensatory mechanism after liposuction has also been reported. OBJECTIVES: To evaluate the possibility of secondary breast hypertrophy and fat redistribution after liposuction, breast size and upper body measurements were obtained and compared for women who did not gain weight postoperatively. METHODS: Eighty-two women who underwent cosmetic surgery, not including breast surgery, were enrolled in this prospective controlled study. Participants represented 1 of 3 procedure groups: cosmetic surgery not including liposuction (n = 24), liposuction (n = 41), and liposuction combined with abdominoplasty (n = 17). Breast measurements were obtained from standardized lateral photographs matched for size and orientation. Results were compared among the study groups. RESULTS: Postoperatively, there were no significant changes in mean body weight among the study groups. No significant increases in upper pole projection, breast projection, or breast area were found in patients treated with liposuction alone and those who received liposuction plus abdominoplasty. Upper body dimensions were unchanged except for a significant (P < .01) decrease in upper abdominal width in women treated with liposuction plus abdominoplasty. The findings were the same for a subset of 17 women with liposuction aspirate volumes >1500 mL. CONCLUSIONS: Results indicate that neither liposuction nor abdominoplasty produces secondary breast enlargement. Upper body dimensions are unchanged, consistent with findings of a previous study and contrary to the theory of fat redistribution. LEVEL OF EVIDENCE: 2.

Pediatric and adolescent breast masses: a review of pathophysiology, imaging, diagnosis, and treatment.

OBJECTIVE: Pediatric breast masses are relatively rare and most are benign. Most are either secondary to normal developmental changes or neoplastic processes with a relatively benign behavior. To fully understand pediatric breast disease, it is important to have a firm comprehension of normal development and of the various tumors that can arise. Physical examination and targeted history (including family history) are key to appropriate patient management. When indicated, ultrasound is the imaging modality of choice. The purpose of this article is to review the benign breast conditions that arise as part of the spectrum of normal breast development, as well as the usually benign but neoplastic process that may develop within an otherwise normal breast. Rare primary carcinomas and metastatic lesions to the pediatric breast will also be addressed. The associated imaging findings will be reviewed, as well as treatment strategies for clinical management of the pediatric patient with signs or symptoms of breast disease. CONCLUSION: The majority of breast abnormalities in the pediatric patient are benign, but malignancies do occur. Careful attention to patient presentation, history, and clinical findings will help guide appropriate imaging and therapeutic decisions.

Breast abscesses: evidence-based algorithms for diagnosis, management, and follow-up.

Radiologists who regularly perform breast ultrasonography will likely encounter patients with breast abscesses. Although the traditional approach of surgical incision and drainage is no longer the recommended treatment, there are no clear guidelines for management of this clinical condition. Breast abscesses that develop in the puerperal period generally have a better course than nonpuerperal abscesses, which tend to be associated with longer treatment times and a higher rate of recurrence. The available literature on treatment of breast abscesses is imperfect, with no clear consensus on drainage, antibiotic therapy, and follow-up. By synthesizing the data available from studies published in the past 20 years, an evidence-based algorithm for management of breast abscesses has been developed. The proposed algorithm is easy to follow and has been validated by a multidisciplinary team approach and applied successfully during the past 2 years. Breast abscesses are a challenging clinical condition, and radiologists have a pivotal role in evaluation and follow-up of these lesions.