Integrated breast massage versus traditional breast massage for treatment of plugged milk duct in lactating women: a randomized controlled trial.

BACKGROUND: Plugged milk duct during lactation is a common problem in breastfeeding. Traditional breast massage (TBM) has been performed in Thailand with reasonable outcomes, but several follow-up sessions are often required. A new massage technique, the integrated breast massage (IBM), was subsequently developed. This study aimed to compare resolution time, reduction in mass size, and pain score after breast massage between the IBM and TBM techniques. METHODS: This randomized controlled trial was conducted at the Lactation Clinic of the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during February 2019-July 2020. Women presenting with acute plugged milk duct were enrolled and randomly allocated to the IBM or TBM/control groups. Mass size in square centimeters (cm2) was calculated by multiplying the perpendicular axes of the mass. Pain score was self-scored by participants using a numerical rating scale. Median time (95% confidence interval [CI]) to resolution of plugged milk duct was derived using Kaplan-Meier survival analysis. Intention-to-treat analysis was performed. RESULTS: Eighty-four women (42 per group) were included. All enrolled study participants completed the study and were included in the final analysis. Twenty-six (61.9%) and 25 (59.5%) participants from IBM and TBM, respectively, had mass diameter > 5 cm. The median (interquartile range [IQR]) mass size was 30 (20-48) and 20 (12-14) cm2 in IBM and TBM (p = 0.05), respectively. The median (95% CI) time to resolution of plugged duct was 0 (not available) and 1 (0.47-1.53) day in IBM and TBM, respectively (p < 0.01). After the first breast massage, the median (IQR) size of mass reduction was 30 (20-48) and 10 (10-26) cm2 in IBM and TBM, respectively (p = 0.01). The median (IQR) reduction in pain score was 8 (7-8) and 6 (4-7) in IBM and TBM, respectively (p = 0.01). No participants developed skin bruising or hematoma after breast massage. CONCLUSIONS: The IBM technique resolved plugged milk duct significantly faster, with significantly less pain, and with significantly greater reduction in mass size after the first massage compared to TBM. TRIAL REGISTRATION: Retrospectively registered in the Thai Clinical Trials Registry on 25 September 2019 ( TCTR20190925001 ).

3D in silico study of magnetic fluid hyperthermia of breast tumor using Fe3O4 magnetic nanoparticles.

Modeling and simulation of the temperature distribution, the mass concentration, and the heat transfer in the breast tissue are hot issues in magnetic fluid hyperthermia treatment of cancer. The breast tissue can be visualized as a porous matrix with saturated blood. In this paper, 3D in silico study of breast cancer hyperthermia using magnetic nanoparticles (MNPs) is conducted. The 3D FEM models are incorporated to investigate the infusion and backflow of nanofluid in the breast tumor, the diffusion of nanofluid, temperature distribution during the treatment, and prediction of the fraction of tumor necrosis while dealing with the thermal therapy. All the hyperthermia procedures are simulated and analyzed on COMSOL Multiphysics. The sensitivity of frequency and amplitude of the applied magnetic field (AMF) is investigated on the heating effect of the tumor. The mesh dependent solution of Penne's bioheat model is also analyzed. The simulated results demonstrate successful breast cancer treatment using MNPs with minimum side effects. Validation of current simulations results with experimental studies existing in literature advocates the success of our therapy. The increase in the amplitude and frequency of the AMF increases of the temperature in the tumor. The variation of mesh from coarser to finer increased the temperature through small fractions. We have also simulated the magnetic induction problem where the magnetic field is generated by current-carrying coil conductors induce heat in nearby breast tumors due to excitation of MNPs by magnetic flux. This research will aid treatment protocols and real-time clinical breast cancer treatments.

ANALYSIS OF STRUCTURAL AND FUNCTIONAL PARAMETERS OF THE THYROID GLAND IN PATIENTS WITH MALIGNANT BREAST TUMORS, WHO SUFFERED FROM THE CHORNOBYL ACCIDENT. / ANALIZ STRUKTURNYKh I FUNKTsIONAL'NYKh POKAZNYKIV ShchYTOPODIBNOÏ ZALOZY U PATsIIeNTIV ZI ZLOIaKISNYMY NOVOUTVORENNIaMY MOLOChNOÏ ZALOZY, IaKI POSTRAZhDALY VID AVARIÏ NA ChAES.

OBJECTIVE: Study the nature of structural and functional changes in the thyroid gland in patients with malignant tumors of the mammary glands that have suffered from the Chornobyl accident. MATERIALS AND METHODS: Examination of 80 patients with malignant tumors of the mammary glands at the age of 27-85 years. In 78 patients were diagnosed with breast cancer with different stages of the spread of the tumor process. The participants in the aftermath of the accident were 12 people, living in radioactive contaminated areas - 68. Mammography was performed with the help of mammographs Senographe 700 T and 800 Tsm. Echo- graphic study of the structure of the mammary gland and the thyroid gland was performed on the ultrasound devices Nemio XG SSA-580. Computed tomography was performed on a multi-detector computed tomography 64 КТ «LightSpeed VCT¼. MRI was performed on a magnetic resonance imager «Magnetom Vision Plus 1,5 T¼. For trepan biopsies, special needles were used in combination with a biopsy system gun «Magnum¼. The functional state of the thyroid gland was studied by studying the level of the thyroid hormone in peripheral venous blood. RESULTS: The results of the ultrasound study on the structural changes in the thyroid gland (TG) and markers that characterize the functional state of the TG in women with breast cancer, show that 60 out of 80 patients who asked for help with various forms of breast cancer and examined in the clinic, revealed the presence of structural changes in the thyroid gland, which is 75 %.Сonclusions. Structural changes in the thyroid gland in patients with breast cancer, who are considered victims of the Chornobyl Nuclear Power Plant accident, were diagnosed in 75 %, of which 71.25 % of patients did not know about the presence of pathological changes in the thyroid gland before the examination in the clinic. In the struc- ture of the identified pathological changes in the thyroid gland, 47.5 % accounted for the nodular goiter, 10 % for small hydrophilic and small fibrous areas, 3.75 % for previously undergone surgery for thyroid removal, 3.75 % for chronic thyroiditis, 7.5 % - CAIT, 2.5 % - cystic changes in the thyroid gland, 3.75 % - nodular goiter and CAIT.

An in vitro correlation of metastatic capacity and dual mechanostimulation.

Cells are under the influence of multiple forms of mechanical stimulation in vivo. For example, a cell is subjected to mechanical forces from tissue stiffness, shear and tensile stress and transient applied strain. Significant progress has been made in understanding the cellular mechanotransduction mechanisms in response to a single mechanical parameter. However, our knowledge of how a cell responds to multiple mechanical inputs is currently limited. In this study, we have tested the cellular response to the simultaneous application of two mechanical inputs: substrate compliance and transient tugging. Our results suggest that cells within a multicellular spheroid will restrict their response to a single mechanical input at a time and when provided with two mechanical inputs simultaneously, one will dominate. In normal and non-metastatic mammary epithelial cells, we found that they respond to applied stimulation and will override substrate compliance cues in favor of the applied mechanical stimulus. Surprisingly, however, metastatic mammary epithelial cells remain non-responsive to both mechanical cues. Our results suggest that, within our assay system, metastatic progression may involve the down-regulation of multiple mechanotransduction pathways.

Comparison of Inductively Coupled Plasma Optical Emission Spectrometry with an Ion Selective Electrode to Determine Sodium and Potassium Levels in Human Milk.

Sodium (Na), potassium (K), and the ratio Na:K in human milk (HM) may be useful biomarkers to indicate secretory activation or inflammation in the breast. Previously, these elements have been measured in a laboratory setting requiring expensive equipment and relatively large amounts of HM. The aim of this study was to compare measurements of Na and K in HM using inductively coupled plasma optical emission spectrometry (ICP-OES) with small portable ion selective electrode probes for Na and K. Sixty-five lactating women donated 5 mL samples of HM. Samples were analyzed with two ion selective probes (Na and K) and also ICP-OES. The data were analyzed using paired t-test and Bland⁻Altman plots. Na concentrations were not significantly different when measured with ion selective electrode (6.18 ± 2.47mM; range: 3.59⁻19.8) and ICP-OES (5.91 ± 3.37 mM; range: 2.59⁻21.5) (p = 0.20). K concentrations measured using the ion selective electrode (11.7 ± 2.21 mM: range: 7.69⁻18.1) and ICP-OES (11.1 ± 1.55 mM: range: 7.91⁻15.2) were significantly different (p = 0.01). However, the mean differences of 0.65 mM would not be clinically relevant when testing at point of care. Compared to ICP-OES, ion selective electrode is sufficiently accurate to detect changes in concentrations of Na and K in HM associated with secretory activation and inflammation in the mammary gland.

Enfermedad de Zuska: fístula crónica mamaria infrecuente / Zuska disease: An uncommon chronic fístula of the breast

No disponible

Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland.

Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events in tumorigenesis remains challenging and requires in vivo validation studies in reliable animal models of human cancer. In this study, we describe a novel strategy for in vivo validation of candidate tumor suppressors implicated in invasive lobular breast carcinoma (ILC), which is hallmarked by loss of the cell-cell adhesion molecule E-cadherin. We describe an approach to model ILC by intraductal injection of lentiviral vectors encoding Cre recombinase, the CRISPR/Cas9 system, or both in female mice carrying conditional alleles of the Cdh1 gene, encoding for E-cadherin. Using this approach, we were able to target ILC-initiating cells and induce specific gene disruption of Pten by CRISPR/Cas9-mediated somatic gene editing. Whereas intraductal injection of Cas9-encoding lentiviruses induced Cas9-specific immune responses and development of tumors that did not resemble ILC, lentiviral delivery of a Pten targeting single-guide RNA (sgRNA) in mice with mammary gland-specific loss of E-cadherin and expression of Cas9 efficiently induced ILC development. This versatile platform can be used for rapid in vivo testing of putative tumor suppressor genes implicated in ILC, providing new opportunities for modeling invasive lobular breast carcinoma in mice.

Does Insulin Explain the Relation between Maternal Obesity and Poor Lactation Outcomes? An Overview of the Literature.

It is well established that obese women are at increased risk of delayed lactogenesis and short breastfeeding duration, but the underlying causal contributors remain unclear. This review summarizes the literature examining the role of insulin in lactation outcomes. Maternal obesity is a strong risk factor for insulin resistance and prediabetes, but until recently a direct role for insulin in milk production had not been elucidated. Over the past 6 y, studies in both animal models and humans have shown insulin-sensitive gene expression to be dramatically upregulated specifically during the lactation cycle. Insulin is now considered to play a direct role in lactation, including essential roles in secretory differentiation, secretory activation, and mature milk production. At the same time, emerging clinical research suggests an important association between suboptimal glucose tolerance and lactation difficulty. To develop effective interventions to support lactation success in obese women further research is needed to identify how, when, and for whom maternal insulin secretion and sensitivity affect lactation ability.

Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells.

Most human breast cancers have diversified genomically and biologically by the time they become clinically evident. Early events involved in their genesis and the cellular context in which these events occur have thus been difficult to characterize. Here we present the first formal evidence of the shared and independent ability of basal cells and luminal progenitors, isolated from normal human mammary tissue and transduced with a single oncogene (KRAS(G12D)), to produce serially transplantable, polyclonal, invasive ductal carcinomas within 8 weeks of being introduced either subrenally or subcutaneously into immunodeficient mice. DNA barcoding of the initial cells revealed a dramatic change in the numbers and sizes of clones generated from them within 2 weeks, and the first appearance of many 'new' clones in tumours passaged into secondary recipients. Both primary and secondary tumours were phenotypically heterogeneous and primary tumours were categorized transcriptionally as 'normal-like'. This system challenges previous concepts that carcinogenesis in normal human epithelia is necessarily a slow process requiring the acquisition of multiple driver mutations. It also presents the first description of initial events that accompany the genesis and evolution of malignant human mammary cell populations, thereby contributing new understanding of the rapidity with which heterogeneity in their properties can develop.

Acceptability of physical examination by male doctors in medical care: Taking breast palpation as an example.

In this study, we conducted an investigation among medical workers, patients and college students concerning their acceptability of breast palpation performed by male doctors (hereinafter referred to as "acceptability", or "the examination", respectively, if not otherwise indicated), to get the information about their acceptability and reasons for accepting or declining the examination among the three population. A questionnaire investigation was conducted in 500 patients with breast diseases, 700 students of medical colleges, and 280 medical workers working in hospitals. The subjects were asked to choose between two options: accept or do not accept (the examination). The subjects were asked to fill out the questionnaire forms on free and anonymous basis and the questionnaire forms were collected on spot, immediately after completion. The questionnaires collected were coded, sorted out and checked. Data of the eligible questionnaires were input into Epidata software and analyzed by SPSS. Upon the establishment of the database, the intra-group data were tested by utilizing χ(2) test. Among 1480 questionnaires, 1293 (90.41%) questionnaires were retrieved. Our results showed that 56.78% of patients reported that they could accept breast palpation by male doctors. About 59.66% of medical staff expressed their acceptance of the examination, but only 35.03% of students said the examination. On the basis of this study, we were led to conclude that the examination is not well accepted by different populations, and therefore, (1) medical professionals and administrators should pay attention to the gender-related ethics in their practice and the feeling of patients should be respected when medical examinations involve private or sensitive body parts; (2) to this end, related departments should be properly staffed with doctors of both sexes, and this is especially true of the departments involving the examination or treatment of private or sensitive body parts; (3) health education should, among other things, include helping female patients to overcome the fear and anxiety in such examinations. This is of great importance since some women may miss the opportunity to get timely diagnosis.

Exome Sequencing of SLC30A2 Identifies Novel Loss- and Gain-of-Function Variants Associated with Breast Cell Dysfunction.

The zinc (Zn) transporter ZnT2 (SLC30A2) is expressed in specialized secretory cells including breast, pancreas and prostate, and imports Zn into mitochondria and vesicles. Mutations in SLC30A2 substantially reduce milk Zn concentration ([Zn]) and cause severe Zn deficiency in exclusively breastfed infants. Recent studies show that ZnT2-null mice have low milk [Zn], in addition to profound defects in mammary gland function during lactation. Here, we used breast milk [Zn] to identify novel non-synonymous ZnT2 variants in a population of lactating women. We also asked whether specific variants induce disturbances in intracellular Zn management or cause cellular dysfunction in mammary epithelial cells. Healthy, breastfeeding women were stratified into quartiles by milk [Zn] and exonic sequencing of SLC30A2 was performed. We found that 36% of women tested carried non-synonymous ZnT2 variants, all of whom had milk Zn levels that were distinctly above or below those in women without variants. We identified 12 novel heterozygous variants. Two variants (D(103)E and T(288)S) were identified with high frequency (9 and 16%, respectively) and expression of T(288)S was associated with a known hallmark of breast dysfunction (elevated milk sodium/potassium ratio). Select variants (A(28)D, K(66)N, Q(71)H, D(103)E, A(105)P, Q(137)H, T(288)S and T(312)K) were characterized in vitro. Compared with wild-type ZnT2, these variants were inappropriately localized, and most resulted in either 'loss-of-function' or 'gain-of-function', and altered sub-cellular Zn pools, Zn secretion, and cell cycle check-points. Our study indicates that SLC30A2 variants are common in this population, dysregulate Zn management and can lead to breast cell dysfunction. This suggests that genetic variation in ZnT2 could be an important modifier of infant growth/development and reproductive health/disease. Importantly, milk [Zn] level may serve as a bio-reporter of breast function during lactation.

Involvement of Different networks in mammary gland involution after the pregnancy/lactation cycle: Implications in breast cancer.

Early pregnancy is associated with a reduction in a woman's lifetime risk for breast cancer. However, different studies have demonstrated an increase in breast cancer risk in the years immediately following pregnancy. Early and long-term risk is even higher if the mother age is above 35 years at the time of first parity. The proinflammatory microenvironment within the mammary gland after pregnancy renders an "ideal niche" for oncogenic events. Signaling pathways involved in programmed cell death and tissue remodeling during involution are also activated in breast cancer. Herein, the major signaling pathways involved in mammary gland involution, signal transducer and activator of transcription (STAT3), nuclear factor-kappa B (NF-κB), transforming growth factor beta (TGFß), and retinoid acid receptors (RARs)/retinoid X receptors (RXRs), are reviewed as part of the complex network of signaling pathways that crosstalk in a contextual-dependent manner. These factors, also involved in breast cancer development, are important regulatory nodes for signaling amplification after weaning. Indeed, during involution, p65/p300 target genes such as MMP9, Capn1, and Capn2 are upregulated. Elevated expression and activities of these proteases in breast cancer have been extensively documented. The role of these proteases during mammary gland involution is further discussed. MMPs, calpains, and cathepsins exert their effect by modification of the extracellular matrix and intracellular proteins. Calpains, activated in the mammary gland during involution, cleave several proteins located in cell membrane, lysosomes, mitochondria, and nuclei favoring cell death. Besides, during this period, Capn1 is most probably involved in the modulation of preadipocyte differentiation through chromatin remodeling. Calpains can be implicated in cell anchoring loss, providing a proper microenvironment for tumor growth. A better understanding of the role of any of these proteases in tumorigenesis may yield novel therapeutic targets or prognostic markers for breast cancer.

Protein identification from dried nipple aspirate fluid on Guthrie cards using mass spectrometry.

Nipple aspirate fluid (NAF) requires investigation as a potential source of biomarkers for early diagnosis or risk assessment in breast cancer and other breast disorders. The present study demonstrated that proteins were easily extracted from dried NAF spots on Guthrie cards and were suitable for mass spectrometry analysis. NAF was obtained from 80 women, collected on Guthrie cards, between 2007 and 2010. The NAF-proteins were extracted from the card by incubating the card in water. These proteins were then quantified and separated using one-dimensional, 12% SDS-PAGE, gel electrophoresis and on high-resolution gradient gels at different concentrations (4-12, 8-16 and 4-20%). The bands with the most abundant proteins were excised from the gradient gels and the proteins were identified by liquid chromatography quadrupole time of flight. Immunoglobulins, Zn-α2-glicoprotein, apoliprotein D and prolactin inducible protein were among those identified. The NAF-Guthrie card collection method has not been applied previously, however, NAF proteins have been identified using other collecting techniques, confirming the feasibility of the NAF Guthrie card collection method for analyzing the proteins within NAF. The NAF-Guthrie card collecting method has multiple advantages, including being inexpensive, non-invasive, reliable and painless, and the cards can be stored at room temperature. Examining NAF may assist in identifying individuals at a higher risk of breast cancer and in improving patient prognosis.

Type 2 diabetes and mammographic breast density among underserved women.

PURPOSE: We conducted a study of women recruited at Meharry Medical College, a historically black medical school, to investigate the relationship between diabetes and mammographic breast density. METHODS: A total of 476 women completed in-person interviews, body measurements, and full-field digital mammograms on a Hologic mammography unit from December 2011 to February 2014. Average percent breast density for the left and right breasts combined was estimated using Quantra, an automated algorithm for volumetric assessment of breast tissue. The prevalence of type 2 diabetes was determined by self-report. RESULTS: After adjustment for confounding variables, the mean percent breast density among premenopausal women with type 2 diabetes [[Formula: see text] 13.8 %, 95 % confidence interval (CI) 11.6-15.9] was nonsignificantly lower than that of women without type 2 diabetes ([Formula: see text] 15.9 %, 95 % CI 15.0-16.8) (p = 0.07); however, there was no association among postmenopausal women. The effect of type 2 diabetes in severely obese women (BMI ≥ 35) appeared to differ by menopausal status with a reduction in mean percent breast density in premenopausal women, but an increase in mean percent breast density in postmenopausal women which could have been due to chance. CONCLUSIONS: Confirmation of our findings in larger studies may assist in clarifying the role of the insulin signaling breast cancer pathway in women with high breast density.

Terminal duct lobular unit involution of the normal breast: implications for breast cancer etiology.

BACKGROUND: Greater degrees of terminal duct lobular unit (TDLU) involution have been linked to lower breast cancer risk; however, factors that influence this process are poorly characterized. METHODS: To study this question, we developed three reproducible measures that are inversely associated with TDLU involution: TDLU counts, median TDLU span, and median acini counts/TDLU. We determined factors associated with TDLU involution using normal breast tissues from 1938 participants (1369 premenopausal and 569 postmenopausal) ages 18 to 75 years in the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center. Multivariable zero-inflated Poisson models were used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) for factors associated with TDLU counts, and multivariable ordinal logistic regression models were used to estimate odds ratios (ORs) and 95% CIs for factors associated with categories of median TDLU span and acini counts/TDLU. RESULTS: All TDLU measures started declining in the third age decade (all measures, two-sided P trend ≤ .001); and all metrics were statistically significantly lower among postmenopausal women. Nulliparous women demonstrated lower TDLU counts compared with uniparous women (among premenopausal women, RR = 0.79, 95% CI = 0.73 to 0.85; among postmenopausal, RR = 0.67, 95% CI = 0.56 to 0.79); however, rates of age-related TDLU decline were faster among parous women. Other factors were related to specific measures of TDLU involution. CONCLUSION: Morphometric analysis of TDLU involution warrants further evaluation to understand the pathogenesis of breast cancer and assessing its role as a progression marker for women with benign biopsies or as an intermediate endpoint in prevention studies.