Invasive Ductal Carcinoma of the Breast in a Transgender Man: A Case Report.

There is limited literature about breast cancer in the transgender population. Very little is known about how gender-affirming hormone therapy affects their breast cancer risk. On the other end, for those diagnosed with breast cancer, there are no clinical guidelines to manage their breast cancer, specifically, how to manage their gender-affirming hormone therapy during breast cancer treatment. Here, we report a 52-year-old transman diagnosed with a grade 2 invasive ductal carcinoma (ER+/PR+/HER2-), and ductal carcinoma in situ (DCIS) of intermediate grade. We discussed his risk factors as well as treatment options.

Evaluating Axillary Lymph Node Yield After Neoadjuvant Chemotherapy.

INTRODUCTION: The benefits that neoadjuvant chemotherapy (NAC) provides in treating patients with breast cancer are well known. However, its effects on axillary lymph nodes and lymph node yield (LNY) following axillary lymph node dissection (ALND) remain unclear. Given the importance of LNY for accurate axillary staging in patients with breast cancer, we retrospectively reviewed a large national cancer database to determine if NAC has an effect on LNY following axillary surgery. METHODS: A retrospective review of the National Cancer Database was performed. Patients diagnosed from 2010 to 2015 with T0-T4, clinical N0-3, and M0 breast cancer who underwent ALND were included. Patients were categorized by NAC and primary surgery (PS). A descriptive analysis of patient and tumor characteristics, as well as extrinsic factors, was performed. A univariate analysis using Student's t-test was performed to evaluate LNY between the two groups. RESULTS: A total of 118,108 patients were included in our study. We found that 29,066 (24.6%) patients underwent NAC, and 89,042 (75.4%) had surgery as initial treatment (PS group). The median LNY by ALND in the NAC group was 11 (Q1, Q3: 6, 16). The median LNY in the PS group was 11 (Q1, Q3: 6, 17), p < 0.001. CONCLUSION: Despite differences in patient characteristics and external factors, we found no difference in LNY following ALND between patients who underwent NAC and those who had initial surgery. Efforts should be made to achieve equivalent LNY whether or not patients receive NAC.

Mindfulness Training for Children with ADHD and Their Parents: A Randomized Control Trial.

OBJECTIVE: The aim of this randomized control trial is to analyze the efficacy of a Mindfulness-based program (MYmind) in improving ADHD symptoms, associated problems, executive functions, and family functioning. METHOD: The sample was composed of 30 children (9-14 years old) with an ADHD diagnosis and their parents. Participants were randomized into two groups, the MYmind group (n = 15) and a wait-list group (n = 15). Participants were assessed in three time periods: pre-, post-intervention, and at 6-month follow-up. RESULTS: After the program, parents reported a decrease in parenting stress and improvements in parenting styles. Six months after the intervention, parents reported significant improvements in children's inattention symptoms, executive functions, learning problems, aggression, and peer relations. Overreactivity was the only variable that showed a decrease in both the post-test and follow-up periods. CONCLUSION: These results suggest that the MYmind program is a promising treatment for children with ADHD and their parents.

Malpractice Cases in Breast Surgery: An Assessment of Litigation Involving Surgeons.

INTRODUCTION: Improving patient safety and quality are priorities in health care. The study of malpractice cases provides an opportunity to identify areas for quality improvement. While the issues surrounding malpractice cases in breast cancer are often multifactorial, there are few studies providing insight into malpractice cases specifically related to common breast cancer surgical procedures. We sought to characterize the factors in liability cases involving breast cancer surgery. METHODS: Closed cases from 2008 to 2019 involving a breast cancer diagnosis, a primary responsible service of general surgery, surgical oncology, or plastic surgery, and a breast cancer procedure were reviewed using data from the Controlled Risk Insurance Company (CRICO) Strategies Comparative Benchmarking System database, a national repository of professional liability data. RESULTS: A total of 174 malpractice cases were reviewed, of which 41 cases were closed with payment. Plastic surgeons were most commonly named (64%, 111/174), followed by general surgeons (30%, 53/174), and surgical oncologists (6%, 10/174). The most common allegation was error in surgical treatment (87%, 152/174), and infection, cosmetic injury, emotional trauma, foreign body, and nosocomial infections represented the top five injury descriptions. On average, indemnity payments were larger for high clinical severity cases. Technical skills, followed by clinical judgment, were the most commonly named contributing factors. The average payment per case was $130,422. CONCLUSION: Malpractice cases predominantly involve technical complications related to plastic surgery procedures. Better understanding of the malpractice environment involving surgical procedures performed for breast cancer may provide practical insight to guide initiatives aimed at improving patient outcomes.

Evaluation of online Spanish and English health materials for preventive mastectomy. are we providing adequate information?

PURPOSE: Breast cancer remains the leading cause of cancer-related death in US Hispanic women. When present, lower health literacy levels potentially within this patient population require tailored materials to address health disparities. We aim to evaluate and compare Spanish and English online health care informative resources on preventive mastectomy. METHODS: A Google web search using "preventive mastectomy" and "mastectomía preventiva" was conducted. The first ten institutional/organizational websites in each language were selected. Assessment of mean reading grade level, cultural sensitivity, understandability, and actionability was carried out utilizing validated tools. RESULTS: The mean reading grade level for English materials was 14.69 compared with 11.3 for Spanish, both exceeding the recommended grade level established by the AMA and NIH. The mean cultural sensitivity score for English information was 2.20 compared with 1.88 for Spanish information, both below the acceptability benchmark of 2.5. English webpages scored 65% and 35% for understandability and actionability, respectively, while Spanish webpages scored 47% and 18%. CONCLUSIONS: Online English and Spanish preventive mastectomy materials were written at an elevated reading level and lacked cultural sensitivity. Spanish language information demonstrated inferior understandability, actionability, and cultural sensitivity. Addressing these issues provides an opportunity to help resolve health literature disparities regarding preventive mastectomy for US Hispanic women.

The Role of Oncotype DX® Recurrence Score in Predicting Axillary Response After Neoadjuvant Chemotherapy in Breast Cancer.

INTRODUCTION: Oncotype DX® recurrence score (RS) is well-recognized for guiding decision making in adjuvant chemotherapy; however, the predictive capability of this genomic assay in determining axillary response to neoadjuvant chemotherapy (NCT) has not been established. METHODS: Using the National Cancer Data Base (NCDB), we identified patients diagnosed with T1-T2, clinically N1/N2, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER +/HER2 -) invasive ductal carcinoma of the breast between 2010 and 2015. Patients with an Oncotype DX® RS who received NCT were included. RS was defined as low (< 18), intermediate (18-30), or high (> 30). Unadjusted and adjusted analyses were performed to determine the association between axillary pathologic complete response (pCR) and RS. RESULTS: This study included a total of 158 women. RS was low in 56 (35.4%) patients, intermediate in 62 (39.2%) patients, and high in 40 (25.3%) patients. The majority of patients presented with clinical N1 disease (89.2%). Axillary pCR was achieved in 23 (14.6%) patients. When stratifying patients with axillary pCR by RS, 11 (47.8%) patients had a high RS, 6 (26.1%) patients had an intermediate RS, and 6 (26.1%) patients had a low RS. Comparing cohorts by RS, 27.5% of patients with high RS tumors had an axillary pCR, compared with only 9.7% in the intermediate RS group, and 10.7% in the low RS group (p = 0.0268). CONCLUSION: Our findings demonstrate that Oncotype DX® RS is an independent predictor of axillary pCR in patients with ER +/HER2 - breast cancers receiving NCT. A greater proportion of patients with a high RS achieved axillary pCR. These results support Oncotype DX® as a tool to improve clinical decision making in axillary management.

Impact of geographic distribution of accredited breast centers.

The National Accreditation Program for Breast Centers (NAPBCs) is dedicated to improving the quality of care in patients with breast disease. Geographic distribution of health care resources is an important measure of quality, yet little is known regarding breast center allocation patterns concerning population demand and impact on health outcomes. The purpose of this study was to analyze the distribution of NAPBC programs in the United States (USA) and evaluate the impact on breast cancer survival. Using the Centers for Disease Control and Prevention 2014 data base, we identified the incidence and mortality rates for breast cancer by state. We also determined the concentration of NAPBC programs in each state (ie, the number of centers per 1000 cases of breast cancer). Data were analyzed using Spearman's (nonparametric) rank correlation coefficients. Five hundred and seventy NAPBC programs were identified. Across the United States, there was a mean of 2.8 programs/1000 breast cancer diagnoses. A positive correlation (r = .45) between breast cancer incidence and the number of programs was identified (P = .0009). There was no statistically significant correlation between mortality and NAPBC program concentration (r = -0.20, P = .16). NAPBC-accredited program distribution within the United States correlates with breast cancer incidence per state. However, the number of NAPBC programs per state did not alter overall mortality rates. Added measures beyond survival, as well as further insight into referral patterns to NAPBC programs, may be required to demonstrate the value and impact of NAPBC accreditation.

The Tyrer-Cuzick Model Inaccurately Predicts Invasive Breast Cancer Risk in Women With LCIS.

BACKGROUND: The Tyrer-Cuzick model has been shown to overestimate risk in women with atypical hyperplasia, although its accuracy among women with lobular carcinoma in situ (LCIS) is unknown. We evaluated the accuracy of the Tyrer-Cuzick model for predicting invasive breast cancer (IBC) development among women with LCIS. METHODS: Women with LCIS participating in surveillance from 1987 to 2017 were identified from a prospectively maintained database. Tyrer-Cuzick score (version 7) was calculated near the time of LCIS diagnosis. Patients with prior or concurrent breast cancer, a BRCA mutation, receiving chemoprevention, or with pleomorphic LCIS were excluded. Invasive cancer-free probability was estimated using the Kaplan-Meier method. RESULTS: A total of 1192 women with a median follow-up of 6 years (interquartile range [IQR] 2.5-9.9) were included. Median age at LCIS diagnosis was 49 years (IQR 45-55), 88% were white; 37% were postmenopausal, 28% had ≥ 1 first-degree family member with breast cancer, and 13% had ≥ 2 second-degree family members with breast cancer. In total, 128 patients developed an IBC; median age at diagnosis was 54 years (IQR 49-61). Five- and 10-year cumulative incidences of invasive cancer were 8% (95% confidence interval [CI] 6-9%) and 14% (95% CI 12-17%), respectively. The median Tyrer-Cuzick 10-year risk score was 20.1 (IQR 17.4-24.3). Discrimination measured by the C-index was 0.493, confirming that the Tyrer-Cuzick model is not well calibrated in this patient population. CONCLUSIONS: The Tyrer-Cuzick model is not accurate and may overpredict IBC risk for women with LCIS, and therefore should not be used for breast cancer risk assessment in this high-risk population.

Bilateral mastectomy operations and the role for the cosurgeon technique: A Nationwide analysis of surgical practice patterns.

Traditionally, bilateral mastectomy (BM) operations are performed by a single surgeon but a two-attending co-surgeon technique (CST) has been described. A questionnaire was sent to members of the American Society of Breast Surgeons to assess national BM practices and analyze utilization and perceived benefits of the CST. Among surgeons responding, most continue to use the single-surgeon approach for BMs; however, 14.1% utilize the CST and up to 31% are interested in future CST use. Time savings, mentorship, cost savings, and opportunity to learn new techniques were identified as perceived CST advantages.

Increase in Utilization of Nipple-Sparing Mastectomy for Breast Cancer: Indications, Complications, and Oncologic Outcomes.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly performed for invasive breast cancer. Growing evidence supporting the oncologic safety of NSM has led to its widespread use and broadened indications. In this study, we examine the indications, complications, and long-term outcomes of therapeutic NSM. METHODS: From 2003 to 2016, women undergoing NSM for invasive cancer or ductal carcinoma in situ (DCIS) were identified from a prospectively maintained database. Patient and disease characteristics were compared by procedure year, while complications were compared by procedure year using generalized mixed-effects models accounting for a random surgeon effect. Overall survival and time to recurrence were examined. RESULTS: Of the 467 therapeutic NSMs, 337 (72%) were invasive cancer, 126 (27%) were DCIS, and 4 (1%) were phyllodes tumors. Median age was 45 years (range 24-75) and median follow-up among survivors was 39.4 months. Three hundred and fifty-seven (76.4%) cases were performed in 2011 or after. When comparing NSMs performed before and after 2011, there was a significant increase in NSMs performed for invasive tumors (58% vs. 77%; p < 0.001). There was no difference in family history, genetic mutations, smoking status, neoadjuvant chemotherapy, prior radiation, nodal involvement, or tumor subtype. Twenty-one (4.5%) nipple excisions were performed, of which 14 were performed for cancer at the nipple margin. Forty-four breasts (9.4%) had complications that required re-operation. Fifteen patients had locoregional recurrence or distant metastasis. CONCLUSIONS: NSM use for invasive carcinoma has doubled at our institution since 2011, while postoperative complications and recurrence rates remain low. Our experience supports the selective use of NSM in the malignant setting with careful patient selection.

Surgeon Variability and Factors Predicting for Reoperation Following Breast-Conserving Surgery.

BACKGROUND: Reoperation after breast-conserving surgery (BCS) is common and has been partially associated with the lack of consensus on margin definition. We sought to investigate factors associated with reoperations and variation in reoperation rates across breast surgeons at our cancer center. METHODS: Retrospective analyses of patients with clinical stage I-II breast cancer who underwent BCS between January and December 2014 were conducted prior to the recommendation of 'no ink on tumor' margin. Patient demographics and tumor and surgical data were extracted from medical records. A multivariate regression model was used to identify factors associated with reoperation. RESULTS: Overall, 490 patients with stage I (n  = 408) and stage II (n  = 89) breast cancer underwent BCS; seven patients had bilateral breast cancer and underwent bilateral BCS procedures. Median invasive tumor size was 1.1 cm, reoperation rate was 22.9% (n  = 114) and varied among surgeons (range 15-40%), and, in 100 (88%) patients, the second procedure was re-excision, followed by unilateral mastectomy (n  = 7, 6%) and bilateral mastectomy (n  = 7, 6%). Intraoperative margin techniques (global cavity or targeted shaves) were utilized in 50.1% of cases, while no specific margin technique was utilized in 49.9% of cases. Median total specimen size was 65.8 cm3 (range 24.5-156.0). In the adjusted model, patients with multifocal disease were more likely to undergo reoperation [odds ratio (OR) 5.78, 95% confidence interval (CI) 2.17-15.42]. In addition, two surgeons were found to have significantly higher reoperation rates (OR 6.41, 95% CI 1.94-21.22; OR 3.41, 95% CI 1.07-10.85). CONCLUSIONS: Examination of BCS demonstrated variability in reoperation rates and margin practices among our breast surgeons. Future trials should look at surgeon-specific factors that may predict for reoperations.

Management of the Axilla in Early Breast Cancer.

Management of the axilla in early breast cancer patients has significantly evolved in the last several decades. With the arrival of the sentinel lymph node biopsy, surgical practice for axillary staging in patients with early breast cancer has become gradually less invasive and formal axillary lymph node dissection has been confined to selected patients. Over the last two decades, evidence from randomized clinical trials have allowed for the de-escalation of axillary surgery in the management of early stage breast cancer. Advances in the staging and treatment of the axilla constitute a key component in determining initial surgical planning and therapeutic strategies in the treatment of early breast cancer. This chapter provides an updated review on the history, evolution, and current practices for axillary management in patients with early breast cancer, with particular attention to the surgical recommendations and controversial scenarios of the evolving management of the axilla.

High-Grade Glioma is not a Feature of Neurofibromatosis Type 2 in the Unirradiated Patient.

BACKGROUND: The Manchester criteria for neurofibromatosis type 2 (NF2) include a range of tumors, and gliomas were incorporated in the original description. The gliomas are now widely accepted to be predominantly spinal cord ependymomas. OBJECTIVE: To determine whether these gliomas include any cases of malignant glioma (WHO grade III and IV) through a database review. METHODS: The prospective database consists of 1253 patients with NF2. 1009 are known to be alive at last follow-up. RESULTS: There was a single case of glioblastoma multiforme (GBM; World Health Organization grade IV) in the series and no WHO grade III gliomas. The GBM was in a patient who had previously undergone stereotactic radiosurgery for a vestibular schwannoma. CONCLUSION: High-grade gliomas are not a feature of NF2 in the unirradiated patient and should be excluded from the diagnostic criteria.

Knockdown of PTRF ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells.

Healthy expansion of human adipose tissue requires mesenchymal stem cells (hMSC) able to proliferate and differentiate into mature adipocytes. Hence, characterization of those factors that coordinate hMSC-to-adipocyte transition is of paramount importance to modulate the adipose tissue expansion. It has been previously reported that the adipogenic program of hMSC can be disrupted by upregulating caveolar proteins, and polymerase I and transcript release factor (PTRF) is an integral component of caveolae, highly expressed in adipose tissue. Here, we hypothesized that the role of PTRF in adipocyte functionality might stem from an effect on hMSC. To test this hypothesis, we isolated hMSC from the subcutaneous fat depot. We found an upregulated expression of the PTRF associated with decreased adipogenic potential of hMSC, likely due to the existence of senescent adipocyte precursors. Employing short hairpin RNA-based constructs to stably reduce PTRF, we were able to restore insulin sensitivity and reduced basal lipolysis and leptin levels in human adipocytes with high levels of PTRF. Additionally, we pinpointed the detrimental effect caused by PTRF on the adipose tissue to the existence of senescent adipocyte precursors unable to proliferate and differentiate into adipocytes. This study provides evidence that impaired adipocyte functionality can be corrected, at least partially, by PTRF downregulation and warrants further in vivo research in patients with dysfunctional adipose tissue to prevent metabolic complications.

Compliance with cochlear implantation in children subsequently diagnosed with autism spectrum disorder.

OBJECTIVE: To assess the compliance with cochlear implantation (CI) in children subsequently diagnosed with autism spectrum disorder (ASD). METHODS: This was a retrospective case review and survey performed at a tertiary referral centre. Children meeting the criteria for CI who were implanted between 1989 and 2015 and who subsequently received a diagnosis of ASD were included. The primary outcome measure was to assess compliance with CI in children subsequently diagnosed with ASD. Secondary outcome measures included assessment of pre-CI risk factors that may have identified children at higher risk of a subsequent diagnosis of ASD, as well as the benefit obtained by these children following CI. RESULTS: 1050 children were implanted between 1989 and 2015. Of these, 22 children were diagnosed with ASD after receiving their CI. The average age at implantation was 2.6 years (median 3, range 1-8 years). The average age for diagnosis of ASD was 5 years, approximately 2 years (median 22 months, range 2-85 months) following CI. Of these, 16/22 (712.7%) regularly use their CI. 6/22 (27.2%) children became non-users of their implant. Some degree of verbal communication was used by 13/22 (59%) of our studied group. CONCLUSION: There is a range of level of disabilities in ASD, with some relatively minor social communication difficulties through to severe language, cognitive, and behavioural difficulties. Compliance with CI is variable and appears to correlate with the severity of the ASD. Preoperative counselling should include information about the possible impact of later diagnosed disabilities such as ASD on performance.

The FAT expandability (FATe) Project: Biomarkers to determine the limit of expansion and the complications of obesity.

BACKGROUND: Obesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells. METHODS/DESIGN: FATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers' predictive performance. DISCUSSION: The work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies.

Young women with breast cancer in the United States and South Korea: comparison of demographics, pathology and management.

BACKGROUND: Breast cancer diagnosed in young women may be more aggressive, with higher rates of local and distant recurrence compared to the disease in older women. Epidemiologic evidence suggests that Korean women have a lower incidence of breast cancer than women in the United States, but that they present at a younger age than their American counterparts. We sought to compare risk factors and management of young women with breast cancer in Boston, Massachusetts (US) with those in Seoul, South Korea (KR). MATERIALS AND METHODS: A retrospective review was performed of consecutive patients less than 35 years old with a diagnosis of breast cancer at academic cancer centers in the US and KR from 2000-2005. Patient data were obtained by chart review. Demographic, tumor and treatment characteristics were compared utilizing Pearson's chi- square or Wilcoxon rank-sum tests where appropriate. All differences were assessed as significant at the 0.05 level. RESULTS: 205 patients from the US and 309 from KR were analyzed. Patients in US were more likely to have hormone receptor positive breast cancer, while patients in KR had a higher rate of triple negative lesions. Patients in US had a higher mean body mass index and more often reported use of birth control pills, while those in the KR were less likely to have a sentinel node procedure performed or to receive post mastectomy radiation. CONCLUSIONS: Patients under 35 diagnosed with breast cancer in the US and KR differ with respect to demographics, tumor characteristics and management. Although rates of breast conservation and mastectomy were similar, US patients were more likely to receive post mastectomy radiation. The lower use of sentinel node biopsy is explained by the later adoption of the technique in KR. Further evaluation is necessary to evaluate recurrence rates and survival in the setting of differing disease subtypes in these patients.