De-escalating indications for excision when breast core needle biopsy returns fibroepithelial lesion-not further characterized.

PURPOSE: Surgical excision is often performed to exclude phyllodes tumor (PT) when Core Needle Biopsy (CNB) of the breast returns fibroepithelial lesion-not further characterized (FEL-NFC). If imaging or CNB pathology features can be identified that predict a very low probability of borderline/malignant PT, thousands of women could be spared the expense and morbidity of surgical excisions. METHODS: This retrospective cohort study includes 180 FEL-NFC from 164 patients who underwent surgical excisional biopsy. RESULTS: The upgrade rate from FEL-NFC to benign PT was 15%, and to borderline/malignant PT 7%. Imaging features predicting upgrade to borderline/malignant PT included greater size (p = 0.0002) and heterogeneous echo pattern on sonography (p = 0.117). Histologic features of CNB predicting upgrade to borderline/malignant PT included "pathologist favors PT" (p = 0.012), mitoses (p = 0.014), stromal overgrowth (p = 0.006), increased cellularity (p = 0.0001) and leaf-like architecture (p = 0.077). A three-component score including size > 4.5 cm (Size), heterogeneous echo pattern on sonography (Heterogeneity), and stromal overgrowth on CNB (Overgrowth) maximized the product of sensitivity x specificity for the prediction of borderline/malignant PT. When the SHO score was 0 (72% of FEL-NFC) the probability of borderline/malignant PT on excision was only 1%. CONCLUSION: The combination of size ≤ 4.5 cm, homogeneous echo pattern, and absence of stromal overgrowth is highly predictive of a benign excision potentially sparing most patients diagnosed with FEL-NFC the expense and morbidity of a surgical excision.

Impact of axillary surgery on outcome of clinically node positive breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: Axillary Lymph Node Dissection (ALND) is recommended for breast cancer patients who present with clinically node positive disease (cN1) especially if they have residual nodal disease (ypN+) following neoadjuvant therapy (NAT). It is unknown whether axillary dissection improves outcome for these patients. METHODS: A prospectively maintained database was used to identify all patients who were diagnosed with cTis-T4N1M0 breast cancer treated with NAT. RESULTS: In our study, of 292 cN1 breast cancer patients who received NAT, we compared ALND with targeted axillary surgery (TAS) in ypN+ patients. ALND was performed in 75% of the ypN+ subgroup, while 25% underwent TAS. Axillary recurrence occurred in four ALND patients, but no recurrence was observed in the TAS group (p = 0.21). Five-year axillary recurrence-free survival was 100% for TAS and 90% for ALND (p = 0.21). Overall survival at five years was 97% for TAS and 85% for ALND (p = 0.39). Disease-free survival rates at five years were 51% for TAS and 61% for ALND (p = 0.9). Clinicopathological variables were similar between the groups, although some differences were noted. ALND patients had smaller clinical tumor size, larger pathological tumor size, more lymph nodes retrieved, larger tumor deposits, higher rates of extranodal extension, and greater prevalence of macrometastatic nodal disease. Tumor subtype and size of lymph node tumor deposit independently predicted survival. CONCLUSION: Axillary recurrence is infrequent in cN1 patients treated with NAT. Our study found that ALND did not reduce the occurrence of axillary recurrence or enhance overall survival. It is currently uncertain which patients benefit from axillary dissection.

Racial-ethnic variations in phyllodes tumors among a multicenter United States cohort.

BACKGROUND AND OBJECTIVES: Previous studies have identified racial-ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial-ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT. METHODS: We performed an 11-institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence-free survival according to race-ethnicity. RESULTS: Women of non-White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non-Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence-free survival in our cohort. CONCLUSIONS: Differences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race-ethnicity. These conclusions are supported by our finding that there were no differences in recurrence-free survival.

"Cancer's a demon": a qualitative study of fear and multilevel factors contributing to cancer treatment delays.

PURPOSE: Delays initiating cancer therapy are increasingly common, impact outcomes, and have implications for health equity. However, it remains unclear (1) whether patients' beliefs regarding acceptable diagnostic to treatment intervals align with current guidelines, and (2) to what degree psychological factors contribute to longer intervals. We conducted a qualitative study with patients and cancer care team members ("providers"). METHODS: We interviewed patients with several common solid tumors as well as providers. Interviews were analyzed using an interpretive approach, guided by modified grounded theory. RESULTS: Twenty-two patients and 12 providers participated. Half of patients had breast cancer; 27% waited >60 days between diagnosis and treatment. Several themes emerged. (1) Patients felt treatment should begin immediately following diagnosis, while providers' opinion on the goal timeframe to start treatment varied. (2) Patients experienced psychological distress while waiting for treatment. (3) Participants identified logistical, social, and psychological sources of delay. Fear related to multiple aspects of cancer care was common. Emotion-driven barriers could manifest as not taking steps to move ahead, or as actions that delayed care. (4) Besides addressing logistical challenges, patients believed that education and anticipatory guidance, from their care team and from peers, may help overcome psychological barriers to treatment and facilitate the start of therapy. CONCLUSIONS: Patients feel an urgency to start cancer therapy, desiring time frames shorter than those included in guidelines. Psychological distress is frequently both a contributor to, and a consequence of, treatment delays. Addressing multilevel barriers, including psychological ones, may facilitate timely treatment and reduce distress.

Improved false-negative rates using a novel patient selection flowchart in initially biopsy-proven node-positive breast cancer undergoing blue-dye alone guided sentinel lymph node biopsy after neoadjuvant chemotherapy.

PURPOSE: Current trials support the application of sentinel lymph node biopsy (SLNB) in node-positive breast cancer treated with neoadjuvant chemotherapy (NAC) with a lower false-negative rate (FNR) if dual-tracer (radioisotope and blue-dye) is used. However, radioisotopes are not available in many areas of the world. In this study, we evaluated the feasibility and accuracy of SLNB mapped with methylene-blue-dye alone. METHODS: This study enrolled 132 patients with biopsy-proven node-positive breast cancer with a clip placed in the positive node who then received NAC. After chemotherapy and before operation, all patients underwent axillary ultrasound (AUS) assessment and were classified as either negative (AUS-) or positive (AUS +) according to the axillary status. All patients underwent both SLNB and axillary lymph node dissection (ALND). SLNB was mapped with methylene-blue-dye alone. FNRs were evaluated on factors potentially affecting false-negative SLN finding. RESULTS: Using methylene-blue-dye alone, the FNR of SLNB was 9.9%. Post-NAC AUS assessment (p = 0.009) and the number of SLNs retrieved (p = 0.029) showed association with FNRs in multivariate analysis. In AUS- group, FNR was as low as 2.5%. In AUS + group, retrieving ≥ 4 SLNs including the clipped node improved FNR from 17.1% to 4.8%. A flowchart was designed with the combination of post-NAC AUS assessment, retrieved SLN number, and the retrieved of clipped node further improve overall FNR to 3.3%. CONCLUSION: In biopsy-proven node-positive breast cancer treated with NAC, using a flowchart to optimize patient selection reduces the FNR of single-tracer (methylene-blue-dye) guided SLNB.

Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results From a Large Multicenter Trial.

OBJECTIVE: To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging. BACKGROUND: It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low. METHODS: Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial. Excised SNs were histopathologically assessed and considered positive if any melanoma was seen. RESULTS: SNs were identified and removed from 2859 patients who had preoperative US evaluation. Among those patients, 548 had SN metastases. US was positive (abnormal) in 87 patients (3.0%). Among SN-positive patients, 39 (7.1%) had an abnormal US. When analyzed by lymph node basin, 3302 basins were evaluated, and 38 were true positive (1.2%). By basin, the sensitivity of US was 6.6% (95% confidence interval: 4.6-8.7) and the specificity 98.0% (95% CI: 97.5-98.5). Median cross-sectional area of all SN metastases was 0.13 mm2; in US true-positive nodes, it was 6.8 mm2. US sensitivity increased with increasing Breslow thickness of the primary melanoma (0% for ≤1 mm thickness, 11.9% for >4 mm thickness). US sensitivity was not significantly greater with higher trial center volume or with pre-US lymphoscintigraphy. CONCLUSION: In the MSLT-II screening phase population, SN tumor volume was usually too small to be reliably detected by US. For accurate nodal staging to guide the management of melanoma patients, US is not an effective substitute for SN biopsy.

Underutilization of Needle Biopsy Before Breast Surgery: A Measure of Low-Value Care.

BACKGROUND: Breast core needle biopsy (CNB) can obviate the need for breast surgery in patients with an unknown breast lesion; however, variation in compliance with this guideline may represent a disparity in health care and a surrogate measure of unnecessary surgery. We evaluated variation in breast CNB rates prior to initial breast cancer surgery. METHODS: We performed a retrospective analysis using Medicare claims from 2015 to 2017 to evaluate the proportion of patients who received a CNB within 6 months prior to initial breast cancer surgery. Outlier practice pattern was defined as a preoperative CNB rate ≤ 70%. Logistic regression was used to evaluate surgeon characteristics associated with outlier practice pattern. RESULTS: We identified 108,935 female patients who underwent initial breast cancer surgery performed by 3229 surgeons from July 2015 to June 2017. The mean CNB rate was 86.7%. A total of 7.7% of surgeons had a CNB performed prior to initial breast surgery ≤ 70% of the time, and 2.0% had a CNB performed ≤ 50% of the time. Outlier breast surgeons were associated with practicing in a micropolitan area (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.29-2.73), in the South (OR 1.84, 95% CI 1.20-2.84) or West region (OR 1.78, 95% CI 1.11-2.86), > 20 years in practice (OR 1.52, 95% CI 1.09-2.11), and low breast cancer surgery volume (< 30 cases in the study period; OR 4.03, 95% CI 2.75-5.90). CONCLUSIONS: Marked variation exists in whether a breast core biopsy is performed prior to initial breast surgery, which may represent unnecessary surgery on individual patients. Providing surgeon-specific feedback on guideline compliance may reduce unwarranted variation.

The Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In Situ in Patients with Intraductal Papilloma without Atypia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 034).

BACKGROUND: Available retrospective data suggest the upgrade rate for intraductal papilloma (IP) without atypia on core biopsy (CB) ranges from 0 to 12%, leading to variation in recommendations. We conducted a prospective multi-institutional trial (TBCRC 034) to determine the upgrade rate to invasive cancer (IC) or ductal carcinoma in situ (DCIS) at excision for asymptomatic IP without atypia on CB. METHODS: Prospectively identified patients with a CB diagnosis of IP who had consented to excision were included. Discordant cases, including BI-RADS > 4, and those with additional lesions requiring excision were excluded. The primary endpoint was upgrade to IC or DCIS by local pathology review with a predefined rule that an upgrade rate of ≤ 3% would not warrant routine excision. Sample size and confidence intervals were based on exact binomial calculations. Secondary endpoints included diagnostic concordance for IP between local and central pathology review and upgrade rates by central pathology review. RESULTS: The trial included116 patients (median age 56 years, range 24-82) and the most common imaging abnormality was a mass (n = 91, 78%). Per local review, 2 (1.7%) cases were upgraded to DCIS. In both of these cases central pathology review did not confirm DCIS on excision. Additionally, central pathology review confirmed IP without atypia in core biopsies of 85/116 cases (73%), and both locally upgraded cases were among them. CONCLUSION: In this prospective study of 116 IPs without atypia on CB, the upgrade rate was 1.7% by local review, suggesting that routine excision is not indicated for IP without atypia on CB with concordant imaging findings.

Limited Reporting of Histopathologic Details in a Multi-Institutional Academic Cohort of Phyllodes Tumors: Time for Standardization.

BACKGROUND: Phyllodes tumors are rare fibroepithelial neoplasms that are classified by tiered histopathologic features. While there are protocols for the reporting of cancer specimens, no standardized reporting protocol exists for phyllodes. METHODS: We performed an 11-institution contemporary review of phyllodes tumors. Granular histopathologic details were recorded, including the features specifically considered for phyllodes grade classification. RESULTS: Of 550 patients, median tumor size was 3.0 cm, 68.9% (n = 379) of tumors were benign, 19.6% (n = 108) were borderline, and 10.5% (n = 58) were malignant. All cases reported the final tumor size and grade classification. Complete pathologic reporting of all histopathologic features was present in 15.3% (n = 84) of cases, while an additional 35.6% (n = 196) were missing only one or two features in the report. Individual details regarding the degree of stromal cellularity was not reported in 53.5% (n = 294) of cases, degree of stromal atypia in 58.0% (n = 319) of cases, presence of stromal overgrowth in 56.2% (n = 309) of cases, stromal cell mitoses in 37.5% (n = 206) of cases, and tumor border in 54.2% (n = 298) of cases. The final margin status (negative vs. positive) was omitted in only 0.9% of cases, and the final negative margin width was specifically reported in 73.8% of cases. Reporting of details was similar across all sites. CONCLUSION: In this academic cohort of phyllodes tumors, one or more histopathologic features were frequently omitted from the pathology report. While all features were considered by the pathologist for grading, this limited reporting reflects a lack of reporting consensus. We recommend that standardized reporting in the form of a synoptic-style cancer protocol be implemented for phyllodes tumors, similar to other rare tumors.

Pharmacists' experiences with the Bloom Program application process.

BACKGROUND: The Bloom Program, which began as a demonstration project, is an ongoing community pharmacy-based mental illness and addictions program funded by the government of Nova Scotia. To be eligible to offer the Bloom Program, interested pharmacists were required to complete a 9-part application on behalf of their pharmacies. A process evaluation was conducted to inform future program implementation changes of program components, including the application process. METHODS: Qualitative interviews from 24 pharmacists were inductively analyzed to determine the challenges and opportunities in the program's application process. RESULTS: Key and impactful components of the application process included training, providing a mental health and addictions resource centre within the pharmacy and completing outreach activities with local mental health and addictions services and support organizations. The training content and format for the program was highly valued. Community outreach to local mental health and addictions resources, and other health care resources in the community, was particularly valuable in supporting patient navigation of the health care system and extending the pharmacists' networks. Components of the application process were challenging for many pharmacists but were beneficial personally and professionally. Dedicated resources (e.g., time and staffing) are required for the efficient completion of the application process. CONCLUSION: Pharmacists viewed the Bloom Program application process as intensive yet necessary and relevant for preparing to deliver the Program. The demonstration project process evaluation was essential for elucidating the strengths of the application process and, importantly, identifying areas for improvement. Can Pharm J (Ott) 2021;154:xx-xx.

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS: Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS: Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).

Effect of delays in initiation of adjuvant endocrine therapy on survival among women with breast cancer.

PURPOSE: Delays in initiating adjuvant endocrine therapy (AET) are a cause for concern among women with breast cancer and clinicians, but the impact of delayed AET on overall survival (OS) is unclear. This study seeks to describe the relationship between delayed AET and OS. METHODS: Retrospective cohort study of women with stage II and III hormone receptor positive, human epidermal receptor 2 negative, invasive breast cancer, identified from the National Cancer Database. The primary exposure delayed AET, was defined as initiation of AET more than 12 months after breast cancer diagnosis. Using logistic regression, we examined predictors of delayed AET. The survival analysis with Cox proportional hazards regression adjusted for patient, tumor, and treatment characteristics. RESULTS: Among the 391,594 included women, 12,162 (3.1%) had delayed AET. Predictors of delayed AET included Black race (adjusted odds ratio [aOR] = 1.61, 95% confidence interval [CI] 1.52-1.70) or Hispanic ethnicity (aOR = 1.25, 95% CI 1.16-1.35) vs white race, Medicare (aOR = 1.13, 95% CI 1.06-1.20) or Medicaid (aOR = 1.41, 95% CI 1.32-1.50) versus private insurance, and cancer stage III (aOR = 1.24, 95% CI 1.19-1.30) vs stage II. With median follow-up of 67.4 months, 67,335 (17.2%) patients died. Delayed AET had no statistically significant effect on the hazard of death (adjusted hazards ratio = 1.01; 95% CI 0.96-1.06) compared to initiation within 12 months of diagnosis. CONCLUSION: This study suggests that there may be no adverse impact on survival if initiation of AET occurs 12 to 24 months after initial diagnosis compared to within 12 months of diagnosis as currently recommended.

Male breast cancer: a closer look at patient and tumor characteristics and factors that affect survival using the National Cancer Database.

OBJECTIVE: To comprehensively describe the tumor and clinical characteristics of breast cancer in a cohort of male patients and to assess the factors that affect survival. BACKGROUND: Much of the standard care of male breast cancer is based on the diagnosis and treatment strategies of female breast cancer. However, important clinical differences between the two have been elucidated, which suggests the need for unique attention to male breast cancer. METHODS: We evaluated the records of male patients who were diagnosed with breast cancer between 2004 and 2015 using the National Cancer Database (NCDB). Data obtained were demographic characteristics, clinical and tumor data, type of therapy, as well as survival data. We used descriptive statistics to characterize our study population. We then performed a survival and Cox proportional hazards analysis. RESULTS: We identified 16,498 patients (median age: 63 years). Several treatment modalities were used, of which surgery was the most common (14,882 [90.4%]). The total follow-up time was 13 years (156 months). Five-year survival was 77.7% (95% CI 76.9-78.4) and 10-year survival was 60.7%. In a Cox proportional hazards model, mastectomy was associated with the greatest survival (hazard ratio [HR] 0.49; p < 0.001). CONCLUSION: We report what is to our knowledge the largest national population-based cohort of male breast cancer patients. Importantly, our data suggests that similar to female patients, several treatment modalities are significantly associated with improved survival in male patients, particularly surgery. Increasing age, black race, government insurance, more comorbidities, and higher tumor stages are associated with decreased survival.

Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing.

BACKGROUND: A paucity of data exists regarding inherited mutations associated with phyllodes tumors (PT); however, some are reported (TP53, BRCA1, and RB1). A PT diagnosis does not meet NCCN criteria for testing, including within Li-Fraumeni Syndrome (TP53). We sought to determine the prevalence of mutations associated with PT. METHODS: We performed an 11-institution review of contemporary (2007-2017) PT practice. We recorded multigenerational family history and personal history of genetic testing. We identified patients meeting NCCN criteria for genetic evaluation. Logistic regression estimated the association of select covariates with likelihood of undergoing genetic testing. RESULTS: Of 550 PT patients, 59.8% (n = 329) had a close family history of cancer, and 34.0% (n = 112) had ≥ 3 family members affected. Only 6.2% (n = 34) underwent genetic testing, 38.2% (n = 13) of whom had only BRCA1/BRCA2 tested. Of 34 patients tested, 8.8% had a deleterious mutation (1 BRCA1, 2 TP53), and 5.9% had a BRCA2 VUS. Of women who had TP53 testing (N = 21), 9.5% had a mutation. Selection for testing was not associated with age (odds ratio [OR] 1.01, p = 0.55) or PT size (p = 0.12) but was associated with grade (malignant vs. benign: OR 9.17, 95% CI 3.97-21.18) and meeting NCCN criteria (OR 3.43, 95% confidence interval 1.70-6.94). Notably, an additional 86 (15.6%) patients met NCCN criteria but had no genetic testing. CONCLUSIONS: Very few women with PT undergo germline testing; however, in those selected for testing, a deleterious mutation was identified in ~ 10%. Multigene testing of a PT cohort would present an opportunity to discover the true incidence of germline mutations in PT patients.

Racial Disparities in Response to a US Food and Drug Administration Safety Communication Regarding the Use of Power Morcellation for the Treatment of Uterine Leiomyoma.

STUDY OBJECTIVE: To investigate whether the rate of increase in the performance of abdominal myomectomy over a laparoscopic approach after the US Food and Drug Administration (FDA) safety communication regarding morcellator use for myomectomy differs among races. DESIGN: Retrospective cohort study. SETTING: The American College of Surgeons National Surgical Quality Improvement data. PATIENTS: Patients aged 18 to 55 years who underwent either laparoscopic or abdominal myomectomy, excluding malignant cases, emergency cases, operations performed by nongynecologic specialists, and cases in which myomectomy was performed during cesarean section. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The odds ratios of abdominal myomectomy over laparoscopic myomectomy before and after the release of the FDA communication were calculated in 3 race categories: white, African American, and other races. In a logistic regression analysis adjusted for possible confounders, including all races, the odds ratio of abdominal myomectomy before and after the FDA communication was 1.30 (95% confidence interval [CI], 1.20-1.41; p <.001). In a logistic regression analysis with a product term of FDA communication exposure and race as a possible effect modifier, the African American population showed a significantly greater change in the odds of abdominal myomectomy over laparoscopic myomectomy in comparison with the white population (1.22; 95% CI, 1.02-1.47; p = .03). In contrast, other races showed no significant change (.83; 95% CI, .64-1.08; p = .17). CONCLUSION: After the FDA communication, the odds ratio of abdominal myomectomy was disproportionately increased in the African American population.

Local Recurrence of Benign, Borderline, and Malignant Phyllodes Tumors of the Breast: A Systematic Review and Meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to investigate local recurrence (LR) rates among the three grades (benign, borderline, and malignant) of phyllodes tumors (PTs). The study also assessed various risk factors for LR. METHODS: Electronic articles published between 1 January 1995 and 31 May 2018, were searched and critically appraised. The authors independently reviewed the abstracts and extracted data for LR rates and LR risk factors. RESULTS: The review incorporated 54 studies with 9234 individual cases. The pooled LR rates were 8% for benign, 13% for borderline, and 18% for malignant PTs. The risk of LR was significantly increased by borderline versus benign PTs (odds ratio [OR] 2.00; 95% confidence interval [CI] 1.68-2.38) and malignant versus borderline PTs (OR 1.28; 95% CI 1.05-1.55). The significant risk factors for LR were mitoses, tumor border (infiltrating vs. pushing), stromal cellularity (moderate/severe vs. mild), stromal atypia (severe vs. mild/absent), stromal overgrowth (severe vs. mild/absent), and tumor necrosis (positive vs. negative). Age and tumor size were not associated with LR risk. The subgroup analysis showed that breast-conserving surgery versus mastectomy and positive versus negative surgical margins were significantly associated with an increased LR risk only in malignant PTs. CONCLUSIONS: The risk of LR was significantly increased from benign to borderline to malignant PTs. Mitoses, tumor border, stromal cellularity, stromal atypia, stromal overgrowth, tumor necrosis, type of surgery, and surgical margin status may be risk factors for LR. Different management strategies could be considered for different PT grades.

Challenges in Clinical Trial Implementation: Results from a Survey of the National Accreditation Program of Breast Centers (NAPBC).

BACKGROUND: Although the results of clinical trials often guide best practices, changing clinical practice based on clinical trial results can be challenging. The objective of this study was to examine provider-reported barriers to adopting best clinical practices according to clinical trial data. METHODS: A cross-sectional survey was conducted of providers from the National Accreditation Program for Breast Centers about barriers that prevent the incorporation of trial findings. Descriptive analyses and multivariable analyses were performed to determine provider characteristics that were significantly associated with reported barriers. RESULTS: Overall, 383 institutions participated (63.5% response rate), with a total of 1226 physicians responding to the survey (80% response rate). Providers identified national guidelines and meetings as the most compelling way to receive practice-changing information. They reported the following internal barriers to trial implementation: patient preference (45%), strongly held beliefs by partners/colleagues (37%), and insufficient time to discuss new practices (30%). External barriers preventing trial implementation included a lack of agreement from multidisciplinary tumor boards (32%), fear of reimbursement loss (23%), and resistance from clinical staff (20%). Reported barriers differed by provider specialty, with plastic surgeons and radiation oncologists reporting that strongly held beliefs by partners/colleagues and disagreement from multidisciplinary tumor boards were the most significant factors preventing clinical trial implementation. CONCLUSIONS: Physician beliefs and patient preferences are the most frequently reported barriers to clinical trial implementation. Tactics to better educate providers about how to explain new clinical trial data to their patients and colleagues are needed.

Transforming Global Health by Improving the Science of Scale-Up.

In its report Global Health 2035, the Commission on Investing in Health proposed that health investments can reduce mortality in nearly all low- and middle-income countries to very low levels, thereby averting 10 million deaths per year from 2035 onward. Many of these gains could be achieved through scale-up of existing technologies and health services. A key instrument to close this gap is policy and implementation research (PIR) that aims to produce generalizable evidence on what works to implement successful interventions at scale. Rigorously designed PIR promotes global learning and local accountability. Much greater national and global investments in PIR capacity will be required to enable the scaling of effective approaches and to prevent the recycling of failed ideas. Sample questions for the PIR research agenda include how to close the gap in the delivery of essential services to the poor, which population interventions for non-communicable diseases are most applicable in different contexts, and how to engage non-state actors in equitable provision of health services in the context of universal health coverage.

Parent Perceptions on Transfers to Pediatric Emergency Departments and the Role of Telemedicine.

OBJECTIVE: Real-time audiovisual consultation (telemedicine) has been proven feasible and is a promising alternative to interfacility transfer. We sought to describe caregiver perceptions of the decision to transfer his or her child to a pediatric emergency department and the potential use of telemedicine as an alternative to transfer. METHODS: Semistructured interviews of caregivers of patients transferred to a pediatric emergency department. Purposive sampling was used to recruit caregivers of patients who were transferred from varying distances and different times of the day. Interviews were conducted in person or on the phone by a trained interviewer. Interviews were recorded, transcribed, and analyzed using modified grounded theory. RESULTS: Twenty-three caregivers were interviewed. Sixteen (70%) were mothers; 57% of patients were transported from hospitals outside of the city limits. Most caregivers reported transfer for a specific resource need, such as a pediatric subspecialist. Generally, caregivers felt that the decision to transfer was made unilaterally by the treating physician, although most reported feeling comfortable with the decision. Almost no one had heard about telemedicine; after hearing a brief description, most were receptive to the idea. Caregivers surmised that telemedicine could reduce the risks and cost associated with transfer. However, many felt telemedicine would not be applicable to their particular situation. CONCLUSIONS: In this sample, caregivers were comfortable with the decision to transfer their child and identified potential benefits of telemedicine as either an adjunct to or replacement of transfer. As hospitals use advanced technology, providers should consider families' opinions about risks and out-of-pocket costs and tailoring explanations to address individual situations.

Interpretation of Optical Coherence Tomography Images for Breast Tissue Assessment.

PURPOSE: Initial studies have shown that optical coherence tomography (OCT) is an effective margin-evaluation tool for breast-conserving surgery, but methods for the interpretation of breast OCT images have not been directly studied. In this work, breast pathologies were assessed with a handheld OCT probe. OCT images and corresponding histology were used to develop guidelines for the identification of breast tissue features in OCT images. METHODS: Mastectomy and breast-conserving surgery specimens from 26 women were imaged with a handheld OCT probe. During standard pathology specimen dissection, representative 1-cm × 1-cm tissue regions were grossly identified, assessed with OCT, inked for orientation and image-matching purposes, and processed. Histology slides corresponding to the OCT image region were digitally photographed. OCT and histology images from the same region were paired by selecting the best structural matches. RESULTS: In total, 2880 OCT images were acquired from 26 breast specimens (from 26 patients) and 48 matching OCT-histology image pairs were identified. These matched image pairs illustrate tissue types including adipose tissue, dense fibrosis, fibroadipose tissue, blood vessels, regular and hyperplastic ducts and lobules, cysts, cyst, fibroadenoma, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, calcifications, and biopsy cavities. Differentiation between pathologies was achieved by considering feature boundaries, interior appearance, posterior shadowing or enhancement, and overall morphologic patterns. CONCLUSIONS: This is the first work to systematically catalog the critical features of breast OCT images. The results indicate that OCT can be used to identify and distinguish between benign and malignant features in human breast tissue.