Timing of Breast Cancer Related Lymphedema Development Over 3 Years: Observations from a Large, Prospective Randomized Screening Trial Comparing Bioimpedance Spectroscopy (BIS) Versus Tape Measure.

BACKGROUND: The PREVENT randomized control trial monitored progression to chronic breast cancer-related lymphedema (cBCRL) following intervention for subclinical breast cancer-related lymphedema (sBCRL) assessed by bioimpedance spectroscopy (BIS) versus tape-measure (TM). This multi-institutional trial demonstrated a 92% risk reduction of developing cBCRL. This secondary analysis reviews the timing of sBCRL and cBCRL following breast cancer (BC) treatment. PATIENTS AND METHODS: Women at risk of cBCRL (n = 919) were screened regularly up to 36 months after BC treatment using either BIS or TM. Following diagnosis of sBCRL, patients underwent a 4-week compression sleeve intervention. The time in months from BC treatment to detection was reviewed at 3-month intervals. RESULTS: In total 209 patients developed sBCRL (BIS: n = 89, TM: n = 120) and were eligible for intervention. 30 progressed to cBCRL postintervention (BIS: 7, TM: 23). More than half of patients had measurements consistent with sBCRL within 9 months of BC treatment. Patients continued to have initial detections of sBCRL, regardless of screening method, with rates remaining consistent in years two and three (p > 0.242) post surgery. Additionally, 39 patients progressed to cBCRL without developing sBCRL or receiving intervention across the 3-year period. CONCLUSIONS: The timing of sBCRL detection demonstrates that patients continue to be at risk years after treatment and may continue to progress to cBCRL years after surgery. Early detection of sBCRL allows for early intervention decreasing the likelihood of progression to cBCRL. Patients should continue to be monitored for a minimum of 3 years following completion of cancer treatment. Specifically, careful targeted monitoring over the initial 9-month period is important.

Impact of measuring quantification of blood loss versus estimation of blood loss during cesarean deliveries.

OBJECTIVE: Our objective was to determine whether there is a numerical difference between quantitative blood loss (QBL) versus visual estimation of blood loss (EBL) during cesarean delivery (CD), and whether initiation of QBL leads to increased recognition and intervention for postpartum hemorrhage. METHODS: A retrospective review was conducted of 250 patients undergoing CD with only EBL documented and 250 patients undergoing CD with both EBL and QBL documented at Montefiore Medical Center between October 2017 and November 2018. Since May 2018, the protocol for all CD included documentation of EBL and QBL. RESULTS: Average EBL when documented alone (897.0 ml ± 301.0 ml) trended lower than average EBL when documented with QBL (940.0 ml ± 371.0 ml, P = 0.161). For CD with both blood loss documented, average EBL (940.0 ml ± 371.0 ml) was significantly lower than average QBL (1065.3 ml ± 649.8 ml, P = 0.0001). CD with both blood loss documented had a greater number of blood transfusions (24 CD, 9.6%) versus only EBL documented (14 CD, 5.6%) (P = 0.125). CONCLUSION: The use of QBL may function in the algorithm to determine up-front resuscitative intervention to improve maternal outcomes and merits further study.

Pain Control in Breast Surgery: Survey of Current Practice and Recommendations for Optimizing Management-American Society of Breast Surgeons Opioid/Pain Control Workgroup.

INTRODUCTION: The opioid epidemic in the United States is a public health crisis. Breast surgeons are obligated to provide good pain control for their patients after surgery but also must minimize administration of narcotics to prevent a surgical episode of care from becoming a patient's gateway into opioid dependence. METHODS: A survey to ascertain pain management practice patterns after breast surgery was performed. A review of currently available literature that was specific to breast surgery was performed to create recommendations regarding pain management strategies. RESULTS: A total of 609 surgeons completed the survey and demonstrated significant variations in pain management practices, specifically within regards to utilization of regional anesthesia (e.g., nerve blocks), and quantity of prescribed narcotics. There is excellent data to guide the use of local and regional anesthesia. There are, however, fewer studies to guide narcotic recommendations; thus, these recommendations were guided by prevailing practice patterns. CONCLUSIONS: Pain management practices after breast surgery have significant variation and represent an opportunity to improve patient safety and quality of care. Multimodality approaches in conjunction with standardized quantities of narcotics are recommended.

Benchmarking the American Society of Breast Surgeon Member Performance for More Than a Million Quality Measure-Patient Encounters.

BACKGROUND: Nine breast cancer quality measures (QM) were selected by the American Society of Breast Surgeons (ASBrS) for the Centers for Medicare and Medicaid Services (CMS) Quality Payment Programs (QPP) and other performance improvement programs. We report member performance. STUDY DESIGN: Surgeons entered QM data into an electronic registry. For each QM, aggregate "performance met" (PM) was reported (median, range and percentiles) and benchmarks (target goals) were calculated by CMS methodology, specifically, the Achievable Benchmark of Care™ (ABC) method. RESULTS: A total of 1,286,011 QM encounters were captured from 2011-2015. For 7 QM, first and last PM rates were as follows: (1) needle biopsy (95.8, 98.5%), (2) specimen imaging (97.9, 98.8%), (3) specimen orientation (98.5, 98.3%), (4) sentinel node use (95.1, 93.4%), (5) antibiotic selection (98.0, 99.4%), (6) antibiotic duration (99.0, 99.8%), and (7) no surgical site infection (98.8, 98.9%); all p values < 0.001 for trends. Variability and reasons for noncompliance by surgeon for each QM were identified. The CMS-calculated target goals (ABC™ benchmarks) for PM for 6 QM were 100%, suggesting that not meeting performance is a "never should occur" event. CONCLUSIONS: Surgeons self-reported a large number of specialty-specific patient-measure encounters into a registry for self-assessment and participation in QPP. Despite high levels of performance demonstrated initially in 2011 with minimal subsequent change, the ASBrS concluded "perfect" performance was not a realistic goal for QPP. Thus, after review of our normative performance data, the ASBrS recommended different benchmarks than CMS for each QM.

Sensitive in vivo Visualization of Breast Cancer Using Ratiometric Protease-activatable Fluorescent Imaging Agent, AVB-620.

With the goal of improving intraoperative cancer visualization, we have developed AVB-620, a novel intravenously administered, in vivo fluorescent peptide dye conjugate that highlights malignant tissue and is optimized for human use. Matrix metalloproteinases (MMPs) hydrolyze AVB-620 triggering tissue retention and a ratiometric fluorescence color change which is visualized using camera systems capable of imaging fluorescence and white light simultaneously. AVB-620 imaging visualizes primary tumors and demonstrated high in vivo diagnostic sensitivity and specificity (both >95%) for identifying breast cancer metastases to lymph nodes in two immunocompetent syngeneic mouse models. It is well tolerated and single-dose toxicology studies in rats determined a no-observed-adverse-effect-level (NOAEL) at >110-fold above the imaging and estimated human dose. Protease specificity and hydrolysis kinetics were characterized and compared using recombinant MMPs. To understand the human translation potential, an in vitro diagnostic study was conducted to evaluate the ability of AVB-620 to differentiate human breast cancer tumor from healthy adjacent tissue. Patient tumor tissue and healthy adjacent breast tissue were homogenized, incubated with AVB-620, and fluorogenic responses were compared. Tumor tissue had 2-3 fold faster hydrolysis than matched healthy breast tissue; generating an assay sensitivity of 96% and specificity of 88%. AVB-620 has excellent sensitivity and specificity for identifying breast cancer in mouse and human tissue. Significant changes were made in the design of AVB-620 relative to previous ratiometric protease-activated agents. AVB-620 has pharmaceutical properties, fluorescence ratio dynamic range, usable diagnostic time window, a scalable synthesis, and a safety profile that have enabled it to advance into clinical evaluation in breast cancer patients.

MACRA and the Changing Medicare Payment Landscape.

BACKGROUND: The Medicare Access and CHIP Reauthorization Act (MACRA) is being implemented in 2017 by the Centers for Medicare and Medicaid Services (CMS) as the Quality Payment Program (QPP) and will have important and far reaching effects on how physicians are reimbursed and on how they practice. The QPP modifies the Medicare physician payment system by eliminating the Sustainable Growth Rate formula and incorporating the existing Physician Quality Reporting System, EHR Incentive Program, and the Value Modifier into a single new Merit-based Incentive Payment System (MIPS). METHODS: The authors reviewed the MACRA legislation as well as the CMS resources on the QPP and other sources to summarize the regulations pertaining to the new program, particularly for the first performance period. RESULTS: CMS has taken great care to create a smooth transition for Medicare physicians. Clinicians can avoid any penalty for performance in 2017 by submitting a minimal amount of quality data, attesting to a single improvement activity, or successfully attaining the base score for the advancing care information portion of MIPS. The reduced reporting period also makes it possible for participants to begin collecting data as late as October 2nd and still achieve the full possible score in the program. CONCLUSIONS: Surgeons should be taking steps now to ensure that they are prepared to succeed in the QPP. The transition period creates a clear pathway for avoiding penalties while providing an opportunity to test one's ability to participate and improve performance.

Intraoperative Tumor Detection Using a Ratiometric Activatable Fluorescent Peptide: A First-in-Human Phase 1 Study.

BACKGROUND: Positive surgical margins remain a significant challenge in breast cancer surgery. This report describes the use of a novel, first-in-human ratiometric activatable cell-penetrating peptide in breast cancer surgery. METHODS: A two-part, multi-institutional phase 1 trial of AVB-620 with a 3+3 dose escalation and dose-expansion cohorts was conducted. The patients received an infusion of AVB-620 2-20 h before planned lumpectomy/mastectomy and sentinel node biopsy/axillary dissection. Imaging analysis was performed on images obtained from the surgical field as well as post-excision surgical specimens. Pathology reports were obtained to correlate imaging results with histopathologic data. Information on physical adverse events and laboratory abnormalities were recorded. RESULTS: A total of 27 patients received infusion of AVB-620 and underwent surgical excision of breast cancer. The findings showed no adverse events or laboratory values attributable to infusion of AVB-620. The 8-mg dose was selected from the dose-escalation cohort for use with the expansion cohort based on imaging data. Region-of-interest (ROI) imaging analysis from the 8-mg cohort demonstrated measurable changes between pathology confirmed tumor-positive and tumor-negative tissue. CONCLUSION: Intraoperative imaging of surgical specimens after infusion with AVB-620 allowed for real-time tumor detection. Infusion of AVB-620 is safe and may improve intraoperative detection of malignant tissue during breast cancer operations.

Surgical Lymphadenectomy: The Impact of Sentinel Node Mapping in Breast Cancer.

Lymphatic mapping continues to grow in utility both as a diagnostic aid and as a method for performing less morbid, potentially therapeutic lymphadenectomies. Its use in breast cancer has become the standard of care for staging and sentinel lymph node dissection is considered sufficiently therapeutic for low-volume axillary disease. Lymphatic mapping has re-emphasized the importance of adequate lymphatic staging both in terms of the amount of lymph nodes resected and the amount of each lymph node that is assessed. Going forward, these concepts continue to be adopted into other tumors, with active investigations ongoing in gastrointestinal cancers, head and neck cancers, and gynecologic cancers.

Measures of Appropriateness and Value for Breast Surgeons and Their Patients: The American Society of Breast Surgeons Choosing Wisely (®) Initiative.

BACKGROUND: Current breast cancer care is based on high-level evidence from randomized, controlled trials. Despite these data, there continues to be variability of breast cancer care, including overutilization of some tests and operations. To reduce overutilization, the American Board of Internal Medicine Choosing Wisely (®) Campaign recommends that professional organizations provide patients and providers with a list of care practices that may not be necessary. Shared decision making regarding these services is encouraged. METHODS: The Patient Safety and Quality Committee of the American Society of Breast Surgeons (ASBrS) solicited candidate measures for the Choosing Wisely (®) Campaign. The resulting list of "appropriateness" measures of care was ranked by a modified Delphi appropriateness methodology. The highest-ranked measures were submitted to and later approved by the ASBrS Board of Directors. They are listed below. RESULTS: (1) Don't routinely order breast magnetic resonance imaging in new breast cancer patients. (2) Don't routinely excise all the lymph nodes beneath the arm in patients having lumpectomy for breast cancer. (3) Don't routinely order specialized tumor gene testing in all new breast cancer patients. (4) Don't routinely reoperate on patients with invasive cancer if the cancer is close to the edge of the excised lumpectomy tissue. (5) Don't routinely perform a double mastectomy in patients who have a single breast with cancer. CONCLUSIONS: The ASBrS list for the Choosing Wisely (®) campaign is easily accessible to breast cancer patients online. These measures provide surgeons and their patients with a starting point for shared decision making regarding potentially unnecessary testing and operations.

Prevention and management of lymphedema after breast cancer treatment.

Lymphedema of the arm after breast cancer treatment continues to challenge clinicians worldwide. In this review, we examine the main modalities, both nonsurgical and surgical, to prevent and treat this as yet incurable condition.

Workup and staging of malignant melanoma.

Melanoma continues to be one of the fastest growing cancers in terms of incidence. The workup of melanoma focuses on risk factors based on the visual aspects of a skin lesion. Risk factors including sun exposure increase the risk of melanoma. Staging is based on depth of invasion, mitotic rate, and spread into lymph nodes and other sites. Once diagnosed, wide excision is indicated for the primary lesion, and sentinel node biopsy for all but the thinnest of melanomas. Routine imaging workup for most thinner melanomas should be minimized, and is questionable in the asymptomatic patients even with thicker melanomas.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. METHODS: Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. RESULTS: There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). CONCLUSIONS: TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

Life expectancy after curative-intent treatment of breast cancer: impact on long-term follow-up care.

Long-term survival rates after treatment for breast cancer are directly influenced by early deaths resulting from disease. For longer-term breast cancer survivors, survival rates appear deceptively low. We hypothesize that the actual survival curve for long-term survivors approaches the overall survival of the general population. The Surveillance, Epidemiology, and End Results database (1988 to 2002) was used to identify patients with nonmetastatic breast cancer who underwent definitive surgical treatment. The survival of the general population was constructed by using national life tables with an age-matched population. Comparisons of survivals were made for 3-, 5-, and 7-year breast cancer survivor cohorts. Of 237,180 patients, 92.4 per cent survived three years, 82.1 per cent five years, and 58.1 per cent seven years. Stage I patients have equivalent or better survivals compared with the age-matched general population in all three cohorts. Stage II patients reached equivalent conditional survival between eight and nine years after diagnosis regardless of cohort. Stage III patients required achieving nine to 10 years after diagnosis to achieve equivalent survival probability, except in 7-year survivors, in whom 10 to 11 years was required. In all stages, once equivalence was reached, survival exceeded the general population over the remaining years. Initial cancer stage influences overall survival for many years after diagnosis. Patients with Stage I cancer return to the general population risk as early as three years after diagnosis, whereas higher stages can require up to nine years to achieve parity with a more generalized population. These findings should be factored into general health screening issues for long-term breast cancer survivors.

Incidence of inflammatory breast cancer in women, 1992-2009, United States.

BACKGROUND: The annual incidence of inflammatory breast cancer (IBC) in the United States reportedly increased during the last quarter of the twentieth century. We investigated whether that increase has continued into the twenty-first century. METHODS: We queried the Surveillance Epidemiology and End Results database for all cases of IBC in women age 20 and older between 1992 and 2009. Cases were breast tumors with at least one of the following codes: extent of disease size 998, extension 70, or ICD-3-O morphology 8530 or 8533. Age-adjusted incidence was also examined. RESULTS: During 1992-2009, the annual incidence of IBC did not increase over time in any age group, nor did it vary significantly from year to year, except between 2003 and 2004, when there was a jump from 1.6 (95 % confidence interval 1.4-1.8) to 3.1 (2.8-3.4) cases per 100,000 women. Similar changes occurred in all age and racial groups before gradually returning to prejump levels. Overall, the incidence of IBC rose steeply with age until reaching a plateau at age 65. The incidence was greatest among black women (3.0; 2.8-3.2), intermediate among white women (2.1; 2.1-2.2), and lowest among Asian women (1.4; 1.3-1.6). CONCLUSIONS: The incidence of IBC has remained essentially stable for nearly two decades. A transient jump in 2003-2004 occurred in all age and racial groups, suggesting adjustment to coding changes at that time. Often described as a disease of younger women, IBC in fact disproportionately affects older women. Racial/ethnic variation in the incidence of IBC suggests that dietary, lifestyle, or genetic factors contribute to its pathogenesis.

Rural and urban disparities in the evolution of sentinel lymph node utilization in breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become the preferred method for axillary nodal staging. The authors examined SLNB utilization in urban versus rural settings as this procedure was adopted and hypothesized that SLNB rates among urban populations increased faster, while the technology shift and acceptance of SLNB were slower at rural centers. METHODS: The Surveillance, Epidemiology and End Results database was used to identify patients with invasive node-negative ductal or lobular breast cancer diagnosed from 1998 to 2008. Exclusion criteria were distant metastatic disease, T4 tumors, or incomplete data. Residential setting was divided into groups on the basis of population density. RESULTS: The overall rate of SLNB increased with time (from 10% in 1998 to 73% in 2008). The adoption of SLNB was slower in rural settings than among urban populations (P < .001). By 2003, only urban areas were using SLNB in >50% of cases. Overall, there was a 2-year lag between the increases in SLNB utilization rates in these groups. There was a significant difference in SLNB rates according to tumor size. CONCLUSION: The overall rate of SLNB remained near 50% and was lower in rural locations in 2004. By 2008, the SLNB rate for T1 and T2 tumors had increased to >50% in all population categories. SLNB utilization was lower in all population categories as tumor size increased. There was an overall 2-year lag in the adoption of SLNB in less populated areas. Although this may represent a more conservative approach, the difference may be attributable to a shortage of experienced surgeons, lack of training, or lack of technological support at smaller institutions.

Trends in radiotherapy after breast-conserving surgery in elderly patients with early-stage breast cancer.

BACKGROUND: The benefit of adjuvant radiotherapy (RT) in elderly breast cancer patients is debatable. The purpose of this study was to evaluate trends in RT rates after breast-conserving surgery. METHODS: Breast cancer patients ≥70 years treated from 2000 to 2009 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were estrogen receptor positive with negative or unknown lymph node status. Trends in RT recommendation over years were evaluated with the Jonckheere-Terpstra test. Multiple logistic regression and Cox proportional hazard tests were used to determine factors associated with radiation recommendation and survival. RESULTS: Of 46,581 patients, 31,989 (68.7 %) were recommended RT and 14,592 (31.3 %) were not. The recommendation for RT decreased from 70.3 % in 2000 to 67.4 % in 2009 (p < 0.0001). Seven of 18 registries exhibited decreased radiation recommendation rates, and 4 of 18 exhibited an increase. Recommendation of RT was associated with earlier year of diagnosis, younger age, Asian/Pacific Islander race, and negative lymph nodes. Predictors of worse survival were no radiation [hazard ratio (HR) 1.68, 95 % confidence interval (CI) 1.61-1.75], no nodes examined (HR 1.83, 95 % CI 1.75-1.91), large (>2-5 cm) tumor size (HR 2.02, 95 % CI 1.86-2.19), older age (80+, HR 2.38, 95 % CI 2.25-2.53), and black race (HR 1.13, 95 % CI1.03-1.23). CONCLUSIONS: Rates of radiation recommendation in the elderly have been steadily decreasing without appreciable acceleration in this decline. This trend was not consistent across all registries. Continued research is necessary to assess differences in clinical practice and its impact on patient outcomes.