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The article discusses the medical condition of an Eggplant penis, which refers to the discolouring and fracturing of the penis, caused by an abrupt bending of an erect penis. Details related to the diagnosis and surgical intervention are provided, to avoid causing penis-related complications such as erectile dysfunction.

There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT. Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were classified into 3 biosignature risk groups using the decision score (DS) and the RRt category: (1) Low Risk (DS ≤2.8 without RRt), (2) Elevated Risk (DS >2.8 without RRt), and (3) Residual Risk (DS >2.8 with RRt). Total and invasive IBR rates were assessed by risk group and treatment. In patients at low risk, there was no significant difference in IBR rates with or without RT (total, P =.8; invasive IBR, P =.7), and there were low overall 10-year rates (total, 5.1%; invasive, 2.7%). In patients with elevated risk, IBR rates were decreased with RT (total: hazard ratio [HR], 0.25; P <.001; invasive: HR, 0.28; P =.005); 10-year rates were 20.6% versus 4.9% (total) and 10.9% versus 3.1% (invasive). In patients with residual risk, although IBR rates decreased with RT after BCS (total: HR, 0.21; P <.001; invasive: HR, 0.29; P =.028), IBR rates remained significantly higher after RT compared with patients with elevated risk (HR, 2.5; 95% CI, 1.2-5.4; P =.018), with 10-year rates of 42.1% versus 14.7% (total) and 18.3% versus 6.5% (invasive). The novel biosignature identified patients with 3 distinct risk profiles: Low Risk patients with a low recurrence risk with or without adjuvant RT, Elevated Risk patients with excellent outcomes after BCS plus RT, and Residual Risk patients with an elevated recurrence risk remaining after BCS plus RT, warranting potential intensified or alternative treatment approaches. [ABSTRACT FROM AUTHOR]

Background: This study compared the surgical results of 2 localization methods-cryo-assisted localization (CAL) and needle-wire localization (NWL)-in patients undergoing breast lumpectomy for breast cancer. Methods: A total of 310 patients were treated in an institutional review board-approved study with 18 surgeons at 17 sites. Patients were randomized 2:1 to undergo either intraoperative CAL or NWL. A cryoprobe was inserted under ultrasound guidance in the operating room and an ice ball created an 8- to 10-mm margin around the lesion. The palpable ice ball then was dissected. NWL was placed according to institutional practice and resection was performed in a standard fashion. Surgical margins, complications, re-excisions, tissue volume, procedure times, ease of localization, specimen quality, and patient satisfaction were evaluated. Positive margins were defined as any type of disease present 1 mm or less from any specimen edge. Results: Positive margin status did not differ between the 2 groups (28% vs. 31%). The volume of tissue removed was significantly less in the CAL group (49 vs. 66 mL, P = .002). Re-excisions were similar in both groups. CAL was superior in ease of lumpectomy, quality of specimen, acute surgical cosmesis, short-term cosmesis, patient satisfaction, and overall procedure time for the patient. CAL had a lower invasive positive margin rate (11% vs. 20%, P = .039) but a higher observed ductal carcinoma in situ-positive margin rate (30% vs. 18%, approaching statistical significance, P = .052). Conclusions: CAL is a preferred alternative to standard wire localization because it provides a palpable template, removes less tissue and improves cosmesis, decreases overall procedure time, and is more convenient for the patient and surgeon. [ABSTRACT FROM AUTHOR]

MRI can delineate finer details of penile anatomy and pathology due to inherent higher soft-tissue contrast and spatial resolution. It can characterize inflammation and identify abscesses, localize penile fractures, guide surgical planning in penile fibrosis and Peyronie's disease, and depict components of the penile prosthesis and its complications. MRI is a great investigative tool for penile neoplasms, including locally infiltrative neoplasms where clinical examination is limited, and local staging is crucial for surgical planning. [ABSTRACT FROM AUTHOR]

Importance: The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor-positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology).Objective: To determine whether the 10-year overall survival of patients with sentinel lymph node metastases treated with breast-conserving therapy and sentinel lymph node dissection (SLND) alone without axillary lymph node dissection (ALND) is noninferior to that of women treated with axillary dissection.Design, Setting, and Participants: The ACOSOG Z0011 phase 3 randomized clinical trial enrolled patients from May 1999 to December 2004 at 115 sites (both academic and community medical centers). The last date of follow-up was September 29, 2015, in the ACOSOG Z0011 (Alliance) trial. Eligible patients were women with clinical T1 or T2 invasive breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases.Interventions: All patients had planned lumpectomy, planned tangential whole-breast irradiation, and adjuvant systemic therapy. Third-field radiation was prohibited.Main Outcomes and Measures: The primary outcome was overall survival with a noninferiority hazard ratio (HR) margin of 1.3. The secondary outcome was disease-free survival.Results: Among 891 women who were randomized (median age, 55 years), 856 (96%) completed the trial (446 in the SLND alone group and 445 in the ALND group). At a median follow-up of 9.3 years (interquartile range, 6.93-10.34 years), the 10-year overall survival was 86.3% in the SLND alone group and 83.6% in the ALND group (HR, 0.85 [1-sided 95% CI, 0-1.16]; noninferiority P = .02). The 10-year disease-free survival was 80.2% in the SLND alone group and 78.2% in the ALND group (HR, 0.85 [95% CI, 0.62-1.17]; P = .32). Between year 5 and year 10, 1 regional recurrence was seen in the SLND alone group vs none in the ALND group. Ten-year regional recurrence did not differ significantly between the 2 groups.Conclusions and Relevance: Among women with T1 or T2 invasive primary breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases, 10-year overall survival for patients treated with sentinel lymph node dissection alone was noninferior to overall survival for those treated with axillary lymph node dissection. These findings do not support routine use of axillary lymph node dissection in this patient population based on 10-year outcomes.Trial Registration: clinicaltrials.gov Identifier: NCT00003855. [ABSTRACT FROM AUTHOR]

Abstract: Background: We present a 4-year update on the efficacy, cosmetic results, and complications of MammoSite breast brachytherapy in patients enrolled in the American Society of Breast Surgeons registry trial. Methods: A total of 1,449 breasts in 1,440 patients with early stage breast cancer undergoing breast-conserving therapy were treated with adjuvant, accelerated partial breast irradiation (APBI) (34 Gy in 3.4-Gy fractions) delivered with the MammoSite device. The median follow-up period for the entire group was 36.1 months. Results: The 3-year actuarial rate of ipsilateral breast tumor recurrence was 2.15%. The 3-year actuarial rate of axillary recurrence was .36%. Complication rates were as follows: infection, 9.5%; seroma, 26.8% (symptomatic seroma, 12.7%); and fat necrosis, 2.0%. The percentages of breasts with good or excellent cosmetic results were as follows: 12 months, 95%; 24 months, 94%; 36 months, 94%; and 48 months, 91%. Conclusions: Locoregional control, complications, and cosmetic outcomes from MammoSite APBI at the 4-year update are acceptable and similar to results seen with other forms of APBI. [Copyright &y& Elsevier]

The article discusses the use of the sentinal-lymph-node biopsy technique in the treatment of breast cancer. It is said that the false negative rate is too high for this approach to be regarded as a proper standard of care. As the first lymph node receiving drainage from a tumor, the sentinal lymph node is helpful in determining the presence or absence of metastases. The use of sentinal-lymph-node biopsy to avoid dissection of regional lymph node basins in the treatment of melanoma has become standard practice. Differences between the treatment of melanoma and breast cancer are analyzed.

Background: Pilot studies indicate that probe-guided resection of radioactive sentinel nodes (the first nodes that receive drainage from tumors) can identify regional metastases in patients with breast cancer. To confirm this finding, we conducted a multicenter study of the method as used by 11 surgeons in a variety of practice settings. Methods: We enrolled 443 patients with breast cancer. The technique involved the injection of 4 ml of technetium-99m sulfur colloid (1 mCi [37 MBq]) into the breast around the tumor or biopsy cavity. “Hot spots” representing underlying sentinel nodes were identified with a gamma probe. Sentinel nodes subjacent to hot spots were removed. All patients underwent a complete axillary lymphadenectomy. Results: The overall rate of identification of hot spots was 93 percent (in 413 of 443 patients). The pathological status of the sentinel nodes was compared with that of the remaining axillary nodes. The accuracy of the sentinel nodes with respect to the positive or negative status of the axillary nodes was 97 percent (392 of 405); the specificity of the method was 100 percent, the positive predictive value was 100 percent, the negative predictive value was 96 percent (291 of 304), and the sensitivity was 89 percent (101 of 114). The sentinel nodes were outside the axilla in 8 percent of cases and outside of level 1 nodes in 11 percent of cases. Three percent of positive sentinel nodes were in nonaxillary locations. Conclusions: Biopsy of sentinel nodes can predict the presence or absence of axillary-node metastases in patients with breast cancer. However, the procedure can be technically challenging, and the success rate varies according to the surgeon and the characteristics of the patient. (N Engl J Med 1998;339:941-6.) [ABSTRACT FROM AUTHOR]

Purpose: A subpopulation of women with ductal carcinoma in situ (DCIS) remains at risk for in-breast recurrence (IBR) following breast-conserving surgery (BCS) and radiation therapy (RT). The NSABP B-43 trial evaluated the role of concurrent RT and trastuzumab in patients with HER2-positive DCIS but did not reach the prespecified endpoint. We hypothesized that a 7-gene biosignature (DCISionRT) with its Residual Risk subtype (RRt) could identify 2 groups of HER2(3+) patients with significantly different IBR risks after BCS plus RT., Patients and Methods: All patients with HER2(3+) DCIS (n = 178) treated with BCS plus RT were selected from a combined multinational patient cohort. Treatment decisions were neither randomized nor strictly rules-based. Biosignature testing was performed on all patients and stratified with previously defined groups: (1) Combined Low Risk group (DS ≤ 2.8) and Elevated Risk group (DS > 2.8) without RRt or (2) Residual Risk subtype. Kaplan-Meier analysis was used to compute IBR curves., Results: Sixty-three percent of HER2(3+) patients (113/178) were classified into the Residual Risk subtype. These patients had significantly higher 10-year rates of IBR compared to the nonresidual risk group (16.2% vs. 1.6%, P = .01). The Residual Risk subtype had more nuclear grade 3 disease (87% vs. 63%, P < .001), but age, size, and grade were not associated with IBR rate (P = NS) on univariate and multivariable analysis. Only the Residual Risk group was associated with IBR (P = .05) in multivariate analysis., Conclusion: The 7-gene biosignature with RRt identified a subset of HER2(3+) patients with greater IBR rates following BCS and RT beyond traditional clinical and pathologic features. Consideration of therapies to reduce these elevated IBR rates should be evaluated, including the incorporation of HER2-targeted therapy., Competing Interests: Disclosure FV is a research advisor for PreludeDx and PreludeDx supported his institution for the conduct and management of a separate clinical trial. FV is also a consultant for ImpediMed, unrelated to this research. CS is a consultant for and has received research funding from PreludeDx for separate research projects. CS is also a consultant for ImpediMed, Videra Surgical and Evicore and has received grant funding from Varian Medical Systems, and VisionRT unrelated to this research. KM and SS are employees of PreludeDx and have stock options for PreludeDx. SW and ML have received grant support from PreludeDx for a previously published validation study. RR has received research funding from PreludeDx for a separate clinical study. Unrelated to this study, RR has stock and other ownership interests in Abbott Laboratories, Bristol-Myers Squibb, Intuitive Surgical, IDEXX Laboratories. FW is a consultant for PreludeDx and was supported by PreludeDx for the conduct and management of previous studies. PW is on an advisory board and has received research funding from PreludeDx. Unrelated to this study, PW has stock and other ownership interests in Reverse Medical, Rebound Medical, Lazarus, Cerebrotech, Targeted Medical Education and Medtronic, is on advisory boards for Medtronic, Lumicell, ImpediMed, and Cianna Medical, and has received research funding from Invitae, Intact Medical, Agendia and ImpediMed. BC has intellectual property rights for ImmunoRestoration and receives consulting fees from Merit Medical unrelated to this research. TB is an employee of PreludeDx, holds intellectual property rights for the DCISionRT test, and has an ownership interest in PreludeDx. JA and MK have no competing interests (Figure 1, Supplemental Figures 1 and 2, Table 1, Table 2, Table 3, Table 4)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Urothelial cancer is the second most common cancer, and cause of cancer death, related to the genitourinary tract. The goals of imaging for pretreatment staging of urothelial cancer are to evaluate for both local and distant spread of the cancer and assessing for synchronous sites of urothelial cancer in the upper tracts and bladder. For pretreatment staging of urothelial carcinoma, patients can be stratified into one of three groups: 1) nonmuscle invasive bladder cancer; 2) muscle invasive bladder cancer; and 3) upper urinary tract urothelial carcinoma. This document is a review of the current literature for urothelial cancer and resulting recommendations for pretreatment staging imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Acute scrotum is a medical emergency that requires prompt accurate diagnosis to appropriately triage potentially surgical conditions. Numerous differential diagnoses with overlapping clinical presentations make this a diagnostic challenge. Ultrasound is the established first-line imaging modality for acute scrotal disease and can be used to diagnose most scrotal disorders promptly and with high accuracy. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations., Methods: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations., Results: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria., Conclusions: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients., Trial Registration: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 )., (© 2024. The Author(s).)

Purpose: We previously described a combined risk score (CRS) that integrates a multiple-ancestry polygenic risk score (MA-PRS) with the Tyrer-Cuzick (TC) model to assess breast cancer (BC) risk. Here, we present a longitudinal validation of CRS in a real-world cohort., Methods: This study included 130,058 patients referred for hereditary cancer genetic testing and negative for germline pathogenic variants in BC-associated genes. Data were obtained by linking genetic test results to medical claims (median follow-up 12.1 months). CRS calibration was evaluated by the ratio of observed to expected BCs., Results: Three hundred forty BCs were observed over 148,349 patient-years. CRS was well-calibrated and demonstrated superior calibration compared with TC in high-risk deciles. MA-PRS alone had greater discriminatory accuracy than TC, and CRS had approximately 2-fold greater discriminatory accuracy than MA-PRS or TC. Among those classified as high risk by TC, 32.6% were low risk by CRS, and of those classified as low risk by TC, 4.3% were high risk by CRS. In cases where CRS and TC classifications disagreed, CRS was more accurate in predicting incident BC., Conclusion: CRS was well-calibrated and significantly improved BC risk stratification. Short-term follow-up suggests that clinical implementation of CRS should improve outcomes for patients of all ancestries through personalized risk-based screening and prevention., Competing Interests: Conflict of Interest Brent Mabey, Elisha Hughes, Matthew Kucera, Timothy Simmons, Brooke Hullinger, Sarah Ratzel, Susanne Wagner, Jerry S. Lanchbury, Katherine Johansen Taber, Thomas P. Slavin, and Alexander Gutin were employed by Myriad Genetics, Inc. at the time of the study and received salaries and stocks as compensation. Holly J. Pederson and Monique Gary have received consulting fees from Myriad Genetics, Inc. Charis Eng has ownership interests in MyLegacy/MyFHH/Family Care Path. Judy Garber has received research funding from Ambry Genetics and Invitae and has other relationships, or an immediate family member with relationships, with AACR, Diana Helis Henry Medical Foundation, James P. Wilmot Foundation, Adrianne Helis Malvin Medical Research Foundation, Breast Cancer Research Foundation, Facing our Risk of Cancer Empowered, Novartis, GTx, Aleta BioTherapeutics, H3 Biomedicine, and Kronos Bio. Ora Gordon has had a consulting or advisory role with GRAIL and Genetic Technologies, has received travel or accommodation expenses from GRAIL, and has received research funding from GRAIL. Jennifer R. Klemp has received consulting fees and speakers’ bureaus fees from AstraZeneca, has ownership interests in Cancer Survivorship Training, is employed by Caris Life Sciences, Inc, and has received a salary as compensation and consulting fees. Olufunmilayo I. Olopade has an ownership interest in 54Gene and Tempus, has an ownership interest and has received a salary from CancerIQ, and has other interests in Color Genomics, Healthy Life for All Foundation, and Roche/Genetech. Mark E. Robson has provided clinical trial services to AstraZeneca and Merck and has received consulting fees from and/or been on advisory boards for Change Healthcare, Intellisphere, MyMedEd, Physician’s Education Resources, and Research to Practice. Pat W. Whitworth has received consulting fees from or had contracted research with Agendia, Biotheranostics, Genomic Health, Impedimed, Myriad Genetics, Inc, Prelude, and Veracyte, and has an ownership interest in Medneon. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Initial imaging evaluation of hydronephrosis of unknown etiology is a complex subject and is dependent on clinical context. In asymptomatic patients, it is often best conducted via CT urography (CTU) without and with contrast, MR urography (MRU) without and with contrast, or scintigraphic evaluation with mercaptoacetyltriglycine (MAG3) imaging. For symptomatic patients, CTU without and with contrast, MRU without and with contrast, MAG3 scintigraphy, or ultrasound of the kidneys and bladder with Doppler imaging are all viable initial imaging studies. In asymptomatic pregnant patients, nonionizing imaging with US of the kidneys and bladder with Doppler imaging is preferred. Similarly, in symptomatic pregnant patients, US of the kidneys and bladder with Doppler imaging or MRU without contrast is the imaging study of choice, as both ionizing radiation and gadolinium contrast are avoided in pregnancy. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: Breast cancer-related lymphedema (BCRL) represents a dreaded complication of breast cancer treatment that can lead to morbidity, diminished quality of life, and psychosocial harm and is associated with increased costs of care. Increasingly, data has supported the concept of prospective BCRL surveillance coupled with early intervention to mitigate these effects., Methods: We performed a systematic review of the literature searching for published randomized and prospective data evaluating prospective BCRL surveillance with early intervention., Results: We identified 12 studies (2907 patients) including 4 randomized trials (1203 patients) and 8 prospective studies (1704 patients). Randomized data consistently demonstrate that early intervention reduces rates of progression to chronic BCRL with multiple paradigms and diagnostic modalities utilized; the strongest data comes from the randomized PREVENT trial, which demonstrated early detection with bioimpedance spectroscopy (BIS), coupled with early intervention with a compression garment applied for 12 h a day over 4 weeks, significantly reduced the rate of chronic BCRL compared to tape measurement coupled with early intervention., Conclusions: Current data support the role of prospective BCRL surveillance with early detection and intervention to reduce rates of chronic BCRL. Breast cancer patients at risk for BCRL should undergo prospective surveillance as part of survivorship. Because level 1 data demonstrate that BIS is superior to conventional tape measure, it should be included as the standard BCRL diagnostic modality unless an equally effective modality is employed., Implications for Cancer Survivors: Breast cancer survivor should undergo prospective BCRL screening with BIS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Ductal carcinoma in situ (DCIS), is a noninvasive breast cancer, representing 20-25% of breast cancer diagnoses in the USA. Current treatment options for DCIS include mastectomy or breast-conserving surgery (BCS) with or without radiation therapy (RT), but optimal risk-adjusted treatment selection remains a challenge. Findings from past and recent clinical trials have failed to identify a 'low risk' group of patients who do not benefit significantly from RT after BCS. To address this unmet need, a DCIS biosignature, DCISionRT (PreludeDx, Laguna Hills, CA), was developed and validated in multiple cohorts. DCISionRT is a molecular assay with an algorithm reporting a recurrence risk score for patients diagnosed with DCIS intended to guide DCIS treatment. In this study, we present results from analytical validity, performance assessment, and clinical performance validation and clinical utility for the DCISionRT test comprised of multianalyte assays with algorithmic analysis., Methods: The analytical validation of each molecular assay was performed based on the Clinical and Laboratory Standards Institute (CLSI) guidelines Quality Assurance for Design Control and Implementation of Immunohistochemistry Assays and the College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) recommendations for analytic validation of immunohistochemical assays., Results: The analytic validation showed that the molecular assays that are part of DCISionRT test have high sensitivity, specificity, and accuracy/reproducibility (≥95%). The analytic precision of the molecular assays under controlled non-standard conditions had a total standard deviation of 6.6 (100-point scale), where the analytic variables (Lot, Machine, Run) each contributed <1% of the total variance. Additionally, the precision in the DCISionRT test result (DS) had a 95%CI ≤0.4 DS units under controlled non-standard conditions (Day, Lot, and Machine) for molecular assays over a wide range of clinicopathologic factor values. Clinical validation showed that the test identified 37% of patients in a low-risk group with a 10-year invasive IBR rate of ~3% and an absolute risk reduction (ARR) from RT of 1% (number needed to treat, NNT=100), while remaining patients with higher DS scores (elevated-risk) had an ARR for RT of 9% (NNT=11) and 96% clinical sensitivity for RT benefit., Conclusion: The analytical performance of the PreludeDx DCISionRT molecular assays was high in representative formalin-fixed, paraffin-embedded breast tumor specimens. The DCISionRT test has been analytically validated and has been clinically validated in multiple peer-reviewed published studies., Competing Interests: DD, SH, and JS are consultant pathologists for PreludeDx. CS is a consultant for ImpediMed, PreludeDX, Videra Surgical and Evicore and has received grant funding from Varian Medical Systems, VisionRT, and PreludeDx. PW has stock and other ownership interests in Reverse Medical, Rebound Medical, Lazarus, Cerebrotech, Targeted Medical Education and Medtronic. PW is on advisory boards for Medtronic, Lumicell, ImpediMed, Cianna Medical, and PreludeDx and has received research funding from InVitae, Intact Medical, PreludeDx, Agendia, and ImpediMed. KM and SS are employees of PreludeDx and have stock options for PreludeDx. TB is an employee of PreludeDx, holds intellectual property rights for the DCISionRT test and has ownership interest in PreludeDx. The authors declare that this study received funding from PreludeDx. Since this is an analytical validation study for a commercially-available Multianalyte Assay with Algorithmic Analyses (MAAA), employees and consultants employed by the funder were necessarily involved in the study design, collection, analysis, interpretation of data, the writing of this article, and the decision to submit it for publication., (Copyright © 2023 Dabbs, Mittal, Heineman, Whitworth, Shah, Savala, Shivers and Bremer.)

Prostate cancer is second leading cause of death from malignancy after lung cancer in American men. The primary goal during pretreatment evaluation of prostate cancer is disease detection, localization, establishing disease extent (both local and distant), and evaluating aggressiveness, which are the driving factors of patient outcomes such as recurrence and survival. Prostate cancer is typically diagnosed after the recognizing elevated serum prostate-specific antigen level or abnormal digital rectal examination. Tissue diagnosis is obtained by transrectal ultrasound-guided biopsy or MRI-targeted biopsy, commonly with multiparametric MRI without or with intravenous contrast, which has recently been established as standard of care for detecting, localizing, and assessing local extent of prostate cancer. Although bone scintigraphy and CT are still typically used to detect bone and nodal metastases in patients with intermediate- or high-risk prostate cancer, novel advanced imaging modalities including prostatespecific membrane antigen PET/CT and whole-body MRI are being more frequently utilized for this purpose with improved detection rates. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: Breast cancer-related lymphedema (BCRL) represents a significant concern for patients following breast cancer treatment, and assessment for BCRL represents a key component of survivorship efforts. Growing data has demonstrated the benefits of early detection and treatment of BCRL. Traditional diagnostic modalities are less able to detect reversible subclinical BCRL while newer techniques such as bioimpedance spectroscopy (BIS) have shown the ability to detect subclinical BCRL, allowing for early intervention and low rates of chronic BCRL with level I evidence. We present updated clinical practice guidelines for BIS utilization to assess for BCRL., Methods and Results: Review of the literature identified a randomized controlled trial and other published data which form the basis for the recommendations made. The final results of the PREVENT trial, with 3-year follow-up, demonstrated an absolute reduction of 11.3% and relative reduction of 59% in chronic BCRL (through utilization of compression garment therapy) with BIS as compared to tape measurement. This is in keeping with real-world data demonstrating the effectiveness of BIS in a prospective surveillance model. For optimal outcomes patients should receive an initial pre-treatment measurement and subsequently be followed at a minimum quarterly for first 3 years then biannually for years 4-5, then annually as appropriate, consistent with previous guidelines; the target for intervention has been changed from a change in L-Dex of 10 to 6.5. The lack of pre-operative measure does not preclude inclusion in the prospective surveillance model of care., Conclusion: The updated clinical practice guidelines present a standardized approach for a prospective model of care using BIS for BCRL assessment and supported by evidence from a randomized controlled trial as well as real-world data., (© 2022. The Author(s).)

Background: As more patients with early-stage breast cancer receive neoadjuvant endocrine therapy (NET), there is a need for reliable biomarkers that can identify patients with HR+ HER2- tumors who are likely to benefit from NET. NBRST (NCT01479101) compared the prognostic value of the 70-gene risk classification and 80-gene molecular subtyping signatures with conventional pathological classification methods in response to neoadjuvant therapy. We evaluated the association of these signatures with clinical response and 5-year outcome of patients treated with NET., Methods: 1091 patients with early-stage breast cancer scheduled to receive neoadjuvant therapy were prospectively enrolled into NBRST, and a sub-analysis of 67 patients treated with NET was performed. Patients received standard of care genomic testing using the 70-gene and 80-gene signatures and were treated with NET, per physician's discretion. The primary endpoint was pathologic partial response (pPR) and secondary endpoints were distant metastasis-free survival (DMFS) and overall survival (OS). Clinical benefit was defined as having a pPR or stable disease (SD) with NET., Results: Overall, 94.4% of patients with genomically (g) Luminal A-Type (50.0% pPR and 44.4% SD) and 95.0% with Luminal B-Type tumors (55.0% pPR and 40.0% SD) exhibited clinical benefit. At 5 years, patients with gLuminal B tumors had significantly worse DMFS (75.6%, 95% CI 50.8-89.1) than patients with gLuminal A (91.1%; 95% CI 74.8-97.1; p = 0.047), with a similar trend for OS, albeit not significant (81.0%, 95% CI 56.9-92.4 and 91.1%, 95% CI 74.8-97.1, respectively; p = 0.13)., Conclusions: Genomic assays offer a broader understanding of the underlying tumor biology, which adds precision to pathology as a preoperative risk classifier. Patients with 70-gene signature Low Risk, gLuminal A tumors treated with endocrine therapy alone have excellent 5-year outcomes. Most patients with genomically-defined Luminal A- and B-Type tumors respond well to NET, suggesting these patients may be safely treated with NET, while those with gLuminal B tumors will also require post-operative chemotherapy or CDK4/6 inhibitors to improve long-term outcomes. Overall, these findings demonstrate that genomic classification, defined by the combined 70- and 80-gene signatures, is associated with tumor response and prognostic of long-term outcomes., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Polygenic risk scores (PRSs) for breast cancer (BC) risk stratification have been developed primarily in women of European ancestry. Their application to women of non-European ancestry has lagged because of the lack of a formal approach to incorporate genetic ancestry and ancestry-dependent variant frequencies and effect sizes. Here, we propose a multiple-ancestry PRS (MA-PRS) that addresses these issues and may be useful in the development of equitable PRSs across other cancers and common diseases., Materials and Methods: Women referred for hereditary cancer testing were divided into consecutive cohorts for development (n = 189,230) and for independent validation (n = 89,126). Individual genetic composition as fractions of three reference ancestries (African, East Asian, and European) was determined from ancestry-informative single-nucleotide polymorphisms. The MA-PRS is a combination of three ancestry-specific PRSs on the basis of genetic ancestral composition. Stratification of risk was evaluated by multivariable logistic regression models controlling for family cancer history. Goodness-of-fit analysis compared expected with observed relative risks by quantiles of the MA-PRS distribution., Results: In independent validation, the MA-PRS was significantly associated with BC risk in the full cohort (odds ratio, 1.43; 95% CI, 1.40 to 1.46; P = 8.6 × 10 -308 ) and within each major ancestry. The top decile of the MA-PRS consistently identified patients with two-fold increased risk of developing BC. Goodness-of-fit tests showed that the MA-PRS was well calibrated and predicted BC risk accurately in the tails of the distribution for both European and non-European women., Conclusion: The MA-PRS uses genetic ancestral composition to expand the utility of polygenic risk prediction to non-European women. Inclusion of genetic ancestry in polygenic risk prediction presents an opportunity for more personalized treatment decisions for women of varying and mixed ancestries.

Importance: National Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration., Objective: To examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making., Design, Setting, and Participants: Patients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022., Exposure: New and/or previous diagnosis of breast cancer., Main Outcomes and Measures: Disease management recommendations that were changed as a result of genetic testing results are reported., Results: Clinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%])., Conclusions and Relevance: In this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

Purpose: The prospective Neoadjuvant Breast Registry Symphony Trial compared the 80-gene molecular subtyping signature with clinical assessment by immunohistochemistry and/or fluorescence in situ hybridization in predicting pathologic complete response (pCR) and 5-year outcomes in patients with early-stage breast cancer., Methods: Standard-of-care neoadjuvant chemotherapy combined with trastuzumab or trastuzumab plus pertuzumab was given to patients with human epidermal growth factor receptor 2 (HER2)-positive tumors (n = 295). pCR was the primary end point, with secondary end points of distant metastasis-free survival and overall survival at 5 years., Results: Among clinically defined HER2-positive (cHER2) tumors, the 80-gene assay identified 29.5% (87 of 295) as Luminal-Type (cHER2/gLuminal), 14.9% (44 of 295) as Basal-Type (cHER2/gBasal), and 55.6% (164 of 295) as HER2-Type (cHER2/genomically classified as HER2 [gHER2]). Patients with cHER2/gHER2 tumors had a higher pCR rate (61.6%) compared with non-gHER2 tumors (26.7%; P < .001). Dual targeting for cHER2/gHER2 tumors yielded a higher pCR rate (75%) compared with those treated with single HER2-targeted therapy (54%; P = .006). For cHER2/gBasal tumors, the 42.9% pCR rate observed with dual targeting was not different from that with trastuzumab alone (46.4%; P = .830). Among those with cHER2/gBasal tumors, 5-year distant metastasis-free survival (68.6%; 95% CI, 49.1 to 81.9) was significantly worse than in patients with cHER2/gLuminal tumors (88.9%; 95% CI, 78.0 to 94.6) and cHER2/gHER2 tumors (87.4%; 95% CI, 80.2 to 92.2; P = .010), with similar corresponding overall survival differences., Conclusion: The 80-gene assay identified meaningful genomic diversity in patients with cHER2 disease. Patients with cHER2/gHER2 tumors, who benefitted most from dual HER2-targeted therapy, accounted for approximately half of the cHER2 cohort. Genomically Luminal tumors had low pCR rates but good 5-year outcomes. cHER2/gBasal tumors derived no benefit from dual therapy and had significantly worse 5-year prognosis; these patients merit special consideration in future trials., Competing Interests: Pat W. WhitworthEmployment: Integra LifeSciences (I)Leadership: Integra LifeSciences (I)Stock and Other Ownership Interests: Targeted Medical Education Inc, Integra LifeSciences (I)Honoraria: Puma BiotechnologyConsulting or Advisory Role: ImpediMed, Prelude Therapeutics, Becton DickinsonResearch Funding: Prelude Therapeutics, Agendia, MedneonTravel, Accommodations, Expenses: Targeted Medical Education Inc Peter D. BeitschEmployment: InvitaeLeadership: Targeted Medical Education IncStock and Other Ownership Interests: Targeted Medical Education Inc, InvitaeResearch Funding: InvitaeExpert Testimony: Dune Medical Devices, ImpediMedUncompensated Relationships: Medneon Paul D. RichardsStock and Other Ownership Interests: NanoViricidesResearch Funding: Carrick Therapeutics (Inst) James V. PellicaneStock and Other Ownership Interests: PreludeDxHonoraria: Agendia, PreludeDxSpeakers' Bureau: Agendia, PreludeDx Beth B. DupreeLeadership: Caliber MedicalStock and Other Ownership Interests: Videra SurgicalHonoraria: Medtronic, Perimeter Medical William DooleyLeadership: Shaga Medical LLCStock and Other Ownership Interests: Shaga MedicalResearch Funding: Agendia, XoftPatents, Royalties, Other Intellectual Property: patent pending—microendoscopy system Shiyu WangEmployment: Agendia Patricia DauerEmployment: AgendiaStock and Other Ownership Interests: AgendiaTravel, Accommodations, Expenses: Agendia Andrea R. MenicucciEmployment: Agendia Erin B. YoderEmployment: AgendiaStock and Other Ownership Interests: AgendiaTravel, Accommodations, Expenses: Agendia Lisa E. BlumencranzEmployment: Agendia William AudehEmployment: AgendiaLeadership: AgendiaStock and Other Ownership Interests: AgendiaConsulting or Advisory Role: Celanese, Private HealthResearch Funding: AgendiaTravel, Accommodations, Expenses: AgendiaNo other potential conflicts of interest were reported.

Background: The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status., Methods: The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18-90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) tumors., Results: MammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%; p = 0.64) or High-Risk tumors (14.5% vs. 11.5%; p = 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype., Conclusion: Intrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer., (© 2022. The Author(s).)

Purpose: The 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer., Methods: Neoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy. Pathologic complete response (pCR) and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed in 477 patients with IHC-defined ER+, HER2- tumors and in a reference group of 229 patients with IHC-defined triple-negative breast cancer (TNBC)., Results: 80-GS reclassified 15% of ER+, HER2- tumors (n = 73) as Basal-Type (ER+/Basal), which had similar pCR compared with TNBC/Basal tumors (34% v 38%; P = .52), and significantly higher pCR than ER+/Luminal A (2%; P < .001) and ER+/Luminal B (6%; P < .001) tumors. The 5-year DMFS (%, [95% CI]) was significantly lower for patients with ER+/Basal tumors (66% [52.6 to 77.3]), compared with those with ER+/Luminal A tumors (92.3% [85.2 to 96.1]) and ER+/Luminal B tumors (73.5% [44.5 to 79.3]). Importantly, patients with ER+/Basal or TNBC/Basal tumors that had a pCR exhibited significantly improved DMFS and OS compared with those with residual disease. By contrast, patients with ER+/Luminal B tumors had comparable 5-year DMFS and OS whether or not they achieved pCR., Conclusion: Significant differences in chemosensitivity and 5-year outcome suggest patients with ER+/Basal molecular subtype may benefit from neoadjuvant regimens optimized for patients with TNBC/Basal tumors compared with patients with ER+/Luminal subtype. These data highlight the importance of identifying this subset of patients to improve treatment planning and long-term survival., Competing Interests: Pat W. WhitworthEmployment: Integra LifeSciencesLeadership: Integra LifeSciencesStock and Other Ownership Interests: Targeted Medical Education, Inc, Cerebrotech Medical Systems, Medneon, Integra LifeSciencesHonoraria: Puma BiotechnologyConsulting or Advisory Role: ImpediMed, Prelude Therapeutics, Becton DickinsonResearch Funding: Prelude Therapeutics, Agendia, MedneonTravel, Accommodations, Expenses: Targeted Medical Education, Inc Peter D. BeitschEmployment: InVitaeLeadership: Targeted Medical Education, IncStock and Other Ownership Interests: Targeted Medical Education, Inc, InVitaeResearch Funding: InVitaeExpert Testimony: Dune Medical Devices, ImpediMedUncompensated Relationships: Medneon James V. PellicaneStock and Other Ownership Interests: PreludeDxHonoraria: Agendia, PreludeDxSpeakers' Bureau: Agendia, PreludeDx Paul L. BaronHonoraria: Myriad GeneticsConsulting or Advisory Role: Myriad GeneticsSpeakers' Bureau: Myriad GeneticsTravel, Accommodations, Expenses: Myriad Genetics William C. DooleyLeadership: Shaga Medical, LLCStock and Other Ownership Interests: Shaga MedicalResearch Funding: Agendia, XoftPatents, Royalties, Other Intellectual Property: Patent pending: microendoscopy system Kenneth H. CowanStock and Other Ownership Interests: United Health GroupConsulting or Advisory Role: MerckResearch Funding: Merck Beth-Ann LesnikoskiEmployment: HCA HealthcareStock and Other Ownership Interests: HCA HealthcareResearch Funding: Agendia (Inst), Seattle Genetics (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/246359 Beth B. DupreeHonoraria: Medtronic Shiyu WangEmployment: AgendiaStock and Other Ownership Interests: Agendia Andrea R. MenicucciEmployment: Agendia Erin B. YoderEmployment: AgendiaStock and Other Ownership Interests: AgendiaTravel, Accommodations, Expenses: Agendia Kate CorcoranEmployment: Agendia Lisa E. BlumencranzEmployment: Agendia William AudehEmployment: AgendiaLeadership: AgendiaStock and Other Ownership Interests: AgendiaConsulting or Advisory Role: Celanese, Private HealthResearch Funding: AgendiaTravel, Accommodations, Expenses: AgendiaNo other potential conflicts of interest were reported.

Background: The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT ® ) that evaluates recurrence risk has been developed and validated. We evaluated the impact of DCISionRT on clinicians' recommendations for adjuvant RT., Methods: The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations., Results: Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-test, 46% of patients had their recommendation changed to omit RT after an initial recommendation for RT. When considered in conjunction with other clinicopathologic factors, the elevated DCISionRT score risk group (DS > 3) had the strongest association with an RT recommendation (odds ratio 43.4) compared with age, grade, size, margin status, and other factors., Conclusions: DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade., (© 2021. The Author(s).)

Purpose: The classification of germline variants may differ between labs and change over time. We apply a variant harmonization tool, Ask2Me VarHarmonizer, to map variants to ClinVar and identify discordant variant classifications in a large multipractice variant dataset., Methods: A total of 7496 variants sequenced between 1996 and 2019 were collected from 11 clinical practices. Variants were mapped to ClinVar, and lab-reported and ClinVar variant classifications were analyzed and compared., Results: Of the 4798 unique variants identified, 3699 (77%) were mappable to ClinVar. Among mappable variants, variants of unknown significance (VUS) accounted for 74% of lab-reported classifications and 60% of ClinVar classifications. Lab-reported and ClinVar discordances were present in 783 unique variants (21.2% of all mappable variants); 121 variants (2.5% of all unique variants) had within-practice lab-reported discordances; and 56 variants (1.2% of all unique variants) had lab-reported discordances across practices. The unmappable variants were associated with a higher proportion of lab-reported pathogenic classifications (50% vs. 21%, p < 0.0001) and a lower proportion of lab-reported VUS classifications (46% vs. 74%, p < 0.0001)., Conclusions: Our study shows that discordant variant classification occurs frequently, which may lead to inappropriate recommendations for prophylactic treatments or clinical management.

Background: Aiming to minimize overtreatment of high-risk breast lesions (HRLs), including atypical ductal hyperplasia, and small breast cancers, including ductal carcinoma in situ (DCIS), we investigated a minimally invasive (MI) approach to definitive diagnosis and management of these conditions., Methods: In the prospective Intact Percutaneous Excision registry study, women aged 31-86 years had removal of small invasive cancers, DCIS, or HRLs using image-guided 12-20 mm radiofrequency basket capture (MI excision). Second-pass 20 mm basket capture obtained shaved margins in cancer patients. Standard imaging (specimen, breast) and histologic criteria were applied. Patient data were registered in an Institutional Review Board approved, Health Insurance Portability and Accountability Act-compliant registry., Results: Of 282 registered patients, 124 had DCIS (n = 52) or invasive cancer (n = 72) and 160 had HRLs. Among cancer patients, 101 (81%) had clear histologic margins [average lesion size was 11 mm for both invasive cancers (4-20 mm) and DCIS (1.5-20 mm)]; 29 patients had re-excision (six despite clear margins). Among 160 HRLs, two were upgraded to DCIS and had MI excision. Two other HRL patients had subsequent standard surgical excision (no cancer found)., Conclusion: For diminutive HRLs, DCIS, and invasive cancers, MI excision can achieve the same procedure goals as standard surgical excision. Because MI excision removes less tissue with small incisions, it may reduce the discomfort and expense associated with standard treatment.

This single-institution experience evaluated the use of bioimpedance spectroscopy to facilitate early detection and treatment of breast cancer-related lymphedema (BCRL) in a cohort of 596 patients (79.6% high risk). Seventy-three patients (12%) developed an elevated L-Dex score with axillary lymph node dissection (P < .001), taxane chemotherapy (P = .008), and regional nodal irradiation (P < .001) associated. At last follow-up, only 18 patients (3%) had unresolved clinically significant BCRL requiring complete decongestive physiotherapy. This rate of BCRL is lower than reported in contemporary studies, supporting recent NCCN guidelines promoting prospective screening, education and intervention for BCRL., (© 2017 The Authors. The Breast Journal Published by Wiley Periodicals, Inc.)

Background: Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping., Methods: Of 308 clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U.S. institutions, 297 received neoadjuvant chemotherapy (NCT) with HER2-targeted therapy and underwent surgery. This study compared the pathologic complete response (pCR) rate of BluePrint versus clinical subtypes with treatment, specifically differences between trastuzumab (T) treatment and trastuzumab and pertuzumab (T/P) treatment., Results: In this study, 60% of the patients received NCT-T, and 40% received NCT-T/P. The overall pCR rate (ypT0/isN0) was 47%. BluePrint classified 161 tumors (54%) as HER2 type, with a pCR rate of 65%. This was significantly higher than the pCR rate for the 91 HER2+ tumors (31%) classified as luminal (18%) (p = 0.00001) and the 45 tumors (15%) classified as basal (44%) (p = 0.0166). The patients treated with T/P had higher pCR rates than those treated with trastuzumab alone. The difference was most pronounced in the BluePrint luminal patients (8 vs. 31%). The highest pCR was reached by the BluePrint HER2-type patients treated with T/P (76%)., Conclusions: The addition of pertuzumab leads to increased pCR rates for all HER2+ patient groups except for the BluePrint basal-type patients. This better response was most pronounced for the BluePrint luminal-type patients.

Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio [PEPI = 0 v PEPI > 0], 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women: A Phase III Study; clinical trial information: NCT01953588).

Purpose: Neoadjuvant therapy (NAT) has been shown to clinically downstage locally advanced breast cancers. This study aimed to determine whether a meaningful change in gene signatures occurs between pre- and post-NAT breast cancers for patients who do not achieve a pathologic complete response., Methods: The current analysis included women from the prospective Neoadjuvant Breast Registry Symphony Trial who had breast cancer and awaited NAT. MammaPrint and BluePrint (Agendia, Inc., Irvine, CA) assays were performed on pre- and post-NAT breast tumor samples., Results: At the completion of NAT, 93 patients with residual disease had their remaining tumor analyzed for MammaPrint and BluePrint. Of 93 patients, 21 switched tumor classification: 16 from high risk (HR) to low risk (LR) and 1 from LR to HR (p < 0.001). Four additional patients switched molecular subtype but remained HR. Although only 17 patients switched in their MammaPrint risk classification, the underlying MPIndex was significantly altered after treatment across all patients (p < 0.001). Additionally, the three BluePrint indices for luminal, human epidermal growth factor receptor 2 (HER2), and basal type also were significantly altered after treatment, in a subtype-dependent manner., Conclusion: This substudy showed that NAT significantly altered the genomic signature of the patient's breast cancer compared with the patient's pretreatment genomic profile. These alterations occurred in a subtype-dependent manner, suggesting that NAT may have either eliminated the most susceptible tumor subclone, leaving the treatment resistant clone with a different genetic signature, or altered molecular characteristics of the original cancer.

Objectives: This study was a multicenter evaluation of the SAVI SCOUT(®) breast localization and surgical guidance system using micro-impulse radar technology for the removal of nonpalpable breast lesions. The study was designed to validate the results of a recent 50-patient pilot study in a larger multi-institution trial. The primary endpoints were the rates of successful reflector placement, localization, and removal., Methods: This multicenter, prospective trial enrolled patients scheduled to have excisional biopsy or breast-conserving surgery of a nonpalpable breast lesion. From March to November 2015, 154 patients were consented and evaluated by 20 radiologists and 16 surgeons at 11 participating centers. Patients had SCOUT(®) reflectors placed up to 7 days before surgery, and placement was confirmed by mammography or ultrasonography. Implanted reflectors were detected by the SCOUT(®) handpiece and console. Presence of the reflector in the excised surgical specimen was confirmed radiographically, and specimens were sent for routine pathology., Results: SCOUT(®) reflectors were successfully placed in 153 of 154 patients. In one case, the reflector was placed at a distance from the target that required a wire to be placed. All 154 lesions and reflectors were successfully removed during surgery. For 101 patients with a preoperative diagnosis of cancer, 86 (85.1 %) had clear margins, and 17 (16.8 %) patients required margin reexcision., Conclusions: SCOUT(®) provides a reliable and effective alternative method for the localization and surgical excision of nonpalpable breast lesions using no wires or radioactive materials, with excellent patient, radiologist, and surgeon acceptance.

Background: The current technique for locating nonpalpable breast lesions is wire localization (WL). Radioactive seed localization and intraoperative ultrasound were developed to improve difficulties with WL. The SAVI SCOUT surgical guidance system was developed to improve these methods. The SCOUT system is a non-radioactive, FDA-cleared medical device that uses electromagnetic wave technology to provide real-time guidance during excisional breast procedures., Methods: Consenting patients underwent localization and excision using an implantable electromagnetic wave reflective device (reflector) and a detector handpiece with a console. Using image guidance, the reflector was placed up to 7 days before the surgical procedure. The primary end points of the study were successful reflector placement, localization, and retrieval. The secondary end points were percentage of clear margins, reexcision rates, days of placement before excision, and physician comparison with WL., Results: This study analyzed 50 patients. The reflectors were placed under mammographic guidance (n = 18, 36 %) or ultrasound guidance (n = 32, 64 %). Of the 50 patients, 10 (20 %) underwent excisional biopsy and 40 (80 %) had a lumpectomy. The lesion and reflector were successfully removed in all 50 patients, and no adverse events occurred. Of the 41 patients who had in situ and/or invasive carcinoma identified, 38 (93 %) had clear margins and 3 (7 %) were recommended for reexcision., Conclusions: These data suggest that the SCOUT system is safe and effective for guiding the excision of nonpalpable breast lesions and a viable alternative to standard localization options. A larger prospective, multi-institution trial of SCOUT currently is underway to validate these findings.