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Background. The benefits of adjuvant radiation therapy (RT) in patients with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Although there is level-I evidence supporting the role of RT in reducing the risk of local recurrence, the absolute benefit is variable. Current guidelines generally recommend RT for all patients having BCS, but it is important to develop prognostic and predictive tools to better assess risk and understand the impact such a tool would have on treatment decisions. The DCISionRT Test(PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score for assessing 10-year risk of recurrence and RT benefit using individual tumor biology as assessed by clinical and pathologic biomarkers. Methods. This is a prospective cohort study for patients diagnosed with DCIS of the breast. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinico-pathologic features are stored in a de-identified registry for participating institutions from a variety of geographic regions across the US. The study will also collect 5- and 10-year recurrence and survival data. The study includes females over age 25 who are candidates for BCS and eligible for RT and/or systemic treatment with sufficient tissue to generate test results. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status and other clinico-pathologic factors. Changes in treatment recommendations will be assessed using McNemar's test with an alpha level of 0.05. Differences in recurrence-free and overall survival will be evaluated by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. A planned early interim analysis based on the first 200 patients has been recently completed and reported. Results. As of July 9, 2021, 1,986 patients have been accrued from 64 institutions. Ten additional institutions are currently in the process of joining the study. We are planning to enroll up to 2,500 patients from up to 100 institutions. Citation Format: Steven C Shivers, Pat W Whitworth, Rakesh Patel, Troy Bremer, Charles E Cox. The PREDICT Registry: A prospective registry to evaluate the effect of a predictive assay on treatment decisions in patients with DCIS following breast conserving therapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-09-02.

Background: The role of adjuvant RT following breast conserving surgery (BCS) for women with ductal carcinoma in situ (DCIS) remains controversial. Although there is level I evidence supporting the role of RT in reducing the risk of local recurrence, prognostic and predictive tools are needed to better stratify individual risks and benefits of RT. The DCISionRT® Test (PreludeDx, Laguna Hills, CA) is a biosignature that uses individual tumor biology in conjunction with clinical and pathologic risk factors. The test provides a validated score (DS) for women receiving BCS that assesses 10-year risk of DCIS recurrence and development of invasive breast cancer with and without adjuvant RT. We established a registry to evaluate the decision impact of DCISionRT on DCIS treatment recommendations. Methods: The PREDICT study is a prospective, multi-institutional registry for patients who received DCISionRT testing as part of their routine care. The registry includes females 26 and older who are diagnosed with DCIS and are candidates for BCS and eligible for RT or systemic therapy. Treating physicians completed treatment recommendation forms before and after receiving test reports to capture surgical, radiation and hormonal treatment (HT) recommendations and patient preferences. The primary endpoint is to identify the proportion of patients where testing led to a change in RT recommendation. Additional analyses include changes in recommendations in patient subgroups based on clinicopathologic factors or type of treating physician. Results: Analysis was performed in 969 patients treated at 55 sites who had definitive BCS and subsequent DCISionRT testing. The median age of patients was 62 years, 19% were 50 or younger, nuclear grade was high in 31% and tumor size was 2.5 cm or greater for 11%. Test results were DS Low risk (DS ≤ 3) for 63% of women and 37% were DS Elevated risk (DS > 3). Overall, RT recommendation (yes/no) was changed for 40% of women after DCISionRT testing and HT recommendation was changed for 11%. There was a net decrease in RT recommendation from 69% pre-assay to 50% post-assay (p TABLE 1. Impact of DCISionRT on adjuvant radiation recommended by clinicopathologic features.RT recommendedPre- to post-test change in RT recommendedTotal change in RT recommendedClinical factorNPre-test(%)Post-test(%)Net change (%)Yes to no (%)No to yes (%)Overall change (%)95% CIp-ValueAge, years< 501648148-3243133730-45% 2.5 cm1109269-2327222619-35% Citation Format: Steven C Shivers, Pat W Whitworth, Rakesh Patel, Troy Bremer, Charles E Cox. Interim analysis of the PREDICT Registry: Changes in treatment recommendation for a biologic signature predictive of radiation therapy (RT) benefit in patients with DCIS [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-12.

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.

Background/Objective: Breast cancer incidence in Asian populations has increased in recent years, and variation in prognosis and tumor subtypes indicates that further study is warranted to characterize these differences and identify actionable targets. Patients of Asian ancestry are underrepresented in US registries, and few studies have characterized molecular profiles for these patients. In the current analysis, we assess clinical, pathological, and molecular profiles from self-reported Asian breast cancer patients (AS), in comparison with age-matched Caucasian (CA) and African American patients (AA), to evaluate the influence of Asian ancestry on differential gene expression in breast tumors. Methods: This meta-analysis included cohorts of self-reported AS, CA, and AA with early-stage, invasive breast cancer (EBC) prospectively enrolled in the US from 2011 to 2020 in FLEX (NCT03053193), MINT (NCT01501487), or IMPACt (NCT02670577) trials. AS were significantly younger (mean, 55 years) than CA (mean, 61 years, p ± 0.5 were considered significant. Results: AS tumors were classified as 59% MP HR, compared with 44% HR in age-matched CA (p=0.08) and 64% HR in age-matched AA (p=0.17). AS had a significantly lower rate of obesity (16%, body mass index ≥30) compared with CA (41%) and AA (67%) (p Conclusions: AS were significantly younger and more often pre/peri-menopausal at diagnosis compared with CA and AA, consistent with the literature. Most clinical-pathological factors were similar between age-matched groups, except for the obesity rate, which was significantly lower in AS than in CA or AA. Although not significant, AS had EBC that was more often MP HR than CA and less often HR than AA; studies with larger patient groups will help confirm these trends. The current analysis revealed different underlying gene expression pathways in AS compared with other ethnic groups, which may result in differential clinical outcomes. As genomic profiling data are not widely available for Asian American EBC patients, further analyses are warranted to elucidate these outcomes and identify appropriate therapeutic strategies. Pathology and Genomic Results(unknowns excluded)Asian (n=103)Caucasian (n=103)African American (n=100)p-valueAS vs. CAp-value AS vs. AAER status (IHC)ER Positive69 (94.5%)89 (98.9%)73 (80.2%)0.1250.010ER Negative4 (5.5%)1 (1.1%)18 (19.8%)PR status (IHC)PR Positive64 (87.7%)81 (90%)63 (69.2%)0.4110.006PR Negative9 (12.3%)9 (10%)28 (30.8%)HER2 (IHC/FISH)HER2 Positive3 (4.2%)3 (3.4%)13 (14.3%)0.1720.017HER2 Negative64 (88.9%)85 (95.5%)77 (84.6%)Equivocal5 (6.9%)1 (1.1%)1 (1.1%)MP/BP resultsLuminal A39 (40.6%)51 (53.7%)28 (30.4%)0.2320.043Luminal B45 (46.9%)38 (40.0%)42 (45.7%)HER2 (MP HR)7 (7.3%)4 (4.2%)5 (5.4%)Basal (MP HR)5 (5.2%)2 (2.1%)17 (18.5%) Citation Format: Margaret Chen, Ava Kwong, Carolyn Hendricks, Nina D'Abreo, Laura Lee, Hatem H. Soliman, Charles Cox, Heather M. Kling, Rajith Bhaskaran, Shiyu Wang, Andrea Menicucci, Sarah Untch, William Audeh, FLEX Investigators Group. Molecular profiles and clinical-pathological features of Asian early-stage breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-69.

Background: Elderly breast cancer (BC) patients are an understudied population, with limited evidence regarding treatment options and outcomes and a lack of research involving prognostic multigene assays for this group. One study in patients 65-89 years old with an Oncotype DX Recurrence Score ≥ 26 concluded that gene expression profiling tests have limited utility in elderly patients, and should only be used for patients aged 65-74 with no/low to moderate comorbidities and not for patients ≥ 75. In this study, the 70-gene risk of distant recurrence signature, MammaPrint (MP), and 80-gene molecular subtyping signature, BluePrint (BP), were evaluated in both the neoadjuvant and adjuvant settings in elderly patients with early stage BC. Methods: This analysis included 211 BC patients classified as cT2-4N0-3M0 (T2 > 3.5 cm if N0) who received neoadjuvant chemotherapy and enrolled in the Multi-Institutional Neoadjuvant Therapy MammaPrint Project (MINT) study from 2011-2016. Lymph node (LN) involvement was established following neoadjuvant treatment. The second analysis included 517 early stage BC patients with 0-3 positive LNs who enrolled in the community based cohort study (COPPER) from 2009-2016. Patients were given adjuvant treatment following standard of care. Patients from both cohorts were divided into age at diagnosis groups: < 65, 65-74, and > 74. MP stratified patients into either Low Risk (LR) or High Risk (HR) groups. BP classified patient samples into Luminal, HER2, or Basal subtype. Kaplan Meier analysis and log-rank test were used to assess differences in overall survival (OS) and distant metastasis free survival (DMFS). Clinical risk assessment based on the MINDACT trial algorithm was performed. Results: From MINT, 35 patients were ≥ 65 years old; 80% were HR and 20% were LR. Pathological complete response (pCR) was achieved in 36% (10/28) of elderly HR patients, of whom 70% were HER2 and 30% were Basal by BP. Nodal downstaging occurred in 55% (11/20) of LN positive elderly HR patients, of whom 64% (7/11) achieved pCR. BP classified patients with nodal downstaging as HER2 (55%), Basal (36%), or Luminal (9%). Importantly, pCR and nodal downstaging were more likely to be achieved in HR tumors and correlated with BP subtype in both young and elderly patients. From the COPPER cohort, 77% of HR patients 65-74 years old received chemotherapy (CT), whereas 74% of LR patients omitted CT. Of patients > 74, 49% of HR patients received CT, whereas 75% of LR patients omitted CT. OS and DMFS probabilities indicated good survival outcomes in LR patients that omitted CT and HR patients that received CT, with no significant difference between age groups. A majority of HR patients treated with CT and over 1/3 of LR patients that omitted CT had high clinical risk. Interestingly, among all patients that had a metastasis event, mortality was less likely to occur in patients that received dose dense AC (doxorubicin and cyclophosphamide). Conclusion: MP and BP may identify HR elderly patients who are likely to achieve nodal downstaging and pCR. Elderly patients were safely spared or assigned adjuvant CT based on MP results independent of clinical risk. Furthermore, these data are in line with previous studies that suggest similar survival benefits between older and younger patients who are candidates for aggressive CT regimens. MP and BP elucidate information about tumor biology and provide prognostic value, which may help inform treatment decisions, independent of patient age. MINTAge group< 6565-74> 74MP resultHRLRHRLRHR# of patients152242177% of patients with pCR35% (53/152)033% (7/21)043% (3/7)# of LN+ patients103181456% of LN+ patients with nodal downstaging49.5% (51/103)22% (4/18)50% (7/14)067% (4/6)% of LN+ patients with pCR & nodal downstaging65% (33/51)071%(5/7)050%(2/4)COPPERAge group< 6565-74> 74MP resultHRLRHRLRHRLR# of patients1409988665569# of patients received CT121256813278# of patients omitted CT116717492052# of patients with unknown treatment873489Groups treated based on MPHR treated with CTLR omitted CTAge group< 6565-74> 74< 6565-74> 745-yr DMFS probability (95% CI)91% (80.2-96.7)87% (60.2-91.4)87% (55.2-96.6)100%98% (84.3-99.7)94% (75.9-98.5)5-yr OS probability (95% CI)94% (80.2-98.2)96% (83.4-98.9)86% (54.7-96.5)100%98% (84.3-99.7)97% (80.4-99.6)% Clinical high risk83% (100/121)76% (52/68)63% (17/27)34% (23/67)37% (18/49)35% (18/52) Citation Format: Peter W. Blumencranz, Mehran Habibi, Lisa Blumencranz, Andrea Menicucci, Shiyu Wang, Amy Truitt, William Audeh, Jolanta L. Baginski, Steven Shivers, Geza Acs, Charles E. Cox, MINT Investigators Group. Mammaprint and blueprint as prognostic indicators for elderly patients with early stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-41.

Background: The main goal of the Multi-Institutional Neo-Adjuvant Therapy MammaPrint (MINT) project was to determine the predictive power of the combination of the molecular assays MammaPrint and BluePrint (Agendia Inc., Irvine, CA) for chemosensitivity as measured by complete pathological response (pCR) in patients with locally advanced breast cancer (LABC). MammaPrint is a 70-gene microarray-based assay that classifies each breast cancer patient as low or high risk to develop metastases within 10 years after diagnosis. The BluePrint test is an 80-gene molecular subtyping profile that discriminates between luminal, basal and HER-2 subtypes. Methods: After appropriate IRB approval, 270 female patients with histologically-proven invasive breast cancer and no distant metastases were enrolled in this study. Patients had a clinical tumor classification of T2-T4 with 0-3 positive lymph nodes. DCIS or LCIS was allowed in addition to invasive cancer at the T2 or T3 levels. At least one lesion had to be accurately measured in two dimensions utilizing mammogram, ultrasound, or MRI images to define specific size and validate pCR. Patients were required to have adequate bone marrow reserves, renal function and hepatic function, as determined by standard blood and serum measurements. Patients under 18 years of age or those with confirmed metastatic disease, inflammatory breast cancer, any serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease were excluded. Patients with any prior chemotherapy, radiotherapy, or endocrine therapy for the treatment of breast cancer were also excluded. Tumor samples were collected via incisional or core needle biopsy and shipped to Agendia for processing of the MammaPrint and BluePrint gene panels, as well as whole human genome expression microarrays. Comparison of response rates between MammaPrint and BluePrint molecular subtypes was conducted using Pearson Chi-square test with chemo-responsiveness measured as a binary response: pCR or residual disease. Results: Of 270 patients enrolled, 56 did not have TNM or RCB staging information reported in the case report form and/or were not submitted for central pathology review. Of 214 patients evaluated by central pathology review, 68 (32%) exhibited a pCR. Patients with a high risk MammaPrint result had a higher pCR rate (37%) compared to patients with a low risk MammaPrint (0%). And patients with a HER-2 or basal molecular subtype by BluePrint had significantly higher rates of pCR (62%, 37%, respectively). Conclusion: Upfront evaluation of LABC tumors using the combination of MammaPrint and BluePrint can help in the clinico-pathologic evaluation to determine which patients are more likely to benefit from neo-adjuvant chemotherapy, ranging from expected minimal response in Luminal A to substantial responses for HER2-type and Basal-type tumors. Additional studies to evaluate the prognostic and/or predictive values of additional gene panels from the whole human genome microarrays are underway. Rate of pCR in MammaPrint and MammaPrint/BluePrint groupsGroupsResidual DiseasepCRP valueMP Risk GroupLow Risk27 (100%)0 (0%)0.0004High Risk114 (63%)67 (37%)BP subtypeBasal42 (63%)25 (37%)2 x 10-9HER220 (38%)33 (62%)Luminal A26 (100%)0 (0%)Luminal B53 (85%)9 (15%) Citation Format: Brian Longbottom, Steven C Shivers, Geza Acs, Charles E Cox. Combined use of MammaPrint and BluePrint assays to evaluate patients for response to neo-adjuvant chemotherapy for locally advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-30.

BACKGROUND: When considering health-related, quality-of-life and monetary costs associated with post-surgical treatments for women diagnosed with Ductal Carcinoma In Situ (DCIS), there remains a need for prognostic and predictive tools to help design individual treatment planning. DCISionRT (PreludeDx, Laguna Hills, CA) is a validated biologic signature to assess the 10-year event risk for DCIS patients managed with breast conserving surgery (BCS). The 10-year risks are provided separately for patients treated with and without adjuvant radiation therapy (RT) after BCS. The study was designed to measure the change in adjuvant RT recommendation. This is a planned interim analysis of the study, which will eventually comprise up to 2,500 patients and 100 sites. METHODS: The registry includes females over the age of 25 who are candidates for breast conserving surgery and eligible for RT. Survey forms are completed pre- and post-DCISionRT test to capture treatment recommendations and patient preferences. This interim analysis was performed to assess changes in RT recommendation for patients treated with BCS in different clinicopathologic subgroups. Specifically, ‘good risk’ profiles were based on the RTOG 9804 and ECOG 5194 study designs. RTOG 9804 like criteria was screening detected tumors with nuclear grade of 1 or 2, size of ≤ 2.5 cm, and clear (≥ 2 mm) surgical margins. ECOG 5194 like criteria was tumors with nuclear grade of 1 or 2, size of ≤ 2.5 cm, and clear surgical margins, or nuclear grade of 3, size of ≤ 1 cm, and clear surgical margins. Statistics were provided as percentages and counts, and McNemar’s test was used to assess change in RT with a p-value of RESULTS: There were 513 patients from 32 sites with testing completed after treatment with BCS. Of these patients, 16% were ≤ 50 years of age, 60% were ≥ 60 years of age, and 26% were ≥ 70 years of age. The DCIS tumor nuclear grade was high in 32% of patients, and the size of the tumor was ≤ 1 cm for 68% of patients. There were 49% of patients who met RTOG 9804 like criteria, 51% who met the ECOG 5194 (grade 1 or 2) criteria, and 45% of patients who met the ECOG 5194 (grade 3) criteria. RT was recommended to 52% and 53% patients for RTOG 9804/ECOG 5194 (grade 1 or 2) criteria pre-testing, and 42% post-testing. For ECOG 5194 (grade 3) like criteria, 64% of patients were recommended RT pre-test, and 40% were recommended RT post-test. In all criteria groups, for patients whom were initially recommended RT pre-test, 51% to 54% were not recommended RT post-test, while patients initially not recommended RT pre-test, 25% to 37% were recommended RT post-test. Overall, the post-test RT recommendation was significantly changed from between 42% and 46% for patients with ‘good-risk’ clinicopathologic criteria. CONCLUSIONS: The PREDICT study interim analysis demonstrates a significant absolute overall change post DCISionRT testing for RT recommendation in patients with ‘good-risk’ clinicopathology. RT recommendations were changed post-test for 42% to 46% of patients meeting RTOG 9804/ECOG 5194 like criteria. Integration of DCISionRT testing had a significant impact on the RT recommendations aimed at reducing overtreatment and minimizing undertreatment. Table 1. Pre-Post DCISionRT Impact by ‘good-risk’ criteria.n% RTPre-testYes% RTPost-test Yes% RTPre-Yes, Post-No% RTPre-No, Post-Yes% Total Decision Change95% CIp-valueRTOG 9804 criteriaGrade 1 or 2, Size ≤ 2.5 cm, screen detected, wide margins2525242543746%40 - 52%1.2E-02ECOG E5194 criteriaGrade 1 and 2, Size ≤ 2.5 cm, wide margins2625342533645%39 - 51%0.010Grade 3, Size ≤ 1 cm, wide margins2316440512542%36 - 48%2.4E-08 Citation Format: Chirag Shah, Frank Vicini, Steven C Shivers, Pat W Whitworth, Rakesh Patel, Charles E Cox, Troy Bremer. Clinical utility of a biologic signature to assess DCIS recurrence risk in patients meeting ‘good-risk’ criteria (RTOG 9804, ECOG 5194): Interim analysis of the DCISionRT PREDICT study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-17.

Background: The benefits of adjuvant radiation therapy (RT) in DCIS patients treated with breast conserving surgery (BCS) remains controversial. Although there is level I evidence supporting the role of RT in reducing the risk of local recurrence, the incremental absolute benefit is variable. Current treatment guidelines generally recommend RT for all patients having BCS. When considered in the context of the economic, health-related, and quality-of-life costs associated with RT, it is critical to identify patients who are at low enough risk to consider foregoing RT. It is important to develop prognostic tools to better assess risk and understand the impact such a tool would have on treatment decisions. The DCISionRT™ Test (PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score for assessing 10-year risk of recurrence and RT benefit using individual tumor biology in conjunction with clinical and pathologic risk factors. Trial Design: This is a prospective cohort study for patients diagnosed with ductal carcinoma in situ (DCIS) of the breast. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinicopathologic features are stored in a de-identified registry for future analysis of data across participating institutions from a variety of geographic regions in the US. The study will also collect 5- and 10-year recurrence and survival data. Eligibility Criteria: The study includes females over the age of 25 who are candidates for BCS and eligible for RT and/or systemic treatment with sufficient tissue to generate test results. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. Specific Aims: The primary objective of this study is to create a de-identified database of patients, test results, treatment decisions and outcomes that can be queried to determine the clinical utility of the DCISionRT Test in actual clinical use for the management of DCIS. The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy after the physician and patient have reviewed the DCISionRT test results, including subgroup analysis by physician type (surgeon, radiation oncologist or tumor board). Secondary endpoints are identification of the key drivers for treatment recommendations, including age, size, grade, architecture, necrosis, palpability, presentation, hormone receptor status, race, ethnicity, family history, etc. Statistical Methods: Study results will be analyzed by summary descriptive statistics, such as patient counts, percentages, means, etc. Changes in treatment recommendations will be assessed using McNemar's chi-squared test for symmetry of rows and columns in a two-dimensional contingency table with an alpha level of 0.05. Differences in recurrence-free and overall survival will be evaluated by Kaplan-Meier survival analysis using the logrank test and/or the Cox Proportional Hazards model. A planned early interim analysis based on the first 200 patients has been recently completed and reported - data are available upon request (contact Steven Shivers, PhD, sshivers@preludedx.com.) Accrual: As of July 1, 2019, 319 patients have been accrued from 56 physicians at 25 institutions. Twenty-two additional institutions are currently in the process of joining the study. We are planning to accrue up to 2,500 patients from up to 100 institutions. Contact Information: We are actively recruiting institutions for participation. For more information, please contact: Mary Kay Hardwick, mkhardwick@tmebcn.com. Citation Format: Steve C Shivers, Pat Whitworth, Rakesh Patel, Troy Bremer, Charles E Cox. The PREDICT registry: A prospective registry study to evaluate the effect of the DCISionRT test on treatment decisions in patients with DCIS following breast conserving therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-09-03.

Background discussion: Genomic signatures are revolutionizing the definition, identification, and treatment of breast cancer. To precisely stratify breast cancers into actionable subgroups, full genome (FG) expression data and matching clinical data must be aggregated into a large, real-world dataset. Such a dataset will accelerate research and discovery, especially for smaller patient subsets that are not as widely represented within the current body of literature. Trial design and aims: FLEX is a multicenter, prospective, population-based, observational trial for patients with Stage I, II, and III breast cancer. All patients with stage I to III breast cancer who receive MammaPrint (MP), with or without BluePrint (BP) on a primary breast tumor are eligible for enrollment. The study’s primary aim is to create a large scale, population-based registry of full genome expression data matched with clinical data to investigate new gene associations with prognostic and/or predictive value in a real-world setting. Secondary objectives include utilizing the shared study infrastructure to examine and generate hypotheses for targeted subset analyses and/or trials based on full genome expression data. The design of FLEX allows targeted sub-studies and sub-analyses to be added as appendices after the initial baseline study is opened. Data collection follows patients from diagnosis through 10 years of follow-up. Patients enrolled in the initial study are also eligible for inclusion in sub-studies for which they meet all criteria and additional consent is not required. Additional clinical data will be collected as specified in the appendix protocols. The FLEX collaborative platform allows participating investigators the opportunity to author their own sub-study protocols, as approved by the FLEX Steering Committee of their peers. 14 sub-studies have already been identified and approved (Table 1). Eligibility and accrual: The study will enroll a minimum of 10000 patients aged ≥18 years with histologically proven invasive stage I, II, or III breast cancer. Since April 2017 over 2362 patients have been enrolled. Trial contact information: NCT03053193 FLEX@agendia.com TABLE 1PIINSTITUTIONTYPEADDITIONAL CONSENTARM(S)DESCRIPTIONMehran HabibiJohns HopkinsLocal SubstudyYesNeoadjuvantComprehensive gene expression profiling of breast cancer in patients receiving short-course endocrine therapy prior to surgeryMehran HabibiJohns HopkinsLocal SubstudyYesAllCorrelation of the microbiome with breast cancer gene expressionThomas LomisValley Breast ClinicCollaborative group substudyYesNeoadjuvantComplementary data collection for patients participating in the ODM-201 trial. FLEX will provide gene expression profiling for exploratory and signature discovery purposesIan GradyNorth Valley Breast CareSubstudyNoAllImpact of genomic risk classification on travel time to receive breast cancer care: a QOL studyPat WhitworthNashville Breast CenterSubstudyNoNeoadjuvantGenomic reclassification of large tumors in patients eligible to receive neoadjuvant therapyAdam BrufskyUniversity of Pittsburgh Medical CenterSubstudyNoNeoadjuvant, adjuvantResponse to standard chemotherapy regimens in clinically ER+/PR+/HER2+ (triple positive) patients according to BluePrint molecular subtypesAdam BrufskyUniversity of Pittsburgh Medical CenterSubstudyNoAllExpression signatures by response to bisphosphonates in ER+ patients receiving adjuvant therapy (SOC option), or for osteoporosis after primary treatmentAdam BrufskyUniversity of Pittsburgh Medical CenterSubstudyNoAllGene expression in breast cancer patients with obesityJennifer A. CrozierBaptist MD Anderson Cancer CenterSubstudyNoAllMP and BP in male breast cancerJennifer A. CrozierBaptist MD Anderson Cancer CenterSubstudyNoAllMP and BP evaluation in breast cancer patients ≥70Jennifer A. CrozierBaptist MD Anderson Cancer CenterSubstudyNoAllFG evaluation in invasive lobular carcinomaJennifer A. CrozierBaptist MD Anderson Cancer CenterSubstudyNoAllMP and BP relation to clinical PR positivityJennifer A. CrozierBaptist MD Anderson Cancer CenterSubstudyNoAllMP and BP relation to clinical Ki67 scoreJennifer A. CrozierBaptist MD Anderson Cancer CenterSubstudyNoAllMP and BP in metaplastic breast cancer Citation Format: Jennifer A Crozier, Gordan Srkalovic, Adam Brufsky, Mehran Habibi, Pat Whitworth, Charles Cox, Ian Grady, Thomas Lomis, Nina D'Abreo, Erin B Yoder, Sarah Untch, Heather Kling, William Audeh, Bastiaan Van der Baan, FLEX Investigators Group. The FLEX real world data platform explores new gene expression profiles and investigator-initiated protocols in early stage breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-17-02.

Objective To assess the safety and efficacy of single-fraction, intra-operative radiation therapy (IORT) delivered with the Xoft® Axxent® Electronic Brachytherapy System® (eBx®) immediately following surgical resection for treatment of early stage breast cancer. Methods This phase 4, open-label, single-arm, prospective, non-randomized trial is still enrolling participants and is currently being conducted at 26 hospitals in the USA (25) and Portugal (1). 878 participants with biopsy-proven ductal carcinoma in situ (DCIS) or invasive ductal carcinoma who met the inclusion criteria underwent lumpectomy followed by single-fraction IORT to the lumpectomy cavity. Briefly, a small, presterilized lead shield piece was placed on the chest wall to reduce the dose to the ribs, and then a balloon applicator, suitable to the surgical bed, was placed in the lumpectomy cavity and inflated with saline (30-75 cc); skin was temporarily closed over the balloon and ultrasound was used to confirm a balloon surface-to-skin distance ≥ 1.0 cm. The Xoft System was used to deliver the 20 Gy dose at the balloon applicator surface. The balloon was deflated, lead shield and balloon removed and the surgical site sutured. The prespecified primary outcome of this 10-year follow-up study is recurrence of ipsilateral breast tumor at 5 years. Prespecified secondary outcomes include 10-year recurrence and cosmesis (Harvard Scale). Trial Registry: ClinicalTrials.gov; Identifier: NCT01644669. Findings Of the 878 participants treated, 877 participants received the prescribed 20 Gy dose with a mean radiation treatment time of 594.5 seconds, whereas one participant received 14 Gy due to a source failure. 569 participants have reached 18-month (333), 2-year (199), and 3-year (37) follow-up. The mean age at enrollment was 65 years (range 41-90). 219 participants had DCIS and 658 had invasive ductal carcinoma. The DCIS nuclear grade was high (N=79), intermediate (N=100), or low (N=40). Invasive cancers were Grade 1 (N=282), 2 (N=282), or 3 (N=94). 664 participants had T1 lesions, 56 had T2 lesions, and 3 were unknown. The mean tumor size was 12.33 ± 10.5 mm. Cosmesis was excellent to good in 90% of participants who reached 2-year follow-up. To date, 155 reported adverse events were Grade 2 or higher. The most frequent side effects were breast pain, seroma, induration, and erythema. There were nine deaths, none of which were breast cancer related, four ipsilateral breast recurrences, and three new contralateral breast cancers. Conclusions Early results from this multi-center trial demonstrate that IORT using the Xoft Axxent eBx System at the time of breast conservation surgery continues to be a promising treatment option for early stage breast cancer. The short course of radiation therapy for select patients has excellent to good cosmetic results and a low rate of high-grade adverse events and recurrences. Funding Funded by Xoft, Inc., a subsidiary of iCAD, Inc. Acknowledgement Medical writing support from Dr. Theresa E. Singleton, Singleton Science, LLC. Citation Format: Syed AMN, Chang H, Schwartzberg BS, Bremmer AK, Boylan S, Lopez-Penalver C, Vito CA, Davis M, Dooley WC, Chakravarthy AB, Croomer C, Proulx GM, Golder SL, Ivanov O, Fernandez KL, Farha M, Gonzalez V, Wengler C, Bhatnagar A, Neuner G, Kopkash K, Rahman S, Corn C, Costa P, Ellenhorn J, Cox C. Two-year follow-up results of a multi-center trial of intra-operative electronic brachytherapy during breast conservation surgery for early stage breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-19.

Introduction: The use of genomic tests for the prediction of breast cancer recurrence is becoming more common. MammaPrint® (MP, Agendia Inc.) is a 70-gene microarray assay designed to assess the 10-year risk of recurrence in an untreated population that was not selected for ER/HER2 results. The Oncotype DX® Recurrence Score® (RS, Genomic Health, Inc.) is a 21-gene RT-PCR assay that is clinically validated to predict the 10-year risk of distant recurrence in ER+ patients treated with Tamoxifen. MammoStrat® (MS, Clarient, Inc.) is an IHC assay that uses 5 antibodies and has been validated in a similar population as RS. Several recent reports show that these assays classify patients differently with significant discordances for all risk groups (Shivers, et al., SABCS 2013; Denduluri, et al., ASCO Breast 2011; Poulet, et al., SABCS 2012; Schneider, et al., ASCO 2013). The present study is an analysis of long-term follow-up in a cohort of patients who have results for all three of these risk-stratifying assays side by side in the same samples. Methods: Patients with ER+ N0-N1 early-stage breast cancer with an MP result obtained as part of their routine clinical care were identified at the University of South Florida (USF, N=65) and Morton Plant Hospital (N=83). After local IRB approval, slides and/or blocks were cut and de-identified at USF and sent to Genomic Health and Clarient for blinded testing. Clinicopathological features were also reviewed by 3 breast pathologists. Results: 148 patients with an MP result had tissue available to send for RS and MS assays. These patients had a median age of 62 years; median tumor size 1.8 cm; 9% low grade, 59% intermediate grade and 32% high grade. In our previous analysis of this study, of 148 patients with MP results, 53% were low risk and 47% were high risk. Of 135 samples that yielded enough RNA to produce an RS result, 53% were low risk, 26% were intermediate risk and 21% were high risk. Of 129 samples that yielded an MS result, 44% were low risk, 28% were moderate risk and 28% were high risk. Of 121 patients with results for all 3 assays, only 22% were concordant for low risk and 9% were concordant for high risk across all 3 assays. Overall, 30% of cases showed a major discordance such as low risk for one assay and high risk for another. After median follow-up of 54 months, 9 patients have had a distant metastasis and/or 8 patients have died (11 patients total). One patient who had bone metastasis and died had been classified as low risk by all 3 assays. Three patients with distant metastases had a major discordance between assays, with two high risk and one low risk result. Seven patients were classified as high or intermediate/moderate risk by all 3 assays. Conclusions: This direct comparison demonstrates that although the assays classify a large proportion of patients differently, the patients who ended up with a distant metastasis and/or died of breast cancer had been classified as high risk by at least two of the three assays. This study has important clinical implications since these assays are used to help make treatment decisions regarding which patients might benefit from chemotherapy. Citation Format: Shivers SC, Russell S, Blumencrancz L, Mehindru A, Acs G, Ellis D, Vrcelj V, Zanchi A, Blumencrancz PW, Carter E, King J, Cox CE. Long-term follow-up of early stage breast cancer patients with results of MammaPrint®, Oncotype DX® and MammoStrat® risk classification assays [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-45.

Background: The gold standard for localizing non-palpable breast lesions for surgical excision is wire localization (WL). Multiple disadvantages for WL include complicated scheduling and migration of the wire after placement. Radioactive seed localization (RSL) mitigates these disadvantages, but regulatory requirements regarding radiation limit more universal adoption. The SAVI SCOUT surgical guidance system (an FDA cleared medical device) eliminates the drawbacks of WL without the regulatory requirements of RSL. SCOUT utilizes electromagnetic wave technology and infrared light to provide intra-operative guidance during surgical excision. The purpose of this study is to describe the learning curve associated with adoption of this new technology. Method: An IRB-approved prospective, single-arm, multi-site trial enrolled women with non-palpable breast lesions requiring localized surgical excision. After informed consent, a radiologist or surgeon used imaging guidance to implant the SCOUT reflector into the target lesion. Intraoperatively, the surgeon used SCOUT for localization of the reflector and removal of the target lesion. We evaluated the association of several independent variables with respect to successful localization and surgical excision including: tumor side, tumor quadrant, distance of reflector from the skin, and the number of SCOUT localized breast excisions performed by operating surgeon up to the 1st five cases. We studied the relationship between these independent variables and the following dependent variables: reflector detection post-placement, reflector detection pre-incision, and reflector localization post-incision.Statistical analysis utilized the z-test to perform a two-sided test of equality at an alpha level of 0.05 with adjustment for multiple comparisons by the Bonferroni method. T-tests were used to perform two-sided tests of equality for numeric variables. Results: Across 11 institutions, 16 surgeons performed a total of 153 surgical excisions. Overall success rates of reflector detection pre-incision and post-incision were 98% (150/153) and 99% (151/153), respectively. The reflectors were successfully removed in 100% (153/153) of cases. Difficulty with reflector detection immediately post placement was significantly associated with reflectors more than 4 cm (P=0.034) or 5 cm (P=0.007) from the skin, or the procedure being the 1st SCOUT case by the operating surgeon (P=0.036). Operating surgeons performing their 1st SAVI localization procedure were significantly associated with difficult reflector detection post-incision (p=0.044). Subsequent procedures, up to the first five SCOUT localizations, noted no significant difficulty with reflector detection. Conclusions: The SAVI SCOUT surgical guidance system is a viable surgical localization procedure for non-palpable breast lesions. Surgeons were 100% successful at removing the reflectors during surgical excision. Difficulty with reflector detection was not noted after the surgeon's 1st SCOUT procedure. Overall, it appears the learning curve for reflector placement and localization for non-palpable breast lesions is relatively short. However, depth of the reflector in relation to skin likely affects reflector detection during this early learning period. Citation Format: Shukla SC, Shivers SC, Mattingly A, Russell S, Mehindru A, Carter E, Cox CE. Learning curve for the SAVI SCOUT breast localization and surgical guidance system [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-11-06.

Background. The benefits of adjuvant radiation therapy (RT) in patients with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) remains controversial. Although there is level-I evidence supporting the role of RT in reducing the risk of local recurrence, the absolute benefit is variable. Current guidelines generally recommend RT for all patients having BCS, but it is important to develop prognostic and predictive tools to better assess risk and understand the impact such a tool would have on treatment decisions. The DCISionRT Test (PreludeDx, Laguna Hills, CA) is a biologic signature that provides a validated score for assessing 10-year risk of recurrence and RT benefit using individual tumor biology as assessed by clinical and pathologic biomarkers.Methods. This is a prospective cohort study for patients diagnosed with DCIS of the breast. Treating physicians complete a treatment recommendation survey before and after receiving DCISionRT test results. Test results, treatment recommendations, patient preferences and clinico-pathologic features are stored in a de-identified registry for participating institutions from a variety of geographic regions across the US. The study will also collect 5- and 10-year recurrence and survival data. The study includes females over age 25 who are candidates for BCS and eligible for RT and/or systemic treatment with sufficient tissue to generate test results. Subjects must not have been previously treated for DCIS or have previous or current invasive or micro-invasive breast cancer. The primary endpoints are changes in treatment recommendations for surgical, radiation and hormonal therapy. Secondary endpoints are identification of key drivers for treatment recommendations, including age, size, grade, necrosis, hormone receptor status and other clinico-pathologic factors. Changes in treatment recommendations will be assessed using McNemar's test with an alpha level of 0.05. Differences in recurrence-free and overall survival will be evaluated by Kaplan-Meier survival analysis using the log-rank test and/or the Cox Proportional Hazards model. A planned early interim analysis based on the first 200 patients has been recently completed and reported. Results. As of July 6, 2020, 1,000 patients have been accrued from 49 institutions. Twenty additional institutions are currently in the process of joining the study. We are planning to enroll up to 2,500 patients from up to 100 institutions. Citation Format: Steve C Shivers, Pat W Whitworth, Rakesh Patel, Troy Bremer, Charles E Cox. The PREDICT registry: A prospective registry to evaluate the effect of a predictive assay on treatment decisions in patients with DCIS following breast conserving therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-08-01.

Background: Male breast cancer (MaBC) is rare, comprising Methods: This analysis included a total of 817 breast tumor samples sent to Agendia, Inc. (Irvine, CA) for MP and BP testing. Full-transcriptome microarray data were available for 1) a subset of 400 post-menopausal FBC patients enrolled in the FLEX Registry (NCT03053193) and 2) 80 MaBC pateints, 32 of whom enrolled in the FLEX registry and 48 non-study patients for whom data were limited to metadata and quality metrics routinely captured for diagnostic testing. Data from all patients were de-indentified. Differences in mean MP indices between FBC (N=400) and MaBC (N=417) according to MP Risk classification (LR or HR) were analyzed using a Z-test. Differential gene expression analysis was performed using the R-limma package in which gene expression data were quantile normalized. Pathway analyses were performed using GOseq. Differentially expressed genes (DEGs) were identified between FBC (N=400) and MaBC (N=80) for whom full transcriptome microarray data were available. DEGs were defined as those with a fold change of > 2 and an adjusted P value of < 0.05. Results: All patients in this study had hormone positive, HER2 negative early-stage breast cancer. There was no statistical difference in the average MP index between MaBC and FBC classified as MP LR (P=0.273) or those classified as MP HR (P=0.692). Gene expression comparison revealed 166 DEGs between MaBC (N=80) and FBC (N=400), 99 DEGs between MP HR MaBC (N=42) and MP HR FBC (N=200), and 290 DEGs between MP LR MaBC (N=38) and MP LR FBC (N=200). Pathway analyses revealed that downregulated genes in MaBC compared to FBC enriched to immune-related functions, including B-cell mediated immunity, whereas upregulated genes were associated with hormone metabolic processes. In all comparisons, expression of MP or BP genes was not significantly different. Conclusions: We found similar MP index distributions between MaBC and FBC. Importantly, differential gene expression between MaBC and FBC provides novel insight into the mechanisms underlying MaBC. Although these data reveal biological distinctions between male and female breast cancer, MP and BP assay performance is preserved across both groups. Further studies are needed to assess clinical outcomes; however, these findings support the use of MP risk of recurrence assay and BP molecular subtyping assay for prognosis and informing treatment decisions in MaBC. Citation Format: Jennifer Crozier, Julie Barone, Kalyan Banda, Beth Lesnikoski, Robert Maganini, Sami Diab, Ian Grady, Thomas Lomis, Charles Cox, Amy Truitt, Benjamin Nota, Andrea Menicucci, Erin Yoder, William Audeh, FLEX Investigators Group. Differential gene expression analysis and clinical utility of MammaPrint and BluePrint in male breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-11.

Background and Objectives: The standard preoperative technique for localizing non-palpable breast lesions is wire localization (WL). Radioactive seed localization (RSL) has been described as an alternative approach to address the number of clear disadvantages associated with WL. Yet, despite its proven advantages, the adoption of RSL has been impacted by considerable regulatory requirements for the handling of radioactive materials. To advance the progress made with RSL and eliminate the issues associated with radioactive components, the SAVI Scout® surgical guidance system has been developed. The SAVI Scout surgical guidance system is an FDA-cleared medical device that utilizes passive non-radioactive electromagnetic wave technology to provide real-time guidance during excisional breast procedures. The purpose of this pilot study is to determine the safety and efficacy of the SAVI Scout system in localizing and directing the removal of non-palpable breast lesions during excisional biopsy and lumpectomy procedures. The preliminary results from two institutions are reported. Materials and Methods: Following a feasibility study using the SAVI Scout system in resected breast tissues ex vivo, Institutional Review Board approval was granted for both institutions for women with a non-palpable breast lesion requiring preoperative localization for excision. Participating patients underwent localization and excision with the SAVI Scout system, which consists of an electromagnetic wave reflective device (reflector), handpiece and console. Using mammographic or ultrasound guidance, the reflector was placed percutaneously up to 7 days prior to the scheduled excisional procedure. At surgical excision, the surgeon used the SAVI Scout handpiece to locate the reflector, which was removed along with the surrounding breast tissue. The console provides audible feedback of reflector proximity to the handpiece. Successful reflector placement, localization and retrieval were the primary endpoints. Results: After the first training case (data not used), a total of 17 patients have participated in the study to date. The reflectors were successfully placed with mammographic guidance in 9/9 patients and with ultrasound guidance in 8/8 patients. Reflectors were placed an average of 1.7 days (range 0-6 days) before surgery. Five patients underwent excisional biopsy and 12 patients had a lumpectomy. The intended lesion and reflector were successfully removed in 17/17 patients. Reflector migration did not occur and no adverse events occurred. Of the 14 patients in which final pathology is currently available, 6 patients had no invasive or in situ carcinoma identified, 4 had no tumor in the excision, and 3/4 patients with tumor had clear margins. One patient had a focally positive margin and was recommended for re-excision. Conclusions: The preliminary data show the SAVI Scout system to be a safe and effective tool for the localization of non-palpable breast lesions. Ongoing accrual to this pilot study will validate these findings with planned enrollment of a total of additional 50 patients in the next 60 days at up to 3 additional sites. Citation Format: Charles E Cox, Melissa Themar-Geck, Ronald Prati, Michelle Jung, Jeff King, Steven C Shivers. Pilot study of a passive non-radioactive electromagnetic wave technology to localize non-palpable breast lesions [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-16-10.

Researchers focused on patient-centered medicine are increasingly trying to identify baseline factors that predict treatment success. Because the quantity and function of lymphocyte subsets change during stress, we hypothesized that these subsets would serve as stress markers and therefore predict which breast cancer patients would benefit most from mindfulness-based stress reduction (MBSR)-facilitated stress relief. The purpose of this study was to assess whether baseline biomarker levels predicted symptom improvement following an MBSR intervention for breast cancer survivors (MBSR[BC]). This randomized controlled trial involved 41 patients assigned to either an MBSR(BC) intervention group or a no-treatment control group. Biomarkers were assessed at baseline, and symptom change was assessed 6 weeks later. Biomarkers included common lymphocyte subsets in the peripheral blood as well as the ability of T cells to become activated and secrete cytokines in response to stimulation with mitogens. Spearman correlations were used to identify univariate relationships between baseline biomarkers and 6-week improvement of symptoms. Next, backward elimination regression models were used to identify the strongest predictors from the univariate analyses. Multiple baseline biomarkers were significantly positively related to 6-week symptom improvement. The regression models identified B-lymphocytes and interferon-γ as the strongest predictors of gastrointestinal improvement ( p < .01), +CD4+CD8 as the strongest predictor of cognitive/psychological (CP) improvement ( p = .02), and lymphocytes and interleukin (IL)-4 as the strongest predictors of fatigue improvement ( p < .01). These results provide preliminary evidence of the potential to use baseline biomarkers as predictors to identify the patients likely to benefit from this intervention.

TPS3155 Background: Genomic signatures are revolutionizing the definition, identification, and treatment of breast cancer. To precisely stratify breast cancers into actionable subgroups, full genome expression data and matching clinical data must be aggregated into a large data set. Such a data set will accelerate research and discovery, especially for smaller patient subsets who are not as widely represented within the current body of literature. Methods: FLEX is a multicenter, prospective, population-based, observational trial for patients with Stage I, II, and III breast cancer. All patients with stage I to III breast cancer who receive MammaPrint, with or without BluePrint on a primary breast tumor are eligible for enrollment. The study’s primary aim is to create a large scale, population-based registry of full genome expression data matched with clinical data to investigate new gene associations with prognostic and/or predictive value. Secondary objectives include utilizing the shared study infrastructure to examine and generate hypotheses for targeted subset analyses and/or trials based on full genome expression data. The design of FLEX allows targeted sub-studies and sub-analyses to be added as appendices after the initial baseline study is opened. Patients enrolled in the initial study are also eligible for inclusion in sub-studies where they meet all criteria and additional consent is not required. Additional clinical data will be collected as specified in the appendix protocols. The FLEX collaborative platform allows participating investigators the opportunity to author their own sub-study protocols, as approved by the FLEX Steering Committee of their peers. 13 sub-studies have already been identified and are under development. Eligibility: The study will enroll a minimum of 10000 patients aged ≥18 years with histologically proven invasive stage I-III breast cancer who signed informed consent. Enrollment began April 2017 and 1506 patients have been enrolled. Clinical trial information: NCT03053193.

Introduction Fibroadenomas are defined as benign breast lesions, usually formed during menarche (15-25 years of age), that can exist as a solitary mass or multiple masses in the breasts of women. In develpment, as lobular structures are added to the breast’s ductal system, yperplastic lobules are often present. Although lobules are associted with normal growth, analysis of the cellular components link yperplastic lesions to fibroadenomas. Fibroadenomas that measure 5 cm are commonly classified as giant fibroadenomas. When these nlarged masses are found in young female patients, they are often alled juvenile fibroadenomas. The lesions are rare, accounting for nly 0.5% of the total diagnosed fibroadenomas, and can grow to arge sizes and cause prominent asymmetry of the breasts. Other structural changes include both stretching of the areola complex and distortion of the dermal tissue. Clinicians are confronted with treatment decisions on whether to manage these rare cases by way of continued routine examinations or to surgically remove the fibroadenomas. Cosmesis and lactation preservation are the main concerns in this population because malignancy is rare in this age group. Malignancy is of lesser concern with giant fibroadenomas due to their more cellular and less lobular his

Cryoablation is a well-established technique to treat fibroadenomas. Pilot studies suggest this could be an effective non-surgical treatment for breast cancer. American College of Surgeons Oncology Group Z1072 is a phase II trial exploring the effectiveness of cryoablation in the treatment of breast cancers. The primary endpoint of Z1072 was the rate of complete tumor ablation, defined as no remaining invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) on pathologic examination of the targeted lesion. A secondary objective was to evaluate the negative predictive value of magnetic resonance imaging (MRI) to determine residual IBC or DCIS. Eligible patients included those with unifocal invasive ductal breast cancer ≤2 cm, with

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.

Because of several disadvantages, alternatives to wire localization (WL) for surgery of non-palpable breast lesions have been widely pursued. Radioactive seed localization (RSL) is a technique that has gained acceptance in many practices throughout the world and has been shown to be a safe, effective alternative to WL. RSL allows the localization procedure to be scheduled on a different day from the operative procedure, the operative incision to be planned with no regard for the entry point used for localization, and ongoing feedback as to the location of and distance from the lesion throughout the operation. Herein we describe the procedure, the available evidence of its effectiveness and safety, and the key issues in starting a RSL program.

n Abstract: As the wave of the baby boomers shifts the age demographic of patients, the current surgical management of breast cancer in elderly women (‡70 years of age) becomes relevant because deviation from standard treatment often occurs in this group. The purpose of this study was to determine the operative mortality when treated with standard surgical procedures and to investigate trends in the surgical management of breast cancer in the elderly. A total of 5,235 patients undergoing either mastectomy or breast conservation surgery (BCS) for invasive and ductal carcinoma in situ (DCIS) were identified in a retrospective review of a prospectively accrued data base between the years of 1994 and 2007 at the Moffitt Cancer Center. Of the 5,235 patients, 1,028 (20%) patients were ‡70 years of age. The 30-day and 90-day mortality in the elderly group (age ‡70 years) was 0.2% (95% CI 0.02‐0.7%) and 0.7% (95% CI 0.3‐1.4%), respectively. The 30-day and 90-day mortality among patients

Previous plastic surgery procedures such as breast augmentation or reduction mammoplasty can potentially alter the lymphatic drainage of the breast. The purpose of this study is to determine the success rates of sentinel node lymphatic mapping in patients with previous plastic surgical procedures of the breast. A total of 83 patients with a history of plastic surgery of the breast that underwent subsequent sentinel node mapping between 1996 and 2008 were retrospectively analyzed. Eight-three patients that underwent a total of 108 sentinel node biopsies. Hundred cases (93%) previously underwent breast augmentation and eight cases (7%) previously underwent reduction mammoplasty. The mean time between the previous plastic surgical procedures and the sentinel node biopsy was 10.3 years (range: 2 months-32 years). Indications for the mapping procedure were invasive cancer (n = 64), ductal carcinoma in situ (n = 17), and prophylactic mastectomy (n = 27). The identification rate of the sentinel node was 95.3% (103/108). The success rate based on type of procedure was 96% (96/100) for augmentation and 87.5% (7/8) for reduction mammoplasty. With a mean follow-up of 3.4 years, there has been only one local axillary recurrence that occurred at the time of an ipsilateral breast recurrence following lumpectomy. Lymphatic mapping can be successfully performed in patients who have previously undergone plastic surgery operations.

Prior ipsilateral completion axillary lymph node dissection (CALND) may be considered a contraindication to performing a sentinel lymph node (SLN) mapping in a patient with recurrent breast carcinoma. However, reoperative SLN biopsy following axillary dissection would determine if alternative lymphatic drainage pathways exist. If nodes were found to contain metastatic disease, staging and locoregional control of the disease could be affected.An institutional breast cancer database and electronic health record (IRB No. 102554) prospectively accrued 6225 patients between 1994 and 2007. Under separate IRB approval (IRB No. 102552), this database was queried for patients with a prior history of CALND who received a SLN biopsy. Patients' demographic, clinical, and treatment variables were recorded.Of the 6225 patients, 45 (0.7%) were identified as having previously undergone breast-conservation surgery, CALND, and ipsilateral reoperative SLN mapping and biopsy. Of the 45 patients, 13 (29%) had a successful ipsilateral reoperative SLN mapping and biopsy. Nonaxillary drainage was identified in 5 patients with reoperative SLN biopsy.Reoperative SLN mapping and biopsy is feasible in the setting of local recurrence after previous CALND. This procedure performed for breast cancer recurrence provides important staging information while identifying extra-axillary drainage that could affect both staging and local control.

Objectives: Considerable morbidity persists among survivors of breast cancer (BC) including high levels of psychological stress, anxiety, depression, fear of recurrence, and physical symptoms including pain, fatigue, and sleep disturbances, and impaired quality of life. Effective interventions are needed during this difficult transitional period. Methods: We conducted a randomized controlled trial of 84 female BC survivors (Stages 0–III) recruited from the H. Lee Moffitt Cancer and Research Institute. All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and/or chemotherapy. Subjects were randomly assigned to a 6-week Mindfulness-Based Stress Reduction (MBSR) program designed to self-regulate arousal to stressful circumstances or symptoms (n=41) or to usual care (n=43). Outcome measures compared at 6 weeks by random assignment included validated measures of psychological status (depression, anxiety, perceived stress, fear of recurrence, optimism, social support) and psychological and physical subscales of quality of life (SF-36). Results: Compared with usual care, subjects assigned to MBSR(BC) had significantly lower (two-sided p

Background Recent studies suggest local surgical therapy improves survival in metastatic breast cancer (MBC). We evaluate the difference in outcome in patients with MBC after mastectomy versus breast conservation (BCT) and factors that influence outcome. Methods In a retrospective review of our prospective database, we identified patients who presented with MBC (1990 to 2007). Patient surgery type and clinicopathologic factors were reviewed. We compared OS between pts dependent on surgery and clinicopathologic factors. Results Of the 566 patients with MBC, 154 (27%) underwent removal of the primary tumor. Surgery was associated with an improved OS (33%) versus no surgery (20%) ( P = 0.0015). Of those undergoing local therapy; mastectomy was associated with a 37% OS vs BCT with a 20% OS ( P = 0.04). Conclusions Our study confirms that removal of the primary tumor in MBC is associated with improved overall survival. It appears that mastectomy is associated with a significantly improved overall survival.

Nipple-sparing mastectomy (NSM) via an inframammary (IM) incision has been described for selected patients with breast cancer. However, the application of sentinel lymph node (SLN) mapping via an IM incision for NSM has yet to be reported. The objective of this study is to determine the technical feasibility of performing SLN through an IM incision without making an axillary counterincision.We retrospectively reviewed our single-institutional experience with SLN biopsy and NSM through IM incisions between January 2006 and March 2008. Clinicopathologic factors were analyzed regarding indications, technical details, postoperative morbidity, and follow-up.Fifty-two patients underwent 87 NSM through an IM incision (17 unilateral, 35 bilateral) with immediate reconstruction and SLN biopsy. Indications for surgery included invasive breast cancer (n = 21), ductal carcinoma in situ (DCIS) (n = 18), and prophylactic (n = 48). Mean tumor size of invasive carcinoma was 2.1 cm. The mean mastectomy specimen weight was 437 g. Subareolar injection consisted of blue dye (n = 43), technetium sulfur colloid (n = 2), or combination injection (n = 42). SLN biopsy through an IM incision was successfully performed in 84 of 87 cases (96.6%). A mean of 2.8 SLN were removed with a positive sentinel node encountered in 8 of 21 patients (38%) with invasive cancer. No complications were observed regarding the SLN portion of the operation. With a median follow-up of 6.5 months (range, 0.4-23 months), there have been no axillary local recurrences.SLN biopsy can be performed through an IM incision during a NSM, avoiding a secondary axillary incision.

Patients with neurofibromatosis type I and breast cancer represent a subset of people who may be considered at high risk for secondary cancers after conventional whole breast radiation therapy and breast conservation surgery. A case of a 49-year-old woman with neurofibromatosis type I is presented. She was diagnosed with a 1.1-cm right breast infiltrating ductal carcinoma. Clinical, diagnostic imaging, and pathologic features are discussed. Her initial treatment plan of breast conserving therapy was thwarted when her sentinel node biopsy was positive for micrometastatic disease in 1/14 lymph nodes. She elected to have a bilateral simple mastectomy. This case addresses the rare dilemma of offering breast conservation therapy as a viable option for patients with neurofibromatosis type I. Current data on radiation-induced secondary cancers such as sarcoma after treatment for breast and other cancers are reviewed.

Locoregional chest wall recurrences involving ribs and/or sternum after primary surgical treatment predict a poor outcome in patients with breast cancer. The precise natural history and surgical outcome of these chest wall recurrences are not fully understood. The objective of this study is to clarify the clinicopathological features of chest wall recurrence of breast cancer and evaluate prognostic factors predicting survival after chest wall resection and reconstruction (CWRR). A total of 28 patients who underwent CWRR at the H. Lee Moffitt Cancer Center between December 1999 and September 2007 were retrospectively analyzed. Overall survival was calculated by the Kaplan–Meier method and the significance of prognostic variables was evaluated by log-rank and Cox regression analyses. The postoperative morbidity and mortality was 21% and 0%, respectively. Overall 5-year survival for the entire cohort was 18%. Disease-free interval

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. 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. 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. 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.

Purpose: Constitutive activation of signal transducer and activator of transcription 3 (Stat3) protein has been observed in a wide variety of tumors, including breast cancer, and contributes to oncogenesis at least in part by prevention of apoptosis. In a study of 45 patients with high-risk breast cancer enrolled in a phase II neoadjuvant chemotherapy trial with docetaxel and doxorubicin, we evaluated the levels of Stat3 activation and potentially associated molecular biomarkers in invasive breast carcinoma compared with matched nonneoplastic tissues. Experimental Design: Using immunohistochemistry and image analysis, we quantified the levels of phospho-Stat3 (pY-Stat3), phospho-Src (pY-Src), epidermal growth factor receptor, HER2/neu, Ki-67, estrogen receptor, Bcl-2, Bcl-xL, Survivin, and apoptosis in formalin-fixed, paraffin-embedded sections from invasive carcinomas and their paired nonneoplastic parenchyma. The levels of molecular biomarkers in nonneoplastic and tumor tissues were analyzed as continuous variables for statistically significant correlations. Results: Levels of activated pY-Stat3 and pY-Src measured by immunohistochemistry were significantly higher in invasive carcinoma than in nonneoplastic tissue (P < 0.001). In tumors, elevated levels of pY-Stat3 correlated with those of pY-Src and Survivin. Levels of pY-Stat3 were higher in partial pathologic responders than in complete pathologic responders. In partial pathologic responders, pY-Stat3 levels correlated with Survivin expression. Conclusions: Our findings suggest important roles for elevated activities of Stat3 and Src, as well as Survivin expression, in malignant progression of breast cancer. Furthermore, elevated Stat3 activity correlates inversely with complete pathologic response. These findings suggest that specific Stat3 or Src inhibitors could offer clinical benefits to patients with breast cancer.

Objective: The purpose of our study is to further clarify the incidence of ductal carcinoma in situ (DCIS) patients that are upstaged upon final pathology and/or have metastatic disease in the axilla. Methods: All patients were diagnosed with DCIS or DCIS with microinvasion (DCISm) on their diagnostic biopsy and received a sentinel lymph node (SLN) biopsy between 1994 and 2004. Six hundred seventy-five patients were divided into 613 patients with DCIS and 62 patients with DCISm. Results: Sixty-six of 675 (10%) were upstaged to invasive cancer. Fifty-five of 613 (9%) patients with DCIS were upstaged, whereas 11 of 62 (18%) patients with DCISm were upstaged. Forty-nine of 675 (7%) patients had SLN. Twenty-two of 49 (45%) patients with SLN had invasive carcinoma or DCISm on final histology. Conclusions: After review of histology, grade, type of biopsy, and mammographic findings, the combined findings of high grade, mass by mammography, and microinvasion predict patients at higher risk for invasive carcinoma. Selective utilization of SLN biopsy in DCIS is recommended. © 2005 Excerpta Medica Inc. All rights reserved.

The purpose of this study was to determine whether breast cancer patients who had prior breast augmentation presented at a more advanced stage than nonaugmented breast cancer patients, and to determine the mode of presentation and effectiveness of lymphatic mapping and sentinel lymph node biopsy in this same group of patients. A total of 4186 breast cancer patients from 1987 to 2002 were reviewed. Patients who had augmentation before their diagnosis of breast cancer were compared with a control group of nonaugmented breast cancer patients. The Wilcoxon rank sum test was used to compare tumor size, node positivity, and stage. The patient's age at presentation was also compared by the two-sided pooled t test. Seventy-six patients who previously underwent augmentation were identified with 78 breast cancers. Seventy percent (48 of 69) were initially detected by palpation, whereas 30 percent (21 of 69) were initially identified mammographically. Fifty-three percent (n = 41) underwent mastectomy and 47 percent (n = 37) underwent a lumpectomy. This compares with a 63.6 percent (2615 of 4110) breast conservation rate in the nonaugmented population during the same time period. The two groups did not differ regarding (tumor) size (p = 0.77), nodal positivity (p = 0.32), or stage (p = 0.34). The mean time between implant placement and a diagnosis of breast cancer was 14 years. The average age of the patients who had previously undergone augmentation at breast cancer diagnosis was 49.5 years (SD, 9.0 years) versus 57.1 years (SD, 13.5 years) for the nonaugmented patients (p < 0.0001). Forty-nine of the patients underwent lymphatic mapping, with a 100 percent success rate in identifying the sentinel lymph node. There have been no clinically detected axillary recurrences in the patients who had a negative sentinel lymph node biopsy. Breast cancer patients who have undergone previous augmentation are more likely to present with a palpable mass. This initial mode of detection does not appear to translate into a larger tumor size or worse prognosis. Breast conservation and lymphatic mapping can be performed successfully in previously augmented patients.

The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant epithelial cells is essential to the staging of breast cancer patients. Recently, increased attention has focused on the possibility that epithelial cells may reach SLNs by benign mechanical means, rather than by metastasis. The purpose of this study was to test the hypothesis that pre-SLN biopsy breast massage, which we currently use to facilitate the localization of SLNs, might represent a mode of benign mechanical transport. We studied 56 patients with invasive and/or in situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell clusters (< or =0.2 mm in diameter and not associated with features of established metastases) detected predominantly in subcapsular sinuses of SLNs on hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells and cell clusters, < or =0.2 mm in size and without features of established metastases, occurred more frequently in the SLNs of patients who underwent pre-SLN biopsy breast massage (P < 0.001, chi2 test). The latter finding supports the hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical transport of epithelial cells to SLNs.

As a result of increased accuracy of staging and decreased patient morbidity, lymphatic mapping and sentinel lymph node (SLN) biopsy for breast cancer has enjoyed a rapid acceptance into clinical practice. Despite the use of lymphatic mapping techniques to obtain nodal staging information, many controversies remain. We have attempted to highlight the major controversies in this report.

Background This trial examines the utility of breast magnetic resonance imaging (MRI) for detection of occult breast disease and its effect on surgical treatment. Methods Between October 2000 and March 2002, 76 of 1,289 patients underwent bilateral breast MRI within 4 months of a mammogram. The MRI scan, mammogram, pathology reports, and physicians' notes were reviewed to determine impact of MRI on surgical treatment. Results Magnetic resonance imaging detected 23 additional lesions in 19 patients not detected by mammogram. Cancer occult to mammography was detected by MRI in 6 women, constituting 7.9%. Magnetic resonance imaging impacted surgical treatment plans in 10 of 76 (13.2%) patients. Conclusions Magnetic resonance imaging is effective at identifying new subclinical breast disease not seen on mammography. Ten of 76 patients (13.2%) who underwent MRI had their surgical management altered due to MRI findings. Specific criteria should be studied to know which subgroups would benefit most from breast MRI.

Purpose/Objectives: To design and test a reliable and valid instrument to determine the frequency of use of complementary and alternative medicine (CAM) therapies among women diagnosed with breast cancer. Design: A descriptive cross-sectional survey. Setting: Women were recruited from the southeastern area and a rural midwestern area of the United States. Sample: 105 predominantly Caucasian women ( — X = 59 years of age) with a diagnosis of breast cancer. Methods: The Use of Complementary and Alternative Therapies Survey was designed with a content validity index, and reliability was determined with the coefficient alpha. Exploratory factor analysis using a principal components analysis identified primary components (factors) embedded within the survey. Frequency of CAM therapy use was calculated for 33 individual therapies listed on the survey and among three survey-defined subscales of CAM therapies (i.e., diet and nutritional supplements, stress-reducing techniques, and traditional and ethnic medicines). Main Research Variables: Psychometric properties of an instrument to assess frequency of use of CAM among women with breast cancer. Findings: The reported prevalence of use of the individual CAM therapies varied considerably. The coefficient alpha estimate for the total survey was 0.86. Estimates for the individual hypothesized subscales were 0.67 for diet and nutritional supplements, 0.79 for stress-reducing techniques, and 0.80 for traditional and ethnic medicines. The principal components analysis resulted in a two-factor solution with nine items that loaded heavily and uniquely on a factor conceptualized as stress and anxiety reduction and six items that loaded heavily and uniquely on a factor conceptualized as dietary and physical manipulation. The remaining five items (vitamins and minerals, prayer and spiritual healing, massage, reflexology, and aromatherapy) indicated moderate loadings on factors one and two and, thus, were interpreted as equivocal items. Conclusions: Preliminary data indicated that the instrument is reliable and valid. Additional work is needed to improve the range of items and to test the instrument with other populations. Implications for Nursing: Use of CAM by women with breast cancer is believed to be increasing. However, limited data exist on the frequency and predictors of its use in this patient population; therefore, reliable and valid instruments are needed to determine use. If nurses can determine which CAM therapies women are employing, nurses can educate patients with breast cancer on the safe use of these therapies.

Background: Wire localization (WL) is the current standard for surgical diagnosis of nonpalpable breast lesions. Many disadvantages inherent to WL are solved with radioactive seed localization (RSL). This trial investigated the ability of RSL to reduce the need for specimen radiographs and operating room delays associated with WL. Methods: A total of 134 women were entered onto an institutional review board–approved study. RSL was performed by placing a titanium seed containing .29 to 20 mCi of iodine-125 to within 1 cm of the suggestive breast lesion. The surgeon used a handheld gamma detector to locate and excise the iodine-125 seed and the lesion. Results: Specimen radiographs were eliminated in 98 (79%) of 124 patients. Surgical seed retrieval was 100% in 124 patients. No seed migration occurred after correct radiographical placement. A total of 26 (21%) of 124 patients required a specimen radiograph; 22 (85%) of these 26 were performed for microcalcifications. Conclusions: After surgical removal, RSL can eliminate specimen radiographs when the radiologist accurately places the seed and the pathologist grossly identifies the lesion. If small microcalcifications are noted before surgery, then specimen radiographs may be necessary. RSL reduced requirements for specimen radiographs, decreased OR time, improved incision placement, and improved resections to clear margins.

Previous reports suggest that problems in sexual functioning may be common among long-term (5 years) breast cancer survivors. To investigate this issue further, we examined the characteristics and correlates of sexual functioning in women diagnosed with breast cancer at least 5 years previously and treated with adjuvant chemotherapy and in an age-matched comparison group of women with no history of cancer.Participants were 58 women initially diagnosed with breast cancer at an average of 7.65 years previously and 61 women with no history of cancer. All participants completed standardized self-report measures of sexual functioning, marital functioning, depression, fatigue, and menopausal symptoms.Compared with women with no history of cancer, long-term breast cancer survivors reported worse sexual functioning (Por = 0.01), characterized by greater lack of sexual interest, inability to relax and enjoy sex, difficulty becoming aroused, and difficulty achieving an orgasm. Additional analyses indicated that severity of vaginal dryness was significantly (Por = 0.05) related to poorer sexual functioning among long-term breast cancer survivors and mediated the relationship between group membership (breast cancer survivor v.s. noncancer comparison subject) and sexual functioning.These findings confirm and extend previous reports of impaired sexual functioning among long-term breast cancer survivors. Results further suggest that relief of vaginal dryness should be an essential component of efforts to improve sexual functioning among long-term breast cancer survivors.

Objective: To document the incidence of metastatic disease in complete axillary lymph node dissections (CALND) of patients with invasive carcinoma after a sentinel lymph node (SLN) biopsy, positive only by immunohistochemical staining for cytokeratin (CK-IHC). Methods: Sections of all SLNs, negative by routine histology, were immunostained and examined for cytokeratin positive cells. Sections of lymph nodes from CALND specimens were interpreted using routine hematoxylin and eosin (H&E) staining. Results: A total of 409 patients (29.6%) had metastatic disease in at least one sentinel lymph node on H&E examination. Of 971 H&E negative patients, 78 (8.0%) were positive only by CK-IHC. Sixty-two of the CK-IHC positive only patients underwent CALND. Nine of these 62 patients (14.5%) had metastases identified in the CALND specimen. Conclusions: Because 14.5% of patients with invasive breast cancer and SLNs positive only by CK-IHC were found to have H&E positive lymph nodes on CALND, we conclude first, that CK-IHC should be used to evaluate SLNs, and second, that CALND should be considered when SLNs are positive by CK-IHC only. This approach will result in an absolute reduction of the false negative rate (absolute false negative rate reduced by 2.6% in our series).

Age and body mass index (BMI) have been shown to correlate with an increased incidence of failure in identifying a sentinel lymph node (SLN). Mapping senior, overweight adults is common; therefore, the relationship of patient age and BMI on SLN biopsy success is essential. This study examines the mapping failures as they relate to age and BMI. From April 1994 to May 1999, patients underwent an injection of radiocolloid (450 mci) and blue dye (5 cc) prior to SLN biopsy. SLN biopsy failure was defined as lymph nodes being unidentifiable by blue dye or having an in vivo node radiocolloid count of less than 3:1 over background count. BMI was measured as (weight in pounds)(703)/(height in inches)(2); 1,356 patients were attempted for SLN mapping, and 54 failed (3.98%). The radioactive node count was inversely proportional to age ( p < 0.0001). The radioactive node count decreased by a mean of 34 counts per node with each additional year ( p < 0.001). The estimated odds ratios for success were 0.945 for age and 0.946 for BMI. Therefore, every increase of 1 year of age or one unit of BMI decreased the odds of success by approximately 5%. The mean BMI was 29.54 in failed patients and was 26.42 in successful mapping patients ( p = 0.042). Surgeons should be aware that node counts will decrease with increasing age and that increased age and BMI are potential risk factors for SLN mapping failure. However, increased age and/or BMI alone do not appear to be contraindications for SLN biopsy in older or overweight patients.

522 Background: Breast cancer risk stratification with the 70-gene signature (70-GS) provides a binary low risk (LR) or high risk (HR) result; by contrast the 21-gene assay (21-GA) provides LR, intermediate (IR), and HR results. Results from these two assays were compared for 769 patients from 5 institutions. Methods: The study included patients from McGill University (n = 86), UPMC (n = 437), USF (n = 135), Morton Plant North Bay Hospital (n = 79), and Cleveland Clinic (n = 32, all 21-GA IR). Results: With the 70-GS, 487 (63%) patients had a LR and 282 (37%) patients had a HR result. Excluding 32 cases selected for 21-GA IR results (n = 737), the 21-GA gave 369 (50%), 250 (34%), and 118 (16%) patients with LR, IR, and HR scores, respectively. Using the TAILORx cutoff, there were 134 (18%), 432 (59%), and 171 (23%) patients with LR, IR, and HR scores, respectively. There were 329 (45%) and 486 (66%) patients who were not classified in the same risk category by both assays using the clinical and TAILORx cutoffs for IR, respectively. Conclusions: In a large multi-institutional study the 70-GS and 21-GA results were discordant in 45-66% of patients, and the proportion of patients with a 21-GA score in the IR range varied from 34-59%. The 70-GS provided clinically actionable results for all patients. [Table: see text]

This provides a contemporary look at the current trends of breast-conserving therapy. Though outcomes are improving, such as local control and survival, the rate of lumpectomy versus mastectomy in breast cancer patients continues to decline. Evolving techniques for the critical roles of tumor localization, margin assessment, and margin control are described. Novel complementary therapies, such as cryoablation, radiofrequency ablation, intraoperative radiation therapy, brachytherapy, partial breast irradiation, and various forms of external beam radiation deployment, are discussed. The concept of oncoplastic breast surgery, combining oncologic principles with plastic surgery techniques, has emerged as an important part of breast-conserving therapy. The combination of oncoplastic repair with partial breast radiation is changing the face of breast conservation. Neoadjuvant chemotherapy, with tumor size reduction, is allowing breast conservation in patients who would traditionally not be eligible. These advances continue to redefine breast conservation therapy.

Women with early-stage breast cancer face the complex decision to undergo one of three equally effective oncologic surgical strategies: breast-conservation surgery with radiation (BCS), mastectomy, or mastectomy with breast reconstruction. With comparable oncologic outcomes and survival rates, evaluations of satisfaction with these procedures are needed to facilitate the decision-making process and to optimize long-term health. Women recruited from the Army of Women with a history of breast cancer surgery took electronically administered surgery-specific surveys, including the BREAST-Q© and a background survey evaluating patient-, disease-, and procedure-specific factors. Descriptive statistics and regression analysis were used to evaluate the effect of procedure type on breast satisfaction scores. Overall, 7,619 women completed the questionnaires. Linear regression revealed that women who underwent abdominal flap, or buttock or thigh flap reconstruction reported the highest breast satisfaction score, scoring an average of 5.6 points and 14.4 points higher than BCS, respectively (p

Metastatic breast cancer to the contralateral axilla (CAM) is defined as stage IV disease. We postulate that CAM represents an extension of local-regional disease rather than distant metastasis and may have a better outcome. A single-institution, retrospective review of breast cancer cases from January 2005 and May 2011 was performed to identify cases with CAM. Eligibility for the study included unilateral primary breast cancer at presentation with synchronous/metachronous documented CAM without a documented primary invasive breast cancer within the contralateral breast by surgery or MRI. Clinicopathologic data was recorded for these patients (pts). Thirteen pts were identified. 12/13 (92%) pts presented with a locally advanced breast tumor or an ipsilateral in-breast recurrence. 10/13 (77%) pts had documented dermal involvement of tumor either at initial presentation or local recurrence. CAM occurred synchronously with the initial primary tumor (5 pts, 38%), concomitant with a local recurrence (5 pts, 38%), metachronously with the initial tumor (1 pt, 8%), and metachronously with a local recurrence (2 pts, 15%). Three patients had other distant disease at presentation. Of the other 10 pts, seven developed distant disease with a mean follow up of 3.6 years (range 0.3-7.6 years). Three pts have no evidence of disease at a mean follow up of 5.8 years (range 1.5-8.2). CAM may have different prognostic implications than other distant metastases and may occur through dermal lymphatic spread. Further study is warranted on the prognosis and management of these challenging and rare cases.

BACKGROUND: Implementation of new procedures, including lymphatic mapping for breast cancer, must be done and overseen by the medical community in a responsible way to ensure that the procedures are performed correctly. This study addresses the issues of adequacy of training and certification of surgeons performing lymphatic mapping. Ensuring quality in surgical care requires outcomes measures that are described in this study. STUDY DESIGN: Sixteen surgeons performed lymphatic mapping in 2,255 patients with breast cancer using a combination blue dye and Tc 99m -labeled sulfur colloid to identify the sentinel lymph nodes (SLNs). All participants were trained in a 2-day CME-accredited course. The Cox learning curve model (total number of mapping failures / total number of mapping cases) for a consecutive series of lymphatic mapping cases is described. The relationship of the Surgical Volume Index, the cases performed in a 30-day period, to the failure rate for each surgeon was modeled as a logistic regression curve (y = e a+bx / [1 + e a+bx ]). RESULTS: Surgeons performing less than three SLN biopsies per month had an average success rate of 86.23% ± 8.30%. Surgeons performing three to six SLN biopsies per month had a success rate of 88.73% ± 6.36%. Surgeons performing more than six SLN biopsies per month had a success rate of 97.81% ± 0.44%. CONCLUSIONS: This experience defines a learning curve for lymphatic mapping in breast cancer patients. Data suggest that increased volumes lead to decreased failure rates. These data provide surgeons performing SLN biopsy with a new paradigm for assessing their skill and adequacy of training and describes the relationship between volume of cases performed and success rate of SLN detection.