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Purpose: Resistance training may offer several unique advantages within breast cancer (BC) survivorship care; however, safety concerns have limited the application of high-intensity compound movements necessary to elicit optimal changes in body composition, strength, and quality of life in this population. The EXERT-BC trial assesses the safety and feasibility of an evidence-based, dose-escalated resistance training regimen among BC survivors, with the goal of improving physical and metabolic function, mobility, muscle mass, and body composition., Methods: Participants included women with breast cancer underwent a 3-month thrice weekly exercise regimen involving dose escalation of high-intensity compound exercises. Coprimary outcomes included safety and adherence. Pre- and post-regimen assessment included body composition testing, functional mobility and balance, total load (weight × repetitions × sets) across compound exercises, and patient reported quality of life. Pairwise comparison was performed via the paired t test., Results: Fourty participants completed a 3-month exercise regimen, with a median age of 57 years (range, 27-74 years) and 73% having stage 0-2 BC. BC therapies concurrent with exercise included anti-estrogen therapy (80%), radiotherapy (30%), and non-hormonal systemic therapy (15%). No adverse events were observed aside from a single case of self-limited knee pain. Session attendance exceeded a prespecified threshold of 75%, and 98% patients reported ongoing compliance to an exercise regimen following regimen completion. Significant reductions in percent body fat (p < 0.001) and increases in percent muscle mass (p = 0.011) were observed. Significant increases in resting metabolic rate (p = 0.023), bilateral grip strength (p < 0.001), functional movement screen (p < 0.001), bilateral Y-Balance testing (p < 0.001), and Godin questionnaire scores (p < 0.001) were observed., Conclusion: A 3-month dose-escalated resistance training regimen comprising high-intensity compound movements appears safe with a high degree of adherence among breast cancer survivors, resulting in demonstrable improvements in body composition, metabolic parameters, strength increases, and patient-reported quality of life., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Although published data have supported the use of hypofractionated regional nodal irradiation (HF-RNI) for breast cancer, limited dosimetric data exist to evaluate predictors of lung toxicity. The ongoing RT CHARM trial limits the percentage of ipsilateral lung volume that receives ≥18 Gy to 35 to 40%. We assessed dosimetry, toxicity, and disease outcomes in patients with breast cancer treated with HF-RNI with a particular focus on pneumonitis., Methods and Materials: We retrospectively reviewed all patients with breast cancer treated with HF-RNI (40-43 Gy in 15-16 fractions) after either lumpectomy or mastectomy at The University of Pittsburgh Medical Center from September 2018 to December 2021 to collect dosimetric and outcomes data. All post-radiation therapy chest computed tomography (CT) scans were manually reviewed for evidence of acute (≤6 months postradiation) or chronic (>6 months postradiation) pneumonitis., Results: One-hundred-ninety-one patients qualified with a median follow-up of 20.3 months (range, 5.1-42.2). Acute grade 1 (G1) pneumonitis was observed in 6.8% of the overall cohort (13 of 191 patients) and 39.4% of the patients (13 of 33) who received a chest CT ≤6 months postradiation therapy. Only 1 patient developed acute G2 pneumonitis. Chronic G1 pneumonitis was observed in 29.8% of the overall cohort (57 of 191 patients) and 77% of patients (57 of 74 patients) who received a chest CT >6 months postradiation therapy. No patients developed acute G3+ or chronic G2+ pneumonitis., Conclusions: Rates of symptomatic pneumonitis were low in this cohort of patients treated with HF-RNI, even with integration of HER2/neu-directed therapy, chemotherapy, hormone therapy, and internal mammary nodal irradiation. Lung V20Gy <26% appeared safe in this cohort to limit symptomatic pneumonitis, though this is not meant to represent the safe upper limit. Given the low event rate of symptomatic pneumonitis, data from larger cohorts will be needed to assess dosimetric predictors and the safe upper limit of lung dose., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine recent modality utilization trends in accelerated partial breast irradiation (APBI) in the National Cancer Database (NCDB) based on the American Society for Radiation Oncology (ASTRO) guidelines., Materials and Methods: A total of 58,194 patients treated with APBI were identified. Patients were segregated by APBI modality (brachytherapy, external beam radiotherapy [EBRT], and intraoperative radiotherapy ([IORT]). These patients were then further classified by suitability to receive APBI based on ASTRO guidelines. Temporal trends in utilization were evaluated using linear regression. Logistic regression was applied to study factors contributing to APBI modality choice and treatment within the ASTRO suitability groups., Results: Patients treated with brachytherapy, EBRT, and IORT comprised 70.5%, 17.5%, and 12.0% of patients treated with APBI. From 2008 to 2017, total APBI cases remained relatively stable (-54.1 cases/year, p = 0.161) while brachytherapy cases decreased by 258.7 cases/year (p < 0.001). EBRT and IORT increased by 51.5 cases/year (p = 0.019) and 153.1 cases/year (p < 0.001), respectively. 40.0% of patients treated with APBI were classified as "suitable", which increased from 2010 to 2017 from 35.3% to 45.3% (slope = 1.51%/year, r 2  = 0.61, p = 0.022). In comparison, 36.0% (36.1% in 2010 to 33.1% in 2017) of patients were classified as "cautionary" (slope = -0.33%/year, r 2  = 0.63, p = 0.019) and 23.9% (28.6% in 2010 to 21.6% in 2017) of patients were classified as "unsuitable" (slope = -1.18%/year, r 2  = 0.67, p = 0.012)., Conclusions: While overall APBI utilization has remained stable since 2008, this has been accompanied by a decline in brachytherapy and a rise in IORT. The causes of these trends should be the topic of future research., Competing Interests: Conflicts of Interest Disclosure Dr. Glaser serves as Co-Chair of the Elsevier Clinical Pathways Gynecological Committee. Dr. Beriwal is employed by Varian Medical Systems, serves on the XofT DSMB Board, and is an Elsevier Pathway Consultant. Dr. Shah serves as a consultant for Impedimed, PreludeDX, and Evicore and has grants from Varian, Prelude, and VisionRT., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Age is one of the most important risk factors for the development of breast cancer. Nearly a third of all breast cancer cases occur in older women (aged ≥70 years), with most cases being oestrogen receptor-positive (ER+). Such tumours are often indolent and unlikely to be the ultimate cause of death for older women, particularly when considering other comorbidities. This Review focuses on unique clinical considerations for screening, detection, and treatment regimens for older women who develop ER+ breast cancers-specifically, we focus on recent trends for de-implementation of screening, staging, surgery, and adjuvant therapies along the continuum of care. Additionally, we also review emerging basic and translational research that will further uncover the unique underlying biology of these tumours, which develop in the context of systemic age-related inflammation and changing hormone profiles. With prevailing trends of clinical de-implementation, new insights into mechanistic biology might provide an opportunity for precision medicine approaches to treat patients with well tolerated, low-toxicity agents to extend patients' lives with a higher quality of life, prevent tumour recurrences, and reduce cancer-related burdens.

Purpose: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS)., Patients and Methods: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years., Results: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years., Conclusion: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy., Competing Interests: Melody A. CobleighConsulting or Advisory Role: Roche/Genentech, Immunomedics, Genomic Health, Puma Biotechnology, Seattle GeneticsResearch Funding: Macrogenics, Radius Health, Genentech/Roche, Seattle Genetics, Zymeworks, SynthonPatents, Royalties, Other Intellectual Property: Genomic HealthTravel, Accommodations, Expenses: Genentech, Immunomedics, Puma Biotechnology, Seattle Genetics Stewart J. AndersonConsulting or Advisory Role: Jazz Pharmaceuticals Kalliopi P. SiziopikouHonoraria: Ventana Medical Systems, Lilly, Merck Douglas W. ArthurStock and Other Ownership Interests: Advanced Radiation Therapy Rachel RabinovitchStock and Other Ownership Interests: Abbott Laboratories, Bristol-Myers Squibb, Intuitive Surgical, IDEXX LaboratoriesResearch Funding: Prelude Therapeutics Dennis L. CarterEmployment: Rocky Mountain Cancer Centers Melissa S. DillmonStock and Other Ownership Interests: Johnson & JohnsonConsulting or Advisory Role: Puma Biotechnology Vivek S. KavadiEmployment: US Oncology Network Matthew L. HillStock and Other Ownership Interests: AstraZeneca, Newlink Genetics, Kazia Therapeutics, Leap Therapeutics, OncoSec, MEI Pharma, PLx Pharma, Radius Health, Crispr Therapeutics, Cassava Sciences Sushil BeriwalHonoraria: Varian Medical Systems, XOFT Eleftherios P. MamounaHonoraria: Genentech/Roche, Genomic Health, PreciscaConsulting or Advisory Role: Genomic Health, BioTheranostics, Roche/Genentech, Merck, Daiichi Sankyo, Puma Biotechnology, PreciscaSpeakers' Bureau: Genomic Health, Genentech/RocheTravel, Accommodations, Expenses: Genomic Health, Genentech/RocheNo other potential conflicts of interest were reported.

Background: Currently it remains difficult to identify patients most likely to benefit from radiotherapy (RT) for ductal carcinoma-in-situ (DCIS), thus leading to wide variation in practice patterns. The genomic risk assessment tool DCISionRT (PreludeDX) has been validated to prognosticate recurrence risk and predict RT benefit. We aimed to study the cost-effectiveness analysis comparing DCIS treatments based on DCISionRT testing to traditional clinicopathologic risk factors., Patients and Methods: A Markov state transition model was constructed to perform a cost-effectiveness analysis comparing breast-conserving surgery with or without RT using DCISionRT testing vs. traditional clinicopathologic risk factors. Clinical parameters were obtained from clinical trial data and cross-validation studies. Cost data were based on 2019 Medicare reimbursement. Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained comparing DCIS treatments using DCISionRT testing to traditional clinicopathologic risk factors and evaluated with a willingness-to-pay threshold of US$100,000 per QALY gained. To account for uncertainty, 1-way and probabilistic sensitivity analyses were performed., Results: Base case analysis showed that DCIS management using DCISionRT testing was a cost-effective strategy, resulting in an ICER of $74,331 per QALY gained compared to clinicopathology-based treatment. Model results were sensitive to a variation of the proportion of genomic-high, low-risk patients receiving RT in DCISionRT testing strategy, and changes in DCISionRT testing cost., Conclusion: DCISionRT testing could potentially be a cost-effective strategy compared to traditional decision making for DCIS treatments, optimizing RT benefit based on an accurate recurrence risk assessment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Overtreatment of early-stage breast cancer with favorable tumor biology in older patients may be harmful without affecting recurrence and survival. Guidelines that recommend deimplementation of sentinel lymph node biopsy (SLNB) (Choosing Wisely) and radiotherapy (RT) (National Comprehensive Cancer Network) have been published., Objective: To describe the use rates and association with disease recurrence of SLNB and RT in older women with breast cancer., Design, Setting, and Participants: This cohort study obtained patient and clinical data from an integrated cancer registry and electronic health record of a single health care system in Pennsylvania. The cohort was composed of consecutive female patients 70 years or older who were diagnosed with early-stage, estrogen receptor-positive, ERBB2 (formerly HER2)-negative, clinically node-negative breast cancer from January 1, 2010, to December 31, 2018, who were treated at 15 community and academic hospitals within the health system., Exposures: Sentinel lymph node biopsy and adjuvant RT., Main Outcomes and Measures: Primary outcomes were 5-year locoregional recurrence-free survival (LRFS) rate and disease-free survival (DFS) rate after SLNB and after RT. Secondary outcomes included recurrence rate, subgroups that may benefit from SLNB or RT, and use rate of SLNB and RT over time. Propensity scores were used to create 2 cohorts to separately evaluate the association of SLNB and RT with recurrence outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HRs)., Results: From 2010 to 2018, a total of 3361 women 70 years or older (median [interquartile range {IQR}] age, 77.0 [73.0-82.0] years) with estrogen receptor-positive, ERBB2-negative, clinically node-negative breast cancer were included in the study. Of these women, 2195 (65.3%) received SLNB and 1828 (54.4%) received adjuvant RT. Rates of SLNB steadily increased (1.0% per year), a trend that persisted after the 2016 adoption of the Choosing Wisely guideline. Rates of RT decreased slightly (3.4% per year). To examine patient outcomes and maximize follow-up time, the analysis was limited to cases from 2010 to 2014, identifying 2109 patients with a median (IQR) follow-up time of 4.1 (2.5-5.7) years. In the propensity score-matched cohorts, no association was found between SLNB and either LRFS (HR, 1.26; 95% CI, 0.37-4.30; P = .71) or DFS (HR, 1.92; 95% CI, 0.86-4.32; P = .11). In addition, RT was not associated with LRFS (HR, 0.33; 95% CI, 0.09-1.24; P = .10) or DFS (HR, 0.99; 95% CI, 0.46-2.10; P = .97). Subgroup analysis showed that stratification by tumor grade or comorbidity was not associated with LRFS or DFS. Low absolute rates of recurrence were observed when comparing the groups that received SLNB (3.5%) and those that did not (4.5%) as well as the groups that received RT (2.7%) and those that did not (5.5%)., Conclusions and Relevance: This study found that receipt of SLNB or RT was not associated with improved LRFS or DFS in older patients with ER-positive, clinically node-negative breast cancer. Despite limited follow-up time and wide 95% CIs, this study supports the continued deimplementation of both SLNB and RT in accordance with the Choosing Wisely and National Comprehensive Cancer Network guidelines.

Purpose: Regional nodal irradiation (RNI) improved disease-free survival by 3% to 5% in 2 large randomized trials, but this small absolute advantage relies on accurate contouring and dose delivery. We audited our network to determine compliance on regional nodal coverage, contouring, and dosimetric parameters with respect to accepted guidelines., Methods and Materials: In our network, we have established a clinical pathway for patients with node-positive breast cancer that guides indications for RNI and dosimetric goals. We reviewed records of 183 patients with nodal macrometastases after upfront surgery or involved nodes of any size after neoadjuvant chemotherapy. Radiation treatment plans were examined to determine lymph node volumes treated, whether nodes were contoured, quality of nodal contours, and whether target coverage and normal organ dosimetric constraints were met when RNI was delivered., Results: Despite the presence of macrometastases on sentinel lymph node biopsy, no lymph nodes were treated in 2.2% (4 of 183). Of 179 patients who received nodal irradiation, 18 received radiation to axillary levels 1 and 2 only, and 161 patients received RNI. Overall, regional nodes were not treated despite strong indications in 7.6% (14 of 183). Treated nodes were not contoured for 2.2% (4 of 179), and lymph node contours were unacceptable in 15.4% (27 of 175). Of patients receiving RNI, 14.9% (24 of 161) did not have adequate nodal target volume coverage, mean heart dose was >4 Gy for 3.1% (5 of 161), and lung V20 Gy was >35% for 8.7% (14 of 161)., Conclusions: Adherence to indications for regional nodal treatment was high, but nodes were either not contoured or had unacceptable contour quality in 18% of plans, and coverage was inadequate in 15%. Because the small disease-free survival advantage seen in trials may be decreased with these deviations, routine clinical practice requires detailed peer review to fully translate results of clinical trials., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies., (Published by Elsevier Inc.)

Background: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival., Methods: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed., Results: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM., Conclusions: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.

We evaluated daily setup reproducibility of deep inspiration breath hold (DIBH) using mega voltage (MV) imaging for left breast cancer radiation therapy. Analysis of 109 left breast cancer patients across UPMC Hillman Cancer Center network treated using DIBH technique with daily MV imaging was done. Patient characteristics, MV imaging procedure used and inter-fraction directional shifts were collected. For the statistical analyses, we separated all patients into 2 groups in each of the following 3 categories; (1) obese (BMI ≥ 30) vs nonobese, (2) mastectomy vs lumpectomy, (3) internal mammary node (IMN) treatment vs no IMN treatment. The group mean inter-fraction directional shifts were as following: (1) 0.7 mm (superior), 0.8 mm (inferior); (2) 0.65 mm (left), 0.64 mm (right); (3) 0.89 mm (anterior), 0.83 mm (posterior). Also, any directional shift ≥ 2 mm, ≥ 3 mm, ≥ 4 mm, ≥ 5 mm, ≥ 10 mm was found to be 52.9%, 37.6%, 30.9%, 21.9%, 3.7% of total fractions, respectively. In the stratified analysis, obese patients had larger directional shifts (p < 0.05) and highly associated with number of fractions for ≥ 5 mm in any directional shift compared to nonobese patients (29% vs 17%; p = 0.04). DIBH setup for left breast cancer treatment at our large cancer center network was reproducible with any mean directional shifts less than 1.0 mm using MV imaging. Daily imaging would be more beneficial for obese patients compared to nonobese patients., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2019 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: Multifocal pattern of regression after neoadjuvant chemotherapy has been identified as a risk factor for ipsilateral breast tumor recurrence (IBTR). We aimed to determine the significance of multifocal regression as a predictor of IBTR after neoadjuvant chemotherapy and breast conservation therapy in the modern era., Methods and Materials: We retrospectively reviewed 346 patients treated between November 2009 and June 2017. Pattern of regression was categorized as pathologic complete response (pCR), unifocal (tumor present as a cohesive mass), limited multifocal (single cells or clusters of cells concentrated in 1 portion of the fibrotic area), or diffuse multifocal (cells spread over entire fibrotic area). IBTR was defined as new ipsilateral invasive or noninvasive breast tumor after breast conservation therapy. Predictive factors were analyzed using Cox regression., Results: Incidence of multifocal regression was 25.7% for the overall cohort and 12.2% for estrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER2) positive, 17.5% for triple-negative, 36.9% for ER+ or PR+/HER2-, and 38.5% for triple-positive (P < .001). With a median follow-up of 41.1 months, 4-year IBTR-free survival after pCR or unifocal regression versus multifocal regression was 94.1% versus 90.9% (P = .411). Pattern of regression (P = .010; compared to pCR, hazard ratio [HR] of 11.2 for diffuse multifocal regression, 1.65 for limited multifocal regression, and 3.81 for unifocal regression), phenotype (P = .001; compared to ER+ or PR+/HER2-, HR of 30.67 for ER-/PR-/HER2+, 25.30 for triple-negative, and 1.60 for triple-positive), and lack of nodal pCR (P = .004; HR of 3.78) predicted for IBTR on multivariate Cox regression. On multivariate subset analysis, pattern of regression and lymphovascular space invasion predicted for IBTR in hormone receptor-negative patients, but pattern of regression was not associated with IBTR for hormone receptor-positive patients., Conclusions: Multifocal regression, hormone receptor-negative phenotype, and lack of nodal pCR predict for increased risk of IBTR after neoadjuvant chemotherapy. Although more common in hormone receptor-positive disease, multifocal regression was associated with worse outcome only in hormone receptor-negative patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose:: The 2018 American Society for Radiation Oncology guidelines state that hypofractionated whole-breast irradiation (HF-WBI) may be used for early-stage breast cancer regardless of age, although evidence to support this became available years ago. Before guideline publication, we sought to change the practice pattern within an integrated, comprehensive radiation oncology network using clinical pathways., Methods:: The breast clinical pathway was amended in January 2016 to allow HF-WBI as a pathway-concordant option for women younger than 50 years of age. In December 2016, the pathway was amended to mandate HF-WBI as the only pathway-concordant option. Women younger than 50 years of age treated for stage 0 to IIA breast cancer, without irradiation of regional nodes, were included. Potential predictors of hypofractionation use were analyzed using binary logistic regression., Results:: We identified 305 patients treated between 2013 and 2017. From 2013 to December 2015, HF-WBI use was 4.2%. After the first and second amendments, use increased to 53.1% ( P < .001) and 96.5% ( P < .001), respectively. Before amendment 1, there was no difference in use of hypofractionation at academic (2.6%) versus community (4.7%) sites ( P = .568). After amendment 1, academic practices were more likely to use hypofractionation (72.0% v 44.6%; P = .026). After amendment 2, there was, again, no difference between academic (100.0%) and community (95.3%) practices ( P = .999)., Conclusion:: With implementation of a clinical pathway that mandated use of HF-WBI regardless of age, HF-WBI use for women younger than 50 years of age rapidly increased from 4.2% to greater than 95%. Clinical pathways effectively standardize patterns of care to reflect the most up-to-date clinical evidence, independently of guideline publication.

Purpose: Underutilization of hypofractionated whole-breast irradiation (HF-WBI) in large-breasted women may be partially explained by concerns about dose heterogeneity. Although modern planning may mitigate this issue, validated dosimetric guidelines are lacking. Our clinical pathway mandates hypofractionation, guided by institutional dosimetric criteria for plan evaluation. We examined acute radiation dermatitis rates with HF-WBI in large-breasted patients when our guidelines are followed and evaluated factors predictive for dermatitis., Methods and Materials: Patients with whole-breast clinical target volumes (WB-CTV) of ≥1000 cm 3 treated with HF-WBI were reviewed. WB-CTV V105, V107, and V110 were assessed. Our guidelines recommend limiting V105 to <10% to 15% and V110 to 0%. The highest grade of acute dermatitis was recorded. Potential clinical and dosimetric predictors of dermatitis were analyzed using logistic regression., Results: From 2012 to 2017, 505 breasts in 502 patients were treated with HF-WBI. The median WB-CTV was 1261.3 cm 3 (interquartile range [IQR], 1115.3-1510.0). Most plans (99%) delivered 42.56 Gy in 16 fractions. A cavity boost of 10 Gy in 4 fractions was delivered in 99% of plans. Electrons were used in 69% of boost plans. Three-dimensional field-in-field technique was used in 68% of plans and inverse-planned intensity modulated radiation therapy in 32%. The median WB-CTV V105 was 9.7% (IQR, 5.6%-13.3%); the median WB-CTV V107 was 0.8% (IQR, 0.0%-2.5%). The WB-CTV V110 was 0% in 97.4% of plans (median, 0.0%; IQR, 0.0%-0.0%). Grade 1, 2, and 3 dermatitis rates were 55.0%, 40.8%, and 3.4%, respectively. On multivariate analysis, age >64 years (P = .016; odds ratio [OR] 4.0; 95% confidence interval [CI], 1.3-12.3), WB-CTV >1500 cm 3  (P = .006; OR, 4.3; 95% CI, 1.5-12.3), body mass index ≥34 (P = .044; OR, 3.9; 95% CI, 1.0-14.5), and WB-CTV V105 >10% (P = .011; OR, 5.3; 95% CI, 1.5-19.3) predicted for grade 3 dermatitis., Conclusions: With our institutional dosimetric guidelines, grade 3 dermatitis rates with HF-WBI in large-breasted women was <5%. WB-CTV V105 should be optimized to <10% to keep grade 3 dermatitis rates <2%., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Clinical pathways outline criteria for dose homogeneity and critical organ dosimetry. Based upon an internal audit showing suboptimal compliance with dosimetric parameters in whole breast irradiation (WBI), we conducted a mandatory web-based teaching conference for the network. This study reports the impact of this initiative on subsequent treatment plans., Methods: Radiation treatment plans were collected for the 10 most recent patients receiving WBI at 16 institutions within the UPMC Hillman Cancer Center network. Subsequently, a web-based conference was conducted to educate staff physicians, physicists, and dosimetrists with goals for dose homogeneity and critical organ dosimetry. Six months post-conference, another 10 plans were collected from each site and compared to pre-conference plans for deviations from dosimetric criteria., Results: Dose homogeneity significantly improved after the conference with breast V 105% decreasing from 15.6% to 11.2% (p = 0.004) and breast V 110% decreasing from 1.3% to 0.04% (p = 0.008). A higher percentage of cases were compliant with dosimetric criteria, with breast V 105%  > 20% decreasing from 22.5% to 7.5% of cases (p = 0.0002) and breast V 110%  > 0% decreasing from 13.8% to 4.4% of cases (p = 0.003)., Conclusions: Implementation of a web-based teaching conference helped improve adherence to clinical pathway dosimetric guidelines for WBI. In radiation oncology networks, this may be an effective model to ensure quality in routine practice and can be extrapolated to other disease sites.

Background: Radiation therapy (RT) is often delivered after lumpectomy for women with breast cancer. A common perceived side effect of RT is fatigue, yet its exact effect on activity levels and sleep is unknown. In this study we analyzed the change in activity levels and sleep using an activity tracking device before, during, and after RT for women with early stage breast cancer and ductal carcinoma in situ who underwent adjuvant RT., Patients and Methods: After institutional review board approval, activity levels were quantified before, during, and after RT with measurements of steps, miles walked, calories burned, and sleep metrics in 10 women fitted with activity trackers. All data were uploaded and tabulated on a secure database. Multivariable linear regressions were used to evaluate changes in these variables over time during the RT course., Results: Median step count was 5047 per day (range, 2741-15,508) and distance traveled was 1.6 miles per day (range, 0.9-5.3). Step count, distance, and calories decreased by an average of 54 steps per day, 0.02 miles per day, and 3 calories per day (median calories 1822; range, 1461-2712) during RT, respectively. These changes were statistically significant (P < .001), but not clinically relevant. There was no significant change in sleep (average 6.8 hours per night; range, 5.5-8.3)., Conclusion: RT has a minimal effect on activity or sleep in women undergoing treatment for breast cancer. Activity levels varied greatly between patients in a population of women undergoing hypofractionated RT. Because increased activity levels correlate with improved outcomes, further studies evaluating attempts to increase physical activity during as well as after treatment with radiation are warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Studies demonstrate safety of omitting axillary nodal dissection for early-stage breast cancer with positive sentinel lymph node (+SLN) biopsy, although trial designs differed in radiation therapy (RT) fields. Regional nodal irradiation was separately shown to improve outcomes in high-risk patients. This led to lack of consensus in RT volumes. Clinical pathways (CPs) standardize care where practice varies unnecessarily. We evaluated the impact of changes to a CP guiding postoperative RT in women with +SLNs on practice patterns throughout a network., Methods and Materials: We implemented a CP for management of breast cancer with postoperative RT designed to promote uniform nodal treatment. The CP recommended modified tangents (MTs) including level I/II nodes for women with micrometastases (pN1mi). For women with macrometastases (pN1a), CPs recommended including level I/II LN in MT and a third supraclavicular node (SCN) LN ± internal mammary nodes for women with adverse factors present., Results: RT fields of 233 women undergoing breast-conserving surgery with +SLN but not axillary nodal dissection were retrospectively reviewed: 25% had pN1mi disease and 75% pN1a. Of 127 women treated before CP changes, 35% with pN1mi and 22% with pN1a were treated with whole-breast irradiation alone. Following CP changes, 106 women were treated: 5% with whole-breast irradiation alone, 58% with MT, and 38% with MT + SCN field. Utilization of MT was associated with CP changes. Utilization of a third SCN field was associated with CP changes, pN stage, extracapsular extension, and total number of adverse factors., Conclusions: CPs translate published data and institutional experience into management plans that promote evidence-based care and eliminate unnecessary practice variations. Recognizing that postoperative RT treatment volumes were heterogeneous, we modified the CP based upon the latest evidence for regional nodal irradiation, after which we found increased compliance and consistency with quality guidelines, which will also aid in tracking outcomes in future investigations., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: There has been significant controversy regarding the equivalency of accelerated partial breast irradiation to whole-breast irradiation. With the recent publication of a large, randomized trial comparing these two treatment modalities, an update on the current state of knowledge of brachytherapy-based accelerated partial breast irradiation, with respect to local control and toxicities, would be useful to practitioners and patients., Methods and Materials: A systematic literature review was conducted examining articles published between January 2000 and April 2016 on the topics "brachytherapy" and "breast." A total of 67 articles met inclusion criteria, providing outcomes on local tumor control and/or toxicity for breast brachytherapy., Results: Reported 5-year local failure rates were 1.4-6.1% for multicatheter interstitial brachytherapy (MIB) and 0-5.7% for single-entry brachytherapy catheters when delivered to patients with standard selection criteria. Toxicity profiles are acceptable, with cosmetic outcomes comparable to whole-breast irradiation. The reported rates of infection were 0-12%. Symptomatic fat necrosis was found in 0-12% and 0-3.2% of patients treated with MIB and single-entry brachytherapy catheters, respectively. Late Grade ≥3 telangiectasias and fibrosis were reported in 0-8% and 0-9.1% of patients treated with MIB, respectively. These side effects were less common with single-entry brachytherapy catheters (0-2.0% and 0%, respectively)., Conclusions: Breast brachytherapy is a treatment technique that provides acceptable rates of local control in select patients, as demonstrated by Level I evidence. The side effect profile of this treatment is well documented and should be shared with patients when considering this treatment modality., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Mammary angiosarcoma (AS) is an aggressive malignancy with high recurrence rates and poor overall survival. Limited data exist to guide treatment. We aimed to identify patterns of failure in the context of adjuvant radiation and to identify prognostic indicators to better guide management., Methods: Thirty-five patients with breast AS at UPMC Magee Women's Hospital from June 1994 to March 2011 were retrospectively reviewed. Pathology was rereviewed for 22 patients by an expert breast pathologist using an objective scoring system, partly based on the Rosen grading scheme. All patients completed R0 resection, with 14 of them receiving adjuvant radiotherapy (RT) (82% of which represented reirradiation for radiation-induced AS)., Results: At a median follow-up of 20 months (range, 3 to 178 mo), the primary mode of failure was local with 32% local first failure. Tumor size >5 cm, radiation-induced etiology, and the omission of adjuvant RT were important prognostic factors of tumor control and survival. Histopathology including necrosis, number of mitotic figures, endothelial tufting, solid/spindle cell foci, and the combined scoring system were prognostic for recurrence patterns., Conclusions: Breast AS has high rates of local failure despite R0 resection, which may be improved with adjuvant RT, even in the reirradiation setting. Histopathology is prognostic for recurrence patterns.

Purpose: Breast cancer diagnostics have the ability to predict disease recurrence and the benefit of chemotherapy. This study measures the use of a diagnostic assay, Oncotype DX, when embedded in a breast cancer decision support algorithm and, on the basis of the assay results, the use of chemotherapy in the adjuvant setting., Methods: UPMC CancerCenter retrospectively reviewed patients with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)Neu-negative disease with zero to three positive nodes navigated in the Via Pathways decision support portal during a 12-month period. The breast algorithm prompted input of the assay recurrence score (RS) and then recommended hormonal therapy alone (HT) for low RS, or chemotherapy followed by HT for high RS. The patient's RS was correlated with the treatment decision., Results: During this time period, 643 patients had ER-positive, HER2Neu-negative disease with zero to three positive nodes. Of those, 596 (92.7%) had diagnostic testing to determine chemotherapy plus HT versus HT alone, and 47 had chemotherapy followed by HT without an RS. For node-negative patients classified with low or high RS, pathway treatment adherence rates were 99.7% and 96.6%, respectively; node-positive patients had 95.7% and 87.5% adherence rates, respectively., Conclusion: This analysis demonstrates the use of a clinical pathway to measure the adoption of a diagnostic test, the Oncotype DX breast assay, and the use of the appropriate therapy on the basis of the RS. As more diagnostics are established to aid in the personalized treatment of diseases, pathways may be important in maintaining clinician awareness of the appropriate disease presentations where these tests should be used, measuring usage of these tests, and tracking the treatment decisions on the basis of test results., (Copyright © 2016 by American Society of Clinical Oncology.)

Purpose: Hypofractionated whole-breast irradiation (HF-WBI) remains underutilized in the United States despite support by multiple clinical trials. We evaluated the success of iterative modifications of our breast cancer clinical pathway on the adoption of HF-WBI in a large, integrated radiation oncology network., Methods and Materials: The breast clinical pathway was modified in January 2011 (Amendment 1) to recommend HF-WBI as the first option for women ≥70 of age with stages 0 to IIA, while maintaining conventional fractionation (CF) as a pathway-concordant secondary option. In January 2013 (Amendment 2), the pathway's HF-WBI recommendation was extended to women ≥50 years of age. In January 2014 (Amendment 3), the pathway mandated HF-WBI as the only pathway-concordant option in women ≥50 years of age, and all pathway-discordant plans were subject to peer review and justification. Women ≥50 years of age with ductal carcinoma in situ or invasive breast cancer who underwent breast conserving surgery and adjuvant WBI were included in this analysis., Results: We identified 5112 patients from 2009 to 2014 who met inclusion criteria. From 2009 to 2012, the overall HF-WBI use rate was 8.3%. Following Amendments 2 and 3 (2013 and 2014, respectively), HF-WBI use significantly increased to 21.8% (17.3% in the community, 39.7% at academic sites) and 76.7% (75.5% in the community, 81.4% at academic sites), respectively (P<.001). Compared to 2009 to 2012, the relative risk of using HF-WBI was 7.9 (95% confidence interval: 7.1-8.6, P<.001) and 10.7 (95% CI: 10.3-11.0, P<.001), respectively, after Amendments 2 and 3, respectively. Age ≥70 and treatment at an academic site increased the likelihood of receiving HF-WBI in 2009 to 2012 and following Amendment 2 (P<.001)., Conclusions: This study demonstrates the transformative effect of a clinical pathway on patterns of care for breast radiation therapy. Although our initial HF-WBI use rate was low (8%-22%) and consistent with national rates, the clinical pathway approach dramatically increased adoption rate to >75%. In contrast to passive guidelines, clinical pathways serve as active tools to promote current best practices., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: For well-selected elderly women who undergo segmental mastectomy for early-stage, estrogen receptor-positive breast cancer, hormonal therapy alone is emerging as an acceptable adjuvant therapy option since the initial publication of Cancer and Leukemia Group B 9343 study in 2004 and update in 2013. The rate of adoption of adjuvant hormonal therapy alone in lieu of radiation therapy (RT) and its associated patterns of care is not known in the United States and was the subject of this study., Methods and Materials: We used the National Cancer Data Base to identify women aged ≥70 diagnosed with T1N0/T1Nx invasive breast cancer who underwent segmental mastectomy between 1998 and 2011. Because hormone receptor status was not specifically and reliably coded, only those who received hormonal therapy were included in this analysis. Univariate and multivariable exploratory analyses of factors associated with the use of RT were performed using SPSS, version 17.0., Results: Of the 182,115 patients who met inclusion criteria, 97,530 (53.6%) patients underwent hormonal therapy and were included in the analysis. The RT utilization rate in this subset decreased with time from 84.9% in 1998 to 75.1% in 2011 (P< .001). Multivariable analysis revealed that the factors associated with decreased use of RT include (in order of association): older age, later year of diagnosis, greater comorbidity score, low grade, lack of insurance, treatment at academic facility, race, rural location, lower median income, and distance from facility., Conclusions: This study assesses the patterns of care associated with the omission of RT in elderly women with early-stage breast cancer who received adjuvant hormonal therapy. Since the publication of major clinical trials, this strategy has been increasingly adopted. The strongest predictors of using this strategy included advanced patient age, high comorbidity score, and low-grade disease., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Hypofractionated whole breast irradiation (HF-WBI) following breast conserving surgery has produced excellent outcomes, but utilization remains limited. We evaluated the impact of a clinical pathway in the adoption of HF-WBI in a large, integrated radiation oncology network., Methods and Materials: We identified patients aged ≥70 years treated for breast cancer or ductal carcinoma in situ. Patients treated with palliative intent, accelerated partial breast radiation, following mastectomy, or with axillary nodal, supraclavicular, or internal mammary fields were excluded. HF-WBI was defined as ≤20 fractions with a dose/fraction ≥2.5 Gy. Multivariate analysis identified variables associated with increased HF-WBI utilization., Results: We identified 2426 patients meeting inclusion criteria. HF-WBI utilization increased significantly from 6.5% (22.0% academic, 2.0% community) before pathway modification to 33.8% afterwards (68.5% academic, 25.3% community, P<.001). For academic physicians, the relative risk of HF-WBI utilization was 3.8 following publication of the seminal HF-WBI trial and 10.6 following pathway modification (P < .001). For community physicians, the relative risk of HF-WBI utilization did not significantly change following publication but was 21.0 following pathway modification (P < .001). The increased adoption of HF-WBI saved an estimated $154,000 annually in our network., Conclusions: We found that our implementation of clinical pathways substantially increased adoption of HF-WBI for breast cancer. We found no significant change in utilization of HF-WBI among community physicians following publication of a seminal trial for HF-WBI until after clinical pathway implementation, which increased the use of HF-WBI by 20-fold. Clinical pathways may be effective in changing practice patterns, disseminating evidence, and realizing health care savings., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies have suggested an association between radiation therapy (RT) of the left breast and increased incidence of coronary artery disease. However, the increased sparing afforded with modern RT may decrease long-term cardiac risk. The aims of our study were to evaluate the association between the RT and cardiac events in breast cancer patients who underwent contemporary RT and to examine whether breast arterial calcification (BAC) seen on mammogram predicts for cardiac events., Methods and Materials: In our observational, descriptive pilot study, 2,439 patients with breast cancer between 1986 and 2007 and a minimum of 3 years since completing RT were asked to complete a questionnaire regarding cardiac events since RT completion. The preoperative and follow-up mammograms were coded for presence/absence of BAC by an experienced radiologist blinded to questionnaire results. Cardiac events were compared between patients who received left- and right-sided adjuvant radiation., Results: At a mean follow-up of 7.5 years (range 3-24), 687 patients completed the questionnaire, with 602 eligible for analysis. Baseline characteristics (age, body mass index [BMI], surgery type, cardiovascular risk factors, and time since RT) were similar in patients who received left- versus right-sided RT. Hypertension before RT and during follow-up, baseline cardiovascular disease, age >50, BMI >30 kg/m², and subsequent development of diabetes were significantly associated with posttreatment cardiac events. BACs were associated with cardiac events reported before breast cancer diagnosis; however, no association was found between left-sided breast RT or BAC and subsequent cardiac events., Conclusion: In a large single-institutional observational study, no association was found between left-sided breast RT or BAC and subsequent cardiac events.

Purpose: Accelerated partial breast irradiation (APBI) with balloon and catheter-based brachytherapy has gained increasing popularity in recent years and is the subject of ongoing phase III trials. Initial data suggest promising local control and cosmetic results in appropriately selected patients. Long-term data continue to evolve but are limited outside of the context of the American Society of Breast Surgeons Registry Trial., Methods and Materials: A retrospective review of 157 patients completing APBI after breast-conserving surgery and axillary staging via high-dose-rate (192)Ir brachytherapy from June 2002 to December 2007 was made. APBI was delivered with a single-lumen MammoSite balloon-based applicator to a median dose of 34 Gy in 10 fractions over a 5-day period. Tumor coverage and critical organ dosimetry were retrospectively collected on the basis of computed tomography completed for conformance and symmetry., Results: At a median follow-up time of 5.5 years (range, 0-10.0 years), the 5-year and 7-year actuarial incidences of ipsilateral breast control were 98%/98%, of nodal control 99%/98%, and of distant control 99%/99%, respectively. The crude rate of ipsilateral breast recurrence was 2.5% (n=4); of nodal failure, 1.9% (n=3); and of distant failure, 0.6% (n=1). The 5-year and 7-year actuarial overall survival rates were 89%/86%, with breast cancer-specific survival of 100%/99%, respectively. Good to excellent cosmetic outcomes were achieved in 93.4% of patients. Telangiectasia developed in 27% of patients, with 1-year, 3-year, and 5-year actuarial incidence of 7%/24%/33%; skin dose >100% significantly predicted for the development of telangiectasia (50% vs 14%, P<.0001)., Conclusions: Long-term single-institution outcomes suggest excellent tumor control, breast cosmesis, and minimal late toxicity. Skin toxicity is a function of skin dose, which may be ameliorated with dosimetric optimization afforded by newer multicatheter brachytherapy applicators and a more rigorous skin dose constraint of ≤100%., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to compare the change in depth of target volume and dosimetric parameters between the supine and lateral decubitus positions for breast boost treatment with electron beam therapy., Methods: We analyzed 45 patients who were treated, between 2009-2010, with whole breast radiation (WBRT) followed by a tumor bed boost in the lateral decubitius position. Tumor bed volume, distance from skin to the maximal depth of the tumor bed, D90 (dose covering 90% of the tumor bed volume), maximal dose, electron energy and doses to heart and lungs were compared. Additional variables of body mass index (BMI) and tumor bed location were also analyzed to see if there was a benefit limited to any subgroup., Results: Median BMI for the 45 patients treated was 30.6 (20.6-42.4). When comparing the supine scan to the lateral decubitus scan, there was no significant difference in the tumor bed volume (p = 0.116). There was a significant difference between depth to the tumor bed in the supine scan and lateral decubitus scan (p < 0.001). The mean maximum doses and D90 between the two scans were 110.7 (100.0-133.0)% vs 106.1 (95.1-116.9)% (p < 0.05) and 93.9 (81.3-01.0-101.0)% vs. 98.2 (89.1-108.0)% (p = 0.004) respectively. There was no difference in dose delivered to the lungs or heart between the two scans (p = 0.848 and p = 0.992 respectively). On subset analysis, there was a difference in depth to tumor that was seen across all BMI classes, including normal (p ≤ 0.001, overweight (p ≤ 0.001) and obese (p ≤ 0.001). The majority of patients had a tumor in the upper outer quadrant (77.8%) and on subset analysis, there was a significant difference in tumor bed volume (p < 0.01), depth to tumor (p < 0.01), tumor bed coverage [D90] (p < 0.05), maximum dose (p < 0.05) and energy (p < 0.001) for this location., Conclusions: Delivering a tumor bed boost in the lateral decubitus position reduces the distance to the tumor bed allowing for a lower energy treatment to be used to treat breast cancer. It improves coverage and decreases maximal dose to the target volume, all of which would help reduce skin morbidities and should be considered for patients with upper outer quadrant disease, irrespective of BMI status.

The objective of this study was to identify predictors of pathologic complete response and tumor volume reduction in triple-negative breast carcinomas. Consecutive cases of 101 triple-negative carcinomas within the last 3 years treated with standard neoadjuvant chemotherapy were identified. However, 56 cases with sufficient material available (for tissue microarray construction) in the pretherapy core biopsy tissue blocks formed the basis of this study. The pretherapy tumor core biopsy slides were examined for various morphologic features including tumor grade. The tumors were immunohistochemically examined for basal phenotype markers (CK5, CK14, CK17, epidermal growth factor receptor), cell adhesion marker E-cadherin, and proliferation marker Ki-67. The overall rate of pathologic complete response was 34% (19 of 56). Neither any morphologic feature nor any basal marker reactivity predicted for pathologic complete response or >50% tumor volume reduction. Ki-67 proliferation index also failed as a predictive marker. Reduced E-cadherin expression (defined as H score ≤200) was initially seen in 47% of cases with pathologic complete response and in only 6% of cases that failed to achieve pathologic complete response (P=0.001); however, in additional 20 cases from a separate validation set, no such difference was identified. Basal marker reactivity in triple-negative breast carcinomas does not predict pathologic complete response after neoadjuvant chemotherapy. As vast majority of triple-negative tumors are highly proliferative, Ki-67 proliferation index appears to have negligible clinical value in predicting pathologic complete response. E-cadherin expression as a predictor of pathologic complete response in triple-negative tumors should be further assessed on larger number of cases.

Estrogen receptor (ER) status is a strong predictor of response to hormonal therapy in breast cancer patients. Presence of ER and level of expression have been shown to correlate with time to recurrence in patients undergoing therapy with tamoxifen or aromatase inhibitors. Risk reduction is also known to occur in ER-negative, progesterone receptor (PR)-positive patients treated with hormonal therapy. Since the 1990s, immunohistochemistry has been the primary method for assessing hormone receptor status. Recently, as a component of its oncotype DX(®) assay, Genomic Health began reporting quantitative estrogen and PR results determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of an ongoing quality assurance program at our institution, we reviewed 464 breast cancer cases evaluated by both immunohistochemistry and oncotype DX(®) assay for estrogen and PR. We found good correlation for ER status between both assays (98.9% concordance), with immunohistochemistry being slightly more sensitive. Concordance for PR was 94.2% between immunohistochemistry and qRT-PCR with immunohistochemistry again more sensitive than RT-PCR. The results also showed linear correlation between immunohistochemistry H-scores and qRT-PCR expression values for ER (correlation coefficient of 0.579), and PR (correlation coefficient of 0.685). Due to the higher sensitivity of hormone receptor immunohistochemistry and additional advantages (ie preservation of morphology, less expensive, faster, more convenient), we conclude immunohistochemistry is preferable to qRT-PCR for determination of estrogen and PR expression.

The distinction between breast and müllerian carcinomas from each other and from tumors with a similar cytokeratin profile can be difficult. We tested the usefulness of 2 new markers, NY-BR-1 and PAX8, by staining a variety of breast and gynecologic carcinomas, along with tumors of pancreas, bile ducts, stomach, and gastroesophageal junction. NY-BR-1 expression (ie, H score >10) was seen in 58.4% of breast carcinomas (111/190), 5.6% of müllerian carcinomas (8/142), 7% of pancreatic tumors (1/15), 0% of cholangiocarcinomas (0/22), 0% of gastric tumors (0/36), and 0% of gastroesophageal carcinomas (0/25). All 188 breast carcinomas were negative for PAX8. PAX8 expression was seen in 72.4% of müllerian tumors (105/145). All pancreatic tumors (n = 15), cholangiocarcinomas (n = 23), and gastric (n = 35) and gastroesophageal junction (n = 25) carcinomas were negative for PAX8. Addition of NY-BR-1 and PAX8 in a panel would be useful in distinguishing breast cancer, gynecologic tumors, and tumors of the upper gastrointestinal tract.

Insulin-like growth factor receptor 1 (IGF-1R) is a receptor protein tyrosine kinase that is activated by ligand (IGF-1) binding and promotes mitogenic, metastatic, and antiapoptotic phenotypes of breast cancer. There is a dearth of studies analyzing IGF-1R expression by immunohistochemistry in breast carcinoma. This biomarker analysis will be important for pharmacologic interventions that target the IGF system. IGF-1R expression pattern was first analyzed in normal breast tissue and a variety of breast lesions (71 diagnoses from 35 patients), followed by analysis in 191 consecutive invasive breast carcinomas. Furthermore, 86 carcinomas treated with neoadjuvant chemotherapy were also analyzed. The carcinomas were classified using immunohistochemical surrogate (to molecular classes) markers-estrogen receptors (ER), progesterone receptors, and human epidermal growth factor receptor 2. IGF-1R is expressed at moderate level in normal breast tissue which was considered as normal expression. Overexpression and lower expression were defined as higher than normal or lower than normal expression, respectively. Among the benign and noninvasive breast lesions, IGF-1R expression was slightly increased in lesions that are hormonally driven (such as atypical ductal hyperplasia and columnar cells changes) whereas it was significantly reduced in ER-negative lesions (such as apocrine metaplasia). Similarly, in 191 consecutive breast carcinomas, IGF-1R overexpression was predominantly seen in ER-positive+ tumors. The tumor group that consistently showed reduced expression was the ERBB2 group (ER negative/progesterone receptors negative/human epidermal growth factor receptor 2 positive). The expression was somewhat heterogeneous in the triple-negative group. IGF-1R expression was not predictive of pathologic complete response or tumor volume reduction in ER-negative tumors, but reduced IGF-1R was associated with pathologic complete response and significant tumor volume reduction in ER+ tumors. Therapies targeting IGF-1R will be useful in majority of ER+ and a subset of triple-negative tumors that express IGF-1R. The consistent presence of IGF-1R in ER+ tumors may explain the lower response rate to neoadjuvant chemotherapy in luminal tumors.

Pathologic complete response to neoadjuvant chemotherapy without trastuzumab in hormone receptor-negative/HER2+ tumors is seen in 27-45% of cases. In contrast, estrogen receptor (ER)+/HER2+ tumors demonstrate pathologic complete response in ∼ 8% of cases and is generally limited to weak-to-moderate ER+/HER2+ tumors. It is speculated that addition of trastuzumab to neoadjuvant chemotherapy regimen will increase the pathologic complete response rates in all HER2+ tumors. A list of HER2+ patients who received neoadjuvant chemotherapy (with trastuzumab) in the years 2007-2010 was obtained from our hospital database. The 104 HER2+ tumors were classified into three groups based on semiquantitative hormone receptor and HER2 results as follows: ERBB2 (ER-/PR-[H-score ≤10]/HER2+), Luminal B-HER2 Hybrid (LBHH; weak to moderate ER+ [H-score 11-199]/HER2+), and Luminal A-HER2 Hybrid (LAHH; strong ER+[H-score ≥200]/HER2+). Pathologic complete response was defined as absence of invasive carcinoma in the resection specimen and in the lymph nodes. Percentage tumor volume reduction was also calculated based on pretherapy size and detailed evaluation of the resection specimen. In all, 52% (25 of 48 cases) of ERBB2 tumors showed pathologic complete response, which was significantly higher than the pathologic complete response rate in LBHH (33%; 10 of 30) and LAHH (8%; 2 of 26) tumors. Average percentage tumor volume reduction was also highest in ERBB2 tumors (86%), followed by LBHH (74%) and LAHH (64%) tumors. We conclude that addition of trastuzumab to neoadjuvant chemotherapy regimen significantly increases the pathologic complete response rates in all HER2+ tumors. However, the benefit of trastuzumab is highest in ER-negative tumors and progressively decreases with increase in tumor ER expression. This information can be utilized to counsel patients considered for neoadjuvant chemotherapy and the same principle could be applied in the adjuvant setting.

Background: The molecular subtype by hormone receptor status predicts recurrence in the adjuvant setting. Here, we report recurrence patterns by molecular subtype following neoadjuvant chemotherapy (NACT) to identify subgroups prone to recurrence., Materials and Methods: We retrospectively analyzed 331 patients receiving NACT plus lumpectomy and whole breast radiation therapy (RT) (n = 155), or mastectomy with (n = 122) or without (n = 50) adjuvant RT. Tumors were classified by immunohistochemical (IHC) surrogate markers into luminal A (strong ER+/PR+; HER2-), luminal B (weak-to-moderate ER+/PR+; HER2-), HER2 (HER2+), and triple-negative/basal subtypes., Results: The median follow-up was 43 months (range 10-104). The 5-year disease-free survival (DFS) was 71.4, 70.1, 70.4, and 62.1% for luminal A, luminal B, HER2, and basal subtypes, respectively. The 5-year distant recurrence rates were 25.8, 28.7, 28.7, and 35.2%. The 5-year locoregional recurrence rates were 3.8, 1.6, 1.3, and 4.2%. Molecular class (p = 0.003) and pathologic complete response (pCR; p = 0.004) predicted distant recurrence, DFS, and overall survival (OS). Only the omission of adjuvant RT following mastectomy (p = 0.006) predicted locoregional recurrence., Conclusions: IHC subclassification and pCR predict distant failure, DFS, and OS in the neoadjuvant setting. While not predictive of locoregional recurrence, the total number of events were small. More work is needed to define if molecular class can predict patients at risk for locoregional recurrence., (Copyright © 2011 S. Karger AG, Basel.)

Estrogen receptor (ER) status is a strong predictor of response to hormonal therapy in women with breast cancer. Not only presence of ER, but also level of expression has been shown to correlate with time to recurrence in patients undergoing therapy with tamoxifen or anastrozole. In addition, risk reduction occurs in ER-negative, progesterone receptor (PR)-positive patients treated with hormonal therapy. Immunohistochemistry (IHC) has been the method of choice for determining hormone receptor status. Recently, Genomic Health began reporting ER and PR status measured quantitatively by reverse transcription-polymerase chain reaction (RT-PCR) as a component of its Oncotype DX assay. As part of our quality assurance program, we reviewed 80 breast cancer cases that had been evaluated by the Oncotype DX assay and also underwent immunohistochemical staining for ER and PR. We found excellent correlation between ER and PR status determined qualitatively by each method. In addition, when hormone receptor expression measured quantitatively by RT-PCR and semiquantitatively by IHC were compared, results showed linear correlation. Given the additional advantages of hormone receptor IHC performed on intact tissue sections, currently there is no definitive reason to switch to RT-PCR for determination of ER and PR expressions.

Background: Complete pathologic response to neoadjuvant chemotherapy (NACT) is predominantly seen in "ERBB2" and "basal-like" tumors using expression profiling. We hypothesize that a similar response could be predicted using semiquantitative immunohistochemistry for estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2)., Methods: ER, PR, and HER2 were used to classify 359 tumors treated with NACT into 6 groups: luminal A (strong ER+, HER2 negative), luminal B (weak to moderate ER+, HER2 negative), triple negative (negative for ER, PR, and HER2), ERBB2 (negative for ER and PR, but HER2+), luminal A-HER2 hybrid (strong ER+ and HER2+), and luminal B-HER2 hybrid (weak to moderate ER+ and HER2+). Complete pathologic response was defined as absence of invasive carcinoma in the breast and regional lymph nodes., Results: Thirteen percent (48 of 359) demonstrated complete pathologic response. The highest rate of complete pathologic response was seen in ERBB2 (33%; 19 of 57) and triple negative (30%; 24 of 79) tumor classes. Among the ER+ "molecular" group, the highest rate of complete pathologic response was seen among luminal B-HER2 hybrid tumors, 8% (2 of 24). Remainder of ER+ tumors demonstrated a very low rate of complete pathologic response, 1.5% (3 of 198). The 5-year survival for patients achieving complete pathologic response was 96% compared with 75% in patients that failed to achieve complete pathologic response. The overall survival was worse in the ER-negative group (ERBB2 and triple negative) compared with the ER-positive group., Conclusions: We confirm the recently defined "triple negative paradox," or rather "hormone receptor negative paradox," that despite the best response to NACT, ERBB2 and triple negative tumors show the worst overall survival because of higher relapse among those with residual disease.

This is a study of 205 consecutive invasive breast carcinomas. The principal aim was to identify morphologic and immunohistochemical features of tumors that belong to the molecular class ERBB2. The invasive breast carcinomas were classified using semiquantitative immunohistochemical results for estrogen receptor (ER), progesterone receptor, (PR), and HER2 into following classes: Luminal A (strong ER+, HER2 negative), Luminal B (weak to moderate ER/PR+, HER2 negative), Triple Negative (TN; ER/PR negative, HER2 negative), ERBB2 (ER/PR negative, HER2 positive), Luminal A-HER2 Hybrid (strong ER+, HER2 positive), Luminal B-HER2 Hybrid (weak to moderate ER/PR+, HER2 positive). Of the 205 tumors, 113 (55%) were classified as Luminal A, 34 (17%) as Luminal B, 32 (15%) as TN, 8 (4%) as ERBB2, 10 (5%) as Luminal A-HER2 Hybrid, and 8 (4%) as Luminal B-HER2 Hybrid. Majority of the ERBB2 tumors were high grade as expected, with average Nottingham score of 8. Moderate lymphoid infiltrate (constituting 25% to 50% of the tumor) was seen in 5 of 8 (63%) cases and necrosis in 3 of 8 (38%) cases. The most striking morphologic feature associated with ERBB2 tumors was the presence of apocrine differentiation seen in 7 of 8 (88%) cases. CK5 immunoreactivity was seen in 5 of 8 cases (63%). Epidermal growth factor receptor staining with 2+ or 3+ score was also seen in 5 cases (63%). Due to low prevalence of ERBB2 tumors, additional data set of 191 cases enriched in ERBB2 and TN tumors was used for confirmation of morphologic findings. We conclude that tumors with apocrine differentiation are most often of ERBB2 type. ERBB2 tumors demonstrate some features classically ascribed to TN basal-like tumors. Epidermal growth factor receptor overexpression in ERBB2 tumors may have additional predictive value.

Androgens exert growth inhibitory effects on estrogen receptor and progesterone receptor-negative breast cancer cell lines that show androgen receptor expression. These laboratory findings may be translated into inexpensive alternative therapies for hormone receptor-negative invasive breast cancers. Our aim was to systematically evaluate androgen receptor expression by immunohistochemistry in invasive breast cancers. Androgen receptor (clone AR441, Dako) expression was analyzed on 189 well-characterized consecutive invasive breast carcinomas represented with threefold redundancy on tissue microarrays. Androgen receptor expression was semi-quantitated using a histochemical score-like method and a score >10 was considered positive. Of the 189 consecutive invasive breast cancers, 151 (80%) were positive and 38 (20%) were negative for androgen receptor. The majority (95%) of estrogen receptor-positive tumors were also androgen receptor positive. Of the estrogen receptor-negative tumors, androgen receptor reactivity was seen in 3 of 30 (10%) triple-negative cases and in 5/8 (63%) estrogen receptor-negative/progesterone receptor-negative/HER2+ cases. Six of eight estrogen receptor-negative/androgen receptor-positive cases showed apocrine differentiation. Androgen receptor expression in estrogen receptor-positive cases was associated with smaller tumor size (P=0.0001), lower Nottingham grade (P=0.002) and less frequent tumor cell necrosis (P=0.0001). Androgen receptor expression in estrogen receptor-negative tumors was associated with lower Nottingham grade (P=0.005) and apocrine differentiation (P=0.039). In conclusion, most estrogen receptor-positive breast tumors also express androgen receptor. Androgen receptor expression in estrogen receptor-negative/progesterone receptor-negative/HER2+ tumors (which commonly show apocrine differentiation) and a subset of triple - negative apocrine tumors suggest that these tumors together comprises the 'molecular apocrine' group described previously. However, these findings should be further confirmed on larger series of triple-negative and estrogen negative/progesterone negative/HER2+ tumors. Androgen receptor-targeted therapy in estrogen/progesterone receptor-negative tumors may provide an inexpensive alternative to usual high-dose chemotherapy with or without trastuzumab.

Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram., Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The area under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram., Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801)., Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients.

To analyze the initial clinical outcomes for breast cancer patients treated with intensity-modulated radiation therapy (IMRT) in a large integrated cancer center network. A total of 495 patients with breast cancer received IMRT following breast conserving surgery among nine cancer centers. Seven community cancer centers span a 100-mile radial distance from the two central academic sites. All nine cancer centers followed the same clinical pathway guidelines for the radiotherapeutic management of breast cancer. IMRT planning for all centers was performed at one central location, D3 Advanced Radiation Planning Service. The median IMRT prescription dose was 50 Gy followed by a boost with median dose of 10 Gy. The median breast volume was 918 cm(3). The median Dose Homogeneity Index (DHI) was 93%. The median % of ipsilateral lung volume receiving >20 Gy was 4.6%. For left breast IMRT, the median % heart volume receiving more than 5% of prescription dose was 13.1. There was no statistical difference in the mean DHI, heart and lung dose between the academic and community sites. For all patients, NCI CTC Grades 0,1,2,3 for acute skin erythema was 16%, 55%, 28%, and 1%, respectively. The rates of Grade 0,1,2,3 acute skin desquamation were 75%, 20%, 4%, and 1%, respectively. There was no statistically significant difference in acute skin toxicities (>grade 2) among the academic and community cancer centers. With centralized processes, IMRT can be safely and effectively delivered in a large health system with an admixture of academic and community centers but long-term follow-up is necessary.

Purpose: To provide longitudinal follow-up and assess the intermediate outcomes in breast cancer patients treated with the MammoSite radiation therapy system., Methods and Material: Ninety-two patients with histologically proven stage 0-II breast cancer were treated with MammoSite accelerated partial breast irradiation after breast-conserving surgery. The catheter was placed at the time of surgery or postoperatively. Treatment prescription was 3.4Gy b.i.d. for a period of five days using high-dose-rate afterloading. Clinical and dosimetric parameters including dose to 90% of PTV, volume of PTV receiving 100% of dose, volume of PTV receiving 150% of dose, edited PTV, and dose homogeneity index were analyzed as variables correlating with late effects., Results: All patients received the prescribed treatment. Seventy-seven percent of patients had intraoperative catheter placement, which was associated with a higher rate of persistent seroma (79%). The presence of seroma did not affect cosmesis. Ten patients developed telangiectasia at a median of 20.5 months. Skin dose and balloon-to-skin distance had a significant correlation with the development of telangiectasia that significantly affected cosmetic grading. The telangiectasia incidence for maximum skin dose of >100% and >125% of the prescription dose were 28% and 63%, compared with 0% (p=0.0001) and 4.2% (p=0.0001) for doses of < or =100% and < or =125%, respectively. Overall, most patients had excellent cosmetic results, and local control of disease was excellent., Conclusions: MammoSite radiation therapy system demonstrates excellent local control and cosmetic outcome with extended followup. The maximum skin dose should be kept below 100% to reduce late effects on skin and improve cosmetic outcome. The persistence of seroma is higher with intraoperative placement of the catheter, and therefore postoperative placement is preferred.

Multiple immunohistochemical stains, including cytokeratin (CK)5/6, are used in a panel format to identify "basal-like" carcinomas. We set out to determine the sensitivity and specificity of the CK5 antibody (clone XM26) and compared its expression with that of CK5/6 (clone D5/16B4) in a variety of breast carcinoma cases. The study was performed on 3 breast carcinoma tissue microarrays (TMAs). TMA-1 consisted of 59 consecutive breast carcinoma cases. TMA-2 (n = 16) and TMA-3 (n = 11) consisted of basal-like breast carcinomas previously characterized morphologically and immunohistochemically at our institution. Of the 86 total cases, 20 were positive for CK5 and CK5/6, 14 were positive for CK5 only, and 52 were negative for both. The sensitivity of CK5 for identifying basal-like tumors was 97% compared with 59% for CK5/6. Both antibodies had comparable specificity of more than 95%. For positive cases, the percentage and intensity of staining was much higher with CK5 than with CK5/6 (P = .0001).

Purpose: The purpose of this study was to determine whether the ClearPath (CP) multicatheter hybrid device was able to achieve acceptable dosimetry in patients in whom the proximity of the breast surgical cavity to the skin precluded treatment with intracavitary MammoSite (MS) brachytherapy., Methods and Materials: The study consisted of 11 patients who had the MS catheter placed and who were subsequently not treated due to inadequate skin distance. A phantom scan of the CP multicatheter hybrid device was superimposed on the MS CT scan and a dosimetric comparison was performed., Results: The median MS balloon size, diameter, and minimum skin distance were 40 cc, 4.1cm, and 5mm, respectively. The D(90), V(100), V(150), and V(200) with MS vs. CP were 95.29% vs. 97.06%, 88.8% vs. 91.3%, 35.7% vs. 38.0%, and 9.4% vs. 9.6%, respectively. The median maximum skin dose was 5.5 Gy vs. 3.9 Gy (p <.0001). The median dose homogeneity index (DHI) was 0.60 vs. 0.59 (p=.09). The median maximum rib, heart, and lung dose were 2.17 Gy vs. 2.18 Gy, 2.17 Gy vs. 2.18 Gy, and 0.50 Gy vs. 0.56 Gy, respectively., Conclusion: The hybrid CP catheter reduced the skin dose significantly without compromising the planning target volume coverage, DHI, or dose to other critical organs. The use of this device has the potential to increase the applicability of accelerated partial breast brachytherapy (APBI) in patients with a surgical cavity close to skin compared with balloon brachytherapy.

Current literature suggests that strong WT1 expression in a carcinoma of unknown origin virtually excludes a breast primary. Our previous pilot study on WT1 expression in breast carcinomas has shown WT1 expression in approximately 10% of carcinomas that show mixed micropapillary and mucinous morphology (Mod Pathol 2007;20(Suppl 2):38A). To definitively assess as to what subtype of breast carcinoma might express WT1 protein, we examined 153 cases of invasive breast carcinomas. These consisted of 63 consecutive carcinomas (contained 1 mucinous tumor), 20 cases with micropapillary morphology (12 pure and 8 mixed), 6 micropapillary 'mimics' (ductal no special type carcinomas with retraction artifacts), 33 pure mucinous carcinomas and 31 mixed mucinous carcinomas (mucinous mixed with other morphologic types). Overall, WT1 expression was identified in 33 carcinomas, that is, 22 of 34 (65%) pure mucinous carcinomas and in 11 of 33 (33%) mixed mucinous carcinomas. The non-mucinous component in these 11 mixed mucinous carcinomas was either a ductal no special type carcinoma (8 cases) or a micropapillary component (3 cases). WT1 expression level was similar in both the mucinous and the non-mucinous components. The degree of WT1 expression was generally weak to moderate (>90% cases) and rarely strong (<10% cases). None of the breast carcinoma subtype unassociated with mucinous component showed WT1 expression.

Oncotype DX is a commercially available reverse transcriptase-polymerase chain reaction based assay that provides a Recurrence Score (RS) and has been shown to provide prognostic and predictive information in estrogen receptor-positive lymph node-negative breast cancers. Independent studies of its utility in routine practice are lacking. Slides and surgical pathology reports from 42 cases of breast carcinomas evaluated by Oncotype DX were retrospectively reviewed to determine patient age, tumor size, histologic grade, estrogen and progesterone receptor (ER and PR) and ERBB2 (HER-2/neu) data, with ER and PR reported as a semi-quantitative score reflecting both intensity of staining and proportion of positive cells. We show here that Recurrence Score is significantly correlated with tubule formation, nuclear grade, mitotic count, ER immunohistochemical score, PR immunohistochemical score, and HER-2/neu status, and that the equation RS=13.424+5.420 (nuclear grade) +5.538 (mitotic count) -0.045 (ER immunohistochemical score) -0.030 (PR immunohistochemical score) +9.486 (HER-2/neu) predicts the Recurrence Score with an R2 of 0.66, indicating that the full model accounts for 66% of the data variability. Although the Oncotype DX Recurrence Score holds potential, further validation of its independent value beyond that of histopathologic analysis is necessary before it can be implemented in clinical decision making.

Objective: This study identifies clinical and pathologic factors predictive of having > or =4 involved axillary lymph nodes in breast cancer patients with a positive sentinel node. These factors may influence radiation therapy decisions., Methods: We reviewed the records of 201 patients with positive SLN who underwent axillary dissection; 34 of these patients had > or =4 positive axillary lymph nodes. Factors associated with > or = 4 lymph nodes were evaluated by chi(2) test, and multivariate logistic regression model was used to identify independent factors., Results: On univariate analysis, presence of lymphovascular space invasion, extracapsular extension, increased number of positive SLN, increased size of tumor, macrometastases within the SLN, and decreased number of negative SLN were all significantly associated with having > or = 4 involved axillary lymph nodes. On multivariate analysis, presence of extracapsular extension (odds ratio [OR] = 3.76, P = 0.004), increased number of positive SLN (OR = 3.99, P = 0.006), increased size of tumor (OR = 3.33, P = 0.011 for size of 2.1 to 5 cm and OR = 8.28, P = 0.018 for size >5 cm), and decreased number of negative SLN (OR = 2.62, P = 0.037) were found to be significant., Conclusion: We have identified primary tumor and SLN variables that predict for a greater probability of having a significant burden of residual disease in the axilla that may affect treatment recommendations.

The purpose of this study was to evaluate the clinical implementation of tangential field IMRT using sliding window technique and to compare dosimetric parameters with 3-dimensional conformal radiation therapy (3DCRT). Twenty breast cancer patients were randomly selected for comparison of intensity modulated radiation therapy (IMRT)-based treatment plan with 3DCRT. Inverse treatment was performed using the sliding window technique, employing the Eclipse Planning System (version 7.1.59, Varian, Palo Alto, CA). The dosimetric parameters compared were V(95) (the percentage of target volume getting > or =95% of prescribed dose), V(105), V(110), and dose homogeneity index, DHI (percentage of target volume getting between 95% and 110% of prescribed dose). The mean V(95), DHI, V(105), and V(110) for target volume for IMRT vs. 3D were 90.6% (standard deviation [SD]: 3.2) vs. 91% (SD: 3.0), 87.7 (SD: 6.0) vs. 82.6 (SD: 7.8), 27.3% (SD: 20.3) vs. 49.4% (SD: 14.3), and 2.8 (SD: 5.6) vs. 8.4% (SD: 7.4), respectively. DHI was increased by 6.3% with IMRT compared to 3DCRT (p < 0.05). The reductions of V(105) and V(110) for the IMRT compared to 3DCRT were 44.7% and 66.3%, respectively (p < 0.01). The mean dose and V(30) for heart with IMRT were 2.3 (SD: 1.1) and 1.05 (SD: 1.5) respectively, which was a reduction by 6.8% and 7.9%, respectively, in comparison with 3D. Similarly, the mean dose and V(20) for the ipsilateral lung and the percentage of volume of contralateral volume lung receiving > 5% of prescribed dose with IMRT were reduced by 9.9%, 2.2%, and 35%, respectively. The mean of total monitor units used for IMRT and 3DCRT was about the same (397 vs. 387). The tangential field IMRT for intact breast using sliding window technique was successfully implemented in the clinic. We have now treated more than 1000 breast cancer patients with this technique. The dosimetric data suggest improved dose homogeneity in the breast and reduction in the dose to lung and heart for IMRT treatments, which may be of clinical value in potentially contributing to improved cosmetic results and reduced late treatment-related toxicity.