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Purpose: Multiple studies have shown a low risk of ipsilateral breast events (IBEs) or other recurrences for selected patients age 65-70 years or older with stage I breast cancers treated with breast-conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy. We sought to evaluate whether younger postmenopausal patients could also be successfully treated without radiation therapy, adding a genomic assay to classic selection factors., Methods: Postmenopausal patients age 50-69 years with pT1N0 unifocal invasive breast cancer with margins ≥2 mm after BCS whose tumors were estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative with Oncotype DX 21-gene recurrence score ≤18 were prospectively enrolled in a single-arm trial of radiotherapy omission if they consented to take at least 5 years of ET. The primary end point was the rate of locoregional recurrence 5 years after BCS., Results: Between June 2015 and October 2018, 200 eligible patients were enrolled. Among the 186 patients with clinical follow-up of at least 56 months, overall and breast cancer-specific survival rates at 5 years were both 100%. The 5-year freedom from any recurrence was 99% (95% CI, 96 to 100). Crude rates of IBEs for the entire follow-up period for patients age 50-59 years and age 60-69 years were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall recurrence were 5.0% (3/60) and 3.6% (5/140), respectively., Conclusion: This trial achieved a very low risk of recurrence using a genomic assay in combination with classic clinical and biologic features for treatment selection, including postmenopausal patients younger than 60 years. Long-term follow-up of this trial and others will help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend.

Purpose: To conduct an appropriate use criteria expert panel update on clinical topics relevant to current clinical practice regarding postmastectomy radiation therapy (PMRT)., Methods and Materials: An analysis of the medical literature from peer-reviewed journals was conducted from May 4, 2010 to May 4, 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to search the PubMed database to retrieve a comprehensive set of relevant articles. A well-established methodology (modified Delphi) was used by the expert panel to rate the appropriate use of procedures., Results: Evidence for key questions in PMRT regarding benefit in special populations and technical considerations for delivery was examined and described. Risk factors for local-regional recurrence in patients with intermediate-risk disease that indicate benefit of PMRT include molecular subtype, age, clinical stage, and pathologic response to neoadjuvant chemotherapy. Use of hypofractionated radiation in PMRT has been examined in several recent randomized trials and is under investigation for patients with breast reconstruction. The use of bolus varies significantly by practice region and has limited evidence for routine use. Adverse effects occurred with both PMRT preimplant and postimplant exchange in 2-staged breast reconstruction., Conclusions: Most patients with even limited nodal involvement will likely benefit from PMRT with significant reduction in local-regional recurrence and potential survival. Patients with initial clinical stage III disease and/or any residual disease after neoadjuvant chemotherapy should be strongly considered for PMRT. Growing evidence supports the use of hypofractionated radiation for PMRT with equivalent efficacy and decreased acute side effects, but additional evidence is needed for special populations. There is limited evidence to support routine use of bolus in all patients. Timing of PMRT regarding completion of 2-staged breast reconstruction requires a discussion of increased risks with radiation postimplant exchange compared with increased risk of failure of reconstruction or surgical complications with radiation preimplant exchange., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Accelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), is an evidence-based treatment option in patients undergoing breast conserving surgery (BCS) for early-stage breast cancer. However, literature regarding reirradiation for patients with ipsilateral breast tumor recurrences (IBTR) is limited. This prospective study assessed the feasibility and efficacy of using APBI in patients who had prior whole breast irradiation., Methods and Materials: This was a single institution, prospective study of patients who were previously treated with BCS and adjuvant whole breast radiation. At the time of enrollment, all had unifocal IBTR, histologically confirmed invasive ductal carcinoma with negative margins after repeat BCS. Patients received either IORT in a single fraction at time of BCS or MammoSite brachytherapy twice daily over 5 days. Follow-up data and patient surveys were collected at 1, 3, 6, 9, and 12 months, then annually for at least a 5-year period., Results: From 2008 to 2014, 13 patients were enrolled. Median time to recurrence after initial course of radiation was 12.5 years. Median follow-up after retreatment was 7.8 years. One patient in the IORT group had a subsequent tumor bed recurrence, yielding a local control of 92%. One patient had distant recurrence. At baseline, 680 reported excellent-good cosmesis compared with 42% at 5 years. All patients indicated total satisfaction with overall treatment experience., Conclusions: APBI using IORT was well tolerated with excellent local control and may be a reasonable alternative to mastectomy for IBTR. Further study is needed to determine the most suitable candidates for this approach., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To update the accelerated partial breast irradiation Consensus Statement published in 2009 and provide guidance on use of intraoperative radiation therapy (IORT) for partial breast irradiation in early-stage breast cancer, based on published evidence complemented by expert opinion., Methods and Materials: A systematic PubMed search using the same terms as the original Consensus Statement yielded 419 articles; 44 articles were selected. The authors synthesized the published evidence and, through a series of conference calls and e-mails, reached consensus regarding the recommendations., Results: The new recommendations include lowering the age in the "suitability group" from 60 to 50 years and in the "cautionary group" to 40 years for patients who meet all other elements of suitability (Table 1). Patients with low-risk ductal carcinoma in situ, as per Radiation Therapy Oncology Group 9804 criteria, were categorized in the "suitable" group. The task force agreed to maintain the current criteria based on margin status. Recommendations for the use of IORT for breast cancer patients include: counseling patients regarding the higher risk of ipsilateral breast tumor recurrence with IORT compared with whole breast irradiation; the need for prospective monitoring of long-term local control and toxicity with low-energy radiograph IORT given limited follow-up; and restriction of IORT to women with invasive cancer considered "suitable.", Conclusion: These recommendations will provide updated clinical guidance regarding use of accelerated partial breast irradiation for radiation oncologists and other specialists participating in the care of breast cancer patients., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer., Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival., Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008)., Conclusions: The combined molecular subtype-RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and molecular subtype could be useful in guiding radiation therapy-based decisions in breast cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Ductal carcinoma in situ (DCIS) is a breast neoplasm with potential for progression to invasive cancer. Management commonly involves excision, radiotherapy, and hormonal therapy. Surgical assessment of regional lymph nodes is rarely indicated except in cases of microinvasion or mastectomy. Radiotherapy is employed for local control in breast conservation, although it may be omitted for select low-risk situations. Several radiotherapy techniques exist beyond standard whole-breast irradiation (ie, partial-breast irradiation [PBI], hypofractionated whole-breast radiation); evidence for these is evolving. We present an update of the American College of Radiology (ACR) Appropriateness Criteria® for the management of DCIS. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions, which are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Although both breast-conserving surgery and mastectomy generally provide excellent local-regional control of breast cancer, local-regional recurrence (LRR) does occur. Predictors for LRR include patient, tumor, and treatment-related factors. Salvage after LRR includes coordination of available modalities, including surgery, radiation, chemotherapy, and hormonal therapy, depending on the clinical scenario. Management recommendations for breast cancer LRR, including patient scenarios, are reviewed, and represent evidence-based data and expert opinion of the American College of Radiology Appropriateness Criteria Expert Panel on LRR.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel.The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Postmastectomy radiation (PMRT) lowers local-regional recurrence risk and improves survival in selected patients with breast cancer. The chest wall and lower axilla are technically challenging areas to treat with homogenous doses and normal tissue sparing. This study compares several techniques for PMRT to provide data to guide selection of optimal treatment techniques. Twenty-five consecutive left-sided patients treated postmastectomy were contoured using Radiation Therapy Oncology Group (RTOG) atlas guidelines then planned using 4 different PMRT techniques: opposed tangents with wedges (3-dimensional [3D] wedges), opposed tangents with field-in-field (FiF) modulation, 8-field intensity modulation radiotherapy (IMRT), and custom bolus electron conformal therapy (BolusECT, .decimal, Inc., Sanford, FL). Required planning target volume (PTV) coverage was held constant, and then dose homogeneity and normal tissue dose parameters were compared among the 4 techniques. BolusECT achieved clincally acceptable PTV coverage for 22 out of 25 cases. Compared with either tangential technique, IMRT and BolusECT provided the lowest heart V25 doses (3.3% ± 0.9% and 6.6% ± 3.2%, respectively with p < 0.0001). FiF had the lowest mean total lung dose (7.3 ± 1.1Gy, with p = 0.0013), IMRT had the lowest total lung V20 (10.3% ± 1.6%, p < 0.0001), and BolusECT had the lowest mean heart dose (7.3 ± 2.0Gy, p = 0.0002). IMRT provided the optimal dose homogeneity and normal tissue sparing compared with all other techniques for the cases in which BolusECT could not achieve acceptable PTV coverage. IMRT generally exposes contralateral breast and lung to slightly higher doses. Optimal PMRT technique depends upon patient anatomy. Patients whose maximal target volume depth is about 5.7cm or less can be treated with BolusECT-assisted 12 or 15MeV electron beams. At these energies, BolusECT has comparable dose-volume statistics as IMRT and lower heart V25 than opposed tangential beams. Patients with larger depths are best treated with IMRT, which provides significant advantages in both dose homogeneity and normal tissue sparing compared with all other techniques., (© 2013 American Association of Medical Dosimetrists.)

Purpose: Use of postmastectomy radiation therapy (PMRT) in breast cancer patients with 1-3 positive nodes is controversial. The objective of this study was to determine whether the size of nodal metastases in this subset could predict who would benefit from PMRT., Methods and Materials: We analyzed 250 breast cancer patients with 1-3 positive nodes after mastectomy treated with contemporary surgery and systemic therapy at our institution. Of these patients, 204 did not receive PMRT and 46 did receive PMRT. Local and regional recurrence risks were stratified by the size of the largest nodal metastasis measured as less than or equal to 5 mm or greater than 5 mm., Results: The median follow-up was 65.6 months. In the whole group, regional recurrences occurred in 2% of patients in whom the largest nodal metastasis measured 5 mm or less vs 6% for those with metastases measuring greater than 5 mm. For non-irradiated patients only, regional recurrence rates were 2% and 9%, respectively. Those with a maximal nodal size greater than 5 mm had a significantly higher cumulative incidence of regional recurrence (P=.013). The 5-year cumulative incidence of a regional recurrence in the non-irradiated group was 2.7% (95% confidence interval [CI], 0.7%-7.2%) for maximal metastasis size of 5 mm or less, 6.9% (95% CI, 1.7%-17.3%) for metastasis size greater than 5 mm, and 16% (95% CI, 3.4%-36.8%) for metastasis size greater than 10 mm. The impact of the maximal nodal size on regional recurrences became insignificant in the multivariable model., Conclusions: In patients with 1-3 positive lymph nodes undergoing mastectomy without radiation, nodal metastasis greater than 5 mm was associated with regional recurrence after mastectomy, but its effect was modified by other factors (such as tumor stage). The size of the largest nodal metastasis may be useful to identify high-risk patients who may benefit from radiation therapy after mastectomy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Targeted intraoperative radiation therapy (IORT) as an alternative to whole breast irradiation (WBI) has been described for patients with early-stage breast cancer. The randomized phase III TARGiT trial demonstrated similar recurrence rates to WBI and a lower overall toxicity profile on short-term follow-up. We report on our early North American surgical experience using the Intrabeam radiotherapy delivery system and review the current literature., Methods: Prospectively gathered estrogen receptor-positive, clinically node-negative patients with invasive breast cancer < 3 cm receiving IORT using the Intrabeam system were reviewed. IORT-related effects and early postoperative outcome were assessed. A literature review was also performed., Results: Forty-two patients (median age 71 years) underwent lumpectomy, sentinel lymph node (SLN) biopsy, and concurrent IORT from January 2011 to July 2011. Ninety-one percent of patients had invasive ductal histology with a median tumor size of 1.0 cm. This review highlights the patient selection criteria, describes commercially available accelerated partial breast irradiation (APBI) treatment options, and discusses outcomes for the variety of APBI techniques currently utilized in clinical practice as well as an institutional review of our early surgical experience using the Intrabeam radiotherapy delivery system., Conclusions: While a variety of APBI techniques are currently available for clinical use, our early North American operative experience with IORT shows it is well tolerated with low morbidity. Delivery of IORT adds moderate operative time and may require creating subcutaneous tissue fl aps. The addition of WBI may be necessary in situations for positive residual margins or microscopic nodal disease in patients who do not undergo additional surgery.

Purpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients., Experimental Design: RSI was tested in 2 previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n = 159) and Erasmus Medical Center (n = 344). RSI was applied as previously described., Results: We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5-year relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, P = 0.0212), but there was no difference between RS/RR patients treated without RT (71% vs. 77%, P = 0.6744), consistent with RSI being RT-specific (interaction term RSI × RT, P = 0.05). Similarly, in the Erasmus dataset, RT-treated RS patients had an improved 5-year distant metastasis-free survival over RR patients (77% vs. 64%, P = 0.0409), but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, P = 0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, HR = 5.53, P = 0.0987, Erasmus, HR = 1.64, P = 0.0758) and in backward selection (removal α of 0.10), RSI was the only variable remaining in the final model. Finally, RSI is an independent predictor of outcome in RT-treated ER(+) patients (Erasmus, multivariable analysis, HR = 2.64, P = 0.0085)., Conclusions: RSI is validated in 2 independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in 5 independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology., (©2012 AACR.)

The objective of this study was to describe the progression of arm lymphedema (ALE) after the initial presentation among patients receiving breast conservation therapy for early stage breast cancer and to identify potential risk factors contributing to ALE progression. The study sample was the 266 stage I or II breast cancer patients with documented ALE who underwent breast conservation therapy that included lumpectomy, axillary staging followed by radiation therapy. ALE were graded according to a difference of 0.5-2 cm (mild), 2.1-3 cm (moderate), and >3 cm (severe) in the circumference between the upper extremities for the treated and untreated sides. ALE at presentation was scored as mild, moderate, and severe in 109 (41%), 125 (47%), and 32 (12%) patients, respectively. One third of patients with ALE progressed to a more severe grade of lymphedema at 5 years of follow-up. Age older than 65 years at the time of breast cancer treatment was associated with higher risk of ALE progression when compared 65 year age or younger (p = 0.04). The patients who had regional lymph node irradiation including posterior axillary boost were at higher risk of lymphedema progression than the patients treated with whole breast irradiation only (p = 0.001). Progression of ALE is a common occurrence. The current study provides support for the utility of routine arm measurements after breast cancer treatment to facilitate timely diagnosis and treatment of ALE., (© 2012 Wiley Periodicals, Inc.)

Despite the success of both breast conserving surgery and mastectomy, some women will experience a local-regional recurrence (LRR) of their breast cancer. Predictors for LRR after breast-conserving therapy or mastectomy have been identified, including patient, tumor, and treatment-related factors. The role of surgery, radiation, and chemotherapy as treatment has evolved over time and many patients now have the potential for salvage after LRR. This review of LRR of breast cancer and management recommendations, including the use of common clinical scenarios, represents a compilation of evidence-based data and expert opinion of the American College of Radiology Appropriateness Criteria Expert Panel on local-regional recurrence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Purpose: Image-guided radiation therapy (IGRT) may be beneficial for accelerated partial breast irradiation (APBI). The goal was to validate the use of intraparenchymal textured gold fiducials in patients receiving APBI., Methods and Materials: Twenty-six patients were enrolled on this prospective study that had three or four textured gold intraparenchymal fiducials placed at the periphery of the lumpectomy cavity and were treated with three-dimensional (3D) conformal APBI. Free-breathing four-dimensional computed tomography image sets were obtained pre- and posttreatment, as were daily online megavoltage (MV) orthogonal images. Intrafraction motion, variations in respiratory motion, and fiducial marker migration were calculated using the 3D coordinates of individual fiducials and a calculated center of mass (COM) of the fiducials. We also compared the relative position of the fiducial COM with the geometric center of the seroma., Results: There was less than 1 mm of intrafraction respiratory motion, variation in respiratory motion, or fiducial marker migration. The change in seroma position relative to the fiducial COM was 1 mm ± 1 mm. The average position of the geometric seroma relative to the fiducial COM pretreatment compared with posttreatment was 1 mm ± 1 mm. The largest daily variation in displacement when using bony landmark was in the anteroposterior direction and two standard deviations (SD) of this variation was 10 mm. The average variation in daily separation between the fiducial pairs from daily MV images was 3 mm ± 3 mm therefore 2 SD is 6 mm., Conclusion: Fiducial markers are stable throughout the course of APBI. Planning target volume margins when using bony landmarks should be 10 mm and can be reduced to 6 mm if using fiducials., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Ductal carcinoma in situ (DCIS) describes a wide spectrum of non-invasive tumors which carry a significant risk of invasive relapse, thus prevention of local recurrence is vital. For appropriate patients with limited disease, management with breast conserving surgery (BCS) followed by whole-breast radiation (RT) is supported by multiple Phase III studies, but mastectomy may be appropriate in selected patients. Omission of RT may also be reasonable in some patients, though which criteria are to be utilized remain unclear, and the existing data are contradictory with limited follow-up. Various RT techniques such as boost to the tumor bed, partial breast radiation or hypofractionated, whole-breast RT are increasingly utilized but the data to support their use specifically in DCIS is limited. Tamoxifen also increases local control for ER + DCIS, adding to the complexity of the local treatment management. This article reviews the existing scientific evidence, the controversies surrounding local management, and clinical guidelines for DCIS based on the group consensus by the ACR Breast Expert Panel. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., (© 2011 American College of Radiology.)

Unlabelled: The current study examined the impact of re-excision and residual disease on local recurrence after breast conservation treatment for patients with negative margins. Patients with residual disease on re-excision had a higher local recurrence rate than other patients. However, with reasonably low local recurrence rates in all subgroups, neither re-excision nor residual disease on re-excision are contraindications for breast conservation treatment., Purpose: To evaluate the impact of re-excision and the presence of residual disease on local recurrence for patients who underwent breast conservation treatment (BCT) with negative final resection margins., Methods: The records of 902 patients with stage I or II unilateral invasive breast cancer who had BCT were reviewed. The study cohort consisted of patients with negative final resection margins and was divided into 3 subgroups: (a) single excision (n = 332 [37%]), (b) re-excision with no residual disease in the re-excision specimen (n = 440 [49%]), and (c) re-excision with residual disease in the re-excision specimen (n = 130 [14%]). The median follow-up was 6.75 years., Results: At 15 years, the rates of local failure were 10% for patients with a single excision, 10% for patients with a re-excision without residual disease, and 16% for patients with a re-excision with residual disease (P = .033). There were no significant differences between the 3 groups for overall survival, cause-specific survival, relapse-free survival, or freedom from distant metastases (all P ≥ .082). Multivariate analysis demonstrated an increased risk of local failure for patients with residual disease in the re-excision specimen that was borderline statistically significant (hazard ratio, 2.16; P = .061)., Conclusions: Despite achieving negative final resection margins, the patients with residual disease in the re-excision specimen had a higher rate of local recurrence than patients who underwent single excision or patients without residual disease on re-excision. However, local recurrence was reasonably low in all 3 subgroups, and, therefore, neither re-excision nor residual disease represent contraindications for BCT., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Locally advanced breast cancer (LABC) is a disease that is heterogeneous in its presentation, potentially curable, and generally necessitating multidisciplinary management. Radiation therapy (RT) plays an important role in the management of LABC. The integration of radiation with surgery, chemotherapy, and sometimes breast reconstruction can be complex. The American College of Radiology Appropriateness Criteria Breast Committee aims to provide guidance for the management of a variety of LABC cases. The American College of Radiology Appropriateness Criteria is evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is either lacking or not definitive, expert opinion may be used to recommend imaging or treatment., (© 2011 American College of Radiology.)

Breast conservation is a safe and effective alternative to mastectomy for the majority of women with early-stage breast cancer. Adjuvant radiation therapy lowers the risk of recurrence within the breast and also confers a survival benefit. Although acute side effects of radiation therapy are generally well tolerated; efforts are ongoing to minimize the long-term side effects of radiation, most prominently atherosclerotic heart disease. Efforts to minimize radiation therapy are also underway. They include omitting treatment altogether in the elderly and using accelerated, hypofractionated whole-breast irradiation, and accelerated partial-breast irradiation. Several randomized studies are ongoing to determine the efficacy, safety, and appropriate patients for these shorter treatments., (© 2011 American College of Radiology.)

Left-sided breast irradiation has been associated with increased risk of cardiac morbidity and mortality in some studies. This study examines the cardiac toxicity of irradiation in left- versus right-sided patients with ductal carcinoma in situ (DCIS). The medical records of 129 patients with DCIS treated with breast conservation therapy (BCT) at the Moffitt Cancer Center from 1986 to 2002 were reviewed and data regarding subsequent breast cancer and cardiac events were recorded. There were 59 left-sided and 70 right-sided patients treated. Mean age was 55 years. At 8 years, there was no significant difference observed between right- and left-sided breast cancer patients in the development of coronary artery disease, myocardial infarction, congestive heart failure, arrhythmia, valvular disease, cardiomyopathy, or cardiac-related death. Among those patients with left-sided breast cancer, 13.5% of patients developed a cardiovascular event compared to 7% of right-sided patients (p = 0.25). The overall survival at 8 years was 96% and the relapse-free survival was 85%. There were no significant differences in cardiac mortality or morbidity between right- and left-sided DCIS patients treated with BCT. Longer follow-up will be required to ascertain whether late events are more prevalent in left-sided patients., (© 2011 Wiley Periodicals, Inc.)

Background: Multiple randomized trials comparing mastectomy to lumpectomy and whole breast irradiation (WBI) have shown equivalent survival outcomes in early-stage breast cancer. WBI requires a treatment course of several weeks, which has resulted in limited access to breast-conserving therapy in certain populations. A shorter accelerated course of partial breast irradiation (APBI) has been investigated recently., Methods: This article reviews the current medical literature, including randomized trials and prospective institutional studies of APBI and the current recommendations regarding the use of this emerging technique., Results: Several APBI techniques have been developed, including brachytherapy and external beam methods. The longest follow-up data are available for multicatheter interstitial brachytherapy, a technique that is not commonly used. Other methods, including balloon brachytherapy and external beam three-dimensional conformal techniques, have limited follow-up that shows similar local control rates to whole breast irradiation in highly selected patients. Guidelines for the appropriate use of APBI have been published., Conclusions: While APBI may increase access to breast conservation therapy for some women with early-stage breast cancer, follow-up data demonstrating the efficacy of this relatively new treatment approach are limited. Therefore, strict evidence-based selection criteria should be applied when evaluating patients who may be appropriate for APBI.

Background: Anemia is common among patients with newly diagnosed cancer, may be exacerbated by cancer therapies, and leads to radioresistance by lowering oxygen levels in the tumor microenvironment. Herein, the effect of breast irradiation on hemoglobin levels and outcomes in breast conservation therapy is reported., Patients and Methods: Medical records of 1368 women with stage 0, I, and II breast cancer treated with breast conservation therapy from 1977-2002 were reviewed. Hemoglobin levels at baseline as well as during and after radiation were recorded. Patterns of hemoglobin changes and the effect of anemia on local control and survival outcomes were assessed. Median follow-up time was 8 years for the normal group and 6 years for the anemic group., Results: Baseline anemia was seen in 18% of the patients, 90% of whom had mild anemia (hemoglobin, 11.9-10.0 g/dL). Anemia was recorded in 21% during radiation. Among patients with normal baseline hemoglobin levels, 6.5% of the patients became anemic during radiation. Of those with baseline anemia, 72% had stable to improved hemoglobin levels during radiation, and 22% declined by a median of 0.3 g/dL. There were no significant differences in local or regional recurrence, overall, disease-free, cause-specific, or distant disease-free survival between patients with baseline anemia or with normal hemoglobin., Conclusion: Radiation does not contribute significantly to anemia during breast conservation treatment, and mild anemia does not affect outcomes. It is unnecessary to obtain routine hemoglobin levels during radiation therapy. There is no difference in outcomes based on hemoglobin levels; thus, there is no reason to transfuse or provide erythropoiesis-stimulating agents for hemoglobin levels > 10 g/dL during radiation treatment of the breast.

Purpose: Arm lymphedema is a potential consequence of the treatment for breast carcinoma. The objective of this retrospective study was to characterize the progression of mild arm lymphedema after breast conservation treatment for breast cancer., Methods and Materials: The study cohort was drawn from 1,713 consecutive Stage I or II breast cancer patients who underwent breast conservation therapy, including axillary staging followed by radiation. Arm lymphedema was documented in 266 (16%) of 1,713 patients. One hundred nine patients, 6% of the overall group and 40% of the patients with arm lymphedema, presented with mild arm lymphedema, defined as a difference of 2 cm or less between the measured circumferences of the affected and unaffected arms., Results: Among the 109 patients with mild arm lymphedema at the time of arm lymphedema diagnosis, the rate of freedom from progression to more severe lymphedema was 79% at 1 year, 66% at 3 years, and 52% at 5 years. The patients who were morbidly obese, had positive axillary lymph nodes, or received supraclavicular irradiation at the time of breast cancer treatment were at higher risk of progression from mild arm lymphedema to more severe edema., Conclusions: Mild arm lymphedema, generally considered to be a minor complication after breast conservation treatment for breast cancer, was associated with a risk of progression to a more severe grade of arm lymphedema in a substantial fraction of patients.

Purpose: To examine the association between radiation treatment (RT) parameters, cardiac diagnostic test abnormalities, and clinical cardiovascular diagnoses among patients with left-sided breast cancer after breast conservation treatment with tangential beam RT., Methods and Materials: The medical records of 416 patients treated between 1977 and 1995 with RT for primary left-sided breast cancer were reviewed for myocardial perfusion imaging and echocardiograms. Sixty-two patients (62/416, 15%) underwent these cardiac diagnostic tests for cardiovascular symptoms and were selected for further study. Central lung distance and maximum heart width and length in the treatment field were determined for each patient. Medical records were reviewed for cardiovascular diagnoses and evaluation of cardiac risk factors., Results: At a median of 12 years post-RT the incidence of cardiac diagnostic test abnormalities among symptomatic left-sided irradiated women was significantly higher than the predicted incidence of cardiovascular disease in the patient population, 6/62 (9%) predicted vs. 24/62 (39%) observed, p = 0.001. As compared with patients with normal tests, patients with cardiac diagnostic test abnormalities had a larger median central lung distance (2.6 cm vs. 2.2 cm, p = 0.01). Similarly, patients with vs. without congestive heart failure had a larger median central lung distance (2.8 cm vs. 2.3 cm, p = 0.008)., Conclusions: Contemporary RT for early breast cancer may be associated with a small, but potentially avoidable, risk of cardiovascular morbidity that is associated with treatment technique.

Background: This study was undertaken to determine the risk of late cardiac morbidity and mortality in patients with preexisting cardiac disease treated with contemporary radiation techniques for early-stage breast cancer., Patients and Methods: Medical records were reviewed for 41 patients with early-stage breast cancer and a history of myocardial infarction, congestive heart failure (CHF), and/or coronary artery disease before radiation therapy. Data were recorded on baseline cardiac disease and tumor characteristics, cardiac morbidity during and after treatment, and survival status of each patient. Patients were stratified for right- versus left-sided breast cancer and compared., Results: There was no significant difference in overall survival (OS) between the right- and left-sided groups (log-rank test; P = .19). The left-sided group had a higher incidence of cardiac deaths (right side, 2 of 26 [9%]; left side, 4 of 15 [27%]; hazard ratio, 4.2; P = .08) 10 years after treatment, including deaths secondary to myocardial infarction, CHF, or coronary artery disease. On the other hand, the right-sided group had a higher proportion of deaths secondary to breast cancer (right, 8 of 26 [31%]; left, 2 of 15 [13%]) and non-breast cancer/noncardiac causes (right, 7 of 26 [27%]; left, 1 of 15 [7%])., Conclusion: Although OS was similar in both groups, radiation was associated with a higher incidence of cardiac death in patients with left-sided breast cancer. Efforts should be made to minimize cardiac exposure and also to promote more vigilant risk factor modification in this group of women.

Background: Breast conservation treatment for early-stage breast cancer has been demonstrated to be equivalent to mastectomy in a large number of randomized trials. A number of earlier studies of surgery with or without radiation did not show an improvement in overall survival despite large reductions in local recurrence rates. Numerous randomized trials have demonstrated that postmastectomy radiation to the chest wall and regional nodes in high-risk early-stage patients provides improvements in local-regional control and overall survival., Methods: This article reviews the medical literature pertaining to long-term cardiac toxicity in early-stage breast cancer patients treated with either breast conservation or postmastectomy radiation., Results: A decrease in breast cancer deaths associated with postoperative irradiation was offset by an increase in cardiovascular deaths in early studies. Cardiac toxicity of breast irradiation is a late event, manifesting clinically 10 or more years after breast cancer treatment. The excess deaths were directly related to radiation techniques that exposed excessive volumes of the heart, leading to the development of new techniques designed to shield the heart and reduce the risk of cardiac toxicity., Conclusions: This review examines the original and contemporary studies of radiation for postmastectomy and breast conservation treatment for early-stage breast cancer, discusses the long-term cardiac mortality and morbidity data from these studies, and reviews the known risk factors associated with cardiac toxicity after irradiation for breast cancer.

Purpose: Breast cancer incidence increases with age and is a major cause of morbidity and mortality in elderly women, but is not well studied in this population. Comorbidities often impact on the management of breast cancer in elderly women., Methods and Materials: From 1979 to 2002, a total of 238 women aged 70 years and older with Stage I or II invasive carcinoma of the breast underwent breast-conservation therapy. Outcomes were compared by age groups and comorbidities. Median age at presentation was 74 years (range, 70-89 years). Age distribution was 122 women (51%) aged 70-74 years, 71 women (30%) aged 75-79 years, and 45 women (19%) aged 80 years or older. Median follow-up was 6.2 years., Results: On outcomes analysis by age groups, 10-year cause-specific survival rates for women aged 70-74, 75-79, and 80 years or older were 74%, 81%, and 82%, respectively (p = 0.87). Intercurrent deaths at 10 years were significantly higher in older patients: 20% in those aged 70-74 years, 36% in those aged 75-79 years, and 53% in those 80 years and older (p = 0.0005). Comorbidities were not significantly more common in the older age groups and did not correlate with cause-specific survival adjusted for age. Higher comorbidity scores were associated with intercurrent death., Conclusions: Older age itself is not a contraindication to standard breast-conservation therapy, including irradiation. Women of any age with low to moderate comorbidity indices should be offered standard breast-conservation treatment if otherwise clinically eligible.

Purpose: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer., Methods and Materials: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies., Results: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median time to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if >or=51 years, 57% if 36-50 years, and 83% if 180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p >or= 0.15)., Conclusion: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.

Purpose: To compare the incidence and distribution of coronary artery disease after left-sided versus right-sided irradiation in patients treated with breast conservation for early-stage breast cancer who subsequently underwent cardiac stress testing and/or catheterization for cardiovascular symptoms., Patients and Methods: The medical records of 961 stage I-II breast cancer patients treated from 1977 to 1995 at the University of Pennsylvania with conventional tangential beam radiation treatment (RT) were screened for cardiac stress tests and catheterizations performed after RT. The results of these tests were analyzed by laterality of RT and compared with baseline cardiovascular risk., Results: At diagnosis, patients with left-sided and right-sided breast cancer had the same estimated 10-year risk (both 7%) of developing coronary artery disease. At a median time of 12 years post-RT (range, 2 to 24 years), 46 patients with left-sided and 36 patients with right-sided breast cancer (total, N = 82) had undergone cardiac stress testing. A statistically significant higher prevalence of stress test abnormalities was found among left (27 of 46; 59%) versus right-side irradiated patients (three of 36; 8%; P = .001). Furthermore, 19 of 27 of left-sided abnormalities (70%) were in the left anterior descending artery territory. Thirteen left-side irradiated patients also underwent cardiac catheterization revealing 12 of 13 with coronary stenoses (92%) and eight of 13 with coronary stenoses (62%) solely in the left anterior descending artery., Conclusion: Patients treated with left-sided radiation as a component of breast conservation have an increased risk of late, radiation-associated coronary damage. Treatment with modern radiation techniques may reduce the risk of cardiac injury.

Purpose: This study was undertaken to determine the incidence of contralateral breast cancer (CLB) after treatment for early-stage breast cancer with breast-conserving treatment (BCT), and to observe patterns of CLB presentation., Methods: Medical records of 1,801 women treated for unilateral AJCC Stage 0-II breast cancer with BCT between 1977 and 2000 were analyzed as a retrospective cohort., Results: The incidence of any CLB at 20 years was 15.4%. The annual risk of developing any CLB remained constant at approximately 0.75% per year after treatment. The median time to any CLB was 8.2 years (range, 0.5-26.5 years). No difference in incidence of CLB was demonstrated in patients with primary invasive carcinoma vs. DCIS (p = 0.84). The majority of patients (83%) developing CLB tumors developed invasive disease. The risk of developing an invasive CLB did not differ significantly for patients with DCIS vs. those with primary invasive carcinoma (p = 0.20). The method of detection of the primary tumor (mammography vs. physical examination) was not predictive of detection of the CLB (p = 0.20). Finally, the location of CLB tumors was not affected by that of prior tumors (p = 0.82)., Conclusions: The risk of development of CLB persists for at least 20 years after treatment for early-stage breast cancer. CLB tumors are frequently invasive, and their location is not influenced by location of prior tumors. Mammography and physical examination remain essential after BCT for detection of a contralateral breast cancer, regardless of the method of detection of the primary tumor.

Purpose: Several studies have reported increased cardiac mortality related to the use of left-sided breast or chest-wall irradiation. This study was undertaken as a comprehensive examination of the long-term cardiac mortality and morbidity after breast irradiation using contemporary irradiation techniques., Methods: The medical records of 961 consecutive patients presenting between 1977 and 1994 with stage I or II breast cancer treated with breast conservation treatment were reviewed. Data was recorded on baseline pretreatment patient, tumor and treatment characteristics and on subsequent cancer or cardiac related events. The median follow-up time was 12 years., Results: There was no difference in overall mortality from any cardiac cause (P = .25). Death from any cardiac cause occurred in 2% of right-sided patients and 3.5% of left-sided patients. However, in the second decade after treatment, there was a higher rate of cardiac deaths in left-sided patients, with a cumulative risk of 6.4% (95% CI, 3.5% to 11.5%) for left-sided compared with 3.6% (95% CI, 1.8% to 7.2%) for right-sided patients at 20 years. There were statistically higher rates of chest pain, coronary artery disease, and myocardial infarction diagnosed in left-sided patients (all P < or = .002). The presence of hypertension was associated with a higher risk of coronary artery disease in left-sided patients., Conclusion: Irradiation to the left breast is not associated with a higher risk of cardiac death up to 20 years after treatment, but is associated with an increased rate of diagnoses of coronary artery disease and myocardial infarction compared with right breast treatment.

This study was undertaken to determine whether overexpression of the oncogene HER-2 is associated with an increase in local recurrence in women with early stage breast cancer treated with breast-conserving therapy (BCT). A retrospective review of the medical records of all women treated with stage I-II invasive breast cancer from 1991 through 2001 was performed. Of 596 eligible patients treated in that time period, immunohistochemical testing for HER-2 expression was performed in 352 patients (59%): 266 patients (76%) were HER-2 negative and 86 patients (24%) were HER-2 positive. Median follow-up was 5.4 years. The patient characteristics for the two groups were compared for age, pathologic T and N stage, number of positive nodes, estrogen receptor (ER) and progesterone receptor (PR) status, radiation treatment, and use of hormonal therapy or chemotherapy. There were no significant differences in any of these parameters between the two groups (all p > or = 0.10). Local recurrence at 5 years was 2% in the HER-2-negative group and 0% in the HER-2-positive group (p = 0.15). There was no difference in local recurrence after BCT between HER-2-positive and negative breast cancers at 5 years. Therefore HER-2 overexpression does not appear to be a contraindication to BCT.

Purpose: We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls., Methods: A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls., Results: There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05)., Conclusion: IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.

Breast conservation treatment (BCT) for early-stage breast cancer is associated with survival rates comparable with mastectomy but has the risk of ipsilateral breast tumor recurrence, including Paget's disease of the nipple. A small number of cases of Paget's disease presenting as local recurrence following BCT for breast cancer have been previously reported. Between 1977 and 2002, 2181 women with early-stage breast cancer were treated with BCT at the Hospital of the University of Pennsylvania. In this cohort, there were 183 local treatment failures, 4 of which were cases of Paget's disease (2.2%), which are reported herein. These local recurrences developed 1.8, 3.8, 7.3, and 9.7 years after diagnosis of the patients' primary tumors. Three of the 4 primary cancers were invasive ductal carcinomas, with an associated intraductal component, and 1 was ductal carcinoma in situ. All 4 patients were successfully given salvage therapy consisting of mastectomy with or without tamoxifen, with follow-up times of 20.9, 10.6, 3.1, and 3.8 years. Paget's disease as local recurrence after BCT is uncommon and can be treated with salvage therapy if detected early.

Background: The objective of the current study was to determine the long-term results of breast-conservation treatment in women with early-stage, invasive lobular carcinoma of the breast., Methods: Between 1977 and 1995, 1093 women with Stage I and II invasive ductal carcinoma of the breast and 55 women with invasive lobular carcinoma of the breast underwent lumpectomy, axillary lymph node dissection, and radiation treatment. Overall, 49% of the women received adjuvant systemic therapy (chemotherapy and/or hormones)., Results: The median age was 52 years for patients in the invasive ductal group and 54 years for patients in the invasive lobular group. The median follow-up was 8.7 years and 10.2 years for patients in the invasive ductal and invasive lobular groups, respectively. A comparison of patients who had invasive lobular carcinoma with patients who had invasive ductal carcinoma showed no difference in the 10-year actuarial rates of overall survival (85% vs. 79%, respectively; P = 0.73), cause-specific survival (93% vs. 84%, respectively; P = 0.85), or freedom from distant metastases (81% vs. 80%, respectively; P = 0.76). The 10-year rates of local failure were 18% for patients with invasive lobular carcinoma and 12% for patients with invasive ductal carcinoma (P = 0.24), and the 10-year rates of contralateral breast carcinoma development for the 2 groups were 12% and 8%, respectively (P = 0.40)., Conclusions: Breast-conservation treatment yielded similar long-term results for women with early-stage, invasive lobular carcinoma and women with the more prevalent invasive ductal carcinoma., (Copyright 2005 American Cancer Society.)

Purpose: To evaluate the daily setup variation and the anatomic movement of the heart and lungs during breast irradiation with tangential photon beams, as measured with an electronic portal imaging device., Methods and Materials: Analysis of 1,709 portal images determined changes in the radiation field during a treatment course in 8 patients. Values obtained for every image included central lung distance (CLD) and area of lung and heart within the irradiated field. The data from these measurements were used to evaluate variation from setup between treatment days and motion due to respiration and/or patient movement during treatment delivery., Results: The effect of respiratory motion and movement during treatment was minimal: the maximum range in CLD for any patient on any day was 0.25 cm. The variation caused by day-to-day setup variation was greater, with CLD values for patients ranging from 0.59 cm to 2.94 cm. Similar findings were found for heart and lung areas., Conclusions: There is very little change in CLD and corresponding lung and heart area during individual radiation treatment fractions in breast tangential fields, compared with a relatively greater amount of variation that occurs between days.

Purpose: To assess the impact of sequencing of tamoxifen and radiation therapy (RT) on outcomes in early-stage breast cancer., Patients and Methods: This retrospective study evaluates the effect of the sequence of tamoxifen with RT on outcomes in stage I to II breast cancer patients who underwent breast-conservation treatment (BCT) and received adjuvant tamoxifen, with or without adjuvant chemotherapy. Patients were grouped as concurrent (tamoxifen given during RT followed by continued tamoxifen; 174 patients) and sequential (RT followed by tamoxifen; 104 patients)., Results: Median follow-up after RT was 8.6 years for both groups. The pathologic T and N stage, race, estrogen and progesterone status, number of positive nodes, and RT were comparable between the two groups (all P >/= .08). More women age 49 years or younger and women who received chemotherapy were in the sequential group than the concurrent group (6% and 25%, respectively; P < .0001). The sequence of tamoxifen therapy did not influence 10-year local recurrence rates (sequential, 7%; concurrent, 3%; P = .52), overall survival (sequential, 86%; concurrent, 81%; P = .64), or relapse-free survival (sequential, 76%; concurrent, 85%; P = .35). When adjusting age and chemotherapy use in the multivariable Cox model, hazard ratios comparing sequential versus concurrent tamoxifen therapy were 1.56 (95% CI, 0.87 to 2.79), 1.23 (95% CI, 0.63 to 2.41), and 1.22 (95% CI, 0.33 to 4.49) for the overall survival, relapse-free survival, and local recurrence, respectively., Conclusion: The therapeutic regimens of tamoxifen given concurrently or sequentially with RT both appear to be reasonable options for patients treated with BCT.

Background: The authors evaluated the risk factors for regional lymph node recurrence and the prognosis of patients with regional nodal recurrence after breast conservation therapy for Stage I-II breast carcinoma., Methods: Between 1977 and 1995, 1293 women with pathologic Stage I and II (T1-2, N0-1) breast carcinoma were treated with breast-conserving therapy including lumpectomy, axillary lymph node dissection, and definitive breast irradiation. A total of 39 women (3%) had any regional lymph node recurrence. The median follow-up was 8.5 years (range, 1.5-24 years)., Results: Among 39 patients with a regional lymph node recurrence, 10 women had regional recurrence only, 16 had simultaneous locoregional recurrence, and 13 had simultaneous regional and distant recurrence. Regional recurrence occurred in the axillary lymph nodes only (n = 21; 51%), supraclavicular lymph nodes only (n = 8; 23%), internal mammary lymph nodes only (n = 3; 8%), infraclavicular lymph nodes only (n = 3; 8%), or multiple lymph node sites (n = 4; 10%). The median time to regional lymph node recurrence was 3.1 years (range, 0.2-20.9 years). Overall survival after regional-only disease recurrence was 44%, locoregional disease recurrence was 26%, and regional with distant disease recurrence was 12%. Cause-specific survival rates at 10 years for the 3 groups were 44%, 40%, and 12%, respectively. For patients who presented with simultaneous regional and distant metastases, the median survival period was 1.1 years, compared with 5.2 years for women who developed distant disease subsequent to regional recurrence., Conclusions: Regional lymph node recurrence after breast conservation therapy may be salvaged, but is associated with a high rate of either simultaneous or subsequent distant metastatic dissemination and poor overall prognosis., (Copyright 2003 American Cancer Society.)

Background: Mammography and physical examination are routine methods for the detection of ipsilateral local recurrence and contralateral breast carcinoma in patients initially undergoing breast conservation treatment. The current study reports the relation between the method of detection of the initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma., Methods: A retrospective review was performed of the records of female patients with initial American Joint Committee on Cancer (AJCC) Stage I and II invasive breast carcinoma who developed ipsilateral local recurrence or contralateral breast carcinoma after breast conservation treatment. The method of detection of local recurrence in the ipsilateral breast and the method of detection of contralateral breast carcinoma were compared with the method of detection of the primary tumor., Results: There were 125 ipsilateral breast local recurrences and 71 contralateral breast carcinoma cases detected. Of the 125 recurrences in the ipsilateral breast, 38% (48 recurrences) were detected by mammography only, 37% (46 recurrences) were detected by physical examination only, and 25% (31 recurrences) were detected by both methods. Of the 71 contralateral breast carcinoma cases, 53% (38 cases) were detected by mammography only, 23% (16 cases) were detected by physical examination only, and 24% (17 cases) were detected by both methods. When the primary tumors were detected by mammography only, 21% of the local recurrences (3 of 14 local recurrences) and 19% of the contralateral breast carcinoma cases (4 of 21 cases) were detected by physical examination only. When the primary tumors were detected by physical examination only, 24% of the local recurrences (14 of 58 local recurrences) and 42% of the contralateral breast carcinoma cases (8 of 19 cases) were detected by mammography only. When stratified by the interval between diagnosis of the primary tumor and ipsilateral local recurrence or contralateral breast carcinoma (< or = 5 years vs. > 5 years) or age of the patient at the time of ipsilateral breast recurrence or contralateral breast carcinoma (age < or = 49 years vs. age > or = 50 years), both breast examination and mammography were found to be important in the detection of locally recurrent tumor and contralateral breast carcinoma in each subgroup of the patients, regardless of the method of presentation of the primary tumor., Conclusions: Both mammography and physical examination were found to be significant in the detection of locally recurrent tumor in the ipsilateral breast and in the detection of contralateral breast carcinoma, regardless of the method of detection of the primary tumor., (Copyright 2003 American Cancer Society.)

Purpose: To evaluate the long-term outcome of combined modality therapy for inflammatory breast cancer., Methods and Materials: The data from 54 women treated between 1983 and 1996 for inflammatory breast cancer were analyzed. Patients with metastatic disease or disease progression on induction chemotherapy were excluded. Induction chemotherapy was given to 52 patients. Mastectomy was performed in 52 patients. Radiotherapy was delivered to the breast or chest wall and regional lymph nodes in all patients. The median follow-up for all patients was 5.1 years., Results: The 5- and 10-year overall survival rate was 56% and 35%, respectively; the corresponding relapse-free survival rates were 49% and 34%. Patients with a pathologic complete response after chemotherapy with or without preoperative radiotherapy had better 5- and 10-year overall survival rates (65% and 46%, respectively) and 5- and 10-year relapse-free survival rates (59% and 50%, respectively) compared with patients without a pathologic complete response. Those patients had a 5- and 10-year relapse-free survival rate of 45% and 27%, respectively. Locoregional failure at 5 and 10 years was 8% and 19%, respectively., Conclusion: The outcomes for patients completing multimodality therapy compare favorably with published data; however, the exclusion of patients with progression during induction chemotherapy may account in part for these results. The pathologic complete response rate was found to be an important prognostic factor. Selected patients with inflammatory breast cancer have the potential for long-term survival.

Purpose: This study examines the factors associated with the presence of residual disease at re-excision in patients with ductal carcinoma in situ of the breast., Methods: Of 143 consecutive patients undergoing breast conservation treatment from 1990 to 1999, 90 patients (63%) underwent re-excision of the tumor bed. Grade was recorded in 70% (N = 63), size in 78% (N = 70), margin status in 96% (N = 86), volume of excision in 90% (N = 81), and extent of residual disease in 99% (N = 89)., Results: There was no significant correlation between extent of residual disease on re-excision and method of detection, tumor size, histology, grade, or first margin status. Of patients undergoing re-excision, 56% (N = 50) had no residual disease, 38% (N = 34) had minimal microscopic residual disease, and only 6% (N = 5) had either extensive microscopic or gross residual disease. For these five patients, the median volume of first excision was similar to that of the other patients (26 vs 36 cc), but the median volume of second excision was smaller (33 vs 63 cc). The median age for these five patients was 41 years, compared with 55 years for the remaining patients. All five patients had comedo (N = 4) or solid tumor (N = 1) histology, with grade 3 (N = 3) or unknown grade (N = 2)., Discussion: Patients with extensive microscopic disease or gross residual at the time of re-excision would be at increased risk for local recurrence after conventional radiation treatment if re-excision had not been performed. Only 6% of patients in this study had such pathology findings. No factor predicted for these adverse pathology findings, although these patients tended to be younger, with high-grade or comedo histology.

Purpose: The purpose of this study was to evaluate the relationship between a family history of breast or ovarian cancer and outcome after breast-conserving surgery and radiation in women presenting with an initial diagnosis of ductal carcinoma in situ (DCIS) of the breast., Methods and Materials: A total of 146 consecutive women with a pathologic diagnosis of ductal carcinoma in situ as their first diagnosis of any breast cancer were identified; 28 (19%) had a positive family history of breast or ovarian cancer in a first-degree relative, 27 (19%) had a positive family history in a second-degree relative, and 91 (62%) had no family history. Pathologic, clinical, and treatment factors, and clinical outcomes for each family history group were compared. Cosmesis and complications were recorded at each follow-up. Patients were treated between 1978 and 1995, and the median follow-up was 7.1 years., Results: Patients with a positive family history in a first- or second-degree relative each had an 8% incidence of local failure at 10 years, while the negative family history group demonstrated a 16% local failure rate (p = 0.33). Overall survival at 10 years for patients with a positive family history in a first- or second-degree relative was 100% and for those with a negative family history was 91% (p = 0.08). The negative family history group had a higher median age that may account for the difference in overall survival. Cause-specific survival (CSS) was 97%, 100%, and 99%, respectively, at 10 years (p = 0.25). There were no differences in the cosmetic results or complication rates between women with a positive or negative family history., Conclusion: We have shown that a family history of breast and/or ovarian cancer is not associated with an adverse outcome for women treated with breast conservation therapy for DCIS. Local recurrence, cause-specific survival, overall survival, cosmesis, and complication rates were comparable to that of similarly treated women with negative family histories. Therefore, a positive family history is not a contraindication for breast conservation therapy in women with DCIS.

Purpose: The optimal sequencing of chemotherapy and radiation therapy in patients with early-stage breast cancer undergoing breast-conservation treatment remains controversial. The purpose of this study is to evaluate the outcome of patients treated with one specific sequence of concurrent chemoradiation followed by additional chemotherapy., Methods: Between 1977 and 1992, 210 patients with stage I and II breast cancer underwent lumpectomy and axillary lymph node dissection followed by treatment with concurrent chemotherapy and radiation therapy, followed by further chemotherapy. Chemotherapy consisted of two 28-day cycles of CF (oral cyclophosphamide, 100 mg/m2 day 1 to 14, and intravenous 5-fluorouracil, 600 mg/m2 days 1 and 8) during radiation therapy, followed in general by six cycles of CMF (CF doses as above plus intravenous methotrexate 40 mg/m2 days 1 and 8) after the completion of radiation therapy. Fifty patients also received hormonal therapy, predominantly tamoxifen. One hundred ten patients had clinical T1 lesions, and 100 had T2 lesions. Fifty-three patients were pathologic N0, and 157 patients were pathologic N1 (123 patients had one to three positive nodes, and 34 patients had four or more positive nodes). Median follow-up for node-negative patients (5.2 years) is shorter than for node-positive patients (7.6 years). Therefore, outcome is reported at 5 and 10 years for node-positive patients but only at 5 years for node-negative patients., Results: For node-positive patients, outcomes at 5 and 10 years, respectively, were 86% and 70% for overall survival, 78% and 67% for no evidence of disease survival, and 82% and 69% for freedom from distant metastases. For node-negative patients, outcomes at 5 years were 94% for overall survival, 94% for no evidence of disease survival, and 94% for freedom from distant metastases. Pathologic nodal status was predictive of outcome after treatment. Local failure in the treated breast was 5% at 5 years and 13% at 10 years for all patients., Conclusions: Concurrent CF with radiation therapy followed by six cycles of CMF after radiation therapy results in excellent survival, freedom from distant metastases, and local control for both node-negative and node-positive patients. This regimen of concurrent chemotherapy and radiation therapy is one option for sequencing, and it avoids the delays in administration of either modality that are associated with other sequencing regimens.

Purpose: Chemotherapy plays an increasingly important role in the treatment of both node-negative and node-positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established. The purpose of this study is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of Stage I and II breast cancer patients treated with breast-conserving therapy., Methods and Materials: The records of 1053 Stage I and II breast cancer patients treated with curative intent with breast-conserving surgery, axillary dissection, and radiation therapy between 1977-1991 were reviewed. Median follow-up after treatment was 6.7 years. Two hundred fourteen patients received chemotherapy alone, 141 patients received hormonal therapy alone, 86 patients received both, and 612 patients received no adjuvant therapy. Patients who received chemotherapy +/- hormonal therapy were grouped according to sequence of chemotherapy: (a) concurrent = concurrent chemotherapy with radiation therapy followed by chemotherapy; (b) sequential = radiation followed by chemotherapy or chemotherapy followed by radiation; and (c) sandwich = chemotherapy followed by concurrent chemotherapy and radiation followed by chemotherapy. Compared to node negative patients, node-positive patients more commonly received chemotherapy (77 vs. 9%, p < 0.0001) and/or hormonal therapy (40 vs. 14%, p < 0.0001). Among patients who received chemotherapy, the majority (243 patients) received concurrent chemotherapy and radiation therapy with two cycles of cytoxan and 5-fluorouracil (5-FU) administered during radiation followed by six cycles of chemotherapy with cytoxan, 5-fluorouracil and either methotrexate (CMF) or doxorubicin(CAF). For analysis of cosmesis, patients included were relapse free with 3 years minimum follow-up., Results: The use of chemotherapy had an adverse effect on cosmetic outcome compared to no chemotherapy, which was of borderline significance at 3 years (92% excellent or good cosmetic outcome vs. 96% respectively, p = 0.057); however, cosmesis was not different at 5 years (91 vs. 93% respectively, p = 0.67). Cosmesis was not significantly different between patients treated sequentially and those treated concurrently (3 year: 87 vs. 93% respectively, p = 0.33), nor was it different between patients who received CMF vs. CAF (3 year: 92 vs. 93% respectively, p = 0.89). Hormonal therapy did not influence cosmetic outcome (p = 0.78). The incidence of Grade 4 or 5 arm edema (> or = 2 cm difference in arm circumference) was 2% without chemotherapy vs. 8% with chemotherapy (p = 0.00002). However, the incidence of arm edema was not affected by sequencing or type of chemotherapy (all p > or = 0.52). Patients treated sequentially had a 10% incidence of Grade 4 or 5 arm edema vs. 7% in the patients treated concurrently (p = 0.52). The incidence was 7 vs. 9% in patients treated with CMF vs. CAF (p = 0.73). The incidence of clinical pneumonitis and rib fracture was not influenced by use of chemotherapy, sequence of chemotherapy or use of hormonal therapy (all p > or = 0.06)., Conclusions: Chemotherapy can be given concurrently with radiation therapy in the treatment of Stage I and II breast cancer with breast-conserving therapy without seriously compromising cosmetic outcome or incidence of complications compared to patients receiving other sequences of chemotherapy. Hormonal therapy did not affect cosmesis or complications. The chemotherapeutic regimen of cytoxan and 5-FU concurrent with radiation therapy followed by more chemotherapy is one reasonable option for breast conservation therapy in patients requiring chemotherapy.