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Background: We aimed to analyze the effects of radiotherapy (RT) on the incidence rate of ipsilateral breast event (IBE) in ductal carcinoma in situ (DCIS) patients with lumpectomy after being stratified by prognostic score., Methods: We identified DCIS patients who received lumpectomy, from the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2015. Cumulative incidence functions for competing risk were used to evaluate the effects of RT on IBE risk over time. Three multivariate regression models (weighted, non-weighted, and Fine-Gray) were applied to compare the IBE risk between the RT and non-RT groups after stratifying patients by prognostic score., Results: Overall, 72,623 DCIS patients were identified from the SEER database and 49,206 (66.8%) patients received RT. During the follow-up period (ranging from 7 to 347 months), the cumulative probability of invasive and in situ IBE was significantly lower in the RT group than in the non-RT group (p < 0.001). After being stratified by prognostic score, the weighted IBE incidence rate increased as the risk level increased (p < 0.050). In multivariate regression models, RT lowered the IBE incidence rate by at least 30% in low-, moderate-, and high-risk DCIS (p < 0.010). In particular, the in situ and invasive IBE incidence rate decreased by over 50% in low-risk DCIS with RT (p < 0.001)., Conclusions: RT is associated with a lowered IBE incidence rate in DCIS patients, regardless of the assigned risk levels for patients. The significant reduction in the IBE incidence rate in low-risk DCIS patients also indicates the potential benefits for recommending RT to such a patient population in clinical practice.

Background: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation., Patients and Methods: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated., Results: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT., Conclusions: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Background: Intraoperative radiotherapy (IORT) with a 50-kV x-ray is used for a tumor bed boost during breast-conserving surgery. This study evaluated the anatomicosurgical factors associated with cancellation of planned IORT., Methods: Patient eligibility for the study included age of 20 years or older, compatibility for lumpectomy, and ductal carcinoma in situ or stages 1-3 invasive carcinoma. All the patients underwent magnetic resonance imaging (MRI) and multidisciplinary team evaluations. Resection margins were assessed by frozen pathology. Pre- and intraoperative variables were compared between the IORT and IORT-cancellation groups., Results: A total of 434 patients underwent surgeries for IORT between August 2014 and December 2017. For 90 of these patients, IORT was canceled because of repeated positive margins leading to a large cavity or total mastectomy (n = 27), insufficient cavity-skin distance (n = 14), satellite lesions leading to a large cavity or total mastectomy (n = 12), MRI findings of a large primary tumor or uncertain margins leading to a large cavity (n = 6), cavity geometry unsuitable for IORT (n = 6), subareolar tumor extension (n = 6), tumor abutting the pectoralis muscle (n = 3), patient refusal (n = 5), intraoperative confirmation of bilateral breast cancer (n = 3) or benign pathology (n = 3), device malfunction (n = 3), or scheduling difficulty (n = 2). A tumor larger than 2 cm (P = 0.014) and the presence of satellite lesions (P = 0.014) were independent predictors of IORT cancellation., Conclusions: Surgical procedures resulting in large cavities were the leading cause of IORT cancellation. Multidisciplinary evaluations using MRI were critical for completion of IORT procedures.

Background: We performed a multicenter phase II study on the efficacy and safety of intraoperative radiotherapy (IORT) as partial breast irradiation using multiple devices., Methods: The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Key inclusion criteria were T < 2.5 cm, age > 50 years, surgical margin > 1 cm, intraoperative pathologically free margins, and sentinel node negative. After resection of the tumor, radiation at 21 Gy was delivered directly to the mammary gland employing an electron linear accelerator in the operating room, otherwise the patient was transported from the surgical suite to the radiation room., Results: Overall, 142 patients were enrolled in this study and 129 underwent IORT. Stage 0: n = 4 (3.1%); stage I: n = 98 (76.0%); and stage IIA: n = 27 (20.9%). Luminal type: n = 116 (89.9%); triple-negative: n = 9 (7.0%); and human epidermal growth factor receptor 2: n = 4 (3.1%). Median follow-up time was 59.5 months (range 27.5-99.0), and the rate of IBTR was 3.1% (95% confidence interval 0.9-7.8). The toxicities included fibrosis in deep-connective tissue: grade 1, 78.1%; wound infection: grade 3, 1.6% and grade 2, 1.6%; and soft tissue necrosis: grade 3, 0.8% and grade 2, 0.8%. Recurrence in the breast occurred in four cases; the site of recurrence was just under the skin near the primary tumor site, with similar histology and subtype., Conclusions: In this multicenter phase II study, the rate of IBTR was low and IORT at 21 Gy was feasible in properly selected patients. It is important to use a careful surgical technique to reduce local recurrence because the skin is not included in the radiation field of IORT.

Background: The role of postmastectomy radiotherapy (PMRT) in breast cancer patients receiving neoadjuvant chemotherapy (NAC) is controversial. We aimed to evaluate the effectiveness of radiotherapy in patients treated with NAC and mastectomy in the Japanese Breast Cancer Registry., Methods: We enrolled patients who received NAC and mastectomy for cT1-4 cN0-2 M0 breast cancer. We evaluated the association between radiotherapy and outcomes, locoregional recurrence (LRR), distant disease-free survival (DDFS), and overall survival (OS) based on ypN status by multivariable analysis., Results: Of the 145,530 patients, we identified 3226 who met the inclusion criteria. Among ypN1 patients, no differences were found in LRR, DDFS, or OS between groups with and without radiotherapy (p = 0.72, p = 0.29, and p = 0.36, respectively). Radiotherapy was associated with improved LRR-free survival (p < 0.001), DDFS (p = 0.01), and OS (p < 0.001) in patients with ypN2-3. Multivariable analysis demonstrated that use of radiotherapy was independently associated with improved LRR [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.45-0.82, p = 0.001] and OS [HR 0.69, 95% CI 0.53-0.89, p = 0.004) for ypN2-3 patients only. The association between radiotherapy and OS was not statistically significant among ypN0 (p = 0.22) and ypN1 patients (p = 0.51)., Conclusions: The results from this nationwide database study did not show significant associations between PMRT and improved survival among ypN0 and ypN1 patients. Radiotherapy may be beneficial only for ypN2-3 breast cancer patients who receive NAC and mastectomy in the modern era.

Background: Despite data from randomized trials supporting omission of radiation therapy (RT) for women ≥ 70 years of age with T1, estrogen receptor-positive (ER+) tumors undergoing breast-conserving therapy (BCT), RT usage remains high. We reviewed our institutional experience to determine if risk factors for local recurrence or comorbidities influenced use., Methods: Women ≥ 70 years of age with T1, ER+, human epidermal growth factor receptor 2-negative (HER2-) tumors undergoing BCT in 2010-2012 were identified from a prospectively maintained database. Ten-year estimated mortality was calculated using the Suemoto index. The associations of clinicopathological features and mortality risk on receipt of RT were examined., Results: Overall, 323 patients with 327 cancers were identified. Median age was 75 years, median tumor size was 1 cm, and all were clinically node negative; 53.7% of patients received RT. RT usage decreased with age (73.6%, age 70-74 years; 49.5%, age 75-79 years; 33.3%, age 80-84 years; 10.7%, ≥ 85 years; p < 0.001). Within age groups, estimated mortality did not impact RT usage. On multivariable analysis, only younger age and larger tumor size were associated with RT use. Recurrence-free survival was 98% versus 93% with and without RT, respectively (p = 0.011). Those who received adjuvant radiation also had improved overall survival (92% vs. 89%), although this effect did not reach statistical significance (p = 0.051)., Conclusion: Neither the factors associated with risk of local recurrence nor the estimated risk of death in 10 years were associated with use of adjuvant radiation in a large cohort of women ≥ 70 years of age with small ER+ breast cancers treated with breast-conserving surgery.

Background: The role of regional nodal irradiation (RNI) in patients with cN1 breast cancer following neoadjuvant treatment (NAT) is still controversial. The Neo-Bioscore staging system has shown promising prospect in assessing individual prognosis after NAT, and we sought to evaluate the role of Neo-Bioscore in guiding RNI following NAT., Methods: Medical records of 163 women with cN1 and ypN0-1 disease treated with NAT between 2009 and 2014 were retrospectively reviewed and a Neo-Bioscore was assigned to each patient. Survivals were calculated using the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was used to identify independent predictors by using Cox proportional hazards models., Results: The median follow-up after surgery was 59.4 months. Of all 163 patients, 119 received RNI. At surgery, 36 patients (22.1%) had pathological complete response (pCR), while 89 patients (54.6%) achieved ypN0. In the whole cohort, RNI significantly improved distant metastasis-free survival (DMFS) on multivariable analysis. In the subgroup of patients with a Neo-Bioscore of 1-3, RNI significantly improved the 5-year DMFS rate of 97.0% versus 76.9% (p = 0.002), 5-year regional node recurrence-free survival rate of 95.5% versus 76.9% (p = 0.007), and 5-year overall survival rate of 100% versus 89.2% (p = 0.005). No significant difference in outcomes was found between the RNI and non-RNI groups in patients with a score of 4-6., Conclusions: In patients with cN1 and ypN0-1, RNI was found to significantly improve DMFS following NAT. Patients with a Neo-Bioscore of 1-3 are more likely to benefit from RNI, however a large prospective study is needed to confirm this finding.

Purpose: Considering the comparable prognosis in early-stage breast cancer after breast-conserving therapy (BCT) and mastectomy, quality of life should be a focus in treatment decision(s). We retrospectively collected PROs and analyzed differences per type of surgery delivered. We aimed to obtain reference values helpful in shared decision-making., Patients and Methods: pTis-T3N0-3M0 patients operated between January 2005 and September 2016 were eligible if: (1) no chemotherapy was administered < 6 months prior to enrolment, and (2) identical surgeries were performed in case of bilateral surgery. After consent, EQ-5D-5L, EORTC-QLQ-C30/BR23, and BREAST-Q were administered. PROs were evaluated per baseline characteristics using multivariable linear regression models. Outcomes were compared for different surgeries as well as for primary (PBC) and second primary or recurrent (SBC) breast cancer patients using analyses of variance (ANOVAs)., Results: The response rate was 68%. PROs in 612 PBC patients were comparable to those in 152 SBC patients. Multivariable analyses showed increasing age to be associated with lower "physical functioning" [β - 0.259, p < 0.001] and "sexual functioning" [β - 0.427, p < 0.001], and increasing time since surgery with less "fatigue" [β - 1.083, p < 0.001]. Mastectomy [β - 13.596, p = 0.003] and implant reconstruction [β - 13.040, p = 0.007] were associated with lower "satisfaction with breast" scores than BCT. Radiation therapy was associated with lower satisfaction scores than absence of radiotherapy., Discussion: PRO scores were associated with age, time since surgery, type of surgery, and radiation therapy in breast cancer patients. The scores serve as a reference value for different types of surgery in the study population and enable prospective use of PROs in shared decision-making.

Background: Two new cancer centers providing radiation therapy opened in Alberta, Canada, in 2010 and 2013, respectively. We aimed to assess whether opening the new RT centers influenced mastectomy rates for breast cancer., Method: Breast cancer patients who underwent surgery from 2004 through 2015 were identified from the Alberta Cancer Registry. Mastectomy rates for 64 predefined health status areas (HSAs) were calculated after adjusting for patient and system factors. Variations in mastectomy rates among the HSAs were quantified using weighted coefficient of variation (CV). Multivariable logistic regressions were performed to determine associations between driving time and mastectomy use in the entire cohort and in subgroups., Results: Of the 21,872 patients, the proportion of patients who lived a ≤ 60 min drive from the nearest RT center significantly increased from 68.8% (95% CI 67.7-69.9%) to 80.7% (95% CI 79.5-81.9%) during the study period. Concurrently, the crude provincial mastectomy rate decreased from 56.2% (95% CI 55.3-57.1%) to 45.3% (95% CI 44.1-46.5%). However, variation in adjusted mastectomy rates (weighted CV) across the 64 HSAs increased from 9.5 to 14.6. Factors associated with mastectomy included age, larger tumor size, lymph node involvement, higher tumor grade, molecular subtype, lobular histology type, more comorbidities, academic institution, region, earlier period of diagnosis, and longer driving time to the nearest RT center., Conclusions: Opening new RT centers in previously underserved regions reduced driving times to the nearest center, and was associated with a reduction in mastectomy rates; however, these reductions among regions across the province were not uniform.

Background: Recent data support the use of post-mastectomy radiation therapy (PMRT) in women with one to three positive lymph nodes; however, the benefit of PMRT in patients with micrometastatic nodal disease (N1mi) is unknown. We evaluated the survival impact of PMRT in patients with N1mi within the National Cancer Database., Methods: The pattern of care and survival benefit of PMRT was examined in women with pT1-2N1mi breast cancer who underwent mastectomy without neoadjuvant chemotherapy. Univariable and multivariable Cox proportional hazard models were employed for survival analysis, and subanalyses of high-risk patients and a propensity score-matched (PSM) cohort were completed., Results: From 2004 to 2014, we identified 14,019 patients who fitted the study criteria. PMRT was delivered in 18.5% of patients and its use increased over the study period. Patients treated with PMRT were younger, had better performance status and larger primaries, were estrogen receptor (ER)-negative, had higher grade, lymphovascular invasion and positive surgical margins, and more often received systemic therapy. PMRT was significantly associated with overall survival (OS) in univariable analysis (hazard ratio [HR] 0.75 [0.64-0.89]), but was not significant in multivariable analysis (adjusted HR 1.01 [0.84-1.20]). There was no survival benefit to PMRT in ER-negative, high-grade, and/or young patients. There were 2 (0.9%) death events in the sentinel lymph node biopsy (SLNB) + PMRT group versus 21 (2.9%) in the SLNB-alone group (log-rank p = 0.053), and 8 (3.9%) death events in the axillary lymph node biopsy (ALNB) + PMRT group versus 27 (3.6%) in the axillary lymph node dissection-alone group (p = 0.82). There was no significant association between PMRT and OS within the PSM subgroup., Conclusion: In this largest reported retrospective study, no OS differences were associated with PMRT, which suggests that PMRT may not benefit every patient with microscopic nodal disease.

Background: Among all in-breast tumor recurrences (IBTR) following breast-conserving therapy (BCT), some comprise metachronous new primaries (NPs) while others are true recurrences (TRs). Establishing this distinction remains a challenge., Methods: We studied 3932 women who underwent BCT for stage I-III breast cancer from 1998 to 2008. Of these, 115 (2.9%) had an IBTR. Excluding patients with inoperable/unresectable recurrences or simultaneous distant metastases, 81 patients with isolated IBTR comprised the study population. An IBTR was categorized as an NP rather than a TR if it included an in situ component. The log-rank test and Kaplan-Meier method were used to evaluate disease-free survival (DFS) and overall survival (OS), and univariate and multivariate analyses were performed using Cox proportional hazards regression models., Results: At a median of 64.5 months from IBTR diagnosis, 28 of 81 patients had DFS events. Five-year DFS was 43.1% in the TR group (p = 0.0001) versus 80.3% in the NP group, while 5-year OS was 59.7% in the TR group versus 91.7% among those with NPs (p = 0.0011). On univariate analysis, increasing tumor size, high grade, positive margins, lymphovascular invasion, node involvement, lack of axillary surgery, chemotherapy, radiation therapy, and IBTR type (TR vs. NP) were significantly associated with worse DFS. Controlling for tumor size and margin status, TRs remained significantly associated with lower DFS (hazard ratio 3.717, 95% confidence interval 1.607-8.595, p = 0.002)., Conclusion: The presence of an in situ component is associated with prognosis among patients with IBTR following BCT and may be useful in differentiating TRs and NPs.

Background: Accelerated partial breast irradiation (APBI) was developed to address disadvantages of overall treatment time and potentially unnecessary radiation associated with whole breast irradiation (WBI). We report updated results of our single institution study using an external beam APBI regimen with a median follow-up of 8 years., Methods: A total of 290 APBI patients with AJCC Stage 0-II breast cancer were compared with 290 WBI patients with matched tumor characteristics. Toxicities were scored based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Cox regression models were used to predict likelihood of freedom from ipsilateral failure., Results: Median follow-up was 8 years in the APBI group and 7.5 years in the WBI group. In the APBI group, there were 18 (6.2%) ipsilateral breast tumor recurrence (IBTR), 13 (72%) had elsewhere failures (EF), and 5 (28%) had local failures (LF) with a median time to failure of 64.1 months. In the WBI group, there were three (1.0%) IBTR; one (33%) was an EF and two (67%) were LF with a median time to failure of 91 months. APBI was 4.6 times more likely (hazard ratio 4.57, 95% confidence interval 1.3-16.2, p = 0.02) to have an IBTR than WBI after adjusting for age, tumor size, histology, grade, and estrogen receptor status. Fatigue, erythema, and desquamation toxicities were significantly less in the APBI group then the WBI group., Conclusions: IBTR rates were higher in external beam APBI group compared with WBI, but APBI had fewer toxicities. Clinicians must weigh the risks and benefits of APBI when making a recommendation for partial breast irradiation after lumpectomy.

Background: Data support the use of accelerated partial-breast irradiation (APBI) for early-stage breast cancer. We initiated a prospective protocol for intraoperative APBI catheter placement using a multi-lumen strut-based device. We hypothesized that with intraoperative pathology assessment of margins and sentinel nodes, all locoregional treatment (surgery and APBI) could be completed within 10 days with acceptable complication rates and cosmesis., Methods: Eligible patients included women age 50 years or older with clinical T1 estrogen receptor positive (ER+) sentinel lymph node (SLN)-negative invasive ductal cancer or pure ductal carcinoma in situ. Patients were prospectively registered. Cosmesis was assessed using photographs graded independently by three investigators for patients with photos taken 6 months or longer after treatment., Results: From October 2012 to August 2015, we enrolled 123 patients; 110 (90 %) underwent intraoperative catheter placement, whereas 13 did not due to intraoperative pathology findings. 109 APBI patients (99 %) completed their prescribed radiotherapy within 5 days, and all their locoregional therapy within 9 days, whereas one patient with a delayed positive SLN received only boost radiotherapy via catheter followed by conventional whole breast radiation. The 30-day complication rate was 6 %. In 81 patients with at least one-year followup, complications occurred in 14 (17 %) (including infection in five patients and symptomatic seroma in five patients) and correlated with device size (p = 0.05) but not with tumor size or location. The local recurrence rate was 1.8 % (two patients). Scored cosmesis was excellent or good in 88 % and fair in 12 % of patients., Conclusions: A protocol for intraoperative strut-based APBI catheter placement using careful patient selection and intraoperative pathology assessment can deliver efficient, effective treatment for early breast cancer.

Background: Reexcision rates in patients undergoing breast-conserving surgery (BCS) for early-stage invasive breast cancer are highly variable. The Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) published consensus guidelines to help standardize practice. We sought to determine reexcision rates before and after guideline adoption at our institution., Methods: We identified patients with stage I or II invasive breast cancer initially treated with BCS between June 1, 2013, and October 31, 2014. Margins were defined as positive (tumor on ink), close (≤1 mm), or negative (>1 mm), and were recorded for both invasive cancer and ductal carcinoma-in situ (DCIS) components. Reexcision rates were quantified, characteristics were compared between groups, and multivariable logistic regression was performed., Results: A total of 1205 patients were identified, 504 before and 701 after the guideline adoption (January 1, 2014). Clinical and pathologic characteristics were similar between time periods. Reexcision rates significantly declined from 21.4 to 15.1 % (p = 0.006) after guideline adoption. A multivariable model identified extensive intraductal component (odds ratio [OR] 2.5, 95 % confidence interval [CI] 1.2-5.2), multifocality (OR 2.0, 95 % CI 1.2-3.6), positive (OR 844.4, 95 % CI 226.3-5562.5) and close (OR 38.3, 95 % CI 21.5-71.8) ductal carcinoma-in situ margin, positive (OR 174.2, 95 % CI 66.2-530.0) and close (OR 6.4, 95 % CI 3.0-13.6) invasive margin, and time period (OR 0.5, 95 % CI 0.3-0.9 for post vs. pre) as independently associated with reexcision., Conclusions: Overall reexcision rates declined significantly after guideline adoption. Close invasive margins were associated with higher rates of reexcision than negative invasive margins in both time periods; however, the effect diminished in the postguideline adoption period. Thus, we expect continued decline in reexcision rates as adherence to guidelines becomes more uniform., Competing Interests: This study was funded in part by NIH/NCI Cancer Center Support Grant P30 CA008748 and presented in poster format at the 2016 American Society of Breast Surgeons Annual Meeting, April 13–17, Dallas, TX. The authors have no conflict of interest disclosures to report.

Background: Standard therapy following lumpectomy for breast cancer has included adjuvant whole-breast radiotherapy. Recent, long-term studies have suggested a possible association between left-sided whole breast radiotherapy and long-term cardiac-related mortality. We sought to determine whether left-sided breast cancers treated with breast-conserving treatment have worse cardiac-related outcomes., Methods: The surveillance, epidemiology, and end results database was queried for female breast cancer cases diagnosed from 1990 to 1999. Subjects who underwent lumpectomy and adjuvant radiotherapy were included for study and grouped according to laterality. The primary outcome measure was the rate of cardiac-related mortality. Secondary outcome measures were overall and cancer-specific survival. A Cox proportional hazards model was constructed to analyze the primary outcome measure and included age, race, grade, stage, hormone receptor status, and histologic subtype., Results: A total of 66,687 subjects were identified. These were divided equally by laterality groups: 33,866 left (50.8 %) and 32,801 right (49.2 %). Median follow-up was 15.5 years, and the groups were otherwise well-matched. Left-sided cancer was not associated with poorer survival for any of the metrics. Fifteen-year overall survival and disease-specific survival were 62.8 and 87.0 % for left-sided and 63.0 and 87.1 % for right-sided breast cancers, respectively (p = 0.260, p = 0.702). Rate of cardiac-related mortality at 5-, 10-, and 15-year follow-up were 1.5, 4.3, and 7.7 % for left-sided cancers and 1.6, 4.4, and 8.0 % for right-sided cancers, respectively (p = 0.435)., Conclusions: In this large population-based study, women receiving left-sided external beam radiation for breast cancer did not have an increase in cardiac-related mortality.

Background: The effectiveness of postmastectomy radiotherapy (PMRT) in terms of survival for breast cancer patients with American Joint Committee on Cancer (AJCC) pT1-2 and one to three tumor positive lymph nodes is controversial, especially in this era of more effective systemic treatment., Methods: Using data from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) program between 1998 and 2008, this study respectively identified 93,793 and 36,299 women with AJCC pT1-2pN1 breast cancer who underwent mastectomy. The association of PMRT use with overall and cause-specific survival was examined using multivariable Cox models in subgroups defined by tumor stage., Results: In the NCDB cohort, 21.5 % of the patients (n = 20,236) received PMRT, and a very similar percentage (21.9 %, n = 7939) received PMRT in the SEER cohort. In the NCDB cohort, PMRT was associated with a 14 % relative risk reduction in all-cause mortality among the patients with two positive lymph nodes and tumors 2-5 cm in size or three positive nodes [hazard ratio (HR), 0.86; 95 % confidence interval (CI), 0.81-0.91; p < 0.0001], but PMRT had no beneficial effect for the patients with one positive node or two positive nodes and tumors 2 cm in size or smaller. Analysis of the SEER cohort confirmed this heterogeneous effect, showing PMRT to be associated with a 14 % relative risk reduction in breast cancer cause-specific mortality among the patients with two positive nodes and tumors 2-5 cm in size or three positive nodes (HR 0.86; 95 % CI 0.77-0.96; p = 0.007) but not in the other subgroup., Conclusion: The effectiveness of radiotherapy depends on the combination comprising the number of positive lymph nodes and tumor size, which may enable more precise patient selection for PMRT.

Purpose: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation with interstitial multicatheter brachytherapy by a cooperative group of institutions., Methods: From 1992 to 2013, a total of 1356 patients were treated with breast-conserving surgery and adjuvant accelerated partial breast irradiation using interstitial multicatheter brachytherapy. A total of 1131 patients had >1 year of data available to assess oncologic and cosmesis outcomes. Median age was 59 years old (range 22-90 years). Histologies treated included 1005 (73 %) invasive ductal carcinoma and 240 (18 %) ductal carcinoma-in situ. T stages were 18 % Tis, 75 % T1, and 8 % ≥T2. Nodal status was 73 % N0 and 6 % N1a. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was positive in 83, 70, and 6 %, respectively. Cox multivariate analysis for local control was performed using histology, age, estrogen receptor status, tumor size, grade, margin, and nodal status., Results: The mean (SD) follow-up was 6.9 years (4.3). The 10-year actuarial risk (95 % confidence interval) of an ipsilateral breast tumor recurrence was 7.6 % (5.6-10.1). Other 10-year actuarial risks (95 % confidence interval) were regional failure 2.3 % (1.4-3.7), distant metastasis 3.8 % (2.5-5.7), cause-specific survival 96.3 % (94.2-97.6), overall survival 86.5 (83.0-89.3), and new contralateral cancers 4.6 % (3.0-6.9). On multivariate analysis, high grade (hazard ratio 2.81) and positive margin status (hazard ratio 18.42) were the only two significant variables associated with an increased risk of local recurrence. Physician-reported cosmesis was excellent/good in 84 % (98 of 116) of patients with >5 years of follow-up., Conclusions: This is the largest report of outcomes with interstitial breast brachytherapy. This treatment resulted in excellent long-term local control and cosmesis outcomes.

Background: Despite a growing body of literature on oncologic and reconstructive outcomes after total skin-sparing mastectomy (TSSM), some questions related to this approach remain unanswered, including strategies for managing tumor involvement of the nipple while maintaining the aesthetic benefits of TSSM., Methods: A prospectively maintained database of patients undergoing TSSM and immediate breast reconstruction from 2005 to 2013 was reviewed. Outcomes included tumor involvement of resected nipple tissue and subsequent management, recurrences after nipple involvement, and trends in management of involved nipple tissue., Results: The study included 1176 breasts in 751 patients treated with TSSM. The follow-up period was 31.3 months. The nipple-areolar complex (NAC) of 32 breasts (2.7 %) had a positive margin or involvement of nipple tissue. Of these breasts, 56 % contained invasive cancer, and 44 % had in situ disease. Management included repeat excision (11 cases, 34 % of cases), radiation of the NAC (as part of the postmastectomy breast field) without further excision (5 cases, 16 %), complete NAC removal (8 cases, 25 %), and no further treatment (8 cases, 25 %). Management by complete NAC skin excision significantly decreased during the study period (p = 0.003). The overall local recurrence rate was 6.2 %. No patients had recurrence in the preserved NAC skin., Conclusions: Despite expanding indications for TSSM, it can be performed safely with low rates of nipple involvement. Over time, tumor involvement of the nipple has been treated with re-excision or other alternative approaches to NAC removal that preserve the aesthetic benefits of total skin-sparing approaches without an early adverse impact on local recurrence.

Background: Several trials are presently randomizing clinically node-negative breast cancer patients treated with breast-conserving therapy (BCT) to sentinel lymph node biopsy (SLNB) or watchful waiting. We aimed to investigate the elective radiation dose at the sentinel lymph node (SLN) site while evaluating two techniques for SLN localization, in breast cancer patients treated with lumpectomy and three-dimensional (3D) whole-breast radiotherapy., Methods: The SLN site of consecutive Tis-2N0 breast cancer patients undergoing lumpectomy and forward intensity-modulated whole-breast radiotherapy was determined by the location of the hotspot on preoperative single-photon emission computed tomography (SPECT)/computed tomography (CT) and by a surgical clip placed at the removed SLN(s) during SLNB. The radiation dose at the SLN site was subsequently determined on the postoperative radiotherapy planning CT. An elective radiation dose to the SLN site was defined as at least 95 % of the breast dose., Results: Of the 42 included patients, the mean percentage of the breast dose on the SLN site was 90 % (standard deviation 26, range 7-132, median 99), with a non-significant difference between the two techniques (surgical clip or SPECT/CT) (p = 0.608). In 32/42 patients (76 %) the SLN site received an elective radiation dose., Conclusions: A surgical clip placed at the removed SLN(s) during SLNB proved to be an adequate method of determining the radiation dose at the SLN site when compared with using SPECT/CT. With the use of 3D radiotherapy, the site of the SLN is treated with an elective radiation dose in the majority of patients who are treated with BCT.

Purpose: We examined the incidence and modern national trends in the management of Paget's disease (PD), including the use of breast-conserving surgery (BCS), mastectomy, axillary surgery, and receipt of radiotherapy., Methods: Using surveillance, epidemiology and end results (SEER) data, we identified 2631 patients diagnosed with PD during 2000-2011. Of these patients, 185 (7%) had PD of the nipple only, 953 (36.2%) had PD with ductal carcinoma in situ (PD-DCIS), and 1493 (56.7%) had PD with invasive ductal carcinoma (PD-IDC). Trends in age-adjusted incidence, primary surgery, sentinel lymph node biopsy (SLNB), and axillary lymph node dissection were examined. Multivariable logistic regression was used to evaluate factors associated with receipt of BCS and radiotherapy., Results: A decrease in the age-adjusted incidence of PD occurred from 2000 to 2011 (-4.3% per year, p < 0.05). The overall rates of mastectomy in the PD only, PD-DCIS, and PD-IDC groups were 47, 69, and 88.9%, respectively. Only in the PD-IDC group did the proportion of patients undergoing BCS increase significantly, from 8.5% in 2000 to 15.7% in 2011 (p = 0.01). Of those who underwent axillary surgery, the proportion of patients undergoing SLNB increased from 2000 to 2011. In adjusted analyses, Paget's subgroup, older age, central tumor location, low/intermediate grade, tumor size <2.0 cm, SEER region, and year of diagnosis after 2006 were significantly associated with receipt of BCS., Conclusions: The incidence of Paget's disease has decreased over time while modern trends in local therapy suggest that BCS, SLNB, and adjuvant radiotherapy remain underutilized.

Background: The adoption of breast brachytherapy into clinical practice for early-stage breast cancer has increased over the last several years. Studies evaluating complication rates following treatment with brachytherapy have shown conflicting results. We compared local toxicity in patients treated with brachytherapy with those treated with whole-breast irradiation (WBI)., Methods: We identified 417 early-stage breast cancer patients treated with breast-conserving surgery and radiation between 2004 and 2010, and compared 271 women treated with intracavitary brachytherapy with 146 women treated with WBI. Long-term complications were assessed using Kaplan-Meier curves with the log-rank test., Results: Median follow-up was 4.6 years, and the 5-year incidence of infectious skin complications (9.7 vs. 11.0 %, p = 0.84), abscess (1.1 vs. 0 %, p = 0.15), telangiectasia (8.0 vs. 5.3 %, p = 0.35), and breast pain (14.2 vs. 9.4 %, p = 0.2) was similar between the brachytherapy and WBI cohorts. The brachytherapy cohort had a higher 5-year rate of seroma (46.5 vs. 18.5 %, p < 0.001), and fat necrosis (39.5 vs. 24.4 %, p < 0.001). Brachytherapy patients trended towards more frequent biopsies as a result of fat necrosis to rule out a recurrence (11.2 vs. 6.7 %, p = 0.13)., Conclusions: Patients treated with intracavitary brachytherapy had more local toxicity, particularly seroma and fat necrosis. Patients should be counseled on the possible increased rate of long-term complications associated with brachytherapy treatment.

Background: Although guidelines exist for radiation delivery in the setting of mastectomy or breast-conservation therapy, radiation delivery after nipple-sparing mastectomy (NSM) remains variable. Our goal is to determine whether patients who undergo therapeutic NSM are more likely to receive radiation than patients who undergo non-NSM and whether National Comprehensive Cancer Network (NCCN) guidelines for radiation after mastectomy are observed in NSM patients., Methods: Female patients who underwent NSM or non-NSM for breast cancer from 2006 to 2010 were isolated from the Surveillance, Epidemiology, and End Results database. Univariate analysis stratified by tumor size and lymph node status, and multivariate analyses were used to compare odds of radiation in NSM and mastectomy patients. Adherence to NCCN guidelines based on tumor size and lymph node status was also investigated., Results: A total of 112,817 patients were included: 470 (0.4 %) underwent NSM, and 112,347 (99.6 %) underwent non-NSM. NSM patients with 0 nodes/size ≤2 cm, 0 nodes/size 2-5 cm, and unexamined axilla/size ≤2 cm had higher odds of radiation when compared with size- and node-matched mastectomy patients. Multivariate logistic regression showed that NSM patients had higher odds of radiation (odds ratio 2.01, p < 0.001) than mastectomy patients. Radiation was given to 18 % of NSM patients who did not meet NCCN guidelines according to size or lymph node involvement, compared with 6 % of mastectomy patients., Conclusions: Patients who undergo therapeutic NSM are more likely to receive radiation compared with mastectomy patients. This may reflect a concern with leaving ductal tissue in the nipple-areolar complex.

Background: During breast-conserving surgery (BCS), surgeons increasingly perform full-thickness closure (FTC) to prevent seroma formation. This could potentially impair precision of target definition for boost and accelerated partial breast irradiation (APBI). The purpose of this study was to investigate the precision of target volume definition following BCS with FTC among radiation oncologists, using various imaging modalities., Methods: Twenty clinical T1-2N0 patients, scheduled for BCS involving clip placement and FTC, were included in the study. Seven experienced breast radiation oncologists contoured the tumor bed on computed tomography (CT), magnetic resonance imaging (MRI) and fused CT-MRI datasets. A total of 361 observer pairs per image modality were analyzed. A pairwise conformity among the generated contours of the observers and the distance between their centers of mass (dCOM) were calculated., Results: On CT, median conformity was 44 % [interquartile range (IQR) 28-58 %] and median dCOM was 6 mm (IQR 3-9 mm). None of the outcome measures improved when MRI or fused CT-MRI were used. In two patients, superficial closure was performed instead of FTC. In these 14 image sets and 42 observer pairs, median conformity increased to 70 %., Conclusions: Localization of the radiotherapy target after FTC is imprecise, on both CT and MRI. This could potentially lead to a geographical miss in patients at increased risk of local recurrence receiving a radiation boost, or for those receiving APBI. These findings highlight the importance for breast surgeons to clearly demarcate the tumor bed when performing FTC.

Background: Randomized trials have established that patients with limited involvement of sentinel lymph node (SLN) do not require axillary lymph node dissection (ALND). The similar outcome in patients with ≤2 positive SLN with or without additional ALND is attributed, in part, to tangential fields (TgF) RT. We evaluated the dose distribution in the SLN biopsy area (SLNBa) as determined intraoperatively by clips placement for radiotherapy (RT) optimization., Methods: This prospective study included 25 patients who had breast conservation. Titanium clips were used intraoperatively to mark the SLNBa. All patients had 3D-conformal RT using standard (STgF) or high tangential fields (HTgF). Axillary levels, SLNBa, and organs at risk were contoured on a CT scan. Dose distribution and overlap between TgF and target volumes were analyzed., Results: The average doses delivered to axilla levels I-III and SLNBa were 25, 5, 2, and 33 Gy, respectively. The average dose delivered to SLNBa was higher using HTgF with better coverage of the axilla. Only 12 of 25 patients (48 %) had their SLNBa completely covered by the TgF. There was no impact of TgF size on ipsilateral lung dose. The mean heart dose delivered using STgF was lower than HTgF., Conclusions: In the era of SLNB, axilla and SNLBa RT technique has to be standardized to deliver adequate dose. We recommend the use of HTgF or direct axillary RT techniques (such as in AMAROS trial) in patients with metastases in SLN without ALND completion, when only TgF are expected to cure potential residual disease in the axilla.

Background: Data on recent trends and correlates of utilization for accelerated partial breast irradiation using brachytherapy (APBI-b) for ductal carcinoma in situ (DCIS) are lacking., Methods: This study included 113,841 DCIS patients from the National Cancer Data Base, of whom 8,709 (6.5 %) underwent APBI-b and 105,132 (93.5 %) underwent external beam irradiation after lumpectomy between 2003 and 2011. Trends in APBI-b use, American Society for Radiation Oncology (ASTRO) guideline concordance, and independent factors related to APBI-b use were examined., Results: APBI-b use increased from 1.6 % in 2003 to 11.9 % in 2008 and then decreased to 9.1 % in 2011 (p < 0.001). Before 2009, 24.6 % of patients undergoing APBI-b were in the ASTRO guideline 'unsuitable' category, but this proportion decreased to 14.6 % after 2009 (p < 0.001). When adjusting for year of diagnosis, patient, tumor, and facility factors, the four strongest independent factors for APBI-b use were year of diagnosis followed by facility location, facility volume, and facility type. APBI-b use was highest in the East South Central census region (13.1 %) and lowest in the New England region (2.0 %). A statistically significant interaction was identified between facility type and volume. Patients in community cancer programs of large volume were more likely to receive APBI-b, whereas patients in larger academic programs were less likely to receive APBI-b., Conclusion: APBI-b for DCIS decreased from 2008 to 2011. After year of diagnosis, facility factors were most strongly associated with APBI-b use as opposed to patient and tumor factors. Reasons for these trends are multifactorial and deserve further study.

Background: The utility of post mastectomy radiotherapy in very young women is understudied. The objective of this study was to evaluate the use of PMRT in very young women to determine the effect on recurrence and survival., Methods: All women aged ≤35 years diagnosed with invasive breast cancer from 1994 to 2003 were identified from the Ontario Cancer Registry. Patient, tumour, treatment and outcome data were abstracted from primary chart review. Local or regional recurrence was the primary endpoint with contralateral, distant recurrence/death treated as competing risks. Propensity score methods were incorporated into multivariable Cox proportional hazards models to evaluate the effect of radiation therapy on the time to local/regional, distant recurrence or death., Results: 588 patients were identified during the study period, of which 382 were eligible for analysis. Overall, 182 (48%) of patients sustained a recurrence after a median follow-up of 2.72 years. The use of PMRT significantly reduced locoregional recurrence (HR 0.54, 95% CI 0.29-0.996) compared with those who did not receive PMRT. There was no significant effect of PMRT on contralateral, distant recurrences, or death without recurrence (HR 0.98, 95% CI 0.66-1.47). Of the patients with known node status (N = 451), isolated local recurrence occurred in 5, 2.5, and 8.5% in patients with N0, N1-3, and N4 positive nodes respectively., Conclusions: We have found a significant reduction in locoregional recurrence with PMRT but no survival benefit in very young women with breast cancer.

Background: In women with breast cancer and calcifications, controversy exists over the need for postexcision/lumpectomy, preradiation mammogram (PEM) after breast-conserving surgery (BCS). Further, the need for excision of remaining or suspicious calcifications after PEM when surgical margins are negative is unclear. We sought to characterize the utility of PEM hypothesizing that its value in directing the need for additional surgery is minimized after achieving negative surgical margins., Methods: We identified 524 women with breast cancer and calcifications treated with BCS with negative margins between 1996 and 2011., Results: PEM was performed in 112 of 524 (21 %) women, with residual calcifications identified in 10 of 112 (9 %); of these, 2 of 112 (1.8 %) had residual disease. Local recurrence occurred in 4 of 112 (4 %) patients, none of whom had residual calcifications identified on PEM. The remaining 412 of 524 (79 %) women did not have PEM but had a postradiation mammogram 6 to 12 months after treatment identifying calcifications in 19 (5 %) women. Tissue diagnosis was benign in 14 women and was not pursued in the remaining 5. Local recurrence occurred in 13 (3 %) patients, none of whom had calcifications on the new post radiation baseline mammogram., Conclusions: Mammographically apparent calcifications representing residual disease occur infrequently after BCS with negative margins. The value of PEM may be to document the new radiographic baseline but should not be required to ensure adequate surgery. Radiation plays an integral role in sterilization of the remaining breast tissue after BCS.

Background: Previous studies have demonstrated an increase in the utilization of accelerated partial-breast irradiation via brachytherapy (APBI-b), but larger, more contemporary studies examining overall APBI use are lacking., Methods: A total of 575,438 nonneoadjuvant American Joint Committee on Cancer stage 0 to II breast conservation patients were selected from the National Cancer Data Base from 2003 to 2010 who underwent either whole-breast irradiation or APBI., Results: Overall, 59,396 patients (10.3 %) underwent APBI. The use of APBI for the entire cohort increased from 3.4 % in 2003 to 12.8 % (p < 0.001) in 2008 and then decreased to 12.4 % in 2010. Three-dimensional conformal radiation increased from 0.8 to 2.2 %, intensity-modulated radiotherapy increased from 0.7 to 1.3 %, and brachytherapy (APBI-b) increased from 2.0 to 8.9 %. The most significant factors associated with APBI use were patient age and facility location. Patients 80-89 years old were 3.8 times more likely to undergo APBI compared to patients 30-39 years old (odds ratio [OR] 3.77, 95 % confidence interval [CI] 3.45-4.10, p < 0.001). Patients living in the West census region were 2.0 times more likely to undergo APBI compared to patients living in the Northeast (OR 2.0, 95 % CI 1.93-2.15, p < 0.001). Using the American Society of Radiation Oncology (ASTRO) guidelines, among patients with noninvasive cancer who received APBI, 95.6 % were categorized as "cautionary" and 4.4 % as "unsuitable." Of the invasive patients, 43.8 % were categorized as "suitable," 47.0 % as "cautionary," and 9.2 % as "unsuitable.", Conclusions: The utilization of APBI has stabilized at approximately 12 % starting in 2008. The majority of APBI is delivered using APBI-b, with patient age being the most significant factor associated with APBI use.

Background: Understanding risk factors for locoregional recurrence (LRR) after accelerated partial breast irradiation (APBI) can help to guide patient selection for treatment with APBI. Published findings to date have not been consistent. More data are needed as these risk factors continue to be defined., Methods: A total of 277 women with early-stage invasive breast cancer underwent lumpectomy and were treated adjuvantly at our institution with APBI using high-dose rate brachytherapy. APBI was delivered using multicatheter interstitial brachytherapy (91 %) or single-entry catheter brachytherapy (9 %) to a dose of 32-34 Gy in 8-10 twice daily fractions. Failure patterns and risk factors for recurrence were analyzed., Results: With a median follow-up of 61 months, the 5-year locoregional control rate was 94.4 %. Negative estrogen receptor (ER) status was strongly associated with LRR on multivariate analysis (p < 0.005). Lobular histology, the presence of an extensive intraductal component, and lymphovascular invasion also were significant but to a lesser degree than ER-negative status. Patients with multiple risk factors were at highest risk for LRR. Age was not significantly associated with increased risk for LRR., Conclusions: The presence of specific pathological features, particularly ER negative status, was associated with increased risk of LRR in this cohort of women treated with APBI. Further investigation is warranted to determine whether patients with adverse pathological risk factors are at higher risk of LRR after APBI than after conventional whole breast irradiation (WBI), as these same features also may place women at risk for LRR after WBI.

Background: The purpose of this study was to examine data on treatment efficacy, cosmesis and toxicities for the final analysis of the American Society of Breast Surgeons MammoSite(®) breast brachytherapy registry trial., Methods: A total of 1,449 cases of early-stage breast cancer underwent breast conserving therapy. The single-lumen MammoSite(®) device was used to deliver accelerated partial breast irradiation (APBI) (34 Gy in 3.4 Gy fractions). Of these, 1,255 cases (87 %) had invasive breast cancer (IBC) and 194 cases had DCIS. Median follow-up was 63.1 months with 45 % of all patients having follow-up of 6 years or longer., Results: There were 41 cases (2.8 %) that developed an ipsilateral breast tumor recurrence (IBTR) for a 5-year actuarial rate of 3.8 % (3.7 % for IBC and 4.1 % for DCIS). Tumor size (odds ratio [OR] = 1.1, p = 0.03) and estrogen receptor negativity (OR = 3.0, p = 0.0009) were associated with IBTR, while a trend was noted for positive margins (OR = 2.0, p = 0.06) and cautionary/unsuitable status compared with suitable status (OR = 1.8, p = 0.07). The percentage of patients with excellent/good cosmetic results at 60, 72, and 84 months was 91.3, 90.5, and 90.6 %, respectively. The overall rates of fat necrosis and infections remained low at 2.5 and 9.6 % with few late toxicity events beyond 2 years. The overall symptomatic seroma rate was 13.4 and 0.6 % beyond 2 years., Conclusions: The final analysis of treatment efficacy, cosmesis, and toxicity from the American Society of Breast Surgeons MammoSite(®) breast brachytherapy registry trial confirms previously noted excellent results and compares favorably with other forms of APBI with similar follow-up and to outcomes seen in selected patients treated with whole breast irradiation.

Purpose: To analyze outcomes in patients with ductal carcinoma-in-situ (DCIS) treated with accelerated partial breast irradiation (APBI) within a pooled set of patients., Methods: A total of 300 women with DCIS underwent APBI between April 1993 and November 2010 as part of American Society of Breast Surgeons MammoSite Registry Trial (n = 192) or at William Beaumont Hospital (n = 108). Patients with pure DCIS <3 cm (n = 125) were assigned to the cautionary risk group per American Society of Radiation Oncology consensus panel guidelines for off-protocol use of APBI and analyzed compared to a pooled invasive suitable (n = 653) risk group and pooled invasive suitable/cautionary (n = 1,298) risk group., Results: The rate of ipsilateral breast tumor recurrence (IBTR) for all 300 DCIS patients was 2.6 % at 5 years with no regional recurrences, while cause-specific survival was 99.5 % and overall survival (OS) was 96.4 %. When comparing the cautionary DCIS group to the invasive suitable/cautionary group, no difference in IBTR was noted (2.6 vs. 3.1 %, P = 0.90) with significant improvements in distant metastases (0 vs. 2.5 %, P = 0.05), disease-free survival (98.5 vs. 94.4 %, P = 0.05), and OS (95.7 vs. 90.8 %, P = 0.03) noted for DCIS patients. When comparing cautionary DCIS patients to invasive suitable patients, no difference in IBTR were noted (2.6 vs. 2.4 %, P = 0.76), while improved OS for DCIS patients was noted (95.7 vs. 90.9 %, P = 0.02)., Conclusions: This analysis of the largest cohort of patients with DCIS treated with APBI supports previously reported excellent outcomes; as a result of small numbers of events, further data are necessary to confirm these findings.

Background: During the breast lumpectomy procedure, surgeons traditionally elect to use either a superficial or full-thickness closure when sealing the wound depending on surgeon preference as well as desired outcomes. The purpose of this study was to examine dosimetric endpoints in patients with superficial versus full-thickness closures with accelerated partial breast irradiation (APBI)., Methods: Patients who underwent breast conservation surgery followed by 3D conformal external-beam APBI were identified (n = 45) and were separated according to the type of cavity closure performed: superficial and full thickness. Data gathered from the retrospective review of patient charts was analyzed according to criteria in the NSABP B-39 protocol in order to quantify the amount of radiation delivered to organs at risk. The patient seroma cavity was further given a cavity visualization score to assess the impact of wound closure on treatment planning., Results: There was no significant difference in the mean CVS score for the 2 groups. There were no statistical differences in all dosimetric endpoints compared for the 2 types of closure, and both groups met NSABP B-39 guidelines for the ipsilateral breast, heart, and ipsilateral lung dosimetry., Conclusions: We found no significant difference in dosimetric outcomes in either the superficial or deep closure treatment groups. Breast surgeons should not alter their preferred closure strategy in anticipation of 3D-CRT APBI.

Background: Breast conserving therapy (BCT) that include breast conserving surgery followed by adjuvant radiation therapy has revolutioned medicine by allowing women to avoid mastectomy. Accelerated partial breast irradiation (APBI) has emerged as a valid alternative to whole-breast irradiation that requires a shorter time commitment. We report our novel experience with APBI at a large public hospital that serves low-income and potentially noncompliant patients., Methods: A retrospective chart review was conducted of women who underwent BCT for stage 0-IIA breast cancer from August 2007 to August 2010 treated with APBI with a brachytherapy catheter., Results: Twenty-four patients (20 African American) were considered for APBI. Average age was 61 years. Four patients could not undergo APBI for technical reasons and completed whole-breast irradiation over a 5 week period. Median follow-up was 19 months. Nine patients (37.5 %) had ductal carcinoma-in-situ, and 15 patients (62.5 %) had invasive ductal carcinoma with an average tumor size of 1.1 cm. All patients had negative margins of >2 mm. Two patients (8 %) treated with the brachytherapy catheter had in-breast tumor recurrence. Thus, all 24 patients initially identified for APBI successfully completed adjuvant radiotherapy., Conclusions: Patient compliance with postoperative irradiation is key to minimize local recurrence after BCT for breast cancer. This success with a brachytherapy catheter in underserved women in a U.S. public hospital setting indicates that outcomes of compliance and complications are comparable to nationally published results.

Background: Mastectomy is still considered the treatment of first choice in patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and whole-breast radiotherapy., Methods: We retrospectively evaluated 161 patients with invasive IBTR who underwent a second BCS in order to describe prognosis, determine predictive factors of outcome, and select the subset of patients with the best local control. Median follow-up after IBTR was 81 months., Results: Median age at IBTR was 53 years. Five-year overall survival after IBTR was 84 % (95 % confidence interval [CI] 78-89). Five-year cumulative incidence of a second local event after IBTR was 29 % (95 % CI 22-37). At the multivariate analysis, IBTR size >2 cm and time to relapse ≤48 months significantly increased the risk of local reappearance (hazard ratio [HR] 3.3, 95 % CI 1.6-7.0; and HR 1.9, 95 % CI 1.1-3.5). The 5-year cumulative incidence of a further local reappearance of the tumor after repeating BCS was 15.2 % in the patients with IBTR ≤2 cm and time to IBTR >48 months, 31.2 % in the patients with IBTR ≤2 cm and time to IBTR ≤48 months, and 71.2 % in patients with IBTR >2 cm (P < 0.001)., Conclusions: The best candidates for a second BCS are those with small (≤2 cm) and late (>48 months) IBTR. The information about the risk of a further local reappearance after repeating BCS should be shared with the patients in the decision making process.

Background: Cutaneous radiation-associated angiosarcoma of the breast (CRAASBr) is a rare complication of radiation therapy (RT) administered for primary breast cancer treatment. Although case series have provided clinical and histological descriptions of this disease, to our knowledge, none have identified trends in presentation and treatments that may contribute to outcomes., Methods: Demographic, clinical, histopathologic, and outcomes data for all patients presenting with CRAASBr for treatment or consultation at our institution from 1987 to 2009 were reviewed., Results: We identified 33 patients (median age at CRAASBr presentation 71.3 years, range 43.1-87.2 years; median latency period 73.5 months, range 39.6-148.5 months). The most common presentation was breast skin ecchymosis (55 %). In four patients, initial biopsy demonstrated atypical vascular lesions suspicious for, but not diagnostic of, angiosarcoma. All patients underwent mastectomy. Median local recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) rates were 18.2, 13.0, and 48.5 months, respectively. Patients who underwent resection of all irradiated breast skin as part of the mastectomy trended toward a better median LRFS (80.8 vs. 10.0 months, p = 0.065), RFS (72.6 vs. 10.0 months, p = 0.098), and OS (not achieved vs. 29.0 months, p = 0.054)., Conclusions: CRAASBr is a potentially devastating consequence of RT for breast cancer, with poor LRFS, RFS, and OS rates. Patients with ecchymotic skin lesions require biopsy. Atypical vascular lesions require careful evaluation to rule out CRAASBr. If the diagnosis is confirmed, radical surgery encompassing both the breast parenchyma and the at-risk radiated skin should be performed.

Background: Radiation therapy (RT) after lumpectomy for breast cancer can be delivered with several different regimens. We evaluated a cost-minimization strategy to select among RT options., Methods: An institutional review board (IRB)-approved retrospective review identified a sample of 100 women who underwent lumpectomy for invasive or in situ breast cancer during 2009. Post lumpectomy RT options included: no radiation in women ≥70 years [T1N0, estrogen receptor (ER)+] per Cancer and Leukemia Group B (CALGB) 9343 (no-RT), accelerated external-beam partial-breast irradiation (APBI), and Canadian fractionation (C-RT), as alternatives to standard whole-breast radiation therapy (WBRT). Eligibility for RT regimens was based on published criteria. RT costs were estimated using the 2011 US Medicare Physician Fee Schedule and average Current Procedural Terminology (CPT) codes billed per regimen at our institution. Costs were modeled in a 1,000-patient theoretical cohort., Results: Median patient age was 56.5 years (range 32-93 years). Tumor histology included invasive ductal cancer (78 %), ductal carcinoma in situ (DCIS) (15 %), invasive lobular cancer (6 %), and mixed histology (1 %). Median tumor size was 1 cm (range 0.2-5 cm). Estimated per-patient cost of radiation was US$5,341.81 for APBI, US$9,121.98 for C-RT, and US$13,358.37 for WBRT. When patients received the least expensive radiation regimen for which they were eligible, 14 % received no-RT, 44 % received APBI, 7 % received C-RT, and 35 % defaulted to WBRT. Using a cost-minimization strategy, estimated RT costs were US$7.67 million, versus US$13.36 million had all patients received WBRT, representing cost savings of US$5.69 million per 1,000 patients treated., Conclusions: A cost-minimization strategy results in a 43 % reduction in estimated radiation costs among women undergoing breast conservation.

Background: Randomized trials demonstrate that lumpectomy plus whole-breast irradiation (WBI) yields survival equivalent to mastectomy. Studies that use WBI, however, typically report higher tumor bed recurrence rates than elsewhere failures (EF) (historically considered new primary lesions). The rate of true recurrence (TR) versus EF was queried for a large patient cohort treated with accelerated partial breast irradiation (APBI)., Methods: A total of 1,449 cases of early-stage breast cancer were treated on the American Society of Breast Surgeons MammoSite(®) Registry Trial with lumpectomy plus balloon-based APBI (34 Gy, 10 BID fractions). A total of 1,255 cases (87 %) had invasive breast cancer, and 194 patients (13 %) had ductal carcinoma in situ. Rates of TR versus EF were calculated and compared to historical WBI controls., Results: Median follow-up was 60 (range 0-109) months. Fifty patients (3.5 %) developed an ipsilateral breast tumor recurrence (IBTR). The 5-year actuarial rate of IBTR was 3.6 % (invasive breast cancer 3.6 %, ductal carcinoma in situ 3.4 %). Fourteen IBTR (1.1 %) were TR, while 36 (2.6 %) were EF. Estrogen receptor-negative status was associated with IBTR for invasive malignancies as well as for EF only (p < 0.001). Trends for increased rates of EF were noted for increased tumor size (p = 0.067) and extensive intraductal component (p = 0.087). No pathologic factors were explicitly associated with TR., Conclusions: IBTR after balloon-based APBI is low and similar to rates reported for WBI. In this data set, APBI had fewer tumor bed recurrences (presumably initial cancer recurrences) than EF (presumably new primary lesions). This suggests that balloon-based APBI has a tumor bed control rate that is at least equal to (and potentially higher than) WBI.

Background: Breast-conserving surgery is often preferred to treat early-stage breast cancer. This method aims to minimize repeat excision and local recurrence rates. The ABLATE Registry expands this to multiple centers with a total accrual goal of 250. This video illustrates an intraoperative radiofrequency ablation (RFA) technique., Methods: Sixteen women with a mean age of 65 years underwent RFA after lumpectomy. The RFA probe was deployed 1 cm circumferentially in the cavity and maintained at 100°C for 15 min. The ablation zone was monitored with color-flow ultrasound. Patients returned 2 weeks later to complete the Subjective Cosmetic Scale and the European Organisation for Research and Treatment of Cancer Body Image Scale., Results: At a mean follow-up of 3.9 months, there were no local recurrences. Two-week cosmesis scores were excellent (n = 9) or good (n = 5)., Conclusions: Our initial experience is encouraging. Continued national accrual will permit evaluation of reduction in repeat excision and local recurrence rate, as well as potentially reduce requirements for adjuvant radiation.

Background: Local recurrence (LR) after breast conservation surgery (BCS) varies with risk factors. This study was designed to evaluate the impact of young age on LR., Methods: All patients (excluding those who received neoadjuvant chemotherapy) who underwent BCS from 1988-2001 at our institution were identified and evaluated for risk factors of LR., Results: A total of 3,064 patients underwent 3,131 BCS. Mean age at surgery was 61 (range, 21-98) years: 175 (5.6%) patients were aged<40 years; 492 (15.7%) were 40-49 years; 761 (24.3%) were 50-59 years; 801 (25.6%) were 60-69 years; and 902 (28.8%) were age 70+years. A total of 212 patients (6.8%) developed LR at a mean of 4.5 (range, 0.1-14.4) years after BCS. Mean follow-up was 8.9 (range, 0-20.2) years. The 5-year LR-free survival rate was 94.9%. The frequencies of LR by age group were: <40 years--11.4%; 40-49 years--5.7%; 50-59 years--6.2%; 60-69 years--7.6%; 70 years and older--6.2%. The 5-year LR-free survival rates for these age groups were 90.5%, 95.4%, 95.5%, 95.4%, and 94.7%, respectively (P=0.09, log-rank test). On univariable analysis, patients aged<40 years were nearly twice as likely to experience LR (hazards ratio (HR), 1.81; P=0.012). Multivariable analysis of patients with complete data (n=2,122) demonstrated that age<40 years and node positivity were associated with increased risk of LR, whereas ER positivity and radiation therapy were associated with decreased risk., Conclusions: Risk factors for LR after BCS include age<40 years, node positivity, ER negativity, and absence of adjuvant radiation therapy. Patients younger than age 40 years are at increased risk of LR after BCS.

Background: The American Society for Radiation Oncology (ASTRO) issued a consensus statement in 2009 regarding patient selection for accelerated partial breast irradiation (APBI) following breast-conserving surgery (BCS) for breast cancer (BC). We reviewed our single-institution experience with APBI in patients considered "cautionary" by ASTRO to determine patterns of recurrence., Methods: An institutional review board-approved, retrospective chart review was conducted from January 2004 to November 2009. We identified 106 "cautionary" patients with 109 BC. All patients were treated with BCS followed by APBI via balloon catheter brachytherapy. "Cautionary" criteria include patients aged 50-59 years, tumor size 2.1-3.0 cm, close margins (<2 mm), focal lymphovascular invasion, estrogen receptor (ER)-negative tumors, invasive lobular carcinoma, or ductal carcinoma in situ (DCIS) ≤ 3 cm. Rates of recurrence at any site were evaluated., Results: Median follow-up was 3 years. There were 3 IBTR (2.8%) at a median of 3.2 years. The 3-year actuarial IBTR rate was 1.8%. Patients with ER-negative invasive cancers had a higher IBTR rate compared with ER-positive patients (11.8% vs. 2.2%), although this did not reach statistical significance (P = 0.18). There were no IBTR in 46 patients with DCIS. On univariate analysis, there was no association between "cautionary" criteria and risk of local, regional, or distant recurrence., Conclusions: Patients considered "cautionary" for APBI based on ASTRO guidelines had low rates of IBTR. ER-negative patients trended toward a higher IBTR rate with APBI compared with ER-positive patients. Longer follow-up is needed to establish the safety of APBI in "cautionary" patients.

Introduction: The objective of this study was to evaluate the safety, toxicity, and planning concerns involved in accelerated partial breast irradiation (APBI) for patients with breast cancer who have a pacemaker or an automatic implantable cardioverter-defibrillator (AICD) and who desire breast conservation., Methods: We performed a review of prospectively obtained data for patients with early-stage breast cancer with a pacemaker or AICD treated between April 2007 and July 2010. Patients were treated with either 3D conformal external beam irradiation (3D-CRT) or high-dose rate balloon brachytherapy (HDRBB) as performed in the National Surgical Adjuvant Breast and Nowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 protocol. Device interrogation was performed after the first and last radiation treatment, with comparative cardiac monitoring performed before and after the first three treatments., Results: Eight patients were treated and have a mean follow-up of 6 months. Three patients received HDRBB delivering 34 Gy in 10 fractions. Mean planning target volume for evaluation (PTV&#95;EVAL) coverage was 93.6%. The maximum radiation dose delivered to any device was 1.03 Gy, with a mean pacemaker distance to lumpectomy cavity (DLC) of 9.1 cm. Five patients received 3D-CRT consisting of 38.5 Gy in 10 fractions. The mean 90% PTV&#95;EVAL coverage was 97.3%. Maximum dose delivered to any device was 1.68 Gy at a DLC of 9 cm. Local toxicity did not exceed grade 1, and no adverse device events were noted., Conclusions: APBI in patients with pacemakers or AICDs who desire breast preservation seems to be a technically safe and reasonable application of targeted radiation therapy.

Background: Accelerated partial breast irradiation (APBI) is emerging as a valid alternative to whole-breast radiation therapy (WBRT) in breast-conserving therapy (BCT) for early-stage breast cancer. Axxent electronic brachytherapy (EBX) is a form of portable, balloon-based APBI that utilizes an electronic source of kilovoltage irradiation delivery with minimal shielding requirements. As such, EBX becomes a logical and convenient modality for delivery of intraoperative radiation therapy (IORT). We report 1-year results and clinical outcomes of a trial that utilizes EBX to deliver IORT for patients with early-stage breast cancer., Methods: Eleven patients were enrolled on an institutional review board (IRB)-approved protocol. Inclusion criteria were patient age >45 years, unifocal tumors with infiltrating ductal or ductal carcinoma in situ (DCIS) histology, tumors ≤3 cm, and uninvolved lymph nodes. Preloaded radiation plans were used to deliver radiation prescription dose of 20 Gy to the balloon surface., Results: The mean time for radiation delivery was 22 min; the total mean procedure time was 1 h 39 min. All margins of excision were negative on final pathology. At mean follow-up of 12 months, overall cosmesis was excellent in 10 of 11 patients. No infection, fat necrosis, desquamation, rib fracture or cancer recurrence has been observed. There was no evidence of fibrosis at last follow-up., Conclusion: IORT utilizing EBX is emerging as a feasible, well-tolerated alternative to postsurgical APBI. Further research and longer follow-up data on EBX and other IORT methods are needed to establish the clinical efficacy and safety of this treatment.

Background: The randomized EORTC 10981-22023 AMAROS trial investigates whether breast cancer patients with a tumor-positive sentinel node biopsy (SNB) are best treated with an axillary lymph node dissection (ALND) or axillary radiotherapy (ART). The aim of the current substudy was to evaluate the identification rate and the nodal involvement., Methods: The first 2,000 patients participating in the AMAROS trial were evaluated. Associations between the identification rate and technical, patient-, and tumor-related factors were evaluated. The outcome of the SNB procedure and potential further nodal involvement was assessed., Results: In 65 patients, the sentinel node could not be identified. As a result, the sentinel node identification rate was 97% (1,888 of 1,953). Variables affecting the success rate were age, pathological tumor size, histology, year of accrual, and method of detection. The SNB results of 65% of the patients (n = 1,220) were negative and the patients underwent no further axillary treatment. The SNB results were positive in 34% of the patients (n = 647), including macrometastases (n = 409, 63%), micrometastases (n = 161, 25%), and isolated tumor cells (n = 77, 12%). Further nodal involvement in patients with macrometastases, micrometastases, and isolated tumor cells undergoing an ALND was 41, 18, and 18%, respectively., Conclusions: With a 97% detection rate in this prospective international multicenter study, the SNB procedure is highly effective, especially when the combined method is used. Further nodal involvement in patients with micrometastases and isolated tumor cells in the sentinel node was similar-both were 18%.

Background: Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC), more difficult to detect mammographically, and usually diagnosed at a later stage. Does delayed diagnosis of ILC affect survival? We used a national registry to compare outcomes of patients with stage-matched ILC and IDC., Methods: Query of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor registry identified 263,408 women diagnosed with IDC or ILC between 1993 and 2003. Survival of patients matched by T and N stage was compared using Kaplan-Meier curves and log-rank analysis., Results: When compared with IDC, ILC was more likely to be >2 cm (43.1 vs. 32.6%; P < 0.001), lymph node positive (36.8 vs. 34.4%; P < 0.001), and ER positive (93.1 vs. 75.6%; P < 0.001). The 5-year disease-specific survival (DSS) was significantly better for patients with ILC than for those with IDC, before (90 vs. 88%; P < 0.001) and after matching for stage T1N0 (98 vs. 96%; P < 0.001), T2N0 (94 vs. 88%; P < 0.001), and T3N0 (92 vs. 83%, P < 0.001). The 5-year DSS for patients with nodal metastasis of ILC vs. IDC was 89% vs. 88% (P = NS) for stage T1N1, 81 vs. 73% (P < 0.001) for T2N1, and 72 vs. 56% (P < 0.001) for T3N1. Multivariate analysis identified a 14% survival benefit for ILC (hazard ratio 0.86, 95% confidence interval 0.80-0.92)., Conclusions: Stage-matched prognosis is better for patients with ILC than for those with IDC. Our findings support a different biology for ILC and are important for counseling and risk stratification.

Background: Approximately 10% of patients with breast cancer who are treated with breast-conserving surgery (BCS) develop an ipsilateral-breast tumor recurrence (IBTR). The optimal local therapy for women with BRCA-associated breast carcinoma remains controversial. We report the outcome of BCS in BRCA mutation carriers followed at a single institution., Methods: A total of 54 women with BRCA1/2-associated breast cancer treated with BCS and whole breast radiotherapy were matched for age, tumor size, and time of surgery with 162 patients with sporadic breast cancer who had the same treatment between February 1994 and October 2007. Primary end points were cumulative incidence of IBTR and contralateral breast cancer (CBC). Median follow-up was 4 years for both groups., Results: Median age was 36 and 37 years for mutation carriers and controls, respectively; mean tumor size was 1.8 cm in carriers and 1.9 cm in controls. Ten-year cumulative incidence of IBTR was 27% for mutation carriers and 4% for sporadic controls (hazard ratio 3.9; 95% confidence interval 1.1-13.8; P = 0.03). Ten-year cumulative incidence of CBC was 25% for mutation carriers and 1% for sporadic controls (P = 0.03)., Conclusions: Our data suggest that IBTR risk after BCS in BRCA1/2 mutation carriers is increased compared with patients who have sporadic breast cancer. Likewise, the risk of CBC seems to be increased in this group. These risks and the likelihood of developing new primary tumors should be discussed with carriers interested in breast conservation as well as when choosing risk-reducing strategies.

Background: The American Society of Breast Surgeons enrolled women onto a registry trial to prospectively study patients treated with the MammoSite Radiation Therapy System (RTS) breast brachytherapy device. This report examines local recurrence (LR), toxicity, and cosmesis as a function of age in women enrolled onto the trial., Methods: A total of 1449 primary early-stage breast cancers were treated in 1440 women. Of these, 130 occurred in women younger than 50 years of age. Fisher's exact test was performed to correlate age (<50 vs. > or = 50 years) with toxicity and with cosmesis. The association of age with LR failure times was investigated by fitting a parametric model., Results: Women younger than 50 were more likely to develop fat necrosis: 4.6% (6 of 130) vs. 1.8% (24 of 1319) (P = .0456). Other toxicities were comparable. At 2 years, cosmesis was excellent or good in 87% of assessable women aged <50 years (n = 74) and in 94% of assessable older women (n = 751) (P = .0197). At 3 years, this difference disappeared: excellent or good in 90% (56 of 62) of younger women vs. 93% (573 of 614) of older women (P = .2902). The crude LR rate for the group was 1.7% (25 of 1449). There was no statistically significant difference in LR as a function of age. In women <50, 3.1% (4 of 130) developed a LR; in the older patients, 1.6% (21 of 1319) developed LR (3-year actuarial LR rates, 2.9% vs. 1.7%, respectively; P = .2284)., Conclusions: Accelerated partial breast irradiation with the MammoSite RTS results in low toxicity and produces similar cosmesis and local control at 3 years in women younger than 50 when compared with older women.