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Purpose: Malignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer, with an incidence of less than 1%. The value of adjuvant radiotherapy (RT) for MPTB has been controversial. The aim of the study was to explore the effect of radiotherapy on the long-term survival of female patients with MPTB at different ages., Methods: Female MPTB patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. A Kaplan-Meier survival analysis was conducted to investigate the value of RT for the long-term survival of MPTB patients in different age groups. Additionally, univariate and multivariate Cox regression analyses were performed for overall survival (OS) and breast cancer-specific survival (BCSS) of MPTB patients. Furthermore, propensity score matching (PSM) was also performed to balance the differences in baseline characteristics., Results: 2261 MPTB patients were included in this study, including 455 patients (20.12%) with RT and 1806 patients (79.88%) without RT. These patients were divided into four cohorts based on their ages: 18-45, 46-55, 56-65, and 65-80. Before adjustment, there was a statistically significant difference in long-term survival between RT-treated and non-RT-treated patients in the younger age groups (age group of 18-45 years: OS P = 0.019, BCSS P = 0.016; age group of 46-55 years: OS P < 0.001, BCSS P < 0.001). After PSM, no difference was found in long-term survival of patients in both younger and older groups regardless of whether they received RT (age group of 18-45 years: OS P = 0.473, BCSS P = 0.750; age group of 46-55 years: OS P = 0.380, BCSS P = 0.816, age group of 56-65 years: OS P = 0.484, BCSS P = 0.290; age group of 66-80 years: OS P = 0.997, BCSS P = 0.763). In multivariate COX regression analysis, RT did not affect long-term survival in patients with MPTB., Conclusion: There is no evidence that long-term survival of MPTB patients in specific age groups can benefit from RT., (© 2024. The Author(s).)

Background: This study aims to evaluate the overall and breast cancer-specific survival (BCSS) after breast-conserving surgery (BCS) plus radiotherapy (RT) compared with mastectomy plus RT in resectable breast cancer. Moreover, the aim is to also identify the subgroups who benefit from BCS plus RT and establish a predictive nomogram for stage II patients. Methods: Stage I−III breast cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1990 and 2016. Patients with available clinical information were split into two groups: BCS plus RT and mastectomy plus RT. Kaplan−Meier survival analysis, univariate and multivariate regression analysis, and propensity score matching were used in the study. Hazard ratio (HR) was calculated based on stratified Cox univariate regression analyses. A prognostic nomogram by multivariable Cox regression model was developed for stage II patients, and consistency index (C-index) and calibration curve were used to evaluate the accuracy of the nomogram in the training and validation set. Results: A total of 24,590 eligible patients were enrolled. The difference in overall survival (OS) and BCSS remained significant in stage II patients both before and after PSM (after PSM: OS: HR = 0.8536, p = 0.0115; BCSS: HR = 0.7803, p = 0.0013). In stage II patients, the survival advantage effect of BCS plus RT on OS and BCSS was observed in the following subgroups: any age, smaller tumor size (<1 cm), stage IIA (T2N0, T0−1N1), ER (+), and any PR status. Secondly, the C-indexes for BCSS prediction was 0.714 (95% CI 0.694−0.734). The calibration curves showed perfect agreement in both the training and validation sets. Conclusions: BCS plus RT significantly improved the survival rates for patients of stage IIA (T2N0, T0−1N1), ER (+). For stage II patients, the nomogram was a good predictor of 5-, 10-, and 15-year BCSS. Our study may help guide treatment decisions and prolong the survival of stage II breast cancer patients.

Background: Intraoperative electron radiotherapy (IOERT) followed by hypofractionated whole breast irradiation (HWBI) provides the shortest possible time of adjuvant breast irradiation. The efficacy of either method has been described in previous reports; however, to our knowledge, the efficacy of combined therapy has not been reported., Aim: To compare the toxicity and cosmetic outcome of IOERT as a tumor bed boost followed by HWBI with conventional whole breast irradiation (CWBI) followed by external electron tumor bed boost (EETBB) after breast conserving surgery (BCS) in patients with invasive breast cancer., Methods: In 2019, a prospective noninferiority trial (IRCT20180919041070N2) was started. After BCS, early-stage breast cancer patients were treated by IOERT (10 Gy) and HWBI (42.56 Gy in 16 fractions) or CWBI (50 Gy in 25 fraction) and EETBB (10 Gy in 5) in a double-arm design. Acute/late toxicity and cosmetic outcome were evaluated by common toxicity criteria (CTC) after 1-year follow-up (FUP) at the level of p < .05., Results: Of 60 eligible patients, 30 were allocated to each group. Regarding acute effects after a median FUP of 12 months, CTC-score of grade II-III erythema (p = .001) and desquamation (p = .005) were significantly higher in CWBI+EETBB compared to IOERT+ HWBI. However, there were no significant differences at the end of radiotherapy and after 1 month, 6 months, and 1 year. Cosmetic outcome after radiation was similar in both groups mostly rating as good/excellent after 1-year FUP., Conclusions: Boost-IOERT/HWBI regimen has comparable acute and late treatment toxicity profiles compared to the CWBI., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background and Purpose: Randomized trials confirmed the efficacy and the safety of hypofractionated whole breast irradiation (HF-WBI) in patients with early-stage breast cancer. However, the role of HF-WBI in patients with DCIS after breast conserving surgery has not yet been clearly established in prospective randomized trials. The aim of this study was to evaluate if HF-WBI can be considered comparable to conventionally fractionated (CF)-WBI in DCIS patients., Materials and Methods: The analysis included DCIS patients from four Italian centers treated with CF-WBI 50 Gy/25 fractions or HFRT 40.5 Gy/15 fractions, without tumor bed boost. A propensity score matching (PSM) analysis was performed using a logistic regression that considered age, grading, presence of necrosis, resection margin status and adjuvant endocrine therapy., Results: Five hundred twenty-seven patients was included (367 in the CF-WBI-group and 160 in the HR-WBI group). After 1:1 matching, 101 patients were allocated to the CF-WBI-group and 104 to the HF-WBI group. No correlation was observed between the type of RT schedule and LRFS (HR 1.68, 95% CI 0.82-3.45; p = 0.152). After PSM, no statistical difference was observed between the two RT group (HR 1.11, 95% CI 0.40-3.04; p = 0.833), with 3- and 5-years LRFS rates of 100% and 97.9% for CF-WBI and 95.6% and 94% for HF-WBI., Conclusion: A short course of radiation therapy seems to be comparable to CF-WBI in terms of clinical outcomes. These data support the use of hypofractionated schedules in DCIS patients, but considering the remaining uncertainties.

Background: We aim to assess the value of locoregional treatment (LRT) including breast-conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer., Methods: Patients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan-Meier analysis, log-rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis., Results: A total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer-specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5-year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p < 0.001). In the PSM cohort, patients treated with BCS alone had lower 5-year BCSS compared to those treated with BCS+RT (43.9% and 52.1%, p = 0.002). However, there were comparable 5-year BCSS between BCS+RT and MAST alone groups (51.3% and 50.1%, p = 0.872), and BCS+RT and MAST+RT cohorts (51.5% and 55.7%, p = 0.333). Similar results were confirmed in multivariate analysis., Conclusions: Postoperative RT improves BCSS in patients with de novo stage IV breast cancer, and BCS+RT shows a non-inferior outcome compared to MAST+RT. BCS+RT may be the optimal local management of de novo stage IV breast cancer., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Incidence of ductal carcinoma in situ (DCIS) has increased in recent decades because of breast cancer screening. This study comprised a long-term survival analysis of DCIS using 10-year territory-wide data from the Hong Kong Cancer Registry., Methods: This study included all patients diagnosed with DCIS in Hong Kong from 1997 to 2006. Exclusion criteria were age <30 years or ≥70 years, lobular carcinoma in situ, Paget's disease, and co-existing invasive carcinoma. Patients were stratified into those diagnosed from 1997 to 2001 and those diagnosed from 2002 to 2006. The 5- and 10-year breast cancer-specific survival rates were evaluated; standardised mortality ratios were calculated., Results: Among the 1391 patients in this study, 449 were diagnosed from 1997 to 2001, and 942 were diagnosed from 2002 to 2006. The mean age at diagnosis was 49.2±9.2 years. Overall, 51.2% of patients underwent mastectomy and 29.5% received adjuvant radiotherapy. The median follow-up interval was 11.6 years; overall breast cancer-specific mortality rates were 0.3% and 0.9% after 5 and 10 years of follow-up, respectively. In total, 109 patients (7.8%) developed invasive breast cancer after a considerable delay. Invasive breast cancer rates were comparable between patients diagnosed from 1997 to 2001 (n=37, 8.2%) and those diagnosed from 2002 to 2006 (n=72, 7.6%)., Conclusion: Despite excellent long-term survival among patients with DCIS, these patients were more likely to die of breast cancer, compared with the general population of women in Hong Kong., Competing Interests: The authors have no conflicts of interest to disclose.

Purpose: To investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival., Patients and Methods: Patients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs)., Results: Multivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2-4) or nodal (ypN2-3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03-0.81), 0.32 (0.16-0.64), 0.43 (0.23-0.79), 0.23 (0.13-0.42), 0.52 (0.20-1.33), and 0.34 (0.13-0.87) in the ypT0, ypT1, ypT2-4, ypN0, ypN1, and ypN2-3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00-4.07), 0.46 (0.26-0.83), 0.18 (0.06-0.51), 0.28 (0.06-1.34), 0.25 (0.10-0.63), 0.47 (0.23-0.88), and 0.32 in the cT0-1, cT2, cT3, cT4, cN0, cN1, and cN2-3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST., Conclusion: WBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to declare. The datasets supporting the study conclusions are included within the manuscript., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hypofractionation is now becoming the standard of care in breast irradiation. The aim of this study was to assess the toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy (HFRT)., Methods: Patients with localized breast cancer who received adjuvant HFRT between 2013 and 2015 with a minimum follow-up of 6 months following radiation were included in this prospective study. Late toxicities were assessed using CTCAE v 4 and included chest/breast pain, limb pain, limb edema, skin pigmentation, skin fibrosis, and shoulder movement restriction. Outcomes assessed included locoregional control, disease-free survival, and overall survival. Statistical analysis was done using Microsoft Excel and SPSS v22., Results: A total of 81 patients fulfilled the inclusion criteria, of which 19 patients had died during follow-up. Regional nodal irradiation was done in 63 (77.8%) patients using the same hypofractionated schedule of 40 Gy in 15 fractions. Late toxicities were assessed for 62 patients. The median follow-up following the course of hypofractionated radiation was 45 months (range 14 - 65 months). Late toxicities were assessed for 62 patients. Grade 1/2 chest/breast pain, limb pain, limb edema, skin pigmentation, skin fibrosis, and shoulder movement restriction were seen in 11%, 12%, 7%, 6%, 8%, and 11% of cases, respectively. Distant recurrences were seen in 8% of cases, and there were no locoregional recurrences. Five-year overall survival was 76.5%., Conclusion: HFRT to whole breast or chest wall and the regional nodal areas was well-tolerated with acceptable rates of late toxicities on follow-up., Competing Interests: None

Background: Given the growing evidence that sarcopenia and inflammation influence the survival of patients with cancer, we evaluated the prognostic significance of the skeletal muscle index (SMI) combined with an inflammation marker in patients with breast cancer who underwent postoperative adjuvant radiotherapy., Methods: We conducted a retrospective analysis of 301 patients with breast cancer who received postoperative adjuvant radiotherapy between 2010 and 2012. The SMI was measured using preradiotherapy computed tomography (CT) simulation images at the level of the fourth thoracic vertebra (T4). Receiver operating characteristic curve analyses were used to determine the optimal cutoff values for the SMI and inflammatory marker. Patients were divided into 2 groups (high SMI and low SMI), based on the SMI cutoff of 10.57 cm 2 /m 2 ., Results: Patients in the high-SMI group had a median overall survival (OS) of 62.4 months, which was significantly shorter than those in the low-SMI group, with a median OS of 68.5 months (P = 0.025). Patients in the high-SMI group had a median recurrence-free survival (RFS) of 62.3 months, which was shorter but not significantly than the median RFS of 65.2 months of the low-SMI group (P = 0.159). Univariate and multivariate survival analyses revealed SMI was an independent predictor of OS (P = 0.044). The SMI-MLR combination was found to be an independent predictor of OS (P = 0.006) and RFS (P = 0.009)., Conclusions: The current findings support the SMI as a promising indicator for predicting clinical outcomes in patients with breast cancer receiving postoperative adjuvant radiotherapy. A high SMI accompanied by systemic inflammation was significantly associated with reduced OS and RFS., (Copyright © 2019. Published by Elsevier Inc.)

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.

Aim: To determine whether the addition of regional nodal irradiation (RNI) to whole-breast irradiation (WBI) would improve outcomes over WBI alone in T1-2N1 breast cancer after breast-conserving surgery (BCS) and adjuvant systematic therapy., Methods: Data were obtained from two randomized controlled trials (NCT00174655 and NCT00312208). Univariate and multivariate Cox-regression analysis were performed to investigate predictors for overall survival and disease-free survival. A 1:1 propensity score matching (PSM) analysis was applied to eliminate selection bias., Results: With median follow-up 80 months (range: 3-155 months), the 5-year local regional recurrence in the WBI group was 2% vs. 5% (p = 0.28) in the WBI + supraclavicular radiotherapy, and the rate of 5-year distant metastasis in the WBI group was 7% vs. 13% in the WBI + supraclavicular radiotherapy (p = 0.0748); In addition, the 5-year local regional recurrence in the WBI group was 3% vs. 9% (p = 0.19) in the WBI + internal mammary irradiation (IMI); However, the rate of 5-year distant metastasis in the in the WBI group was significantly lower than that in the WBI + IMI (8% vs. 24%, p = 0.036). After PSM, cox-regression analysis indicated that neither RNI nor IMI in combination with WBI in T1-2N1 breast cancer was associated with an improved overall survival and disease-free survival when compared to WBI alone., Conclusion: The addition of RNI to WBI in T1-2N1 breast cancer after BCS and adjuvant systematic therapy did not improve outcomes in comparison with WBI alone. Further studies are still needed to identify patients who would most benefit from RNI in this patient population., Competing Interests: Declaration of competing interest None., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved overall survival (OS) in patients with breast cancer, but it is unclear how post-NACT response influences radiation therapy administration in patients presenting with node-positive disease. We sought to determine whether nodal pCR is associated with likelihood of receiving nodal radiation and whether radiation therapy among patients experiencing nodal pCR is associated with improved OS., Methods and Materials: Clinical N1 (cN1) female breast cancer patients diagnosed during 2010 to 2015 who were ypN0 (ie, nodal pCR; n = 12,341) or ypN1 (ie, residual disease; n = 13,668) after NACT were identified in the National Cancer Database. Multivariate logistic regression was used to identify factors associated with receiving radiation therapy. Cox proportional hazards modeling was used to estimate the association between radiation therapy and adjusted OS., Results: The study included 26,009 patients; 43.9% (n = 5423) of ypN0 and 55.3% (n = 7556) of ypN1 patients received nodal radiation. Rates of nodal radiation remained the same over time among ypN0 patients (trend test, P = .29) but increased among ypN1 patients from 49% in 2010 to 59% in 2015 (trend test, P < .001). After adjusting for covariates, nodal pCR (vs no stage change) was associated with decreased likelihood of nodal radiation after mastectomy (∼20% decrease) and lumpectomy (∼30% decrease; both P < .01). After mastectomy, nodal (vs no) radiation conferred no significant survival benefit in ypN0 patients, but it approached significance for ypN1 patients (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.69-0.99, P = .04; overall P = .11). After lumpectomy, nodal radiation was associated with improved adjusted OS for ypN0 (HR, 0.38; 95% CI, 0.22-0.66) and ypN1 patients (HR, 0.44; 95% CI, 0.30-0.66; both P < .001), but this improvement was not significantly greater than that associated with breast-only radiation., Conclusions: ypN0 patients were less likely to receive nodal radiation than ypN1 patients were, suggesting that selective omission already occurs and, in the context of limited survival data, could potentially be appropriate for select patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To explain the association between adjuvant radiation therapy after breast conserving surgery (BCS RT) and overall survival (OS) by quantifying bias due to confounding in a sample of elderly breast cancer beneficiaries in a multi-state region of Appalachia., Methods: We used Medicare claims linked registry data for fee-for-service beneficiaries with AJCC stage I-III, treated with BCS, and diagnosed from 2006 to 2008 in Appalachian counties of Kentucky, Ohio, North Carolina, and Pennsylvania. Confounders of BCS RT included age, rurality, regional SES, access to radiation facilities, marital status, Charlson comorbidity, Medicaid dual status, institutionalization, tumor characteristics, and surgical facility characteristics. Adjusted percent change in expected survival by BCS RT was examined using Accelerated Failure Time (AFT) models. Confounding bias was assessed by comparing effects between adjusted and partially adjusted associations using a fully specified structural model., Results: The final sample had 2675 beneficiaries with mean age of 75, with 81% 5-year survival from diagnosis. Unadjusted percentage increase in expected survival was 2.75 times greater in the RT group vs. non-RT group, with 5-year survival of 85% vs 60%; fully adjusted percentage increase was 1.70 times greater, with 5-year rates of 83% vs 71%. Quantification of incremental confounding showed age accounted for 71% of the effect reduction, followed by tumor features (12%), comorbidity (10%), dual status(10%), and institutionalization (8%). Adjusting for age and tumor features only resulted in only 4% bias from fully adjusted percent change (70% change vs 66%)., Conclusion: Quantification of confounding aids in determining covariates to adjust for and in interpreting raw associations. Substantial confounding was present (60% of total association), with age accounting for the largest share (71%); adjusting for age plus tumor features corrected for most of the confounding (4% bias). The direct effect of BCS RT on OS accounted for 40% of the total association.

Background: American College of Surgeons Oncology Group Z0011 confirms the safety of omitting axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) in breast cancer patients with one to two positive sentinel lymph nodes (SLNs), without compromising disease-free survival (DFS) and overall survival (OS). In contrast, the NCIC MA20 trial showed improved DFS in node-positive patients undergoing ALND and RNI. We sought to examine how these data have influenced the management of patients with limited nodal burden., Methods: Using the National Cancer Database, patients diagnosed between 2010 and 2015 and who met the criteria for Z0011 were identified. Logistic regression was used to analyze factors associated with practice patterns. The Cox proportional hazards model was used to assess the association of ALND and RNI with OS., Results: Omission of ALND in Z0011-eligible patients reached 89.2% in 2015. This Z0011-compliant group was more likely to undergo RNI compared with the non-compliant group (36.4% vs. 31.3%; p < 0.05), with RNI increasing to 43.8% by 2015. Factors associated with the use of RNI included later year of diagnosis [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.6-2.1], hormone receptor-negative tumor (OR 1.2, 95% CI 1.1-1.4), grade 3 tumor (OR 1.2, 95% CI 1.1-1.3), treatment at a non-academic site (OR 1.2, 95% CI 1.1-1.3) and two versus one positive SLN (OR 2.0, 95% CI 1.8-2.2). With 43 months median follow-up, RNI was not associated with improved OS., Conclusion: Since the publication of Z0011, the omission of ALND has become widespread; however nearly half of these women now receive RNI. The optimal radiation therapy approach for this low nodal burden population warrants further study.

Background and Objectives: Irradiation after breast-conserving surgery (BCS) decreases the incidence of ipsilateral breast tumor recurrence (IBTR) and breast cancer-related death. However, daily radiation treatments are burdensome to elderly patients, whose risk of IBTR is relatively low. Since 2001, we have offered BCS without radiation to patients meeting our selection criteria. This study assessed the prognosis of the patients who chose this option., Methods: Between 2001 and 2014, 203 patients met the selection criteria: aged ≥60 years; pathologically node-negative, hormone-positive breast cancer; a negative surgical margin; and no lymphovascular invasion. Among these patients, 84 and 119 underwent BCS with or without radiation, respectively. IBTR, overall survival (OS), and breast cancer-specific survival (BCSS) were evaluated., Results: The median follow-up duration was 6.2 years. There were no significant differences in tumor size or the number of patients with adjuvant therapy between the groups. The 5-year IBTR rates were 0.9% and 1.6% in the non-irradiated and irradiated groups, respectively (p = 0.308). The 5-year OS rates were 94.1% and 98.7% (p = 0.391). Similarly, the 5-year BCSS rates were 97.2% and 98.7% (p = 0.812)., Conclusion: It is suggested that the omission of irradiation could be an option for elderly breast cancer patients who satisfy our criteria., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Deintensification of adjuvant therapy is being considered for older women with early-stage, biologically favorable breast cancer. Although radiation therapy (RT) can be omitted in some cases, toxicity from hormone therapy (HT) is not trivial, and adherence rates vary. We hypothesized that adjuvant RT alone would produce survival outcomes comparable to those with adjuvant HT alone among elderly patients treated with lumpectomy., Methods and Materials: We searched the National Cancer Database (2010-2014) for healthy women (aged ≥70 years, Charlson/Deyo [CD] score 0-1) with T1N0 hormone-receptor-positive, HER-2-negative breast cancer treated with lumpectomy and adjuvant HT or RT. Propensity scores were used to match patients for analysis., Results: We identified 2995 patients (median age, 78 years), most (81%) with a CD score of 0, clinical stage IA (77%), of whom 65% received HT alone and 35% received RT only after lumpectomy. On multivariate analysis of the matched cohort, older age (hazard ratio [HR] 1.10; 95% confidence interval [CI] 1.07-1.13; P < .001), CD score 1 (HR 1.92; 95% CI 1.37-2.70; P = .0002), and living in a metropolitan (vs urban) area (HR 3.09; 95% CI 1.43-6.67; P = .004) were associated with inferior overall survival (OS), whereas treatment with HT (vs RT) was not (HR 1.13; 95% CI 0.85-1.49; P = .406). At a median follow-up of 45 months, no difference was found in OS between HT versus RT cohorts (85% and 86%, respectively; P = .44)., Conclusions: For healthy, older women with biologically favorable breast cancer treated with lumpectomy, adjuvant RT or HT is associated with equivalent 5-year OS rates. A randomized controlled trial is warranted to explore these adjuvant monotherapy options in elderly patients with hormone receptor-positive breast cancer., (Published by Elsevier Inc.)

Three recently published prospective trials on regional nodal irradiation (RNI) in early breast cancer showed a reduction on breast cancer mortality, any first breast recurrence and/or distant recurrence rate. The positive outcomes of the modern trials reflect the development in radiotherapy by being more precise nowadays in radiation dose delivery to the lymph nodes, while reducing the radiation dose to heart and lungs. The possibility of axillary radiotherapy (ART) to replace axillary node dissection (ALND) after positive sentinel node (SLNB) biopsy is explored in a few trials. In the AMAROS trial both ALND and ART provide excellent and comparable LRR in SN+ patients. While the lymphedema was 2 times higher after ALND compared to ART. The ACOSOG Z0011 10 years results did not show a significant difference in locoregional recurrence rate or survival. These equal results were seen despite that in 27.4% of the patients had additional positive nodes removed beyond SLN in the patients who received axillary dissection (ALND). The IBCSG 23-01 phase III trial showed that there is no need for extra treatment of the axilla after micro-metastases in SLNB, however in this trial nearly all patients received breast irradiation including part of the axilla, often combined with adjuvant therapy. The introduction of neo- adjuvant systemic treatment (NACT) may lead to less RNI in early breast cancer, especially as NACT leads to pCR in axillary lymph nodes in about one third of the patient., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: We evaluated the long-term outcomes and late toxicity of conventional fractionated (CF) and hypofractionated (HF) postmastectomy radiotherapy (PMRT) in terms of locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS), and late toxicity., Methods: A cohort of 1640 of breast cancer patients receiving PMRT between January 2004 and December 2014 were enrolled. Nine hundred eighty patients were treated with HF-PMRT: 2.65 Gy/fraction to a total of 42.4-53 Gy and 660 patients were treated with CF-PMRT: 2 Gy/fraction to a total of 50-60 Gy., Results: The median follow-up time was 71.8 months (range 41.5-115.9 months). No significant difference was found in the rates of 5-year LRRFS, DFS, and OS of HF-PMRT vs CF-PMRT; 96% vs. 94% (p = 0.373), 70% vs. 72% (p = 0.849), and 73% vs. 74% (p = 0.463), respectively. We identified a cohort of 937 eligible breast cancer patients who could receive late toxicities assessment. With a median follow-up time of this patient cohort of 106.3 months (range 76-134 months), there was a significant higher incidence of grade 2 or more late skin (4% vs 1%) and subcutaneous (7% vs 2%) toxicity in patients treated with HF-PMRT vs CF-PMRT. Patients who received additional radiation boost were significantly higher in the HF-PMRT group. Grade 2 or more late RTOG/EORTC lung toxicity was significant lesser in HF-PMRT vs CF-PMRT (9% vs 16%). Grade 1 brachial plexopathy was also significant lesser in HF-PMRT vs CF-PMRT (2% vs 8%). Heart toxicity and lymphedema were similar in both groups., Conclusions: HF-PMRT is feasible to deliver with comparable long-term efficacy to CF-PMRT. HF-PMRT had higher grade 2 or more skin and subcutaneous toxicity but less lung and brachial plexus toxicity.

Background/aim: The aim of this study was to evaluate the treatment results of patients undergoing adjuvant radiotherapy (ART) after breast surgery with the diagnosis of ductal carcinoma in situ (DCIS)., Materials and Methods: A total of 61 women who had undergone radiotherapy following extensive surgical excision were enrolled. All patients underwent 50 Gy ART. Survival analysis was performed using Kaplan–Meier analysis and SPSS 20.0., Results: The median age was 52 years (range: 28–86). The median follow-up period after RT was 92 months (range: 23–237). The median overall survival and distant and regional recurrence-free and disease-specific survival was 96 months (range: 26–240), while disease-free and local recurrence-free survival was 96 months (range: 22–240). While the 15-year and 20-year overall survival rates were 87% and 87%, respectively, the recurrence-free survival rates were 98% and 98%, respectively; the rates of disease-specific survival were 100% and 100%, respectively., Conclusion: The results of this study with a long follow-up period have shown that ART in DCIS is an effective treatment method to provide local disease control. However, further large studies are needed to identify the prognostic factors., (This work is licensed under a Creative Commons Attribution 4.0 International License)

Background: The treatment sequence involving a mastectomy and immediate breast reconstruction (IBR) via the latissimus dorsi flap technique after chemotherapy and radiotherapy is not common. Our experience of this alternative to the standard treatment at our institute is reported herein., Patients and Methods: This was a single-center, retrospective study. We enrolled patients who received this so-called "inverse" sequence for invasive, nonmetastatic breast cancer between 2009 and 2016., Results: Fifty-two patients, aged between 24 and 65 years, with a mean body mass index of 24.5 underwent this treatment. Most involved T2 (59.6%, n = 32), multifocal (55.8%, n = 29) tumors, and 57.7% (n = 30) of the patients presented with axillary lymph node involvement. All patients had received sequential chemotherapy and 50 Gy of radiation. Pathological complete response (pCR) was found in 51.3% (n = 20), of cases in the traditional inverse sequence group, using Chevalier and Sataloff classifications (T and N pCR). Postoperatively, 1 patient required surgical revision because of a hematoma, 42 (80.8%) presented with lymphocele, 3 had impaired would healing, and 2 had more than 5 cm of skin necrosis on the front flap. Median follow-up was 61.9 months and the median time between diagnosis and surgery was 9.7 months. Three patients presented with metastases, 2 with local recurrence, and 1 patient died of cancer. No contralateral or lymph node recurrence was discovered., Conclusion: This treatment sequence, the feasibility of which was shown in this study, is an alternative for patients who want an IBR to avoid the time spent without one breast. This practice requires upstream multidisciplinary cooperation for optimal patient screening., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose/objective(s): Radiation treatment to the regional nodes results in an improvement in survival in breast cancer according to a meta-analysis of randomized trials. However, different volumes were targeted in these studies: breast or chestwall only (WBI/CWI), inclusion of the medial supraclavicular region and axillary apex (MS + WBI/CWI) or additional inclusion of the internal mammary chain (IM + MS + WBI/CWI). The benefit of treating the medial supraclavicular region and axillary apex compared to tangential breast or chestwall irradiation only remains unclear., Materials/methods: A literature search was conducted identifying trials for adjuvant radiation volumes in nodal irradiation after breast surgery and axillary treatment. Events and effect sizes were extracted from the publications for the endpoints of overall survival (OS), breast cancer-specific survival (BCSS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional control (LRC). A network meta-analysis was performed using MetaXL V5.3 with the inverse variance heterogeneity model., Results: We found two randomized studies (n = 5836) comparing comprehensive nodal irradiation to sole breast treatment as well as one randomized (n = 1407) and one prospective cohort study (n = 3377) analysing the additional treatment of the internal mammary chain against sole local and supraclavicular and axillary apex radiation. Compared to WBI/CWI alone the treatment of IM + MS + WBI/CWI (HR = 0.88; CI:0.78-0.99; p = 0.036) results in improved OS unlike MS + WBI/CWI (HR = 0.99; CI:0.86-1.14; p = 0,89). These results are confirmed in BCSS: IM + MS + WBI/CWI (HR = 0.82; CI:0.72-0.92; p = 0.002) and MS + WBI/CWI (HR = 0.96; CI:0.79-1.18; p = 0.69). PFS is significantly improved with the treatment of MS + WBI/CWI (OR = 0.83; CI:0.71-0.97; p = 0.019). Both nodal treatment volumes improve LRC (MS + WBI/CWI OR = 0.74; CI:0.62-0.87; p = 0.004 and IM + MS + WBI/CWI OR = 0.60; CI:0.43-0.86; p < 0,001). Yet only the internal mammary nodes provide a benefit in DMFS (MS + WBI/CWI HR = 0.97; CI:0.81-1.16; p = 0.74 and IM + MS + WBI/CWI HR = 0.84; CI:0.75-0.94; p = 0.002)., Conclusion: Expanding the radiation field to the axillary apex and supraclavicular nodes after axillary node dissection reduced loco-regional recurrences without improvement in overall and cancer-specific survival. A prolongation in survival due to regional nodal irradiation is achieved when the internal mammary chain is included. This derives from a reduction in distant metastasis.

Background: As the efficacy of radiotherapy and chemotherapy for treatment of phyllodes tumors (PTs) remains unclear, this study aimed to review all available data and evaluate the roles of radiotherapy and chemotherapy in PT treatment., Methods: We performed a comprehensive search of databases, including PubMed, Web of Science and the Cochrane Library. The outcomes of interest included the local recurrence (LR) rate, metastasis rate, disease-free survival rate and overall survival rate., Results: Seventeen studies enrolling 696 patients were included in this random effect meta-analysis. Subgroup analysis and meta-regression were also conducted to determine study heterogeneity. A pooled local recurrence rate of 8% (95% CI: 1-22%) was observed with a statistical heterogeneity of I 2  = 86.6% (p < 0.01) for radiotherapy. This was lower than the recurrence rate of 12% for simple surgical treatment (95% CI: 7-18%). Meta-regression analysis found that surgical margin status was the main source of heterogeneity (p = 0.04). The metastasis rate of 4% (95% CI: 0-11%) for patients receiving radiotherapy without significant heterogeneity was also lower than the rate for the simple surgery group (8, 95% CI: 3-15%). The available data for chemotherapy were too limited to support meta-analysis. Accordingly, we offer a pure review of these data., Conclusion: Our findings suggest that radiotherapy is effective in achieving local disease control and preventing metastasis.

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: Given the lack of established indications for elective nodal irradiation (ENI) in ypN0 patients after neoadjuvant chemotherapy (NAC) and breast-conserving surgery (BCS), we set out to investigate the role of ENI in ypN0 patients according to subtype and pathologic complete remission (pCR) status., Patients and Methods: We analyzed 261 patients who received NAC followed by BCS and adjuvant radiotherapy in 13 institutions of the Korean Radiation Oncology Group from 2005 to 2011. The tumors were classified into one of 3 subtypes: luminal (estrogen receptor positive or progesterone receptor positive and HER2 negative), HER2 (HER2 positive), or triple negative (estrogen receptor, progesterone receptor, and HER2 negative). We compared locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) according to ENI in different subgroups generated by the subtype and pCR statuses., Results: In all patients, the 5-year LRC, DFS, and OS rates were 96.0%, 91.0%, and 96.8%, respectively. In all patients, axillary lymph node dissection was found to be the only favorable factor for LRC (P = .023) and DFS (P = .001). Age ≥ 50 years (P = .027), negative resection margin (P = .002), and axillary lymph node dissection (P = .002) were all favorable factors for OS. ENI did not affect LRC, DFS, or OS. Subgroup analysis by tumor subtype and pCR showed that ENI was not associated with greater LRC or DFS in any subgroups., Conclusion: In ypN0 patients after NAC and BCS, ENI did not improve LRC or survival, regardless of subtype or primary tumor response. This result should be verified through larger prospective trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The prognostic equivalence between mastectomy and breast-conserving surgery (BCS) followed by radiotherapy was shown in pivotal trials conducted decades ago. Since then, detection and treatment of breast cancer have improved substantially and recent retrospective analyses point towards a survival benefit for less extensive breast surgery. Evidence for the association of such survival data with locoregional recurrence rates is largely lacking., Methods: The Swedish Multicentre Cohort Study prospectively included clinically node-negative patients with breast cancer who had planned sentinel node biopsy between 2000 and 2004. Axillary lymph node dissection was undertaken only in patients with sentinel node metastases. For the present investigation, adjusted survival analyses were used to compare patients who underwent BCS and postoperative radiotherapy with those who received mastectomy without radiotherapy., Results: Of 3518 patients in the Swedish Multicentre Cohort Study, 2767 were included in the present analysis; 2338 had BCS with postoperative radiotherapy and 429 had mastectomy without radiotherapy. Median follow-up was 156 months. BCS followed by whole-breast irradiation was superior to mastectomy without irradiation in terms of both overall survival (79·5 versus 64·3 per cent respectively at 13 years; P < 0·001) and breast cancer-specific survival (90·5 versus 84·0 per cent at 13 years; P < 0·001). The local recurrence rate did not differ between the two groups. The axillary recurrence-free survival rate at 13 years was significantly lower after mastectomy without irradiation (98·3 versus 96·2 per cent; P < 0·001)., Conclusion: The present data support the superiority of BCS with postoperative radiotherapy over mastectomy without radiotherapy. The axillary recurrence rate differed significantly, and could be one contributing factor in a complex explanatory model., (© 2018 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Purpose: This study aimed to identify predictors for distant metastatic behavior and build a related prognostic nomogram in breast cancer., Materials and Methods: A total of 1,181 patients with non-metastatic breast cancer between 2003 and 2011 were analyzed. To predict the probability of distant metastasis, a nomogram was constructed based on prognostic factors identified using a Cox proportional hazards model., Results: The 7-year overall survival and 5-year post-progression survival of locoregional versus distant recurrence groups were 67.6% versus 39.1% (p=0.027) and 54.2% versus 33.5% (p=0.043), respectively. Patients who developed distant metastasis showed early and late mortality risk peaks within 3 and after 5 years of follow-up, respectively, but a broad and low risk increment was observed in other patients with locoregional relapse. In multivariate analysis of distant metastasis-free interval, age (≥ 45 years vs. < 45 years), molecular subtypes (luminal A vs. luminal B, human epidermal growth receptor 2, and triple negative), T category (T1 vs. T2-3 and T4), and N category (N0 vs. N1 and N2-3) were independently associated (p < 0.05 for all). Regarding the significant factors, a well-validated nomogram was established (concordance index, 0.812). The risk score level of patients with initial brain failure was higher than those of non-brain sites (p=0.029)., Conclusion: The nomogram could be useful for predicting the individual probability of distant recurrence in breast cancer. In high-risk patients based on the risk scores, more aggressive systemic therapy and closer surveillance for metastatic failure should be considered.

Purpose: We used the National Cancer Data Base to analyze practice patterns of adjuvant breast radiotherapy (RT) in elderly patients to see if a difference in overall survival (OS) could be detected. Additionally, we investigated factors that affected OS in these patients., Patients and Methods: Women aged ≥ 65 years with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative pathologic T1-T2N0M0 invasive breast cancer measuring up to 3 cm who were treated with breast conservation and adjuvant endocrine therapy without adjuvant chemotherapy were identified and stratified by use of adjuvant RT. Multivariable Cox proportional hazards modeling was used to examine the association of treatment and mortality adjusting for demographic, socioeconomic, and clinicopathologic factors. Kaplan-Meier analysis was used to estimate overall 5-year survival in patients who did or did not receive adjuvant RT, and to compare those groups., Results: A total of 61,395 patients with a median follow-up of 48.7 months (range, 0-107 months) were identified. On Cox regression analysis, improved OS was associated with treatment at an academic facility, younger age, higher income level, lower Charlson-Deyo comorbidity index, and receipt of adjuvant RT (all P < .05). The overall 5-year survival rate was 93.0% (95% confidence interval 92.7-93.3) in the adjuvant RT group and 83.6% (95% confidence interval 82.5-84.7) in the nonadjuvant RT group (P < .0001)., Conclusion: Improved survival is associated with the receipt of adjuvant RT for older women with early-stage hormone receptor-positive HER2-negative breast cancer who received adjuvant endocrine therapy. However, there are many limitations inherent to a retrospective database study such as ours, so the findings should be taken with caution., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Importance: Circulating tumor cells (CTCs) represent the liquid component of solid tumors and are a surrogate marker for residual cancer burden. Although CTC status is prognostic of recurrence and death in breast cancer, its role in guiding clinical management remains unknown., Objective: To determine whether CTC status is predictive of radiotherapeutic benefit in early-stage breast cancer., Design, Setting, and Participants: The cohort studies in the present analysis included patients with stages pT1 to pT2 and pN0 to pN1 breast cancer and known CTC status from the National Cancer Database (NCDB) and the multicenter phase 3 SUCCESS clinical trial. Multivariable parametric accelerated failure time models were used to evaluate the association of CTC status and radiotherapy (RT) with survival outcomes. Data were collected from January 1, 2004, through December 31, 2014, from the NCDB cohort. The SUCCESS trial collected data from September 1, 2005, through September 30, 2013. The analyses were completed from November 1, 2016, through December 17, 2017., Exposure: Adjuvant RT., Main Outcomes and Measures: Overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS)., Results: A total of 1697 patients from the NCDB (16 men [0.9%] and 1681 women [99.1%]; median age, 63 years; interquartile range, 53-71 years) and 1516 patients from the SUCCESS clinical trial (median age, 52 years; interquartile range, 45-60 years) were identified. Circulating tumor cells were detected in 399 patients (23.5%) in the NCDB cohort and 294 (19.4%) in the SUCCESS cohort. The association of RT with survival was dependent on CTC status within the NCDB cohort (4-year OS, 94.9% for CTC-positive RT vs 88.0% for CTC-positive non-RT vs 93.9% for CTC-negative RT vs 93.4% for CTC-negative non-RT groups; P < .001) and 5-year DFS within the SUCCESS cohort (88.0% for CTC-positive RT vs 75.2% for CTC-positive non-RT vs 92.3% for CTC-negative RT vs 88.3% for CTC-negative non-RT; P = .04). In the NCDB cohort, RT was associated with longer OS in patients with CTCs (time ratio [TR], 2.04; 95% CI, 1.55-2.67; P < .001), but not in patients without CTCs (TR, 0.80; 95% CI, 0.52-1.25; P = .33). In the SUCCESS cohort, CTC-positive patients treated with RT exhibited longer LRFS (TR, 2.73; 95% CI, 1.62-4.80; P < .001), DFS (TR, 3.03; 95% CI, 2.22-4.13; P < .001), and OS (TR, 1.83; 95% CI, 1.23-2.72; P = .003). Among patients from both cohorts who underwent breast-conserving surgery, RT was associated with longer OS in patients with CTCs (TR, 4.37; 95% CI, 2.71-7.05; P < .001) but not in patients without CTCs (TR, 0.87; 95% CI, 0.47-1.62; P = .77). Radiotherapy was not associated with OS after mastectomy in CTC-positive or CTC-negative patients., Conclusions and Relevance: Treatment with RT was associated with longer LRFS, DFS, and OS in patients with early-stage breast cancer and detectable CTCs. These results are hypothesis generating; a prospective trial evaluating CTC-based management for RT after breast-conserving surgery in women with early-stage breast cancer is warranted.

Purpose: A meta-analysis of 22 randomized trials accrued from 1964 to 1986 demonstrated significantly higher rates of locoregional failure (LRF) and breast-cancer mortality in women with 1-3 positive nodes without postmastectomy radiotherapy (PMRT) after mastectomy (mast.). Recent data demonstrate that PMRT reduces distant metastases (DM) in women with pN1 disease. The challenge today is whether all patients with pathologic T1-2pN1 disease have similar substantial LRF/DM risk that routinely warrants PMRT., Methods: We reviewed patients with pT1-2N1 breast cancer treated with mast. ± adjuvant systemic therapy without PMRT from 2000 to 2013. The endpoints were LRF and DM rates, estimated by cumulative incidence method., Results: We identified 468 patients with median follow-up of 6.3 years. Most (71%) were estrogen receptor/progesterone receptor + human epidermal growth factor receptor 2 (HER2). There were 269 patients with 1+ node, 140 patients with 2+ nodes, and 59 patients with 3+ nodes. The 6-year LRF/DM rates were 4.1%/8.4%. Patients with 1+, 2+, and 3+ nodes had 6-year LRF of 2.3, 5.1 and 8.9%, respectively (p = 0.13). The 6-year DM rate was higher in patients with 3+ nodes versus 1-2+ nodes: 15.7% versus 7.4% (p = 0.02). Several subgroups had low 6-year LRF and DM rates, including T1/1+ node (0.8%/4.1% LRF/DM) and micrometastases (0%/5.8% LRF/DM)., Conclusions: Patients with pT1-2pN1 represent a heterogeneous group with a wide range of LRF/DM rates. In particular, patients with pT1 tumors and 1 + LN, and patients with micrometastases, had low event rates. These groups would derive small absolute reductions in LRF and DM with addition of PMRT, underscoring the importance of patient selection for PMRT in pT1-2pN1 breast cancer.

Background/objective: Guidelines concur that postmastectomy radiation therapy (PMRT) in T1-2 tumors with one to three positive (+) lymph nodes (LNs) decreases locoregional recurrence (LRR) but advise limiting PMRT to patients at highest risk to balance against potential harms. In this study, we identify the risks of LRR after mastectomy in patients with T1-2N1 disease, treated with modern chemotherapy, and identify predictors of LRR when omitting PMRT., Methods: Patients with T1-2N1 breast cancer undergoing mastectomy between 1995 and 2006 were categorized by receipt of PMRT. The Chi square test compared the clinicopathologic features between both groups, and Kaplan-Meier and Cox regression analysis was used to determine the rates of LRR, recurrence-free survival (RFS), and overall survival (OS)., Results: Overall, 1087 patients (924 no PMRT, 163 PMRT) were included in the study, with a median follow-up of 10.8 years (range 0-21). We identified 63 LRRs (56 no PMRT, 7 PMRT), and 10-year rates of LRR with and without PMRT were 4.0% and 7.0%, respectively. Patients receiving PMRT were younger (p = 0.019), had larger tumors (p = 0.0013), higher histologic grade (p = 0.029), more positive LNs (p < 0.0001), lymphovascular invasion (LVI) (p < 0.0001), extracapsular nodal extension (p < 0.0001), and macroscopic LN metastases (p < 0.0001). There was no difference in LRR, RFS, or OS between groups. On multivariate analysis, age < 40 years (p < 0.0001) and LVI (p < 0.0001) were associated with LRR in those not receiving PMRT., Conclusion: Consistent with the guidelines, 85% of patients with T1-2N1 were spared PMRT at our center, while maintaining low LRR. Age < 40 years and the presence of LVI are significantly associated with LRR in those not receiving PMRT.

Purpose: Multiple studies have evaluated the omission of radiation therapy (RT) in elderly women with invasive carcinoma; no studies to date have assessed this question for metaplastic breast cancer (MBC). This study is the only known study describing national practice patterns and addressing the impact of RT versus observation on survival in elderly women with T1-2N0 MBC., Methods: The National Cancer Data Base was queried (2004-2013) for women aged ≥70 years with T1-T2N0 MBC that underwent lumpectomy. Multivariable logistic regression ascertained factors associated with RT administration. Kaplan-Meier analysis evaluated overall survival (OS) between patients treated with or without postoperative RT. Cox proportional hazards modeling determined variables associated with OS. Propensity matching was performed in order to address indication bias., Results: Of 547 total patients, 176 (32%) underwent observation, and 371 (68%) received postoperative RT. Temporal trends revealed that withholding RT steadily declined over the studied time period. RT delivery was less likely in patients not undergoing hormonal therapy or those ≥80 years old. In both the overall population and following propensity matching, delivery of RT was associated with higher OS (p < 0.001 for both). On Cox multivariate analysis, poorer OS was independently associated with advancing age, higher T stage, high-grade disease, and omitting postoperative RT (p < 0.05 for all)., Conclusions: Although level I evidence exists to omit RT in select elderly women, this is the only study evaluating this notion for MBC. These results do not support the routine withholding of RT in T1-2N0 MBC owing to the independent association with worse survival., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Studies of cohorts of breast cancer (BC) patients diagnosed before 1990 showed radiotherapy (RT) to be associated with increased cardiovascular (CVD) and lung cancer mortality many years after diagnosis. In the late 1990s, improvements in RT planning techniques reduced radiation doses to normal tissues. Recent studies did not consistently report higher RT-related mortality for CVD and second cancers. Aim of the study was to analyze specific causes of death after 3D-conformal RT in a recent BC cohort., Methods: Stage I-III BC patients diagnosed 2001-2005 and enrolled in the population based MARIEplus study were followed-up for 11.9 years (median). Associations between adjuvant RT and cause-specific mortality were analyzed by using competing risks models, yielding subdistribution hazard ratios (SHR) for RT directly related to cumulative incidences. Models were adjusted for differences in baseline characteristics applying inverse-probability-of-treatment-weighting (IPTW)., Results: Of the 2951 patients, 2439 (83.0%) received RT. No significant association of RT with lung cancer mortality (SHR IPTW 0.88, 0.35-2.12), other cancer mortality (SHR IPTW 1.04, 95% CI 0.62-1.73) or cardiac mortality was observed (SHR IPTW 1.57, 0.75-3.29). Mortality from lung and other diseases were significantly lower in irradiated women (SHR IPTW 0.39, 95% CI 0.17-0.90 and SHR IPTW 0.58, 95% CI 0.34-0.97, respectively)., Conclusion: In line with recent studies, 3D-conformal RT did not significantly increase mortality from non-BC causes in the German MARIEplus cohort. Since long-term data are still sparse and event rates low in BC-cohorts, who received modern RT, investigation of possible late RT effects on mortality beyond 14 years of follow-up is warranted., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Metaplastic breast cancer (MBC) is a rare, aggressive form of breast cancer with limited data to guide management. This study of a large, contemporary US database described national practice patterns and addressed the impact of radiotherapy (RT) on survival., Methods: The National Cancer Data Base was queried (2004-2013) for women with non-metastatic MBC. Multivariable logistic regression ascertained factors associated with RT administration. Kaplan-Meier analysis evaluated overall survival (OS) between patients treated with either lumpectomy or mastectomy with or without RT, while substratifying patients into pT1-2N0 and pT3-4/N+ subcohorts. Cox proportional hazards modeling determined variables associated with OS., Results: Of 5211 total patients, 447 (9%) had lumpectomy alone, 1831 (35%) had post-lumpectomy RT, 2020 (39%) had mastectomy alone, and 913 (18%) had post-mastectomy RT (PMRT). Most patients underwent chemotherapy (79%), and mastectomy was the most common surgical approach (56%). RT delivery was impacted by many factors, including higher nodal disease (p < 0.001), but not T classification or estrogen receptor status (p > 0.05 for both). Post-lumpectomy RT was associated with higher OS in both the pT1-2N0 and pT3-4/N+ subsets (p < 0.001 for both), while PMRT was associated with OS benefits in pT3-4/N+ cases (p < 0.001), but not in pT1-2N0 cases (p = 0.259)., Conclusions: In the largest study to date evaluating MBC, practice patterns of surgery, systemic therapy, and RT are described. The addition of RT in the post-lumpectomy setting was associated with higher OS, in addition to pT3-4/N+ in the post-mastectomy setting. Although not implying causation, further work is required to corroborate the conclusions herein.

Objective: To assess the impact of delay in initiation of adjuvant chemotherapy and/or radiotherapy on the outcomes of breast cancer patients referred for adjuvant treatment., Methods: This is a pooled analysis of patient-level data of 3390 breast cancer patients referred for adjuvant chemotherapy in three clinical trials. Overall and relapse-free survivals were assessed according to "surgery to chemotherapy interval" through Kaplan-Meier analysis. Likewise, among patients who received adjuvant radiotherapy, relapse-free survival was assessed according to "surgery to radiotherapy interval" through Kaplan-Meier analysis. Univariate and Multivariate analysis of factors affecting overall and relapse-free survival was then conducted through Cox regression analysis., Results: Kaplan-Meier analysis of overall survival according to surgery to chemotherapy interval ( 6 weeks) was conducted. When stratified by the hormone receptor status, the longer interval was associated with worse overall survival in hormone receptor-negative patients (P = 0.006); while it was not associated with overall survival difference in hormone receptor-positive patients (P = 0.268). In multivariate Cox regression analysis, the test of interaction between "surgery to chemotherapy interval" and hormone receptor status was significant (P = 0.015). Moreover, when the multivariate analysis was restricted to hormone receptor-negative patients, longer surgery to chemotherapy interval was associated with worse overall survival among this subset of patients (P = 0.004). On the other hand, in multivariate analysis of factors affecting relapse-free survival, surgery to radiotherapy interval did not impact relapse-free survival (P = 0.439)., Conclusion: Among hormone receptor-negative patients, delaying chemotherapy initiation beyond 6 weeks (after surgery) is associated with worse patient outcomes. Moreover, delaying radiotherapy initiation beyond surgery does not compromise outcomes in patients receiving long course adjuvant chemotherapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To analyze postmastectomy radiation therapy (PMRT) usage and its association with overall survival (OS) in breast cancer patients with pathologically positive lymph nodes after neoadjuvant chemotherapy (NAC)., Methods and Materials: Using the National Cancer Database, we identified women with nonmetastatic breast cancer diagnosed from 2004 to 2013 who had received NAC and undergone mastectomy with macroscopic pathologically positive lymph nodes. Joinpoint regression models were used to assess temporal trends in annual PMRT usage. Multivariable regression models were used to identify factors associated with PMRT use. A time-dependent Cox model was used to evaluate the predictors of mortality., Results: The study included 29,270 patients, of whom 62.5% received PMRT. PMRT was markedly underused among all nodal subgroups, in particular, among ypN2 (68.4%) and ypN3 (67.0%) patients. Hispanic patients and those with Medicaid or Medicare insurance were less likely to receive PMRT than were non-Hispanics and patients with other insurance carriers. The adjusted 5-year OS rates were similar in ypN1 and ypN2 patients with or without PMRT but were significantly greater in ypN3 patients receiving PMRT (66% vs 63%; P=.042). On multivariable analysis, PMRT was associated with improved survival only among ypN3 patients after adjusting for patient, facility, and tumor variables (multivariable hazard ratio 0.85; 95% confidence interval 0.74-0.97)., Conclusions: A considerable portion of breast cancer patients with advanced residual nodal disease after NAC did not receive appropriate adjuvant radiation. We also found socioeconomic disparities in national PMRT practice patterns. Patients with ypN3 disease might derive a survival benefit from PMRT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: According to the seventh edition of tumour-node-metastasis (TNM) classification, pN3a status in breast cancer patients consists of presence of an infraclavicular lymph node metastasis (LNM) and/or presence of ≥10 axillary LNMs. The aim of this study was to determine whether prognosis of pN3a based on at least an infraclavicular LNM differs from ≥10 axillary LNMs., Methods: Data were obtained from the Netherlands Cancer Registry. All patients were diagnosed between 2005 and 2008 with primary invasive epithelial breast cancer and pN2a or pN3a status as pathologic result. Patients with pN3a were subdivided in pN3a based on at least an infraclavicular LNM or ≥10 axillary LNMs. Disease-free survival (DFS) included any local, regional or contralateral recurrence, distant metastasis or death within 5 years. Kaplan-Meier curves provided information on 5-year DFS and 8-year overall survival (OS). In addition, Cox proportional hazards model was used to measure the effect of relevant clinicopathological variables on DFS and OS., Results: A total of 3400 patients with pN2a and 1788 patients with pN3a were included. In 83 patients, pN3a was based on at least an infraclavicular LNM (4.6%) and in 1705 patients because of ≥10 axillary LNMs (95.4%). After multivariable analyses, DFS and OS were inferior in patients with pN3a based on ≥10 axillary LNMs compared to infraclavicular LNM (DFS 48.8% versus 63.8%, hazard ratio [HR] 1.59, p = 0.036; OS 46.6% versus 63.9%, HR 1.46, p = 0.042). Furthermore, pN2a and pN3a based on infraclavicular LNM had comparable DFS and OS., Conclusion: PN3a status based on an at least an infraclavicular LNM is rare, yet its prognosis is superior to ≥10 axillary LNMs. Reclassification of infraclavicular LNM in the next TNM should therefore be considered into pN2a., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the prognostic value of sequencing of adjuvant radiotherapy and chemotherapy following breast-conserving surgery for patients with breast cancer. Methods: A total of 1 154 patients withT1-2N0-3M0 breast cancer retrospectively reviewed. All patients received sequential radiotherapy and chemotherapy following breast-conserving surgery. Among them, 603 patients received radiotherapy first and 551 patients received chemotherapy first. Log-rank tests were used to determine significance of disease-free survival (DFS) and overall survival (OS) rates in the Kaplan-Meier curve. Results: The 5-year DFS and OS rates for all patients were 93.0% and 97.8%. The 5-year OS rate was 98.6% in the radiotherapy first group and 96.4% in the chemotherapy first group ( P =0.191), and the corresponding DFS rate was 92.7% and 93.2% ( P =0.430), respectively. Among the patients with Luminal A subtype, the 5-year OS rate was 99.6% in the radiotherapy first group and 97.8% in the chemotherapy first group ( P =0.789). Among the patients with Luminal B subtype, the 5-year OS rate was 94.2% and 96.0%, respectively ( P =0.680). Among the patients with triple negative breast cancer, the 5-year OS rate was 100% and 90.9%, respectively, with statistically significant differences ( P =0.019). Among the patients with HER-2 positive breast cancer, The 5-year DFS rate was 80.1% and 100%, respectively ( P =0.045). Conclusions: The OS and DFS rates in the chemotherapy first group are not significantly different from those of radiotherapy first group after breast-conserving surgery. Patients with HER-2 positive breast cancer in chemotherapy first group have a much higher DFS rate than that of radiotherapy first group, whereas patients with triple negative breast cancer in radiotherapy first group have a better OS rate than that of chemotherapy first group. Further research is warranted to investigate the benefit of different molecular types in different sequencing of radiotherapy and chemotherapy after breast-conserving surgery.

Purpose: Malignant phyllodes tumor of the breast (MPTB) accounts for less than 1% of whole breast neoplasm. Surgery is regarded as the primary treatment of choice in patients with MPTB, but the necessity of postoperative radiation therapy (RT) has been a subject of debate. Our aim was to evaluate effects of postoperative RT for MPTB using a large population database., Methods: Using the Surveillance, Epidemiology, and End Results Program (SEER) database (1983-2013), clinico-pathologic prognostic factors were evaluated. Postoperative RT, tumor extent, grade, and lymph node (LN) metastasis were included in the analysis. Univariate and multivariate Cox proportional hazards regressions were performed to evaluate prognostic power of variables on cancer specific survival (CSS)., Results: A total of 1974 patients with MPTB were reviewed. Of these, 825 (42%) and 1149 (58%) patients underwent mastectomy and breast conserving surgery (BCS), respectively. In each group, 130 (16%) and 122 (11%) patients received postoperative RT. For patients with adverse risk factors including high grade and large tumor size, postoperative RT was more likely to be performed. In multivariate analysis, age, ethnicity, tumor size, tumor extension and LN status were correlated with prognosis in mastectomy group, while postoperative RT did not affect CSS. In BCS group, age and grade were significant prognostic factors on CSS, meanwhile postoperative RT did not impact CSS in multivariate analysis., Conclusion: Although patients with more adverse prognostic factors underwent postoperative RT, RT groups were not inferior to non-RT group on CSS regardless of surgery (mastectomy or BCS)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The role of postmastectomy radiotherapy (PMRT) for women with pT3N0M0 breast cancer is controversial. We sought to determine the benefit of PMRT in this cohort using the National Cancer Database (NCDB)., Methods: We analyzed women with pT3N0M0 breast cancer who received mastectomy with or without PMRT between 2004 and 2012. We excluded men, women ≤18 years, neoadjuvant or unknown radiation or chemotherapy status, unknown estrogen or progesterone receptor status, unknown surgical margin status, histology other than invasive ductal or lobular carcinoma, and if death occurred <3 months after diagnosis. A total of 4291 patients was included for analysis. Chi-squared analysis was used to compare patient characteristics. Univariate (UVA) and multivariate (MVA) Cox proportional hazards modeling was used to identify factors associated with survival. Propensity score matching was performed to address confounding variables. Survival analysis was performed using Kaplan-Meier and shared frailty models., Results: Of the 4291 women analyzed, 2030 (47%) received PMRT. On MVA, PMRT (HR 0.72, p < 0.001), chemotherapy (HR 0.51, p < 0.001), and hormone therapy (HR 0.63, p < 0.001) were associated with improved overall survival (OS). After propensity score matching, a matched cohort of 2800 women was analyzed. At 5 years, OS was 83.7% and 79.8% with and without PMRT, respectively (p < 0.001). This difference in OS benefit increased with time. At 10 years, OS was 67.4% and 59.2% with and without PMRT, respectively., Conclusions: PMRT was associated with improved OS in women with pT3N0M0 breast cancer, which strongly suggests PMRT may provide a survival advantage and should be considered., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: To evaluate locoregional recurrence, overall survival, disease-free survival and prognostic influence of the number of positive lymph nodes and other variables in breast cancer treatment., Patients and Methods: A total of 377 patients with pT1-T2, pN0-N1 invasive breast carcinoma treated from 2005 to 2013 were retrospectively evaluated. Patients underwent conservative surgery followed by whole-breast radiotherapy. Clavicular region irradiation was not performed., Results: With a median follow-up of 4 years, locoregional recurrence rate was 3.4% (nodal recurrence=1.06%). Expression of progesterone receptors was significantly associated with better disease-free survival, tumor size (T>2 cm) with poorer disease-free survival, locoregional recurrence and poorer overall survival; the presence of three nodal metastases was related to significantly poorer overall survival (p=0.024)., Conclusion: Whole-breast adjuvant radiotherapy without nodal irradiation after breast-conserving surgery led to low rate of locoregional recurrence and high rates of overall survival and disease-free survival in patients with pT1-T2 pN0-N1 breast cancer., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS)., Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR., Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034)., Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Investigators of registry-based studies report improved survival for breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer. As these studies did not present long-term overall and breast cancer-specific survival, the effect of breast-conserving surgery plus radiotherapy might be overestimated. In this study, we aimed to evaluate 10 year overall and breast cancer-specific survival after breast-conserving surgery plus radiotherapy compared with mastectomy in Dutch women with early breast cancer., Methods: In this population-based study, we selected all women from the Netherlands Cancer Registry diagnosed with primary, invasive, stage T1-2, N0-1, M0 breast cancer between Jan 1, 2000, and Dec 31, 2004, given either breast-conserving surgery plus radiotherapy or mastectomy, irrespective of axillary staging or dissection or use of adjuvant systemic therapy. Primary outcomes were 10 year overall survival in the entire cohort and breast cancer-specific survival in a representative subcohort of patients diagnosed in 2003 with characteristics similar to the entire cohort. We estimated breast cancer-specific survival by calculating distant metastasis-free and relative survival for every tumour and nodal category. We did multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs) for overall and distant metastasis-free survival. We estimated relative survival by calculating excess mortality ratios using life tables of the general population. We did multiple imputation to account for missing data., Findings: Of the 37 207 patients included in this study, 21 734 (58%) received breast-conserving surgery plus radiotherapy and 15 473 (42%) received mastectomy. The 2003 representative subcohort consisted of 7552 (20%) patients, of whom 4647 (62%) received breast-conserving surgery plus radiotherapy and 2905 (38%) received mastectomy. For both unadjusted and adjusted analysis accounting for various confounding factors, breast-conserving surgery plus radiotherapy was significantly associated with improved 10 year overall survival in the whole cohort overall compared with mastectomy (HR 0·51 [95% CI 0·49-0·53]; p<0·0001; adjusted HR 0·81 [0·78-0·85]; p<0·0001), and this improvement remained significant for all subgroups of different T and N stages of breast cancer. After adjustment for confounding variables, breast-conserving surgery plus radiotherapy did not significantly improve 10 year distant metastasis-free survival in the 2003 cohort overall compared with mastectomy (adjusted HR 0·88 [0·77-1·01]; p=0·07), but did in the T1N0 subgroup (adjusted 0·74 [0·58-0·94]; p=0·014). Breast-conserving surgery plus radiotherapy did significantly improve 10 year relative survival in the 2003 cohort overall (adjusted 0·76 [0·64-0·91]; p=0·003) and in the T1N0 subgroup (adjusted 0·60 [0·42-0·85]; p=0·004) compared with mastectomy., Interpretation: Adjusting for confounding variables, breast-conserving surgery plus radiotherapy showed improved 10 year overall and relative survival compared with mastectomy in early breast cancer, but 10 year distant metastasis-free survival was improved with breast-conserving surgery plus radiotherapy compared with mastectomy in the T1N0 subgroup only, indicating a possible role of confounding by severity. These results suggest that breast-conserving surgery plus radiotherapy is at least equivalent to mastectomy with respect to overall survival and may influence treatment decision making for patients with early breast cancer., Funding: None., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: This study compared treatment outcomes of radiotherapy concurrent with endocrine therapy and radiotherapy sequential with endocrine therapy in breast cancer., Materials and Methods: Eligible studies of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were retrieved through extensive searches of the PubMed, Medline, Embase, Cochrane library, FEBM, FMJS, Web of science, Wiley, CBM, CNKI, Wang fang, Cqvip databases from 2000 to 2014. Original English and Chinese publications of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were included. The primary endpoint was radiation-induced toxicity including upper than grade 2 skin related toxicity, radiation pneumonia and pulmonary fibrosis; the second endpoint was survival date, including local recurrence, distant metastasis, 5-year OS, 10-year OS., Results: Eleven eligible trials were identified, six in English and five in Chinese. Totally, there were 1291 women in concurrent groups, and 1179 in sequential groups. Statistical analysis showed that there was no statistical difference between concurrent and sequential groups in skin related toxicity (RR 1.20, 95% CI 0.92-1.56, P = 0.17), radiation pneumonia (RR 1.11, 95% CI 0.46-2.70, P = 0.81) and pulmonary fibrosis (RR 1.35, 95% CI 0.75-2.41, P = 0.32). Meanwhile, no statistical difference was found in survival data, (RR 0.97, 95% CI 0.79-1.28, P = 0.26), (RR 0.86, 95% CI 0.66-1.12, P = 0.27) in local recurrence and distant metastasis respectively, (RR 1.01, 95% CI 0.96-1.06, P = 0.65), (RR 0.98, 95% CI 0.93-1.02, P = 0.32) in 5-year and 10-year overall survival respectively. Stratification analysis was proceeded, grouped by tamoxifen and AI in different treatment timing, however, no statistical difference was found in radiation-induced toxicity and survival outcomes., Conclusion: Radiotherapy concurrent with endocrine therapy didn't increase or decrease neither the incidence of radiation-induced toxicity nor the survival rate compared with that of sequential group; Endocrine therapy drugs didn't influence outcomes in different treatment timing., (Copyright © 2016. Published by Elsevier Ltd.)

Purpose of Review: Ductal carcinoma in situ (DCIS) accounts for approximately 20% of mammographically diagnosed breast cancers. Currently, there is a trend to consider DCIS as a lesion for which treatment deescalation is advocated to avoid overtreatment, that is, radiotherapy in addition to breast-conserving surgery or even surgery at all., Recent Findings: The long-term follow-up updates of the four first-generation randomized trials comparing lumpectomy with and without radiation therapy have confirmed that radiation halves the local failure rates. However, radiotherapy is not associated with a survival benefit just as affirmed by the recently published evaluation of the Surveillance, Epidemiology, and End Results registries database, including 108,196 women with DCIS. Nevertheless, the risk of dying of breast cancer increases about factor 18 after experience of an invasive local recurrence. That means at least some DCIS have the potential to progress to a life threatening disease. At the same time, none of the recently updated prospective trials that tested the outcome after excision alone in low-risk DCIS achieved a 10-year local failure rate below 10%., Summary: DCIS is not a uniform disease. Its clinical behaviour is heterogeneous, but up to date no citeria are available that allow a precise identification of patients with low or very low progression risk who do not need irradiation. Therefore, excision followed by radiotherapy is still the standard of care in patients undergoing breast conservation. Promising new approaches for risk estimation have to be validated prospectively before their use in daily practice can be recommended.

Purpose: Mastectomy is often recommended for women ≤40 years of age with breast cancer, as young women were under-represented in the landmark trials comparing breast conservation therapy (BCT) to mastectomy. We hypothesized that, in the modern treatment era, BCT and mastectomy result in equivalent local control rates in young women., Methods and Materials: Breast cancer cases arising between 1975 and 2013 in women ≤40 years old were collected from the tumor registries of 2 large healthcare systems in Utah. Kaplan-Meier estimates and Cox proportional hazards models were used to analyze freedom from locoregional recurrence (FFLR), overall survival (OS), and relapse-free survival (RFS)., Results: This analysis identified 853 BCT candidates. A comparison of BCT to mastectomy after 2000 showed FFLR, RFS, and OS were all similar. Rate for FFLR at 10 years was 94.9% versus 92.1% for BCT and mastectomy, respectively (P=.57). For women whose cancer was diagnosed after 2000, who received BCT, FFLR and RFS rates were improved compared to those whose cancer was diagnosed prior to 2000 (P<.05), whereas OS (P=.46) rates were similar. Among those who underwent mastectomy, FFLR, OS, and RFS were significantly improved (P<.05) with diagnosis after 2000., Conclusions: FFLR rates for young women, ≤40 years of age, have significantly improved for BCT and mastectomy over time. If patients were treated after 2000, BCT appears to be safe and equivalent to mastectomy at 10 years in terms of FFLR, OS, and RFS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: to evaluate if time between surgery and the first adjuvant treatment (chemotherapy, radiotherapy or hormone therapy) in patients with breast cancer is a risk factor for lower overall survival (OS)., Method: data from a five-year retrospective cohort study of all women diagnosed with invasive breast cancer at an academic oncology service were collected and analyzed., Results: three hundred forty-eight consecutive women were included. Time between surgery and the first adjuvant treatment was a risk factor for shorter overall survival (HR=1.3, 95CI 1.06-1.71, p=0.015), along with negative estrogen receptor, the presence of lymphovascular invasion and greater tumor size. A delay longer than 4 months between surgery and the first adjuvant treatment was also associated with shorter overall survival (cumulative survival of 80.9% for delays ≤ 4 months vs. 72.6% for delays > 4 months; p=0.041, log rank test)., Conclusion: each month of delay between surgery and the first adjuvant treatment in women with invasive breast cancer increases the risk of death in 1.3-fold, and this effect is independent of all other well-established risk factors. Based on these results, we recommend further public strategies to decrease this interval.

Introduction: Although hypofractionated radiotherapy (HFRT) has become an accepted option for whole-breast irradiation after breast-conserving surgery, there is limited evidence to support HFRT to the chest wall following mastectomy. We retrospectively analysed post-mastectomy patients treated with HFRT in Christchurch to determine whether HFRT yields acceptable efficacy and toxicity., Methods: The Christchurch oncology database was used to identify breast cancer patients treated with adjuvant HFRT to the chest wall following a mastectomy between 2003 and 2008. Eligible post-mastectomy patients were treated with 40 Gy in 16 daily fractions. Treatment outcomes assessed included local recurrence-free survival, breast cancer survival, overall survival and acute toxicities., Results: One hundred thirty-three patients were identified. The median follow-up period was 5.03 years. Three patients had a local recurrence as a first event, resulting in 5-year local recurrence-free survival of 97.6%. Five-year overall survival and 5-year breast cancer survival were 74.7% and 77.7%, respectively. The prospectively assessed acute toxicities were mostly grade 1. In particular, the incidence of grade 2 skin toxicity was 10.7%, and no patients experienced grade 3 skin toxicity., Conclusion: The high local control rate with HFRT, combined with acceptable toxicity and the practical benefits of a shorter treatment time, supports its ongoing use in the eligible patient group. A randomised controlled trial would be necessary to more completely assess the acute and long-term toxicity of HFRT compared with standard fractionation., (© 2014 The Royal Australian and New Zealand College of Radiologists.)

Objectives: The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node., Methods: We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients)., Results: The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients., Conclusions: PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.