Search

Importance: The potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear., Objective: To assess the activity and safety of combining radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive breast cancer and brain metastases., Design, Setting, and Participants: This was a single-arm, single-center, phase 2 nonrandomized clinical trial with a safety run-in phase. Between January 2020 and August 2022, patients with ERBB2-positive breast cancer and brain metastases were enrolled. The data cutoff date was February 1, 2023., Interventions: Patients received either fractionated stereotactic radiotherapy or whole-brain radiotherapy. Treatment with pyrotinib (400 mg, once daily) and capecitabine (1000 mg/m2, twice daily, on days 1-14 of each 21-day cycle) was initiated from the first day of radiotherapy to the seventh day after the completion of radiotherapy and continued until disease progression or unacceptable toxic effects., Main Outcomes and Measures: The primary end point was 1-year central nervous system (CNS) progression-free survival (PFS) rate. Secondary end points included CNS objective response rate (ORR), PFS, overall survival (OS), safety, and changes in neurocognitive function., Results: A total of 40 female patients (median age, 50.5 years [IQR, 46-59 years]) were enrolled and received treatment, including 3 patients in safety run-in phase. With a median follow-up of 17.3 months (IQR, 10.3-26.9), the 1-year CNS PFS rate was 74.9% (95% CI, 61.9%-90.7%), and the median CNS PFS was 18.0 months (95% CI, 15.5 to not reached). The 1-year PFS rate was 66.9% (95% CI, 53.1%-84.2%), and the median PFS was 17.6 months (95% CI, 12.8-34.1). The CNS objective response rate was 85% (34 of 40). Median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse event was diarrhea (7.5%). Asymptomatic radiation necrosis was identified in 4 of 67 lesions (6.0%) treated with fractionated stereotactic radiotherapy. Most patients maintained neurocognitive function, as evaluated by the Mini-Mental State Examination at different points., Conclusions and Relevance: The results of this trial suggest that radiotherapy combined with pyrotinib and capecitabine is associated with long intracranial survival benefit in patients with ERBB2-positive advanced breast cancer and brain metastases with an acceptable safety profile. This combination deserves further validation., Trial Registration: ClinicalTrials.gov Identifier: NCT04582968.

Background: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients., Methods: The SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants., Discussion: The results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www., Clinicaltrials: gov/ct2/show/NCT05059379 ., (© 2024. The Author(s).)

Background: Breast cancer brain metastases (BCBM) are highly heterogenous with widely differing survival. The prognosis of the oligometastatic breast cancer (BC) patients with brain metastases (BM) has not been well studied. We aimed to investigate the prognosis of BCBM patients with limited intracranial and extracranial metastatic lesions., Methods: Four hundred and forty-five BCBM patients treated between 1st January 2008 and 31st December 2018 at our institute were included. Clinical characteristics and treatment information were obtained from patient's medical records. The updated breast Graded Prognostic Assessment (Breast GPA) was calculated., Results: The median OS after diagnosis of BM were 15.9 months. Median OS for patients with GPA 0-1.0, 1.5-2, 2.5-3 and 3.5-4 were 6.9, 14.2, 21.8, 42.6 months respectively. The total number of intracranial and extracranial metastatic lesions, in addition to the Breast GPA, salvage local therapy and systemic therapy (anti-HER2 therapy, chemotherapy and endocrine therapy) were demonstrated to be associated with prognosis. One hundred and thirteen patients (25.4%) had 1-5 total metastatic lesions at BM diagnosis. Patients with 1-5 total metastatic lesions had a significantly longer median OS of 24.3 months compared to those with greater than 5 total metastatic lesions with a median OS of 12.2 months (P < 0.001; multivariate HR 0.55, 95% CI, 0.43-0.72). Among the patients with 1-5 metastatic lesions, median OS for GPA 0-1.0 was 9.8 months, compared to 22.8, 28.8 and 71.0 for GPA 1.5-2.0, 2.5-3.0 and 3.5-4.0 respectively, which is much longer than the corresponding patients with greater than 5 total metastatic lesions, with medium OS of 6.8, 11.6, 18.6 and 42.6 months respectively for GPA 0-1.0, 1.5-2.0, 2.5-3.0 and 3.5-4.0., Conclusions: The patients with 1-5 total metastatic lesions demonstrated better OS. The prognostic value of the Breast GPA and the survival benefit of salvage local therapy and continuation of systemic therapy after BM were confirmed., (© 2023. The Author(s).)

Purpose: We aimed to examine whether elective inclusion of the posterolateral supraclavicular node (SCL) region to the standard medial SCL target volume improves SCL control and survival outcomes in patients with high-risk node-positive breast cancer undergoing regional nodal irradiation (RNI)., Methods and Materials: We retrospectively reviewed 544 consecutive women with high-risk breast cancer treated with postoperative chest wall/breast and RNI in our center from January 2015 to December 2016. High-risk features were defined as clinical or pathologic stage N2-3b disease. Patients were classified into the medial SCL irradiation (M-SCLI) group and the entire SCL irradiation (E-SCLI) group, which included both the medial and the posterolateral SCL region. SCL recurrence (SCLR), disease-free survival (DFS), and overall survival (OS) were estimated and compared. Propensity-score matching (PSM) and multivariate cox regression were used for analysis., Results: The median follow-up time was 64.2 months. Before PSM, there was no significant difference in the cumulative incidence of SCLR between the 2 groups, with 5-year rates of 2.0% in the M-SCLI group and 0.6% in the E-SCLI group (P = .1). After PSM, there was also no significant difference in the cumulative incidence of SCLR (2.1% vs 0.5%; P = .2). Only 2 patients had recurrence in the posterolateral SCL region, with 1 patient in each group. Similarly, there was no significant difference in DFS and OS between the M-SCLI and E-SCLI group both before PSM (5-year rates of 78.5% vs 78.8%, P = .8; 92.2% vs 90.0%, P = .2) and after PSM (76.7% vs 77.2%, P = .8; 91.5% vs 88.4%, P = .1). Multivariate analysis demonstrated that E-SCLI was not independently prognostic for DFS and OS., Conclusions: E-SCLI does not appear to be associated with improved SCL control and survival outcomes in high-risk node-positive breast cancer. These data do not support the routine use of E-SCLI in N2-3b disease. We initiated a multicenter randomized controlled phase 3 study comparing M-SCLI and E-SCLI to further validate these results., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Currently, the prognostic value of molecular subtypes in ductal carcinoma in situ (DCIS) remains unclear. In this study, we explored whether molecular subtypes could predict second breast events (SBEs) in patients after breast-conserving surgery (BCS)., Methods: From January 2008 to December 2016, 291 DCIS patients treated with BCS were retrospectively analyzed. Patients were classified into four molecular subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) overexpression, and triple-negative breast cancer (TNBC). The SBE incidence was calculated by the competing risk model and compared by Gray's test. The disease-free survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. Prognostic factors were evaluated by univariate and multivariate COX proportional hazards regression model., Results: With a median follow-up of 66 months, 12 SBEs were identified. The 5-year overall SBE incidence of luminal A, luminal B, HER2 overexpression, and TNBC was 2.18%, 4.25%, 15.15%, and 0.00%, respectively. In the univariate analysis, the HER2 overexpression subtype was the predictor of overall (p = 0.005), in situ (p = 0.004), and ipsilateral SBEs (p = 0.008). Patients with endocrine therapy were less likely to develop in situ SBEs (p = 0.039). Additionally, patients with closed (<2 mm) or involved margins were related to a higher risk of contralateral SBEs (p = 0.029). In the multivariate analysis, the HER2 overexpression subtype remained of prognostic values for overall (p = 0.006), in situ (p = 0.029), and ipsilateral SBEs (p = 0.012)., Conclusions: The molecular subtype, especially the HER2 overexpression subtype, was the independent prognostic factor for DCIS patients who underwent BCS., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To evaluate the incidence of symptoms related to brachial plexus neuropathy (BPN) and the dose distribution to the brachial plexus (BP) in patients with breast cancertreated with supraclavicular (SCV) irradiation and boost., Methods and Materials: In this study, 117 patients with initial ipsilateral supraclavicular lymph node (SLN) metastasis and 39 with recurrent SLN metastasis between 2008 and 2018 in our cancer center were retrospectively analyzed. All patients were treated with 50 Gy of SCV irradiation in 25 fractions and a boost (median dose, 10 Gy; range, 10-16 Gy) to involved nodes in the SCV area. Symptoms related to BPN (including ipsilateral arm numbness, pain, and weakness) were recorded and graded according to the Common Terminology Criteria for Adverse Events, version 5.0. The BP was delineated on simulation computed tomography, and the dose distributions to the BP were evaluated. Meanwhile, 297 patients treated with SCV irradiation without boost during the same period were identified as a control group to compare the incidences of BPN-related symptoms and dosimetric data with patients who received an SCV boost., Results: The 5-year overall survival rate was 80.3% for patients with initial SLN metastasis and 51.0% for patients with recurrent SLN metastasis. For patients who received an SCV boost, incidence rates of ipsilateral arm numbness, pain, and weakness were 23.9%, 18.3%, and 34.3%, respectively. Four patients (5.6%) developed grade 2 numbness and 3 (4.3%) developed grade 2 arm weakness. In the control group, incidence rates of arm numbness, pain, and weakness were 31.6%, 21.9%, and 36.0%, respectively. The incidence of BPN-related symptoms was not significantly different between the 2 groups. Symptoms of grade 3 were not observed in either cohort. The mean doses to the BP in patients who received boost and who did not were 56.8 and 46.8 Gy, respectively (P < .001). The maximum doses to the BP in patients who received boost and who did not were 64.5 and 53.5 Gy, respectively (P < .001). The BP volumes receiving at least 50 Gy, 60 Gy, 61 Gy, and 62 Gy were also significantly higher in the boosted group compared with the control group (P < .001)., Conclusions: This study found that an SCV boost of 10 Gy did not increase the incidence of BPN-related symptoms and that the toxicity to the BP was acceptable. Comprehensive treatment including SCV irradiation and boost led to satisfactory survival outcomes in patients with breast cancer who had SLN metastasis., (Copyright © 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Primary squamous cell carcinoma of the breast (PSCCB) is a rare clinical classification of breast tumors. Little is known about its clinicopathological features, prognosis and potential therapeutic strategies. The purpose of this study is to evaluate the effect of postoperative radiotherapy (PORT) on patients with squamous cell carcinoma (SCC) of the breast., Methods: We retrospectively analyzed patients diagnosed with PSCCB in our center. All pathological slides were reviewed by an experienced pathologist to confirm the diagnosis. Furthermore, we searched the public database for patients with SCC of the breast. Then, we analyzed the clinicopathological features, treatment methods and patient outcomes., Results: We identified 14 patients with primary SCC of the breast in our center. Additionally, 739 patients with SCC of the breast from the Surveillance, Epidemiology and End Results (SEER) database were diagnosed between 1975 and 2016. Only 453 patients who underwent surgery were included in this study. Patients from the SEER database had a more advanced tumor node metastasis (TNM) stage than patients from our center. The median overall survival (OS) of all patients was 104 months (95% confidence interval [CI], 87.2-120.8 months), and the 5-year OS was 60.8% (95% CI, 56.1%-65.5%). Most of the patients (58%) tested negative for hormonal receptor expression. Multivariate analysis showed that PORT was an independent prognostic factor for OS., Conclusion: The results of our study demonstrate that SCC of the breast presents aggressive behavior with unique clinical characteristics. PORT improved OS significantly in patients with SCC of the breast. Longer-term studies are needed to confirm our findings., (© 2020 John Wiley & Sons Australia, Ltd.)

Purpose: Postmastectomy radiation therapy (PMRT) in T1-T2 tumors with 1-3 positive axillary lymph nodes (ALNs) is controversial. This study was to identify prognostic factors of locoregional control (LRC) following mastectomy with or without PMRT for patients with T1-2N1 breast cancer and to discuss the selection of patients who might omit PMRT., Materials and Methods: Between January 2006 and December 2012, the data of 1474 postmastectomy patients staged pT1-2N1 were analyzed. PMRT was applied in 663 patients. LRC and disease-free survival (DFS) were calculated using the Kaplan-Meier method. Cox regression model was applied in the univariate and multivariate analyses to recognize the recurrence risk factors., Results: With the median follow-up duration of 93 months (range, 5-168 months), 78 patients (5.3%) failed to secure LRC and 220 patients (14.9%) experienced any recurrence. The 7.7-year LRC and DFS was 94.9% and 85.4% respectively in the entire cohort. PMRT significantly improved 7.7-year LRC from 93.4% to 96.6% (p = 0.005), but not the DFS (p = 0.335). Multivariate analysis revealed that PMRT was an independent prognostic factor of LRC (p < 0.001), meanwhile, age ≤ 40 years (p = 0.012), histological grade 3 (p = 0.004), 2-3 positive nodes (p < 0.001) and tumor size of 3-5 cm (p = 0.045) were significantly associated with decreased LRC. The 7.7-year LRC for patients with 0, 1, and 2-4 risk factors was 97.7% / 98.9% (p = 0.233), 95.3% / 98.0% (p = 0.092), and 80.3% / 94.8% (p < 0.001) in the non-PMRT and PMRT group, respectively., Conclusions: In patients with T1-2N1 breast cancer, clinical-pathological factors including young age, histological grade 3, 2-3 positive nodes, and tumor size of 3-5 cm were identified to be predictors of a poorer LRC following mastectomy. Patients with 0-1 risk factor might consider the omission of PMRT., (© 2021. The Author(s).)

Background: Ductal carcinoma in situ with microinvasion (DCISM) represents ~1% of all breast cancer cases and is arguably a more aggressive subtype of ductal carcinoma in situ (DCIS). Lacking studies with a large population, the survival outcomes of DCISM are still poorly understood and the treatment recommendations remain controversial. This study aims to investigate the long-term outcome of patients with DCISM, potential risk factors for their prognosis, and the difference of survival between patients treated with breast-conserving surgery plus radiotherapy (BCT + RT) and mastectomy only., Methods: In total, 1299 patients from 2008 to 2019 with DCISM were retrospectively retrieved. Clinicopathological features were analyzed. Subgroup analysis was conducted between patients who underwent BCT + RT and mastectomy only. Univariate and multivariate analyses were performed to identify prognostic factors for survival. Differences of survival between two groups were compared using the log-rank test., Results: Totally, 1286 patients had follow-up information, the median follow-up is 54.57 months, the 5-year local-regional-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 98.6%, 97.1%, and 99.4%, respectively, two deaths were due to breast cancer. Multivariate analysis identified age <40 (p = 0.028) and close margin (≤2 mm) as independent negative prognostic factors for LRFS. No prognostic factors were identified for DMFS and OS. The 5-year LRFS, DMFS, and OS of patients who had DCIS component ≥5 cm and underwent mastectomy without adjuvant radiotherapy were 100%, 98.4%, and 98.4%, respectively. After propensity score matching (PSM), no survival difference was observed between patients treated with BCT + RT or mastectomy only., Conclusions: DCISM patients had a good survival, even those with DCIS component ≥5 cm. Patients aged <40 or with close margin (≤2 mm) had a poorer LRFS, but not DMFS or OS. BCT + RT is a feasible choice for DCISM patients., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: To investigate the impact of biological subtypes in locoregional recurrence in Chinese breast cancer patients receiving postmastectomy radiotherapy (PMRT)., Methods and Materials: About 583 patients who received postmastectomy radiation between 2010 and 2012 were retrospectively analyzed. According to immunohistochemical staining profile, patients were classified into: Luminal A-like, Luminal B-like, HER2-positive, and triple-negative breast cancer (TNBC). Local and regional recurrence (LRR) cumulative incidences were calculated by competing risks methodology and the power of prognostic factors was examined by Gray's test and the test of Fine and Gray., Results: The median follow-up was 70.9 months. About 34 LRR events occurred. For Luminal A, Luminal B, HER2-positive, and TNBC patients, the 5-year LRR cumulative incidence rates were 1.57%, 4.09%, 10.74%, and 10.28%. Compared with Luminal A, HER2-positive subtype and TNBC had a significant increased risk of LRR (HR was 5.034 and 5.188, respectively). In univariate analysis, predictive factors for higher LRR were HER2-positive subtype (HR = 4.43, P < .05), TNBC (HR = 4.70, P < .05), and pN3 (HR = 5.83, P < .05). In the multivariate model, HER2-positive subtype (HR = 5.034, P < .05), TNBC (HR = 5.188, P < .05), and pN3 (HR = 9.607, P < .01) were independent predictors of LRR. LRR without trastuzumab was similar to that of TNBC (without vs TNBC, 17.88% vs 10.28%, P > .05) in HER2-positive subtype patients, while LRR with trastuzumab was approximate to Luminal A (with vs Luminal A, P > .05). Additionally, endocrine therapy also significantly reduced LRR incidence in the luminal subtype cohort (without vs with therapy, 6.25% vs 2.89%, HR = 0.365, P < .1)., Conclusions: Biological subtype was a prognostic factor of LRR in the PMRT setting among Chinese breast cancer patients., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Regional nodal irradiation (RNI) improves disease outcome in breast cancer patients, but the contribution of internal mammary node irradiation (IMNI) in the context of modern systemic treatment is still controversial. The aim of our study is to evaluate the effect of IMNI in patients with modern systemic treatment in real-world setting., Methods: We retrospectively analyzed patients with primary breast cancer treated with surgery followed by adjuvant chemotherapy and adjuvant chestwall/breast irradiation and RNI from 5/2007-12/2010. RNI was delivered to the ipsilateral supraclavicular region and infraclavicular region + / - IMNs. We separated two groups based on the presence and the absence of IMNI. The primary end point was disease-free survival (DFS). DFS and overall survival (OS) were evaluated with Kaplan-Meier method. Differences between two groups were compared with the log-rank test (p < 0.05 considered significant). We used two methods to account for potential confounders: propensity score matching (PSM) and Cox regression analysis., Results: We analyzed 872 patients who received RNI with IMNI (n = 390) or without IMNI (n = 482). Median radiation dose was 50 Gy. Median follow-up was 98 months. IMNI improved 8-year DFS rates versus no IMNI: 75.9% and 64.9% (p < 0.001). After PSM, baseline characteristics were well balanced between the two groups. IMNI significantly improved DFS (p < 0.001) in patients after PSM. IMNI was an independent prognostic factor for DFS., Conclusions: In this study, we found that IMNI improved DFS and OS in breast cancer patients in the context of modern systemic treatment. These data continue to support that IMNI is a key component of RNI.

Objective: The aim of this study was to determine the impact of postmastectomy radiotherapy (PMRT) on reoperation rates in women with breast cancer undergoing mastectomy and breast reconstruction., Methods: Between June 2001 and December 2015, 832 breast cancer patients treated with mastectomy and breast reconstruction with (n = 159) or without (n = 673) PMRT were analyzed retrospectively. Reoperations following breast reconstruction were categorized into the following three types: anticipated, unanticipated, and others. Multivariable logistic regression models were used to evaluate the impact of PMRT on overall and unanticipated reoperations according to different breast reconstruction types after adjusting for relevant covariates., Results: With a median follow-up of 58.5 months, a total of 1298 operations were performed in 832 breast cancer patients. The rates of overall and unanticipated reoperations were 46.2% and 7.7%, respectively. Multivariable analysis showed that PMRT was not associated with overall reoperations in either implant-based reconstruction patients (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.43-2.37, p = 0.995) or autologous reconstruction patients (OR 0.85, 95% CI 0.52-1.40, p = 0.533); however, the impact of PMRT on unanticipated reoperations differed by reconstruction type. In patients who received implant-based reconstructions, PMRT was associated with a 3.05-fold (95% CI 1.20-7.75, p = 0.019) higher odds of unanticipated reoperations, while there was no difference in patients who underwent autologous reconstruction (OR 1.17, 95% CI 0.51-2.66, p = 0.713). Delayed reconstruction or delayed-immediate reconstructions were associated with an increased risk of both overall and unanticipated reoperations in both reconstruction cohorts., Conclusions: PMRT appears to be associated with an increased risk of unanticipated reoperations among patients receiving implant-based reconstruction, but not among those receiving autologous reconstruction. The risk of reoperation should be taken into consideration when selecting the appropriate breast reconstruction type when PMRT is planned.

Purpose: The indication for internal mammary node irradiation (IMNI) after preoperative systemic therapy in breast cancer remains vague. This study was designed to evaluate the effect of IMNI in patients with clinical stage II-III breast cancer after preoperative systemic therapy and surgery., Methods and Materials: Between August 2005 and December 2013, 497 patients with clinical stage II-III breast cancer underwent anthracycline- or taxane-based preoperative systemic therapy, surgery, and postoperative radiation therapy. A median dose of 50 Gy (range, 46-60 Gy) in 25 fractions was delivered to the chest wall or breast with IMNI (n = 236) or without IMNI (n = 261). Disease-free survival (DFS) and overall survival (OS) rates with or without IMNI were evaluated using the Kaplan-Meier method and compared with the log-rank test. Propensity score matching was performed to adjust for the unbalanced characteristics between the 2 groups. Prognostic factors associated with survival were evaluated by univariate and multivariate analysis., Results: The median follow-up time was 64 months. Patients with IMNI presented with more advanced clinical T stage, pathologic N stage, positive lymph-vascular invasion, and medically or centrally located disease (P < .05). The 5-year DFS and OS rates were 73.7% and 86.3% in the IMNI group and 71.5% and 86.7% in the non-IMNI group, respectively (P > .05). Multivariate analysis demonstrated that IMNI was an independent prognostic factor for DFS (P = .018) and resulted in a borderline improvement in OS (P = .067). After propensity score matching, characteristics were well balanced. The 5-year DFS rates of IMNI and non-IMNI group were 76.8% and 63.4%, respectively (P = .030), and the 5-year OS rates were 88.9% and 84.1%, respectively (P = .083). IMNI was independently prognostic for DFS (P = .014) and OS (P = .047) in matched patients., Conclusions: IMNI improves survival outcomes in patients with clinical stage II-III breast cancer after preoperative systemic therapy. Further prospective studies are warranted to identify the role of IMNI in the preoperative systemic therapy setting., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objective: Dysregulation of DNA polymerase iota (Pol ι) in breast cancer might contribute to the accumulation of genomic mutations and promotes breast cancer progression. In this study we explored the clinical relevance and biological function of Pol ι in breast cancer., Methods: qRT-PCR was used to determine the expression levels of Pol ι in 31 breast cancer tissues. Then the stable overexpression of Pol ι and knockdown of Pol ι breast cancer cell lines were constructed. Wound-healing assay and transwell assay were performed to evaluate cell migratory and invasiveness, respectively. Signaling pathway was analyzed by western blot., Results: The expression levels of Pol ι is overexpressed in breast cancer tissues and significantly higher in breast cancer tissues with lymph node metastasis compared to those without lymph node metastasis. Elevated Pol ι expression promoted migratory and invasiveness of breast cancer cells. Signaling pathway analysis indicated EGFR-ERK cascade works as a mediator of Pol ι-induced EMT of breast cancer cells., Conclusions: These data demonstrate the underlying mechanism by which Pol ι promotes breast cancer progression, suggesting that Pol ι may be a potential therapeutic target against breast cancer.

BACKGROUND This study aimed to evaluate differences in the radiosensitivities of triple-negative breast cancer (TNBC) and luminal-type breast cancer cells and to investigate the effects of estrogen receptor (ER) expression on the biological behaviors of the cells. MATERIAL AND METHODS Colony-forming assays were performed to detect differences in radiosensitivities in breast cancer cell lines. Gene transfection technology was used to introduce the expression of ERα in TNBC cells to compare the difference in radiosensitivity between the TNBC cells and ERα transfected cells. CCK-8 assays were used to observe changes in the proliferation of TNBC cells after ERα transfection. Immunofluorescence was used to detect the number of γH2AX foci in nuclei. Flow cytometry was used to detect changes in cell cycle distribution and apoptosis. Western blotting was used to detect changes in autophagy-associated proteins. RESULTS The radioresistance of the TNBC cell line MDA-MB-231 (231 cells) was greater than that of ERα-positive luminal-type breast cancer cell line MCF-7. Moreover, 231 cell proliferation and radioresistance decreased after ERα transfection. Interestingly, ERα-transfected 231 cells showed increased double-stranded breaks and delayed repair compared with 231 cells, and ERα-transfected 231 cells showed increased G2/M phase arrest and apoptosis after irradiation compared with those in 231 cells. ERα transfection in 231 cells reduced autophagy-related protein expression, suggesting that autophagy activity decreased in 231 ER-positive cells after irradiation. CONCLUSIONS TNBC cells were more resistant to radiation than luminal-type breast cancer cells. ERα expression may have major roles in modulating breast cancer cell radiosensitivity.

Growing evidence has demonstrated that human epidermal growth factor receptor 2 (HER2) is involved in the radiation response to breast cancer. However, the underlying mechanism remains elusive. Therefore, we investigated if HER2 overexpression is associated with radiosensitivity of breast cancer. We constructed breast cancer cell lines differing in HER2 expression by transducing HER2 cDNA or short hairpin RNA against HER2. We then assessed the radiosensitivity and investigated the potential mechanism by using cell proliferation assay, cell adhesion assays, anoikis assays, colony formation assays, and western blotting analyses. We found that HER2 introduction in breast cancer cell lines MCF-7 (low HER2 expression) and MDA-MB-231 (HER2 is not expressed) promoted cell proliferation and invasion and enhanced cell adhesion and resistance to anoikis. Moreover, HER2 reduced radiosensitivity in these two cells compared with the corresponding control. The opposite results were observed when HER2 was silenced in breast cancer cell lines ZR-7530 and SK-BR-3 (both cells with high expression of HER2) using HER2 shRNA. In addition, animal experiment results showed HER2 could enhance the radioresistance of xenograft tumors. Further studies showed HER2 promoted the phosphorylation of focal adhesion kinase (Fak) and thereby up-regulated the expression of proteins associated with the epithelial-to-mesenchymal transition such as Claudin-1, ZO-1, and ZEB-1. The inhibition of Fak activity using the Fak inhibitor (PF-562281) restored the radiosensitivity in HER2-overexpressing cells. In conclusion, HER2 reduces the radiosensitivity of breast cancer by activating Fak in vitro and in vivo. Fak might be a potential target for the radiosensitization of HER2-overexpressed breast cancer., Competing Interests: The authors declare no conflicts of interest.

To evaluate the value of F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-FDG PET/CT) and pretherapeutic Ki67 in predicting pathologic response in locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC).As a training set, total 301 LABC patients treated with NAC were retrospectively analyzed to evaluate the potential predictive value of pretherapeutic Ki67 for pathologic complete response (pCR) after NAC. Another 60 LABC patients were prospectively included as a validation set to evaluate the value of Ki67 combined PET/CT as pCR predictors. Ki67 was assessed in pretherapy core needle biopsy specimens and PET/CT scans were performed at baseline (before initiating NAC), after the 2nd, and 4th cycle of NAC. Maximum standardized uptake value (SUVmax) and its changes relative to baseline (ΔSUVmax%) were used as parameters of PEC/CT.In the training set, Ki67 was a predictor of pCR to NAC, with area under the curve (AUC) of 0.624 (P = 0.003) in receiver-operating characteristic (ROC) analysis. In the validation set, Ki67 alone did not show significant value in predicting pCR in the validation set. ΔSUVmax% after then 2nd or 4th course are predictors of pCR to NAC with the AUC of 0.774 (P = 0.002) and 0.791 (P = 0.002), respectively. When combined with ΔSUVmax% after the 2nd and 4th course NAC, Ki67 increased the value of ΔSUVmax% in predicting pCR with the AUC of 0.824 (P = 0.001). Baseline SUVmax and after 2nd, 4th course NAC had no predictive value for pCR, but SUVmax after the 2nd and 4th course showed remarkable predictive value for nonpathologic response (Grade 1 in Miller-Payne Grading System) with the AUC of 0.898 (P = 0.0001) and 0.801 (P = 0.003).Both PET/CT and Ki67 can predict pCR to NAC in LABC patients in the early phases of treatment. PET/CT combined Ki67 is a better pCR predictor for response to NAC. This helps the physician to predict the probability of pCR, and facilitates the optimization of individual treatment plan in case of ineffective and/or excessive chemotherapy.

Purpose: To present the clinical experience in our cancer center with multibeam inverse intensity-modulated radiotherapy (IMRT) for early stage breast cancer (BC) patients with whole breast irradiation (WBI)., Methods: We retrospectively analyzed 622 patients with Stage 0 to III BC treated from 2008 to 2011 with wide local excision and WBI, using an inverse IMRT technique. All of the patients were prescribed a total dose of 50 Gy to the whole breast in 2-Gy fractions, followed by a tumor bed boost of 10 Gy in 5 fractions using an electron beam., Results: Of all of the patients, 132 (21.2%) received whole breast plus regional lymph node (RLN) irradiation. 438 of 622 patients had records of acute skin toxicity based on common terminology criteria (CTC) for adverse events. Two hundred eighty (64%) patients had Grade 0/1 toxicity, 153 (35%) had Grade 2 and only 4 patients experienced grade 3 toxicity. Seventy patients (16%) had moist desquamation. Univariate analysis revealed that breast planning target volume was the only predictive factor for Grade ≥2 acute dermatitis (P = 0.002). After 4 years, 170 patients reported cosmetic results by self-assessment, of whom 151 (89%) patients reported good/excellent cosmetic results, and 17 (11%) patients reported fair assessments. For invasive cancer, the four-year rate of freedom from locoregional recurrence survival was 98.3%. Regarding carcinoma in situ, no patients experienced recurrence., Conclusions: BC patients who underwent conservative surgery followed by inverse IMRT plan exhibited acceptable acute toxicities and clinical outcomes. Longer follow-up is needed.

There has not been a clear answer about the efficacy of intraoperative radiotherapy (IORT) for women with early-stage breast cancer.The aim of this meta-analysis was to summarize the available evidence comparing the efficacy and safety of IORT with those of whole-breast external beam radiotherapy (EBRT) for women with early-stage breast cancer.MEDLINE, EMBASE, the Web of Science, and the Cochrane Library were searched up to October 2014. Two authors independently conducted the literature selection and data extraction.Studies that compared IORT with whole-breast EBRT were included in the systematic review. IORT was defined as a single dose of irradiation to the tumor bed during breast-conserving surgery rather than whole-breast irradiation.Qualities of RCTs were evaluated according to the PEDro scale. Qualities of non-RCTs were evaluated according to the Methodological Index for Non-Randomized Studies (MINORS). The risk ratios (RRs) of ipsilateral breast tumor recurrence, overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were pooled using a random-effects model.Four studies with 5415 patients were included in this meta-analysis, including 2 randomized controlled trials (RCTs) and 2 non-RCTs. Ipsilateral breast tumor recurrence was significantly higher in patients with IORT compared to those with whole-breast EBRT (RR 2.83, 95% CI 1.23-6.51), but with significant heterogeneity (I = 58.5%, P = 0.065). Comparing IORT with whole-breast EBRT, the pooled RRs for overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were 0.88 (95% CI: 0.66-1.17), 1.20 (95% CI: 0.77-1.86), 0.76 (95% CI: 0.44-1.31), and 0.95 (95% CI: 0.61-1.49), respectively.IORT had a significantly higher risk of ipsilateral breast tumor recurrence than whole-breast EBRT. Overall mortality did not differ significantly. IORT should be used in conjunction with the prudent selection of suitable patients. It is imperative to identify women with a low risk of local recurrence.

The study compares the physical and biologically effective doses (BED) received by the heart and cardiac substructures using three-dimensional conformal RT (3D-CRT), intensity-modulated radiotherapy (IMRT), and simple IMRT (s-IMRT) in postoperative radiotherapy for patients with left-sided breast cancer. From October 2008 to February 2009, 14 patients with histologically confirmed left-sided breast cancer were enrolled and underwent contrast-enhanced computed tomography (CT) simulation and 18F-FDG positron emission tomography-CT to outline the left cardiac ventricle (LV) and other substructures. The linear-quadratic model was used to convert the physical doses received by critical points of inner heart to BED.The maximal dose, minimum dose, dose received by 99% of volume (D99) and dose received by 95% of volume (D95) in target areas were significantly better using IMRT and s-IMRT when compared with 3D-CRT (P < 0.05). IMRT and s-IMRT significantly reduced the maximal cardiac dose (5038.98 vs 5346.47 cGy, P = 0.002; 5146.66 vs 5346.47 cGy, P = 0.03). IMRT reduced the maximal dose to LV by 4% (P = 0.05) in comparison with 3D-CRT. The average doses to heart and LV in 3D-CRT plan were significantly lower than those in IMRT plan (P < 0.05). The average cardiac volumes receiving ≥25 Gy (V25 Gy) in IMRT, s-IMRT, and 3D-CRT plans were 73.98, 76.75, and 60.34 cm, respectively. The average LV volumes receiving ≥25 Gy (V25 Gy) in IMRT, s-IMRT and 3D-CRT plans were 23.37, 24.68, and 17.61 cm, respectively. In the IMRT plan, the mean BED to the critical points of inner heart located within the high physical dose area were substantially lower than in 3D-CRT or s-IMRT.Compared with 3D-CRT technique, IMRT and s-IMRT had superior target dose coverage and dose uniformity. IMRT significantly reduced the maximal RT dose to heart and LV. IMRT and s-IMRT techniques did not reduce the volume of heart and LV receiving high doses.

Whole brain radiotherapy (WBRT) is the most widely used treatment for brain metastasis (BM), especially for patients with multiple intracranial lesions. The purpose of this study was to examine the efficacy of systemic treatments following WBRT in breast cancer patients with BM who had different clinical characteristics, based on the classification of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) and the breast cancer-specific Graded Prognostic Assessment (Breast-GPA). One hundred and one breast cancer patients with BM treated between 2006 and 2010 were analyzed. The median interval between breast cancer diagnosis and identification of BM in the triple-negative patients was shorter than in the luminal A subtype (26 vs. 36 months, respectively; P = 0.021). Univariate analysis indicated that age at BM diagnosis, Karnofsky performance status/recursive partitioning analysis (KPS/RPA) classes, number of BMs, primary tumor control, extracranial metastases and systemic treatment following WBRT were significant prognostic factors for overall survival (OS) (P < 0.05). Multivariate analysis revealed that KPS/RPA classes and systemic treatments following WBRT remained the significant prognostic factors for OS. For RPA class I, the median survival with and without systemic treatments following WBRT was 25 and 22 months, respectively (P = 0.819), while for RPA class II/III systemic treatments significantly improved OS from 7 and 2 months to 11 and 5 months, respectively (P < 0.05). Our results suggested that triple-negative patients had a shorter interval between initial diagnosis and the development of BM than luminal A patients. Systemic treatments following WBRT improved the survival of RPA class II/III patients.

Background: The objective of this study was to evaluate and identify patterns of failure and prognostic factors for locoregional recurrence (LRR) that could justify postmastectomy radiotherapy after modified radical mastectomy in patients with early stage triple-negative breast cancer., Methods: Between January 2000 and July 2007, the authors retrospectively analyzed 390 patients who had triple-negative breast cancer with T1/T2 tumors and from zero to 3 positive lymph nodes (pathologic T1-T2N0-N1) who underwent modified radical mastectomy without postmastectomy radiotherapy at the author's institution. The 5-year cumulative incidence for events was calculated using Kaplan-Meier analysis, and subgroups were compared using the log-rank test. Multivariate analysis was performed using a Cox proportional hazards model., Results: Overall, 86.4% of patients received chemotherapy. At a median follow-up of 60.5 months, the 5-year cumulative rates of local recurrence, regional recurrence, LRR, and distant metastasis were 5.4%, 4.7%, 8%, and 13.4%, respectively. On multivariate analysis, age <50 years, the presence of lymphovascular invasion, grade 3 tumor, and 3 involved lymph nodes were associated significantly with an increased risk of LRR. The 5-year LRR rate for patients who had 0 or 1 risk factor, 2 risk factors, and 3 or 4 risk factors was 4.2%, 25.2%, and 81% (P < .0001), respectively. The presence of lymphovascular invasion and having 3 involved lymph nodes were statistically significant predictors of regional recurrence, and the patients who had regional recurrence had a significantly greater risk of distant metastases compared with patients who had local recurrence (59.1% vs 20.9%; P < .0001)., Conclusions: Several risk factors were identified in this study that correlated independently with a greater incidence of LRR in patients who had early stage triple-negative breast cancer. The current results indicated that postmastectomy radiotherapy should be considered for those patients who have 2 or more of these factors., (Copyright © 2013 American Cancer Society.)