Combined angiogenesis and PD-1 inhibition for immunomodulatory TNBC: concept exploration and biomarker analysis in the FUTURE-C-Plus trial.

BACKGROUND: Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients. METHODS: We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes. RESULTS: CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2-92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4-18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival. CONCLUSION: This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019.

Building radiation-resistant model in triple-negative breast cancer to screen radioresistance-related molecular markers.

BACKGROUND: To build the triple-negative breast cancer (TNBC) radiation resistance model in vitro and vivo, and screen the molecular markers that related to radiation resistance. METHODS: We used X-ray to irradiate MDA-MB-231 cells repeatedly to build radioresistant cell (231-RR), then select one gemcitabine-resistance of MDA-MB-231 cell (231-GEM). We screen differentially expressed genes of these cell lines. Then, we would select 2 genes of them associated with DNA damage repair or cell cycle, and build RNAi lentivirus vector to knock down related gene. We also used X-rays repeatedly exposure TNBC tumor xenograft to build tumor with radioresistance properties, and then verify previously screening differentially expressed genes using IHC. Finally, we used The Cancer Genome Atlas (TCGA) database to validate the relationships between radioresistance related genes and the prognosis of breast cancer. RESULTS: We got 161 up-regulated genes and 156 down-regulated genes from three cell lines. Cellular results show the 231-cell with knock-down CDKN1A or SOD2 gene, its radiation sensitivity was significantly enhanced. We successfully got the TNBC xenograft tumor with radioresistance properties. Immunohistochemical results show that the radioresistance of tumor tissue with higher p21 (CDKN1A encoding protein) and SOD2 expression (P<0.01). The prognosis of patients with low SOD2 expression is better than that of high expression, but have no statistical significance (P=0.119); patients with low CDKN1A expression is significantly better than high expression (P=0.000). Multivariate cox analysis manifest that CDKN1A gene expression level is an independent prognostic factor in breast cancer patient (P=0.008). CONCLUSIONS: Construction of radiation resistance cell and xenograft tumor with radio-resistant properties model for radiation biology research is feasible. High SOD2 and CDKN1A is associated with the poor prognosis in breast cancer patients. These two genes could be used as a predicted makers of breast cancer radiation sensitivity.

Association between breast cancer and thyroid cancer: A study based on 13 978 patients with breast cancer.

BACKGROUND: Thyroid cancer (TC) is one of the most commonly seen secondary malignancy in breast cancer (BC) survivors. MATERIALS AND METHODS: A retrospective study was conducted in BC patients in our center from 1999 to 2013. Patients were divided into BC-TC group and BC-alone group. RESULTS: In total, 13 978 BC patients were identified, among whom 247 (1.8%) had TC. The standardized incidence ratio (SIR) of TC was 4.48 compared with Chinese females, and up to 98.0% of cases were thyroid papillary carcinomas. A family history of malignancy was the only independent risk factor (odds ratio = 1.457, P = 0.025) for development of TC in patients with BC. We also identified inferior survival in patients with synchronous versus metachronous BC-TC (P = 0.016). Synchronous BC-TC (risk ratio = 5.597, P = 0.018) was an independent prognostic factor for inferior RFS. CONCLUSIONS: We observed high co-occurrence of TC in patients with BC. There might be different mechanisms behind synchronous and metachronous BC-TC.

Highlights on molecular targets for radiosensitization of breast cancer cells: Current research status and prospects.

In the past, searching for effective radiotherapy sensitization molecular targets and improving the radiation sensitivity of malignant tumors was the hot topic for the oncologists, but with little achievements. We will summarize the research results about breast cancer irradiation sensitization molecular targets over the past two decades; we mainly focus on the following aspects: DNA damage repair and radiation sensitization, cell cycle regulation and radiation sensitization, cell autophagy regulation and radiation sensitization, and radiation sensitivity prediction and breast cancer radiotherapy scheme making. And based on this summary, we will put forward some of our viewpoints.

Prognostic factors in breast phyllodes tumors: a nomogram based on a retrospective cohort study of 404 patients.

The aim of this study was to explore the independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low-risk group, while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence-free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence-free survival at 1, 3, and 5 years. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain.

Long-term results of paclitaxel plus cisplatin with concurrent radiotherapy for loco-regional esophageal squamous cell carcinoma.

AIM: To evaluate the long-term effectiveness and late toxicities of paclitaxel (PTX) plus cisplatin (DDP) with concurrent radiotherapy for locally advanced esophageal squamous cancer. METHODS: Between 2008 and 2011, 76 patients were enrolled in a phase II study on the treatment of loco-regionally advanced esophageal cancer with radiotherapy (68.4 Gy/44 fractions or 61.2 Gy/34 fractions) combined with 4-cycle chemotherapy consisting of DDP (25 mg/m2 per day for 3 d) and PTX (175 mg/m2 for 3 h). The primary endpoints were overall survival and progression-free survival, and the secondary endpoints were toxicity and the treatment failure pattern. RESULTS: A total of 76 patients were enrolled in this study, of whom 63.2% finished the whole regimen. The 5-year survival rates for the per-protocol population and intent-to-treat population were 25.4% and 26.4%, respectively, and the median survival rates were 23.7 mo and 28.5 mo, respectively. Grade 3 or 4 late toxicity was observed in only one patient (heart failure). In log-rank analysis, the pretreatment stage (stage II + III: 36.1 mo vs stage IV: 14.9 mo) and the completed cycle (1-3 cycles: 16.1 mo vs 4 cycles: 35.5 mo) were significant prognostic factors (P = 0.037 < 0.05 and P = 0.013 < 0.05). CONCLUSION: Radiotherapy combined with chemotherapy consisting of PTX and DDP is a safe and effective definitive treatment for loco-regionally advanced esophageal squamous cancer.

The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy.

MK-8776 is a recently described inhibitor that is highly selective for checkpoint kinase 1 (Chk1), which can weaken the DNA repair capacity in cancer cells to achieve chemo-sensitization. A number of studies show that MK-8776 enhances the cytotoxicity of hydroxyurea and gemcitabine without increasing normal tissue toxicities. Thus far, there is no evidence that MK-8776 can be used as a radiotherapy sensitization agent. In this study, we investigated the effects of MK-8776 on the radiosensitivity of 3 human triple-negative breast cancer (TNBC) cell lines MDA-MB-231, BT-549 and CAL-51. MK-8776 dose-dependently inhibited the proliferation of MDA-MB-231, BT-549 and CAL-51 cells with IC50 values of 9.4, 17.6 and 2.1 µmol/L, respectively. Compared with irradiation-alone treatment, pretreatment with a low dose of MK-8776 (100-400 nmol/L) significantly increased irradiation-induced γH2A.X foci in the 3 TNBC cell lines, suggesting enhanced DNA damage by MK-8776, inhibited the cell proliferation and increased the radiosensitivity of the 3 TNBC cell lines. Similar results were obtained in MDA-MB-231 xenograft tumors in nude mice that received MK-8776 (15 or 40 mg/kg, ip) 26 d after irradiation. To explore the mechanisms underlying the radio-sensitization by MK-8776, we used TEM and found that irradiation significantly increased the numbers of autophagosomes in the 3 TNBC cell lines. Moreover, irradiation markedly elevated the levels of Atg5, and promoted the transformation of LC3-I to LC3-II in the cells. Pretreatment with the low dose of MK-8776 suppressed these effects. The above results suggest that MK-8776 increases human TNBC radiosensitivity by inhibiting irradiation-induced autophagy and that MK-8776 may be a potential agent in the radiosensitization of human TNBC.

Intraoperative radiotherapy for the treatment of thyroid cancer: a pilot study.

We preliminarily evaluated the clinical feasibility and efficacy of intraoperative radiotherapy in patients with thyroid carcinoma. Nine thyroid cancer patients received intraoperative radiotherapy using an Intrabeam system. The dose was 3-4 Gy and the irradiation time ranged from 1 min 32 s to 7 min 33s. One case was a primary thyroid carcinoma, while the other cases were recurrent disease. Adverse effects, recurrence and survival were analyzed. In one patient, poorly differentiated thyroid carcinoma recurred 5 months after treatment, one patient developed a postoperative tracheal skin fistula, and one patient developed a wound infection. Because the affected areas were treated with both surgical resection and then radiotherapy, it is difficult to know which of those led to the adverse effects. Nonetheless, our results indicate that intraoperative radiotherapy can relieve the symptoms associated with thyroid cancer and improve the quality of life for these patients. It thus appears feasible to treat thyroid cancer patients with intraoperative radiotherapy.

Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy.

The benefit of adjuvant trastuzumab in disease-free and overall survival for human epidermal receptor 2-positive (HER2+) breast cancer patients is well established. However, the effect of trastuzumab on locoregional control remains unclear, particularly in patients treated with adjuvant radiotherapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER2+ breast cancer after adjuvant RT.Using a single institutional database, we identified 278 patients with stage II/III invasive HER2+ breast tumors receiving adjuvant RT between January 2008 and July 2011. We compared the locoregional outcomes of 134 patients who received trastuzumab to 144 patients without trastuzumab within the same period. Clinical and biological factors that might impact on the locoregional benefit of trastuzumab were also assessed.At the median follow-up of 45 months, trastuzumab significantly lowered the risk of locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with a more significant locoregional benefit in the hormone receptor-positive (HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and without trastuzumab (P = 0.027). For HR-/HER2+ breast tumor patients, the 3-year LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However, statistical significance was not found (P = 0.179). Both univariate and multivariate analyses confirmed that trastuzumab treatment was the only significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence interval, 1.07-15.35; P = 0.039).Adjuvant trastuzumab in addition to RT is associated with significant reduced LRR risk in HER2+ breast cancer.

Postoperative chemoradiotherapy versus chemotherapy for R0 resected gastric cancer with D2 lymph node dissection: an up-to-date meta-analysis.

BACKGROUND: This meta-analysis aims to provide more evidence on the role of postoperative chemoradiotherapy (CRT) for gastric cancer (GC) patients in Asian countries where D2 lymphadenectomy is prevalent. METHODS: We conducted a systematic review of randomized controlled trials (RCTs), extracted data of survival and toxicities, and pooled data to evaluate the efficacy and toxicities of CRT compared with chemotherapy (CT) after D2 lymphadenectomy. RESULTS: A total of 960 patients from four RCTs were selected. The results showed that postoperative CRT significantly reduced loco-regional recurrence rate (LRRR: RR = 0.50, 95 % CI = 0.34-0.74, P = 0.0005) and improved disease-free survival (DFS: HR = 0.73, 95 % CI = 0.60-0.89, P = 0.002). However, CRT did not affect distant metastasis rate (DMR: RR = 0.81, 95 % CI = 0.60-1.08, P = 0.15) and overall survival (OS: HR = 0.91, 95 % CI = 0.74-1.11, P = 0.34). The main grade 3-4 toxicities manifested no significant differences between the two groups. CONCLUSIONS: Overall, CRT after D2 lymphadenectomy may reduce LRRR and prolong DFS. The role of postoperative CRT should be further investigated in the population with high risk of loco-regional recurrence.

Incidence and risk of hypertension associated with ramucirumab in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Ramucirumab, a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting vascular endothelial growth factor receptor-2 (VEGFR-2), has been approved for the treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma. Hypertension has been described as a common adverse event with ramucirumab, but the incidence and risk have not been well determined. We conduct this meta-analysis to investigate the overall incidence and risk of developing hypertension associated with use of ramucirumab. MATERIALS AND METHODS: Databases from PubMed, Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) meeting up to May 31, 2014, were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating ramucirumab in cancer patients with adequate data on hypertension. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR), and 95% confidence intervals (CIs) by using either random--effect or fixed--effect models according to the heterogeneity of included studies. RESULTS: A total of 2,649 patients with a variety of solid tumors from eight prospective clinical trials were included in our analysis. The incidence of all--grade and high-grade hypertension associated with ramucirumab was 16.4% (95%CI: 11.9-22.3%) and 9.8% (95%CI: 7.2-13.0%), respectively. Patients treated with ramucirumab had a significantly increased risk of developing all-grade (RR: 2.28, 95%CI: 1.61-3.24, P < 0.001) and high-grade (RR: 3.59, 95%CI: 2.32-5.53, P < 0.001) hypertension compared with patients treated with control medication. No evidence of publication bias was observed. CONCLUSIONS: The use of ramucirumab is associated with a significantly increased risk of developing hypertension when compared with controls. Close monitoring and appropriate managements are recommended during the therapy.

The efficacy of postoperative radiotherapy in localized primary soft tissue sarcoma treated with conservative surgery.

BACKGROUND: To evaluate the efficacy of postoperative radiotherapy (RT) on local failure-free survival (LFFS), distant metastasis-free survival (DMFS) and overall survival (OS) in patients with localized primary soft tissue sarcoma (STS) and to identify prognostic factors. METHODS AND MATERIALS: Between January 2000 and July 2010, 220 consecutive patients with localized primary STS, who received conservative surgery with or without postoperative RT, were enrolled in the study. Survival curves were constructed by the Kaplan-Meier method and log-rank test was used to assess statistical significance. Multivariate analysis was applied to identify the prognostic factors. RESULTS: After a median follow-up of 68 months (range, 5-127 months), the 5-year LFFS, DMFS and OS were 70.0, 78.2 and 71.2 %, respectively. Tumor size, histological subtypes, margin status and postoperative RT were independent predictors for OS. Postoperative RT was associated with a significant reduced local recurrence risk versus surgery alone (hazard ratio [HR] = 0.408, 95 % confidence interval [CI] 0.235-0.707, P = 0.001), with 5-year LFFS of 81.1 and 63.6 %, respectively (log-rank, P = 0.004). The log-rank test showed that postoperative RT had a tendency of improving OS compared with surgery alone, with 5-year OS of 74.8 and 65.0 %, respectively (P = 0.089). Multivariate analysis demonstrated that postoperative RT significantly reduced mortality rate compared with surgery alone (HR = 0.512, 95 % CI 0.296-0.886, p = 0.017), especially in patients with liposarcoma (p = 0.034). CONCLUSION: Postoperative radiotherapy reduce both local recurrence and STS mortality in patients with localized primary STS. The efficacy of RT on survival warrants further prospective study.

Early Local Recurrence Presents Adverse Effect on Outcomes of Primary Breast Sarcoma: A Retrospective Study From Single Institute in China.

Primary breast sarcomas (PBSs) are spectrum heterogeneous sarcomas in breast and the optimal treatment for them is still under discussion. Our study was to investigate clinical characteristics and identify potential prognostic factors for this rare malignancy. The authors retrospectively reviewed 38 patients with PBSs between October 2000 and February 2014 in FuDan University Shanghai Cancer Center. Local control rate and overall survival (OS) were determined by Kaplan-Meier actuarial method. Univariate analysis and Cox proportional hazards model were applied to identify potential prognostic factors. With median follow-up of 40.19 months, 14 patients (14/38) were found with local recurrence. Extensive operation like mastectomy was not superior to local resection (P = 0.167). Three-year recurrence-free survival and OS rate were 61.9% and 89%, respectively. Larger tumor size and local recurrence were indicated as unfavorable prognostic factors in univariate analysis. Cox model identified narrow interval of recurrence free survival as an unfavorable factor (P = 0.048). Surgery remains crucial treatment for PBSs. Mastectomy, however, is not routinely necessary if clear margin could be achieved by local excision. Early recurrence indicates a poor OS.

Diagnostic performance of core needle biopsy in identifying breast phyllodes tumors.

BACKGROUND: A retrospective analysis of diagnoses was performed in patients with phyllodes tumors of the breast (PTB) who received preoperative core needle biopsy (CNB) and had breast surgery at Fudan University Shanghai Cancer Center from January 1, 2002 to April 1, 2013. The resulting data allowed us to compare the accordance between CNB and excision diagnoses of PTB patients and evaluate the accuracy of CNB in preoperative diagnosis. METHODS: Data from 128 patients with PTB who had undergone preoperative CNB and breast surgery were retrospectively analyzed. We reviewed the medical history, clinical follow-up data, and CNB diagnostic data. A diagnostic test was used to evaluate the sensitivity and specificity of CNB in diagnosing benign, borderline, and malignant phyllodes tumors. RESULTS: The accuracy of CNB for diagnosing PTB was 13.3% (17/128). Of the remaining patients, 98 (75.5% of the PTB patients) were diagnosed with fibroadenoma or fibroepithelial lesions. The sensitivity of CNB at diagnosing benign, borderline, and malignant phyllodes tumors were 4.9% (2/41), 4.2% (3/71), and 25.0% (4/16), respectively, whereas the corresponding specificity were 92.0%, 98.2%, and 100%, respectively. Some clinical features, such as large tumor size, rapid growth, or surgical history of fibroadenomas, were indicative of an increased possibility of PTB. CONCLUSIONS: CNB provides a pathological basis for the preoperative diagnosis of PTB, but it has a poor accuracy and offers limited guidance for surgical decisions. Considering CNB along with multiple histologic features may improve the ability to accurately diagnose PTB. An integrated assessment using CNBs in combination with clinical data and imaging features is suggested as a reliable strategy to assist PTB diagnosis.

Phyllodes tumors of the breast: diagnosis, treatment and prognostic factors related to recurrence.

Phyllodes tumors of the breast are rare tumor types that consist of 0.3-1.0% in all breast tumors. The naming and classification of breast phyllodes tumor have been debated for years. Based on the classification criteria modified by WHO in 2003, this review mainly introduced the clinicopathologic characteristics, pre-operational diagnosis and the treatment of breast phyllodes tumors, and also summarized the prognostic factors related to tumor recurrence.

Is internal mammary nodes irradiation as a part of breast cancer postoperative radiotherapy necessary?

Postoperative radiotherapy plays an important role in the multidisciplinary treatment of breast cancer. However, it remains a controversy whether it is necessary to carry out prophylactic internal mammary nodes irradiation (IMNI). This review will focus on this topic. In our opinion, the total risk of relapse should be considered during the decision-making on IMNI; in particular, IMNI is recommended for high-risk patients whose tumor is located at the central/medial area or in patients with positive axillary lymph nodes.

A Phase II Study of Concurrent Chemoradiotherapy With Paclitaxel and Cisplatin for Inoperable Esophageal Squamous Cell Carcinoma.

OBJECTIVES: A phase II study was performed to investigate the efficacy and the safety of a 3-week schedule of paclitaxel (PTX) plus cisplatin (DDP) combined with concurrent radiotherapy for esophageal squamous cell cancer. PATIENTS AND METHODS: Patients with newly diagnosed esophageal squamous cell cancer who had histologic proof of local-regional carcinoma of the esophagus, a Karnofsky performance status of 80 or greater, and normal liver, renal, and bone marrow functions were enrolled in the phase II trial. Chemotherapy consisted of DDP (25 mg/m/d) for 3 days plus PTX (175 mg/m) given for 3 hours, every 3 weeks for 4 cycles. The total dose of concurrent radiation with 68.4 Gy/44 Fx (late course-accelerated radiotherapy) or 61.2 Gy/34 Fx (conventional radiotherapy) was given at the first day of chemotherapy. RESULTS: Between July 2008 and November 2011, 76 patients were enrolled in this trial. The median age was 58 years (range, 37 to 74 y). The stages were stage II (21 patients), stage III (27 patients), and stage IV (28 patients). A total of 89.5% (68/76) and 63.2% (48/76) patients completed ≥2 cycles and all 4 cycles of chemotherapy, respectively. With the median follow-up of 36 months, the overall median survival time was 28.5 months and the progression-free survival time was 14.7 months. One- and 3-year survival rates were 75% and 41%, respectively. Neutropenia grade 3 and 4 occurred in 30.3% and 31.6% of the patients, respectively. CONCLUSIONS: Radiotherapy concurrent with a 3-week schedule of PTX and DDP resulted in an encouraging overall survival rate, but a relatively higher hematological toxicity.

Early cardiac toxicity following adjuvant radiotherapy of left-sided breast cancer with or without concurrent trastuzumab.

PURPOSE: To evaluate the influence of concurrent trastuzumab on the cardiotoxicity in patients receiving left-sided adjuvant radiotherapy. MATERIALS AND METHODS: Medical records of stage I-III left-sided breast cancer patients, including 64 receiving concurrent trastuzumab with radiotherapy and 73 receiving radiotherapy alone were retrospectively reviewed. All of the patients had normal LVEF after adjuvant chemotherapy. Information of doses volume to cardiac structures was collected. Cardiac events were assessed according to CTC 2.0. RESULTS: Median follow-up of LVEF and clinical assessment of cardiac function from the initiation of radiotherapy was 6.7 months (range 3-60.9) and 26 months (range 6.4-60.9), respectively. Grade 1 LVEF dysfunction occurred in 5 (7.8%) and 3 (4.1%) patients of the concurrent-trastuzumab and radiotherapy alone cohort, respectively. Trastuzumab was the only significant factor influencing absolute LVEF decrease in univariate analysis. In multivariate analysis of concurrent-trastuzumab cohort, IMC radiotherapy and start trastuzumab during radiotherapy were independent risk factors. For concurrent cohort, mean heart dose, as well as D10-D30, D50-D55, V5-V20 of the heart and D30-D45, D65-D75, V6-V15 of the LV were significantly higher in patients developing LVEF dysfunction. CONCLUSIONS: Concurrent trastuzumab and left-sided radiotherapy is well tolerated in terms of cardiotoxicity in patients with normal baseline cardiac function after adjuvant chemotherapy. However, increases in mean dose and low-dose volume of cardiac structures are associated with a higher risk of acute LVEF dysfunction.

Management experiences of primary angiosarcoma of breast: a retrospective study from single institute in the People's Republic of China.

BACKGROUND: Primary angiosarcoma of breast (PAOB) is a rare and highly aggressive malignancy. There is no general agreement on optimal treatments or prognostic factors for this orphan disease. The objective of this study was to investigate the clinicopathologic features and management experiences of PAOB. METHODS: We performed a retrospective review of medical and pathologic records of 17 consecutive patients diagnosed with PAOB between January 2000 and February 2014 at FuDan University Shanghai Cancer Center. We evaluated the clinical characteristics, multimodality treatments, and associated clinical outcomes. RESULTS: A total of 16 patients were included in this retrospective study (median age at PAOB presentation 33.5 years, range: 19-56 years). Palpable tumor with or without breast skin ecchymosis presented as the most common initial symptom. All patients underwent surgery with curative intent. Median disease-free survival and overall survival (OS) were 9 months and 13.6 months, respectively. One-year and 3-year disease-free survival rates were 43.8% and 6.3%, with OS rates of 93.8% and 78.1%, respectively. High histologic grade indicated poorer OS by univariate analysis (P=0.01). However, neither adjuvant chemotherapy nor radiotherapy contributed to clinical outcomes in our series. CONCLUSION: PAOB is considered as an infrequent breast neoplasm with aggressive characteristics. Histologic grade and early metastasis (within 12 months after diagnosis) are associated with poor prognosis. Regardless of grade, additional benefit was not observed with adjuvant therapy.

Development of triple-negative breast cancer radiosensitive gene signature and validation based on transcriptome analysis.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with highest loco-regional recurrence among breast cancer subtypes. Radiotherapy is indispensable for TNBC loco-regional control. However, intrinsic radiosensitivity differences exist in TNBC patients and RT is still prescribed mainly based on conventional clinicopathologic features of patients without considering the differences. The purpose of the present study is to develop and validate a TNBC radiosensitive gene signature (RSGS) and to guide therapeutic decisions. In this study, we compared transcriptome profiles of 12 locally recurrent TNBCs to 20 non-locally recurrent TNBCs treated with surgery radio-chemotherapy and developed a seven-gene RSGS and a simplified three-gene RSGS by using pathway analysis, univariate Cox proportional hazards regression model and rank-based linear algorithm. They were validated by using transcriptome profiles of 166 TNBC patients. Two gene signatures specifically identified a radiosensitive population that had an improved recurrence-free survival in patients treated with surgery radio-chemotherapy (Radiosensitive patients vs radioresistant patients, for seven-gene RSGS: P = 0.024, HR = 0.35, 95 %CI 0.14­0.87 and for three-gene RSGS: P = 0.035, HR = 0.38, 95 %CI 0.15­0.94). In contrast, there was no significant difference in outcome between predicted radiosensitive and radioresistant patients that treated with other treatment modality. RSGSs provide a useful tool for identification of radiosensitive/radioresistant TNBC patients and they could lead to a better selection of patients for RT protocols.