As most erb‐b2 receptor tyrosine kinase 2 (HER2)‐positive breast cancer (BC) patients currently receive dual HER2‐targeting added to neoadjuvant chemotherapy, improved methods for identifying ...individual response, and assisting postsurgical salvage therapy, are needed. Herein, we evaluated the 41‐gene classifier trastuzumab advantage risk model (TRAR) as a predictive marker for patients enrolled in the NeoSphere trial. TRAR scores were computed from RNA of 350 pre‐ and 166 post‐treatment tumor specimens. Overall, TRAR score was significantly associated with pathological complete response (pCR) rate independently of other predictive clinico‐pathological variables. Separate analyses according to estrogen receptor (ER) status showed a significant association between TRAR score and pCR in ER‐positive specimens but not in ER‐negative counterparts. Among ER‐positive BC patients not achieving a pCR, those with TRAR‐low scores in surgical specimens showed a trend for lower distant event‐free survival. In conclusion, in HER2‐positive/ER‐positive BC, TRAR is an independent predictor of pCR and represents a promising tool to select patients responsive to anti‐HER2‐based neoadjuvant therapy and to assist treatment escalation and de‐escalation strategies in this setting.
TRAR‐low score is an independent predictor of pathological complete response (pCR) to anti‐HER2 agents in patients with HER2‐positive and ER‐positive breast cancer of the NeoSphere study. The higher risk of relapse observed in these patients likely depends on modification by treatment of tumor proliferation and ER activity. TRAR is a promising tool to assist escalation and de‐escalation of anti‐HER2‐based treatment strategies.
Summary Background Vascular endothelial growth factor (VEGF) has a crucial role in angiogenesis, and is a valid target in metastatic breast cancer. Motesanib is an investigational oral inhibitor of ...VEGF receptors. We aimed to determine whether treatment with motesanib plus paclitaxel is better than placebo plus paclitaxel in patients with HER2-negative locally recurrent or metastatic breast cancer. Methods Between Dec 1, 2006, and July 4, 2008, patients with untreated HER2-negative metastatic breast cancer were randomly assigned (using a randomisation list created by personnel not associated with the study) in a 1:1:1 ratio to paclitaxel (90 mg/m2 on days 1, 8, and 15 every 3 weeks) plus either masked motesanib 125 mg orally once per day (n=91), masked placebo orally once per day (n=94), or open-label bevacizumab 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle (n=97), after stratification according to adjuvant or neoadjuvant chemotherapy (taxane-containing regimens vs other regimens vs none), number of metastatic sites (<3 vs ≥3), and hormone receptor status (positive vs negative). Placebo was provided as a replica of motesanib 25 mg tablets. The primary endpoint was objective response rate (ORR) based on the population as assigned to treatment. This trial is registered with ClinicalTrials.gov , number NCT00356681. Findings ORRs for the motesanib group and the placebo group did not differ significantly (49% vs 41%; absolute difference 8% 95% CI −6 to 22; p=0·31). The ORR in the bevacizumab group (52%) was similar to that in the motesanib group. The most common grade 3 or higher adverse events included diarrhoea (18 of 92 patients in the motesanib group, none of 89 patients in the placebo group, and four of 96 patients in the bevacizumab group), fatigue (11, eight, and six), hypertension (11, one, and seven), and peripheral sensory neuropathy (ten, seven, and 19). More patients in the motesanib group had serious adverse events than did those in the placebo or bevacizumab groups (34, 26, and 21 patients, respectively); the most common of these in the motesanib group were gastrointestinal in nature. Interpretation Data from this trial do not support the further investigation of motesanib at this dose and schedule in this population. Funding Amgen.
Background.
This study aims to describe and compare health‐related quality of life (HRQL) in patients with node‐positive and high‐risk node‐negative HER2‐positive early breast cancer receiving ...adjuvant docetaxel and trastuzumab‐based or docetaxel‐based regimens alone.
Methods.
Eligible patients (n = 3,222) were randomly assigned to either four cycles of adjuvant doxorubicin and cyclophosphamide followed by four cycles of docetaxel (AC→T) or one of two trastuzumab‐containing regimens: adjuvant doxorubicin and cyclophosphamide followed by docetaxel plus trastuzumab administered for 1 year (AC→TH) or six cycles of docetaxel plus carboplatin combined with trastuzumab administered for 1 year (TCH). The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and BR‐23 were administered at baseline, the start of cycle 4 (mid), and the end of chemotherapy (EOC), as well as at 6, 12, and 24 months after chemotherapy.
Results.
Compliance rates for the EORTC questionnaires were acceptable at 72%–93% of eligible patients out to the 12‐month assessment. Systemic side effect (SE) change scores were significantly improved for TCH‐treated patients compared with AC→TH and AC→T at EOC, suggesting improved tolerability. Physical functioning (PF) was only slightly worse at midpoint for those receiving TCH, compared with patients who were just starting on taxane in an AC→TH regimen, but was otherwise similar between arms. All treatment arms recovered from the deterioration in SE, PF, and Global Health Scale scores by 1 year and median future perspective change scores continued to improve throughout treatment and follow‐up.
Conclusion.
HRQL outcomes for adjuvant docetaxel and trastuzumab‐based regimens are favorable and support TCH as a more tolerable treatment option.
摘要
背景： 本研究旨在对接受基于多西他赛和曲妥珠单抗或仅基于多西他赛化疗的淋巴结阳性/高危淋巴结阴性的人表皮生长因子受体2（HER‐2）阳性早期乳腺癌患者的健康相关生活质量（HRQL）进行比较和描述。
方法： 符合标准的患者（n = 3 222）被随机分组，接受4个疗程多柔比星和环磷酰胺辅助治疗继以4个疗程多西他赛化疗（AC→T）或下述2个含曲妥珠单抗的方案之一：多柔比星和环磷酰胺辅助治疗继以多西他赛和曲妥珠单抗化疗1年（AC→TH）或6个疗程多西他赛、卡铂和曲妥珠单抗联合化疗1年（TCH）。于基线、第4疗程开始时（中点）、化疗结束（EOC）和化疗结束后6个月、12个月和24个月时评测欧洲癌症研究与治疗组织（EORTC）生活质量问卷C30和BR‐23。
结果： 符合标准的患者在12个月评估时EORTC问卷的依从率良好（72%~ 93%）。EOC时，与接受AC→TH和AC→T化疗的患者相比，接受TCH化疗的患者全身不良反应（SE）变化评分显著改善，提示耐受性改善。中点时，TCH化疗患者的躯体功能（PF）仅稍劣于接受AC→TH化疗的患者（后者此时刚开始接受紫杉烷类治疗），但两组间PF相似。治疗1年时，各组患者的SE、PF和总体健康量表评分恶化均好转，对未来展望评分变化幅度的中位值在整个治疗和随访期间持续改善。
结论： 接受基于多西他赛和曲妥珠单抗辅助化疗患者的HRQL转归良好，且本研究支持TCH是一种耐受性更好的治疗选择。
In the BCIRG 006 trial, eligible patients were randomly assigned to either four cycles of adjuvant doxorubicin and cyclophosphamide followed by four cycles of docetaxel or one of two trastuzumab‐containing regimens: adjuvant doxorubicin and cyclophosphamide followed by docetaxel plus trastuzumab administered for 1 year or six cycles of docetaxel plus carboplatin combined with trastuzumab administered for 1 year. Health‐related quality‐of‐life outcomes for adjuvant docetaxel and trastuzumab‐based regimens were favorable and support docetaxel plus carboplatin combined with trastuzumab as a more tolerable treatment option.
Pt and
Pt radionuclides are therapeutically attractive Auger electron emitters with notably high Auger electron yield per decay. The present paper summarizes the first step of research on the ...applications of core-shell (Au@Pt) nanoparticles for electron Auger therapy of HER2+ (human epidermal growth factor receptor 2) breast cancer and hepatocellular carcinoma. Gold nanoparticles (30 nm) were synthesized covered with a platinum shell at high efficiency (>80%) and were further evaluated for in vitro studies such as binding affinity, internalization and cytotoxicity. To find the mechanism(s) responsible for platinum cytotoxicity in HepG2 cells, the platinum concentration in isolated cell nuclei and cytoplasm was determined using ICP-MS (inductively coupled plasma mass spectrometry). Lack of platinum in cell nuclei suggests that the cytotoxic effect is associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Studies carried out on the SKOV-3 cell line with the use of a synthesized targeting bioconjugate (Au@Pt-PEG-trastuzumab) revealed a high affinity of this preparation to HER2+ cells, its internalization, its placement in the perinuclear area and partial intranuclear location. The specific binding for HER2 negative cells, MDA-MB-231, was negligible and Au@Pt-PEG-trastuzumab did not enter these cells. The results obtained are promising and warrant future investigation of Auger electron therapy using
Pt and
Pt based radiopharmaceuticals.
ObjectiveTherapeutic management of ductal carcinoma in situ (DCIS) is heterogeneous among countries worldwide, and some treatment indications are still controversial. To investigate DCIS management ...in different countries; identify both consensual practices and controversial topics; and survey opinions about the future management of DCIS. Materials and MethodsThe Senologic International Society network members participated to an online survey using a questionnaire, between November 2021 and February 2022. ResultsTwenty-two responses from 20 different countries showed that organized breast cancer screening programs were present for 87% participants, and DCIS cases represented 13.7% of all breast cancers. Most participants used the grade classification (100%), the morphological classification (78%) and performed immunohistochemistry assays (73%). In case of conservative treatment, the mean re-excision rate was 10.3% and clear margins of mean 2.5 mm were considered healthy. Radical mastectomy rate was 35.5% with a breast reconstruction rate of 53%. Tumor bed boost indications were heterogeneous, and 73% of participants indicated hormone therapy for hormone-positive DCIS. Surgery and radiotherapy omission for some low-risk DCIS were considered by 73% of participants. Multigene assays were used by 43% of participants. Concerning future changes in DCIS management, participants mostly answered surgical de-escalation (48%), radiotherapy de-escalation (35) and/or active surveillance for some cases (22%). ConclusionThis survey provided an overview of the current practices of DCIS management worldwide. It showed that some areas are rather consensual: incidence increases over time, treatment in young women, pathological classifications, definition of healthy margins, the skin-sparing mastectomy and immediate breast reconstruction. However, some topics are still debated and result in heterogeneous practices, such as evolution in the age of diagnosis, the benefit of de-escalation in low-risk DCIS among elderly women, indications for hormone therapy, radiotherapy omission, or multigene assays. Further evidence is needed to reach consensus on these points, and innovative approaches are still under evaluation in clinical trials. The International Senologic Society, by its members, encourages precision medicine and personalized treatments for DCIS, to avoid overtreatment and overdiagnosis, and provide better healthcare to women with DCIS.
To collect cancer epidemiology data in South Eastern European countries as a basis for potential comparison of their performance in cancer care.
The South Eastern European Research Oncology Group ...(SEEROG) collected and analyzed epidemiological data on incidence and mortality that reflect cancer management in 8 countries - Croatia, Czech Republic, Hungary, Romania, Poland, Slovakia, and Serbia and Montenegro in the last 20-40 years.
The most common cancer type in men in all countries was lung cancer, followed by colorectal and prostate cancer, with the exception of the Czech Republic, where prostate cancer and colorectal cancer were more common. The most frequent cancer in women was breast cancer followed by colorectal cancer, with the exceptions of Romania and Central Serbia where cervical cancer was the second most common. Cancer mortality data from the last 20-40 years revealed two different patterns in men. In Romania and in Serbia and Montenegro, there was a trend toward an increase, while in the other countries mortality was declining, after increasing for a number of years. In women, a steady decline was observed over many years in the Czech Republic, Hungary, and Slovakia, while in the other countries it remained unchanged.
There are striking variations in the risk of different cancers by geographic area. Most of the international variation is due to exposure to known or suspected risk factors which provides a clear challenge to prevention. There are some differences in incidence and mortality that cannot be explained by exposure to known risk factors or treatment availabilities.
The objective of this study was to develop a new real time PCR-based method for quantitative detection of topoisomerase II alpha (
TOP2A) aberrations and to evaluate its clinical utility in breast ...cancer.
The method applied dually labelled hydrolysis probes and Pfaffl quantification method. The study group consisted of 83 consecutive breast cancer patients.
In the examined tumour samples median
TOP2A gene dosage was 1.08 (range 0.34–7.55).
TOP2A amplifications were found in 12 tumours (14.5%), no deletion was detected. Statistically significant positive correlation of
TOP2A gene dosage with nodal status, tumour grade, and HER2 protein status was found.
TOP2A status also correlated with disease free survival.
The newly developed real time PCR assay showed to be fast and easy to perform. Determined by the method
TOP2A gene dosage was shown to be a potent prognostic factor in breast cancer.
The main purpose of the study was to compare topoisomerase 2α (TOP2A) status in invasive breast carcinomas to the outcome of a therapy containing neoadjuvant treatment with anthracyclines (a ...combination chemotherapy treatment for breast cancer, namely AC cyclophosphamide, doxorubicin). To achieve these goals we created a method of evaluation with criteria based on two methods used in the present study (immunohistochemical IHC and fluorescence in situ hybridization FISH). The threshold for positive immunohistochemically evaluated status was set for all cases with: nuclear stain intensity score 3+ in 10% or more nuclei and nuclear stain intensity score 2+ in 50% or more nuclei. Our results suggest that TOP2A status may be used as a predictive factor for patient selection for protocols which include anthracyclines as one of the chemotherapeutics. Both methods, IHC and FISH, are suitable for implementation for diagnostic purposes, but IHC positive status measured according to the criteria presented above is the best predictor of longer disease-free survival (DFS) according to our study. Immunohistochemical also gave satisfactory results in all analyzed cases in comparison to only 60% of cases analyzed by FISH.
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