Evaluating the role of magnetic resonance imaging post‐neoadjuvant therapy for breast cancer in the NEONAB trial
Caitlin MurphyViolet MukaroRobert ToblerRebecca AsherEmma GibbsLinda WestBruno GiuffrèSally Baron‐HayMustafa Khasraw
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Magnetic resonance imaging (MRI) accuracy after neoadjuvant systemic therapy (NST) for breast cancer varies according to hormone receptor (HR), human epidermal growth factor receptor type-2 (HER2) subtype and Ki-67 proliferation index. Whether MRI accuracy varies by genomic signatures is unknown. We examined the accuracy of MRI in the NEONAB trial (Clinicaltrials.gov #: NCT01830244).To examine the accuracy of MRI to predict pathological response to neoadjuvant therapy for breast cancer in the NEONAB trial.Patients with stages II-III breast cancer received sequential epirubicin, cyclophosphamide and nab-paclitaxel and trastuzumab if they were HER2+. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to assess the utility of preoperative MRI to predict pathological complete response (pCR). Bland-Altman plots were used to assess agreement between MRI and pathological assessment of residual disease.MRI correctly predicted pCR in 64.1% of the cohort. Sensitivity and specificity were 52% and 78%, respectively; PPV 73% and NPV 58%. MRI predicted pCR most accurately in HER2-positive patients; sensitivity 58%, specificity 100%, PPV 100% and NPV 38%. MRI had higher PPV and NPV in tumours with Ki-67 ≥ 15% than tumours with Ki-67 < 15%, 75% versus 50% and 57.5% versus 50%, respectively. In this study, MRI underestimated residual tumour size by 1.65 mm (limits of agreement: 43.07-39.77 mm).MRI appears more accurate for predicting pCR in HER2+ disease than other subtypes and in cancers with Ki-67 ≥ 15% compared to those with Ki-67 < 15%. Accuracy of MRI in our HR+, RS ≥ 25 cohort is comparable to previous reports of unselected HR+ disease. MRI post-NST should be interpreted in conjunction with HER2 status and Ki-67 index of the primary.Keywords:
Neoadjuvant Therapy
Epirubicin
Breast MRI
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The French Epirubicin Study Group carried out a randomized trial comparing epirubicin alone 75 mg/m2 with fluorouracil (5FU) 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 50 mg/m2 (FEC 50) and 5FU 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 75 mg/m2 (FEC 75) as first treatment for advanced breast cancer patients. Patients were stratified according to whether or not there were bone metastases only. Four hundred twelve patients entered this trial; 378 were assessable for tolerability and 365 for efficacy. The overall response rates were comparable between FEC 50 (44.6%) and FEC 75 (44.7%), but both were better than the epirubicin alone (30.6%) (P = .04 and P = .0006, respectively). The complete response rate was better in FEC 75 (15.5%) than in FEC 50 (7%) (P = .025) or epirubicin (4%) (P = .002). Similar results were obtained in the group of patients without bone-only metastases. No difference in the three treatments was observed in the patients with bone metastases only. Mean durations of response were similar in the three groups, being 412 days, 440 days, and 350 days for FEC 50, FEC 75, and epirubicin, respectively. Patients without previous adjuvant chemotherapy fared better than those with previous treatment (without anthracyclines). Tolerability was fair in the three groups. Overall, the epirubicin-alone group showed better tolerance than the two other groups, which did not differ significantly. Time to progression and survival were not different among the three groups, but more early relapses occurred in the epirubicin and FEC 50 groups; survival seemed to be better during the first 8 months in the FEC 75 group, and the survival difference between the epirubicin group and the FEC 75 group was of borderline significance. No difference in survival was observed between epirubicin- and FEC 50-group patients, even though the response rate was significantly worse in the monochemotherapy group.
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乳癌(BC ) 在 ≥ 被诊断；65 个岁女人在关于盒子的一半。专家们当前建议，那全身的治疗基于他们的全面条件和预期寿命与 BC 被提供给老病人，好处将超过治疗的风险，这能相当被期望。为年轻题目，相似对人的表皮的生长因素 receptor-2 (HER-2 ) 的 monoclonal 抗体， trastuzumab，代表一种有效治疗学的选择什么时候 BC 在表示上这受体。不幸地， trastuzumab 的管理与左室的机能障碍和长期的心失败(CHF ) 的出现被联系，因为有 homeostatic 的干扰，可能在心 HER-2 工作。基于登记的、回顾的分析在在没为 BC 给任何治疗的那些与 10%-15% 相比收到 trastuzumab 的老女人在 25% 附近报导了 CHF 的发生，并且 CHF 的风险被估计了在 > 更高双重；60-65 岁 trastuzumab 用户对非用户。极其先进的年龄和先存在的心脏病被显示了预先安排到 trastuzumab cardiotoxicity。因此，为有 trastuzumab 的治疗的更老的病人的选择应该主要基于他们的一般地位和 comorbidities 的存在；特别与 anthracyclines，以前的化疗应该也被考虑。一旦治疗开始了，努力应该被作保证常规心脏的监视。选择 biomarkers 的角色，例如心脏的 troponin，或新成像技术(三尺寸，织物 Doppler echocardiography，磁性的回声成像) 是有希望的，但是必须进一步在特别被调查老。而且，另外的研究被需要以便更好理解 trastuzumab 由影响旧心的机制。
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Epirubicin
Nephrology
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Objective To develop a method of determining the characteristics of epirubicin resistance and to study the reversal of such resistance in the intravesical treatment of superficial bladder cancer, using sensitive and resistant derivatives of a bladder cancer cell line in vitro . Materials and methods Epirubicin fluorescence and flow cytometry were used to measure the intracellular levels of epirubicin in both sensitive and resistant live cultured bladder tumour cells, with and without different doses of the resistance‐reversing agent verapamil. Results There was a reliable, highly significant and consistent difference in intracellular epirubicin concentration between the resistant and sensitive bladder tumour cells. In addition, it was possible to substantially reverse the features of resistant cell subline with additional verapamil. Conclusion Application of this assay to clinical specimens should allow better targeting of epirubicin intravesical chemotherapy and avoid the premature termination of such treatment in patients whose tumours remain sensitive to this agent. Furthermore, the addition of verapamil to intravesical epirubicin may permit effective treatment of those patients whose tumours have inherent or acquired resistance to epirubicin.
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To investigate the stability of epirubicin bladder instillation, prepared from two different epirubicin formulations, under refrigerated storage, transportation and clinical use conditions.A sequential study design was used. Epirubicin instillation (1 mg/mL) in polypropylene syringes was sequential incubated for periods of 84 days at 8 degrees C followed by 2 h at 25 degrees C and 1 h at 37 degrees C, the latter two temperatures replicating transport and intravesical conditions, respectively.The instillation was both chemically and physically stable under those incubation conditions. The formulation of epirubicin used to prepare the instillation infusions did not affect stability.
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A bstract : Trastuzumab (Herceptin™) is an excellent model of rationally designed targeted cancer treatment. However, less than 35% of patients with ErbB2‐positive breast tumors respond to trastuzumab as a single agent, and 2‐5% of trastuzumab‐treated patients suffer from severe side effects, including cardiac dysfunction. Recent progress in understanding the mechanisms of trastuzumab antitumor function and cellular defects leading to trastuzumab resistance is summarized. Also explored is the potential of combination therapies for reversing trastuzumab resistance.
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Abstract Trastuzumab is a biologic therapy indicated for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer and metastatic gastric cancer. Trastuzumab was originally approved as an intravenous (IV) formulation but has since been developed for subcutaneous (SC) administration for patients with HER2-positive breast cancer. Both formulations demonstrate generally comparable pharmacological and clinical profiles. Therefore, when deciding between treatment options, factors such as the route of administration, patient preference, value and cost must be considered. Studies comparing IV with SC trastuzumab indicate that each formulation offers unique advantages to patients depending on their individual needs. Concurrent with the development of SC trastuzumab, IV trastuzumab biosimilars comprise another treatment option that, in view of their reduced cost, might improve patient access and increase cost-effectiveness for healthcare providers and payers. In this review, we seek to raise awareness of the current options available for trastuzumab so that healthcare providers can optimally treat patients according to their individual situations and preferences.
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Trastuzumab is one of the most important agents that target human epidermal growth factor receptor 2, but its cardiotoxic effect limits to use it. The mechanism of cardiac dysfunction-related trastuzumab is still unclear. In literature, there is no definite information about the cumulative dose of trastuzumab for cardiotoxicity. In presented case, we reported a breast cancer patient who has been receiving long-term trastuzumab. We have not found any cardiac problems for duration of over four years. According to our case and literature review, we may say that trastuzumab is safely used with periodically echocardiographic control in patients with breast cancer.
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Weekly Trastuzumab Therapy Cannot Prevent Severe Trastuzumab-induced Thrombocytopenia: A Case Report
Abstract Background: Trastuzumab can significantly prolong the survival of patients with positive human epidermal growth factor receptor-2 breast cancer. Until now, trastuzumab has been used by millions of people, and trastuzumab-induced thrombocytopenia is rare. There is no report of acute grade 4 thrombocytopenia after weekly trastuzumab therapy. We report a breast cancer patient with severe thrombocytopenia due to trastuzumab (8mg/Kg) who experienced a recurrence of severe thrombocytopenia after attempting weekly trastuzumab therapy (4mg/Kg). Case presentation ：A 52-year-old woman with positive human epidermal growth factor receptor-2 breast cancer developed acicular rash with dense skin all over the body and gingival bleeding within 24 hours of trastuzumab infusion (8mg/Kg) and was confirmed to have severe thrombocytopenia, which was quickly recovered after high-dose corticosteroid pulse therapy. When the platelet count recovered, we tried weekly trastuzumab therapy (4mg/kg), Unfortunately, thrombocytopenia recurred within 24 hours. No third trastuzumab treatment was attempted. Conclusion: We are the first report to try weekly trastuzumab therapy after thrombocytopenia induced by first trastuzumab. The patient showed that reducing the dose of trastuzumab was ineffective in preventing trastuzumab-induced thrombocytopenia.
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