Pathological complete response to trastuzumab and paclitaxel in a patient with inflammatory local recurrence following breast conserving surgery

We encountered a case of inflammatory local recurrence of breast cancer after breast conserving surgery which attained pathological CR after combination therapy with trastuzumab and paclitaxel. The patient was a 49-year-old premenopausal woman whose left breast cancer(T2N0M0)was treated by breast conserving surgery (Bp+Ax). The pathological diagnosis was scirrhous carcinoma, g, ly1, v0, t2, n0, ER (-), PgR (+) and stage I A. Postoperatively, the residual breast was treated by 50 Gy irradiation followed by hormone therapy(Tamoxifen citrate+LH-RH analog). At 26 months after the surgery, local recurrence developed as inflammatory breast cancer. As the recurrent tumor was confirmed to be HER2-positve (3+ by IHC), combination therapy with trastuzumab and paclitaxel was started. After the 6 courses of pharmacotherapy were completed, she was judged to have clinical CR, and subsequently underwent total breast excision(Bt)and skin grafting. No visible cancer cell was observed in the resected specimens, pathological CR was diagnosed. Postoperatively, the patient is receiving trastuzumab alone every other week, and at present 10 months after the second operation, the patient is in CR status and is visiting the outpatient clinic. No severe side effects (over grade 3) from this therapy have been observed. It is suggested that combination therapy with trastuzumab and paclitaxel for inflammatory local recurrence after breast conserving surgery is a treatment of choice.     

Translational research in breast cancer

Translational research (TR) involves both the development of novel diagnostics and novel therapeutics. These two major developmental areas are often associated with each other and these associations often bring new paradigms in the management of cancer patients. For example, the development of trastuzumab-based treatments has been conducted in harmony with the development of new methodologies to assess the expression of the Her-2 gene or protein, and from this, a therapeutic modality was established for breast cancer patients as a novel and individualized treatment system. TR covers a broad spectrum, from diagnosis to treatment, and it seems to act as a catalyst for developing novel paradigms. Therefore, it is crucial to conduct TR in clinical trials, in particular, prospective clinical trials. In this regard, TR can accelerate the development of new methodologies and increase trial efficiency. In this review, we describe the importance of TR, particularly that related to novel therapeutics.     

Current status of antibody therapy for breast cancer

Antibody therapy with trastuzumab has greatly impacted breast cancer treatment. Combination treatment with trastuzumab is regarded currently as a first-line therapy for metastatic breast cancers that overexpress Her-2. It has become routine practice to examine the status of Her-2 expression in primary tumors. The impact of this therapy might be as great as that of endocrine therapy from a historical point of view. A number of new approaches using trastuzumab for seeking individualized treatment are being tested in current clinical trials. We reviewed recent advances in trastuzumab treatment and discuss the future of antibody therapy for breast cancer.     

Sensitization of chemotherapy by anti-HER

This article reviews the current state of efforts targeting human epidermal growth factor receptor-2 (erbB2/HER2)in breast cancer therapy. The results of recently conducted clinical studies with trastuzumab and several other compounds are presented. Trastuzumab, a humanised monoclonal antibody(mAb)directed against the extracellular domain of HER2, has been shown to be active against HER2-overexpressing metastatic breast cancer, either as a single agent or when used in combination with chemotherapy. In preclinical models, trastuzumab has shown additive and even synergistic anti-tumor activity with the chemotherapeutic agents. In a large, randomised, phase III trial, the combination of trastuzumab and chemotherapy was shown to improve the response rate and survival in patients with metastatic breast cancer. The high incidence of cardiotoxicity seen with the combination of trastuzumab plus anthracycline drugs prompted several clinical studies combining trastuzumab with other chemotherapeutic agents, including taxanes, vinorelbine and platinum salts. This article summarises the available data on trastuzumab-based combination chemotherapies and novel drugs targeting HER2 and signal transduction molecules for the treatment of breast cancer.     

注射用曲妥珠单抗治疗晚期乳腺癌临床验证结果

目的 验证单克隆抗体制剂注射用曲妥珠单抗(trastuzumab,商品名赫赛汀^*)对晚期乳腺癌的疗效和不良反应。方法 对经病理诊断的晚期乳腺癌应用赫赛汀^*治疗。第1次给予负荷剂量4mg／kg静脉滴注,以后剂量改为2mg／kg,每周1次。注射3个月以上评价临床疗效。结果 3l例患者中,治疗后完全缓解(CR)2例,部分缓解(PR)6例,稳定(SD)7例,进展(PD)16例,CR PR共8例,有效率为25.8％(ITT分析)。患者年龄、一般状况对疗效有一定影响,而病理类型、病变部位、既往治疗和病理her-2阳性程度对疗效无明显影响。该药不良反应轻微,而且和一般化疗不同。结论 赫赛汀^*对中国乳腺癌患者疗效肯定,安全性较好,为一较安全、有效的新型乳腺癌治疗药物。     

Metastatic breast cancer of HER2 scored 2+ by IHC and HER2 gene amplification assayed by FISH has a good response to single agent therapy with trastuzumab: A case report

We report that single agent therapy with trastuzumab had a significant effect on metastatic breast cancer, which was confirmed to be HER2 positive by Herceptest showing 2+staining, and gene amplification positively detected by FISH analysis. A 48-year-old woman underwent extended radical mastectomy (T2N0M0 stage II). Three years after the operation supraclavicular lymph node metastasis was noted. Bone scintigraphy showed metastases to the left ribs 5 years after operation. She was treated with chemo-endocrine therapy, but nonetheless could not bear the back pain caused by the bone metastases. Another chemotherapy course could not be permitted because of leukopenia. Immunohistochemistry (IHC) analysis with Herceptest showed 2+staining for HER2 and FISH analysis showed gene amplification of HER2. We started single agent therapy with trastuzumab and she subsequently had remarkably improved back pain. Physical examination and ultrasonography showed disappearance of the previous palpable supraclaviclar lymph nodes. Serum tumor markers were also reduced after the first administration of trastuzumab. The patient is currently alive, with no further progression of the lymph node or bone metastases.     

治疗乳腺癌所致的心脏毒性及评价

在乳腺癌治疗中,蒽环类药物、紫杉类药物和靶向治疗药物曲妥单抗均具有心脏毒性,第三代芳香化酶抑制剂会增加冠状动脉粥样硬化性心脏病(冠心病)的风险,放疗也会引起心脏毒性。尤其以蒽环类化疗药物及其联合化疗方案的心脏毒性最为突出。因此,早期心脏毒性的检测对于预防和治疗心脏损害至关重要,心脏毒性的评价方法有多种,如心电图、心肌活检、超声心动图等,常规超声心动图是最常用的方法,超声心动图及其新技术的应用对心脏毒性的检测有重要价值。     

A randomized phase II trial of trastuzumab plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxanes: WJOG6110B/ELTOP

BackgroundFor human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies.Patients and methodsWomen with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA.ResultsEighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55–1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26–1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX.ConclusionIn women with HER2-positive MBC previously treated with trastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX.Trial registration numberUMIN000005219.     

Cardiac toxicity in breast cancer patients: From a fractional point of view to a global assessment

When focusing on heart disease, most available studies split the two different parts of the adjuvant treatment, i.e., systemic therapies and radiation therapy, making it difficult to implement efficient strategies for preventing treatment-induced cardiac toxicity. This paper reviews the current understanding of treatments-induced cardiac toxicity in a global approach. Many factors should be considered when assessing the cardiac hazard. Treatment-related risk factors include heart dose exposure, chemotherapy, targeted agents such as HER2 inhibitors, but also endocrine agents, or anesthetic procedure. Patients’ characteristics should also be taken into account. Age, menopausal status, stress, previous history of cardiac disease, genetic profile, and body mass index could all impact on cardiac function after adjuvant therapies. Cardiac toxicity should not be analyzed as the consequence of a specific therapy, but should be considered as the result of additive or supra-additive toxicities. By this way, it will be possible to implement new strategies for preventing treatment-induced cardiac toxicity.