Severe tinnitus and migraine headache in a 37-year-old woman treated with trastuzumab for breast cancer: A case report

BACKGROUNDTrastuzumab is a generally safe agent prescribed in the systemic treatment of breast cancer. Tinnitus is not a currently known adverse event related to trastuzumab. Here, we describe a rare case of severe tinnitus and a migraine headache induced by trastuzumab used for adjuvant therapy.CASE SUMMARYA 37-year-old woman was diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer. After surgery, she was treated with four cycles of epirubicin and cyclophosphamide; she then received docetaxel and a loading dose of trastuzumab plus pertuzumab. Less than half an hour after trastuzumab infusion, the patient complained of severe tinnitus and left-sided migraine headache. Trastuzumab monotherapy was discontinued immediately, and symptoms disappeared after 10 min. Trastuzumab was readministered, and severe tinnitus and migraine headache recurred. Trastuzumab was stopped, and severe tinnitus diminished after 10 min. Pertuzumab and docetaxel therapy was then administered, and no adverse events were observed. Subsequent infusions of trastuzumab every three weeks did not show the same symptoms.CONCLUSIONAlthough trastuzumab is well-tolerated in most patients, we should pay attention to the risk of severe tinnitus and migraine.     

辅助化疗联合曲妥珠单抗显著提高人类表皮生长因子受体过表达乳腺癌的疗效

4背景 曲妥珠单抗是拮抗人类表皮生长因子受体2（human epidermal growth factor receptor 2，HER-2）的重组单克隆抗体，该单抗在治疗HER-2过表达的晚期乳腺癌中获得了较好的临床疗效，于是国际多中心开展了NSABP B-31、NCCTG N9831和HERA随机对照研究，旨在探讨曲妥珠单抗联合辅助化疗对早期乳腺癌的有效性和安全性。     

The art of healing broken hearts in breast cancer patients: Trastuzumab and heart failure

Breast cancer, a leading cause of increased morbidity and mortality among women, overexpresses the human epidermal growth factor receptor 2 in approximately 20% to 30% of cases. Trastuzumab (Trz), a monoclonal antibody against the human epidermal growth factor receptor 2, improves survival in breast cancer patients in both the adjuvant and metastatic settings. Despite the therapeutic benefits of Trz, there is an increased incidence of cardiotoxicity, particularly when administered following anthracycline-based chemotherapy. The pathogenesis underlying Trz-mediated cardiotoxicity remains poorly understood. The present review focuses on the current understanding of Trz-mediated cardiotoxicity from both the basic and clinical science perspectives.     

Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study

Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyondprogression is associated with improved outcome. However retreatment with trastuzumab after lapatinibprogression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy inHER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods:Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated withtrastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: Themedian age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis.All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had receivedtwo lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapyline for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53patients received trastuzumab-based chemotherapy following lapatinib progression while one patient receivedtrastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine(n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression.Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39),median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months(95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions:Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treatedMBC patients.     

Surgical resection of advanced gastric cancer following trastuzumab/oxaliplatin/capecitabine combination therapy

Late-stage gastric adenocarcinoma patients have a poor prognosis because of high recurrence rates. To improve long-term outcomes, perioperative chemotherapies are combined with surgery. Human epidermal growth factor receptor 2 (HER2) overexpression had been noted in gastric cancer; therefore, trastuzumab has been used occasionally in this setting. A 63-year-old male Chinese patient, who was diagnosed with adenocarcinoma in the gastric antrum, as well as lymph node metastases along the left gastric and hepatic artery, and left adrenal area, was admitted to our hospital. HER2 expression was positive, and cluster amplification was detected in a fluorescence in situ hybridization assay. The patient received three cycles of a neoadjuvant trastuzumab/oxaliplatin /capecitabine regimen. He subsequently underwent distal gastrectomy, D2+ lymphadenectomy, left adrenalectomy, cholecystectomy and Billroth II anastomosis. Treatment was continued with another five postoperative cycles of the same medication and trastuzumab application for 1 year. No recurrence has been observed 18 mo after the operation. Trastuzumab as perioperative and adjuvant medication, in combination with oxaliplatin and capecitabine for a HER2-overexpressing advanced gastric adenocarcinoma, led to recurrence-free survival of at least 18 mo after surgery.     

HER2 testing in gastric cancer: An update

Human epidermal growth factor receptor 2(HER2) overexpression is increasingly recognized as a frequent molecular abnormality in gastric and gastroesophageal cancer. With the recent introduction of HER2 molecular targeted therapy for patients with advanced gastric cancer, determination of HER2 status is crucial in order to select patients who may benefit from this treatment. This paper provides an update on our knowledge of HER2 in gastric and gastroesophageal cancer, including the prognostic relevance of HER2, the key differences between HER2 protein expression interpretation in breast and gastric cancer, the detection methods and the immunohistochemistry scoring system.     

ERBB2-Mutated Metastatic Non–Small Cell Lung Cancer: Response and Resistance to Targeted Therapies

IntroductionErb-b2 receptor tyrosine kinase 2 gene (ERBB2) (also called HER2) has long been recognized as an oncogenic driver in some breast and gastroesophageal cancers in which amplification of this gene confers sensitivity to treatment with Erb-b2 receptor tyrosine kinase 2 (ERBB2)-directed agents. More recently, somatic mutations in ERBB2 have been reported in 1% to 2% of patients with lung adenocarcinoma. Previous case series have suggested clinical tumor responses using anti-ERBB2 small molecules and antibody therapies.MethodsHere we report the outcomes of nine patients with metastatic lung adenocarcinoma with ERBB2 mutations being treated with ERBB2-targeted therapies.ResultsFour of the nine patients had response to targeted therapies, with durations of response ranging from 3 to 10 months. We identified a de novo phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation and ERBB2 copy number gain as potential resistance mechanisms.ConclusionsWe showed patients with ERBB2-mutated lung adenocarcinoma can respond to targeted therapies, and we identified potential resistance mechanisms upon progression to targeted therapies.