Correction to: Clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens in patients with advanced HER2 positive gastric cancer

81 Background: We recently reported the clinical significance of IHH in trastuzumab (T-mab) based chemotherapy using surgical specimens; namely homogeneously HER2 positive GC was associated with longer survivals compared with heterogeneously HER2 positive GC (ASCO-GI 2015). However, three quarters of patients were diagnosed as having GC by endoscopic biopsy and no data are available as to whether IHH using endoscopic biopsy specimens predict T-mab efficacy. In this study, we addressed clinical usefulness of IHH using endoscopic biopsy specimens. Methods: Patients who received T-mab based chemotherapy and had endoscopic biopsy specimens available for IHC test were retrospectively examined. When all biopsy specimens which contained cancer cells were diagnosed HER2 IHC3+, it was defined as “Inter-specimens homogeneously HER2 positive (Inter-homo)”, and the others were defined “Inter-hetero”. When all tumor cells showed HER2 overexpressed within a specimen, it was defined “Intra-specimen homogeneously HER2 positive (Intra-homo), and the others were defined “Intra-hetero”. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods and compared using the log-rank test. Results: 57 patients were enrolled in this study. The median age was 67 years old and 70% were male. PS 0, GEJ cancer, intestinal type histology, and visceral metastasis (lung or liver) were found in 74% , 25% , 60% , and 53% , respectively. After the median follow-up period of 12.1 months, the median PFS and OS were 7.6 and 16.9 months, respectively. Significant survival differences were shown only in the comparison between inter-homo and inter-hetero; inter-homo group (n = 34) showed significantly longer PFS (8.5 vs. 5.1 months, HR 0.52 95%CI 0.27-0.98, p = 0.038) and OS (27.6 vs. 12.1 months, HR 0.27 95%CI 0.12-0.61, p = 0.001), respectively. Conclusions: Our data suggest that, in contrast to surgical specimens, the assessment of HER2 heterogeneity using endoscopic biopsy specimens may be useful for negative selection of patients who are unlikely to benefit from T-mab based chemotherapy.

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Mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after trastuzumab-based chemotherapy for HER2-positive gastric cancer: a case report

Surgical Case Reports ◽

10.1186/s40792-020-0774-7 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Hiromi Nagata ◽

Hironori Tsujimoto ◽

Yoshihisa Yaguchi ◽

Keita Kouzu ◽

Yujiro Itazaki ◽

...

Keyword(s):

Gastric Cancer ◽

Rare Case ◽

Metastatic Tumor ◽

Endoscopic Biopsy ◽

Her2 Status ◽

Resected Specimen ◽

Her2 Positive ◽

Standard Regimen ◽

Mixed Adenoneuroendocrine Carcinoma ◽

Her2 Positivity

Abstract Background Trastuzumab (T-mab)-based chemotherapy is a standard regimen for human epithelial growth factor 2 (HER2)-positive gastric cancer. However, some patients have demonstrated a change in HER2 status after T-mab-based treatment of breast cancer. We report a rare case of mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after T-mab-based chemotherapy for HER2-positive gastric cancer. Case presentation A 60-year-old man presented with a mass of the upper abdomen, which was diagnosed as adenocarcinoma with a HER2 score of 3+ by endoscopic biopsy. He received seven cycles of combination chemotherapy with capecitabine, cisplatin, and T-mab. Subsequently, he underwent open total gastrectomy, distal pancreatosplenectomy, and extended left hepatic lobectomy as a conversion surgery. The surgically resected specimen demonstrated both adenocarcinoma and neuroendocrine components; therefore, it was diagnosed as HER2-negative mixed adenoneuroendocrine carcinoma. Although the patient received additional chemotherapy, multiple liver metastases appeared at 3 months postoperatively and he died at 6 months postoperatively because of the rapidly progressing metastatic tumor. Conclusions We encountered a rare case of rapidly progressive mixed adenoneuroendocrine carcinoma that was negative for HER2 expression after T-mab treatment combined with chemotherapy.

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Abstract 3772: Comprehensive characterization of the phosphoproteome of gastric cancer from endoscopic biopsy specimens

10.1158/1538-7445.am2020-3772 ◽

2020 ◽

Author(s):

Jun ADACHI ◽

Yuichi Abe ◽

Hidekazu Hirano ◽

Hirokazu Shoji ◽

Daigo Gunji ◽

...

Keyword(s):

Gastric Cancer ◽

Endoscopic Biopsy ◽

Biopsy Specimens ◽

Comprehensive Characterization

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Significance of accurate HER2 testing as a new biomarker in advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.106 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 106-106

Author(s):

Tetsuya Kusumoto ◽

Hajime Ohtsu ◽

Hiroyuki Kawano ◽

Koji Ando ◽

Satoshi Ida ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Gastroesophageal Junction ◽

Tumor Biology ◽

Japanese Patients ◽

Her2 Expression ◽

Her2 Positive ◽

Her2 Testing ◽

Gastroesophageal Junction Cancer ◽

Her2 Heterogeneity

106 Background: The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2)-positive advanced or recurrent gastric or gastroesophageal junction cancer, which demonstrated that trastuzumab plus chemotherapy improved overall survival in the overall population (hazard ratio 0.74). HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity and incomplete membrane staining. The aim of the present study was to evaluate the frequency of HER2-positive cases by application of the standard criteria in Japanese patients with advanced gastric cancer (AGC) and to investigate the relationships between HER2 expression and therapeutic responses. Methods: A total of 199 tumor samples were assessed for HER2 expression both by immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ hybridization (FISH). HER2-positive status was defined as IHC2+ and FISH-positive or IHC3+. Objective responses were evaluated in the patients with AGC who were treated with chemotherapy plus trastuzumab or chemotherapy alone based on the HER2 expression status. Results: HER2-positive tumors were identified in 12 patients (5.5%), less than 28.1% in the Japanese subgroup analyses of ToGA study. The positive rates varied with histological type; 14%, 5.3% and 0.95% in the well, moderately and poorly differentiated adenocarcinoma, respectively. Although high concordance between the results of IHC and FISH in all samples was found, IHC2+ samples retested here showed FISH-negative. Of all 10 patients with AGC, 3 patients with HER2-positive tumor were treated with capecitabine/cisplatin plus trastuzumab, and partial response was found in 2 cases; response rates were 67%. Conclusions: Specific consideration and scoring modification are required before embarking on HER2 testing in gastric cancer. Accurate and reliable HER2 testing and scoring will allow appropriate selection of patients eligible for treatment with trastuzumab.

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