scholarly journals Local and Central Evaluation of HER2 Positivity and Clinical Outcome in Advanced Gastric and Gastroesophageal Cancer—Results from the AGMT GASTRIC-5 Registry

2020 ◽  
Vol 9 (4) ◽  
pp. 935
Author(s):  
Florian Huemer ◽  
Lukas Weiss ◽  
Peter Regitnig ◽  
Thomas Winder ◽  
Bernd Hartmann ◽  
...  
Keyword(s):  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Individual Treatment ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Negative Results ◽  
First Line Therapy ◽  
Her2 Positivity

Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still remains difficult. However, it is a crucial prerequisite for optimal treatment. The GASTRIC-5 registry was designed as an observational, multi-center research initiative comparing local and central HER2 testing. HER2 status was assessed by immunohistochemistry (IHC) and in equivocal cases (IHC score 2+) by additional in-situ hybridization. Between May 2011 and August 2018, tumor samples of 183 patients were tested in local and central pathology laboratories, respectively. Central testing revealed HER2 positivity in 38 samples (21%). Discordant HER2 results were found in 12% (22 out of 183) with locally HER2 positive/centrally HER2 negative results (9%, 17 out of 183), exceeding locally HER2 negative/centrally HER2 positive results (3%, 5 out of 183). Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870–24,530) vs. 6.9 months (95% CI: 3.980–9.820), p = 0.016). The findings of the GASTRIC-5 registry corroborate the challenge of HER2 testing in gastric/GEJ cancer and highlight the necessity for central quality control to optimize individual treatment options. Centrally HER2 positive patients not receiving trastuzumab had the worst outcome in a Western real-world gastric/GEJ cancer cohort.

Metastatic breast cancer: A regional audit of HER2 testing and trastuzumab access

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6097-6097
Author(s):  
P. Scullin ◽  
A. T. Drake ◽  
V. M. Coyle ◽  
J. J. McAleer
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Number Of Patients

6097 Background: Clinical trials have clearly established that patients receiving taxane-based chemotherapy for metastatic breast cancer (MBC) should be treated with trastuzumab if their tumour is shown to overexpress the human epidermal growth factor receptor 2 (HER2) receptor. This is based on median survival gains for patients with HER2 positive tumours treated with trastuzumab plus taxane chemotherapy compared to taxane alone. Methods: Patients commencing chemotherapy for MBC in Northern Ireland in 2004 were identified from pharmacy records. Their case notes were retrospectively reviewed to determine whether patients in routine clinical practice had HER2 testing and trastuzumab treatment if indicated. Results: One hundred and fifty six patients commenced chemotherapy, of whom 145(93%) had HER2 testing. In 69(44%) patients the HER2 result was already available at the time of this relapse. In the remaining 76(49%) patients the result became available in a median of 41.5 (range 0–368) days. Of those tested, 48 patients (33%) were HER2 positive (immuno-histochemistry 3+ or fluorescence in situ hybridization positive). Thirty eight of these patients were treated with trastuzumab, either as a single agent or in combination with chemotherapy. There were valid reasons for trastuzumab omission in 7 of 10 patients not given trastuzumab (4 given first line anthracycline-based regimen, 1 had cardiac dysfunction, 1 had extensive lung metastastes and 1 was unfit for treatment). The data were examined for variations in chemotherapy and trastuzumab use across the 4 health boards which comprise the region. The number of patients commencing chemotherapy ranged from 6.9 to 11.4 patients per 100,000 population indicating a significantly different utilisation (p<0.001). Conclusions: In our region 145 of 156 patients who received chemotherapy for MBC were tested for overexpression of the HER2 receptor (93%). Of those patients who were eligible to receive trastuzumab 31 out of 34 (91%) received trastuzumab. There were inequalities in the region regarding chemotherapy for MBC and the time required to obtain a HER2 result averaged 41.5 days. Testing of HER2 status at time of original diagnosis would streamline management of metastatic disease. No significant financial relationships to disclose.

scholarly journals Peptide Based Imaging Agents for HER2 Imaging in Oncology

2020 ◽  
Vol 19 ◽  
pp. 153601212096025 ◽  
Author(s):  
Maxwell Ducharme ◽  
Suzanne E. Lapi
Keyword(s):  
Breast Cancer ◽  
Pet Imaging ◽  
Imaging Techniques ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Cancer Type ◽  
Her2 Positive ◽  
Positron Emission ◽  
Imaging Probes

Breast cancer continues to be the most lethal cancer type in women and one of the most diagnosed. Understanding Breast cancer receptor status is one of the most vital processes for determining treatment options. One type of breast cancer, human epidermal growth factor receptor 2 (HER2) positive, has approved receptor-based therapies including trastuzumab and pertuzumab that can significantly increase the likelihood of survival. Current methods to determine HER2 status include biopsies with immunohistochemical staining and/or fluorescence in situ hybridization. However, positron emission tomography (PET) imaging techniques using 89Zr-trastuzumab or 89Zr-pertuzumab are currently in clinical trials for a non-invasive, full body diagnostic approach. Although the antibodies have strong specificity to the HER2 positive lesions, challenges involving long post-injection time for imaging due to the blood circulation of the antibodies and matching of long-live isotopes leading to increased dose to the patient leave opportunities for alternative PET imaging probes. Peptides have been shown to allow for shorter injection-to-imaging time and can be used with shorter lived isotopes. HER2 specific peptides under development will help improve the diagnosis and potentially therapy options for HER2 positive breast cancer. Peptides showing specificity for HER2 could start widespread development of molecular imaging techniques for HER2 positive cancers.

Assessment of HER2 status from an epidemiology study in tumor tissue samples of gastric and gastro-esophageal junction cancer: Spanish results of the HER-EAGLE study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4089-4089
Author(s):  
Lourdes Gomez ◽  
Angel Concha ◽  
Tomas Garcia-Caballero ◽  
Jose Ignacio Busteros ◽  
Emilio Burgos ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
International Study ◽  
Surgical Excision ◽  
Phase Iii ◽  
Her2 Status ◽  
Her2 Positive ◽  
Tissue Samples ◽  
Screening Population ◽  
Spanish Cohort ◽  
Her2 Positivity

4089 Background: Overexpression of HER2 is an important biomarker in gastroesophageal junction (GEJ) and gastric cancer (GC) and a predictive factor for trastuzumab (T, Herceptin). The ToGA phase III trial showed the benefit in overall survival of adding trastuzumab to chemotherapy inHER2-positive advanced GEJ/GC patients, following validated scoring criteria by a central laboratory. This study examines the incidence of HER2 positivity (local laboratories) in GEJ/GC according to EMA Herceptin label. Methods: HER-EAGLE was an epidemiological, non–interventional, international study assessing HER2 status by IHC/ISH in tumor samples from any stage GEJ/GC patients. Neutral buffered 10% formalin embedded tissues (surgical excision specimens or minimum 6-8 biopsies) analyzed via validated Ventana and Dako methods and scoring criteria used in ToGA: HER2-positive if IHC 3+ or IHC 2+ (FISH/SISH confirmed; HER2/CEP17 ratio ≥ 2.0); HER2-negative if IHC 0 or IHC 1+. Overall and subgroup estimates calculated with 95%CI. Data from the Spanish cohort are presented. Results: The Spanish cohort of HER-EAGLE included 1,954 participants (63.7% males) from 33 hospitals (Dec2010 to Aug2011), with 469 biopsies (24.0%) and 1,479 excisions (75.7%). Samples were 13.7% GEJ and 86.3% GC, and the adenocarcinomas were 1,137 intestinal (58.2%), 510 diffused (26.1%), 163 mixed (8.3%; Laureen classification), and 144 not available (7.3%). Median time from sampling to HER2 analysis of 5.1 years (range from days to 12 years). Total of 210 cases tested IHC 3+ (10.7%), 215 IHC 2+ (11.0%), 308 IHC 1+ (15.8%), and 1,221 IHC 0 (62.5%). Overall, HER2 positivity (IHC 3+ or IHC2+/ISH+) was 14.1% (95%CI 12.61 – 15.75). HER2 positivity by histological type was higher in intestinal adenocarcinomas (19.5%) compared to diffused (4.5%) or in mixed (9.2%). Conclusions: HER-EAGLE confirmed the feasibility of community based HER2 testing in GC as the first study with a high number of samples analyzed by local laboratories. The incidence of HER2-positivity (EMA label definition) was similar to the ToGA screening population, and it was again higher in adenocarcinomas of intestinal type (19.5%).

A prospective study of repeat endoscopic biopsy to identify HER2-positive tumors following an initial HER2-negative biopsy in unresectable or metastatic gastric cancer: Gasther-1.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 27-27 ◽  
Author(s):  
Yoon-Koo Kang ◽  
Sook Ryun Park ◽  
Young Soo Park ◽  
Jeong Hoon Lee ◽  
Baek-Yeol Ryoo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Metastatic Gastric Cancer ◽  
Tumor Location ◽  
Endoscopic Biopsy ◽  
Repeat Biopsy ◽  
Her2 Status ◽  
Her2 Positive ◽  
Initial Biopsy ◽  
Her2 Positivity

27 Background: The intratumoral heterogeneity of HER2 expression in gastric cancer (GC) is a major challenge for identifying patients (pts) who would benefit from anti-HER2 therapy. The aim of this study is to evaluate the significance of re-evaluation of the HER2 status by repeat endoscopic biopsy in pts with HER2-negative GC on initial endoscopic biopsy. Methods: Pts with unresectable or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma who would receive 1st line chemotherapy were eligible if the HER2 was negative on the initial endoscopic biopsy. HER2 positivity was defined as IHC 3+ or IHC 2+/FISH+ using the GC scoring system. A repeat endoscopic biopsy was performed in ≥6 different primary tumor sites immediately after obtaining initial HER2-negative results. Results: From May 2011 to April 2013, a total of 183 pts were enrolled. Baseline characteristics at the time of the initial biopsy were as follows: tumor location, GEJ~fundus/body~antrum/diffuse stomach = 22 (12.0%)/115 (62.9%)/46 (25.1%); Lauren classification, intestinal/diffuse/mixed = 53 (29.0%)/111 (60.7%)/19 (10.4%); and HER2 IHC score, 0/1/2 = 149 (81.4%)/26 (14.2%)/8 (4.4%). The median number of biopsy pieces was 5 (range, 1-15) and 10 (1-15) in the initial and repeat biopsy, respectively (p<0.0001). As HER2 positive tumor was identified in 16 pts, HER2 positivity rate on repeat biopsy was 8.7% (95% CI 4.6-12.8%). The detection of HER2 positivity on repeat biopsy was associated with tumor location (diffuse stomach vs others = 0% vs 11.7%, p=0.013), Bormann type (IV vs others = 0% vs 11.7%, p=0.013), and the HER2 IHC score on the initial biopsy (0 vs 1/2 = 6.7% vs 18.2%, p=0.045). In multivariate analysis, the HER2 IHC score (1/2 vs 0, OR = 3.30; p=0.041) was an independent predictor of HER2 positivity in repeat biopsy. Conclusions: In pts with metastatic or unresectable GC, repeat endoscopic biopsy could detect HER2-positive GC which initial biopsy had missed. As anti-HER2 therapy improves the survival of pts with HER2 positive GC, in pts who showed HER2 negativity on initial biopsy, repeat biopsy should be considered subsequently.

HER2-overexpression/amplification and survival in patients with resectable esophageal/gastroesophageal junction adenocarcinoma (E/GEJ-AC) treated with neoadjuvant carboplatin/paclitaxel-based chemoradiation.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 239-239
Author(s):  
Yening Feng ◽  
Cristobal Tomas Sanhueza Condell ◽  
Christopher Leigh Hallemeier ◽  
Shanda H Blackmon ◽  
Joleen M. Hubbard ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Her2 Status ◽  
Similar Proportion ◽  
Her2 Overexpression ◽  
Lower Grade ◽  
Prognostic Impact ◽  
Her2 Positive ◽  
Her2 Positivity

239 Background: After trastuzumab (T) approval for advanced HER2-positive E/GEJ-AC, HER2 testing has increased in patients (pts) with resectable disease. Neoadjuvant carboplatin/paclitaxel chemoradiation (nCP-CRT) is a common therapy approach. We performed the largest evaluation, to our knowledge, of the prognostic impact of HER2 in E/GEJ-AC pts treated with nCP-CRT. Methods: We retrospectively reviewed medical records of all trimodality-eligible (T2+ or N+) pts with E/GEJ-AC who started nCP-CRT (usually 50.4 Gy) with planned surgery at Mayo Clinic (2014-2019). HER2 was tested using standard criteria for HER2 positivity (ie, immunohistochemistry 3+ or amplification by in situ hybridization). Clinicopathologic data and time to recurrence (TTR), disease free survival (DFS), overall survival (OS), survival after recurrence (SAR), and pathologic complete response (pCR – ie, no residual tumor in primary or nodes) were collected. Kaplan Meier and multivariate Cox analysis were used. Results: Of 161 consecutive eligible pts, HER2 status was available in 107 pts (HER2-positive n=26, HER2-negative n=81) of whom n=82 had surgery and n=19 had pCR. Most tumors were clinical T3 (80%) or N+ (81%), histologic grade 3 of 3 (62%). HER2 positivity was significantly associated with lower grade, but not with age, clinical T or N, or ECOG performance status (PS). A similar proportion of HER2-positive ( vs negative) pts had surgery. Among pts who had surgery, pCR rates were lower in HER2-positive ( vs negative) pts (11% [2/19] vs 27% [17/63]). After a median follow up of 23 mo, DFS and TTR were significantly shorter in HER2 positive ( vs negative) pts, independent of other pretreatment covariables (Table). Yet OS was comparable. Lung recurrence was enriched in HER2 positive ( vs negative) pts. Among pts with recurrence, SAR was longer in HER2-positive vs -negative pts. A total of 53% (10/19) of previously HER2-positive pts received T-based therapy after recurrence, and these pts were the drivers of favorable SAR (median 22 mo in n=10 HER2-positive pts who received T vs 11 mo in n=9 HER2-positive pts who did not receive T vs 11 mo in n=40 HER2-negative pts; P log-rank=.01). Conclusions: HER2 positivity ( vs negativity) is independently associated with shorter TTR and DFS, but more comparable OS. The adverse association of HER2 on tumor response and TTR may have been largely overcome through enhanced survival after recurrence, although OS data are maturing. These data may have implications for the design of endpoints in future curative-intent anti-HER2 trials. [Table: see text]

scholarly journals Review: Radionuclide Molecular Imaging Targeting HER2 in Breast Cancer with a Focus on Molecular Probes into Clinical Trials and Small Peptides

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6482
Author(s):  
Shushan Ge ◽  
Jihui Li ◽  
Yu Yu ◽  
Zhengguo Chen ◽  
Yi Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Imaging Techniques ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Molecular Probes ◽  
Her2 Status ◽  
Developmental Trend ◽  
Her2 Positive ◽  
Monitor Treatment Response

As the most frequently occurring cancer worldwide, breast cancer (BC) is the leading cause of cancer-related death in women. The overexpression of HER2 (human epidermal growth factor receptor 2) is found in about 15% of BC patients, and it is often associated with a poor prognosis due to the effect on cell proliferation, migration, invasion, and survival. As a result of the heterogeneity of BC, molecular imaging with HER2 probes can non-invasively, in real time, and quantitatively reflect the expression status of HER2 in tumors. This will provide a new approach for patients to choose treatment options and monitor treatment response. Furthermore, radionuclide molecular imaging has the potential of repetitive measurements, and it can help solve the problem of heterogeneous expression and conversion of HER2 status during disease progression or treatment. Different imaging probes of targeting proteins, such as monoclonal antibodies, antibody fragments, nanobodies, and affibodies, are currently in preclinical and clinical development. Moreover, in recent years, HER2-specific peptides have been widely developed for molecular imaging techniques for HER2-positive cancers. This article summarized different types of molecular probes targeting HER2 used in current clinical applications and the developmental trend of some HER2-specific peptides.

HER2 testing in gastric cancer diagnosis: Insights on variables influencing HER2-positivity from a large, multicenter, observational study in Germany.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 15-15
Author(s):  
Gustavo Bruno Baretton ◽  
Hans Heinrich Kreipe ◽  
Peter Schirmacher ◽  
Timo Gaiser ◽  
Ralf D. Hofheinz ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Tumor Location ◽  
Her2 Positive ◽  
Related Factors ◽  
Multicenter Observational Study ◽  
Her2 Testing ◽  
Testing Method ◽  
Testing Rate ◽  
Gastroesophageal Junction Cancer ◽  
Her2 Positivity

15 Background: HER2 testing is routine for metastatic gastric or gastroesophageal junction cancer (mGC/GEJC). Differing HER2-positivity rates are considered to be potential indicators of inter- and intra-laboratory deviations in testing quality. The influence of patient-, sample-, or method-related factors on HER2-positivity has not been assessed systematically. Methods: This observational, prospective study collected routine HER2 test result, patient- and tumor-related factors, sample source, and testing method data to identify factors influencing HER2-positivity rates in mGC/GEJC. Influencing factors were identified using stepwise multiple logistic regression and a statistical model was developed to predict probability of HER2-positivity. Institutes with deviations in HER2-positivity rates were identified by comparing 95% confidence intervals (CI) of documented and predicted rates. Results: From Jan 2013 to Dec 2015, data were collected from 2761 mGC/mGEJC routine diagnostic specimens at 50 pathology institutes in Germany. Final analyses included 2033 specimens with HER2 test results (1554 mGC and 479 mGEJC cases). Overall HER2-positivity rates across centers was 19.8% for mGC and 30.5% for mGEJC. Lauren classification showed the highest correlation with HER2-positivity, followed by HER2 testing rate, tumor location, type of sample (resection vs biopsy), and testing method (immunohistochemistry vs fluorescence in situ hybridization) (all P < .05). Four institutes were identified with predicted HER2-positivity rates outside the 95% CI of the documented rate. Conclusions: This is the first study to report on multifactorial parameters that impact HER2-positivity rates in routine mGC/GEJC diagnostics. Results suggest that effective assessment of HER2 testing quality based on positivity rates should consider tumor characteristics, testing rate, type of specimen, and testing method, as they affect HER2-positivity. As therapy options for HER2-positive mGC/GEJC continue to evolve, reliably identifying the right patients is key.

HER2 Expression in Gastric Cancer and Gastroesophageal Junction Cancer

2020 ◽  
Vol 22 (2) ◽  
pp. 79-82
Author(s):  
Md Azizur Rahman ◽  
Abdullah Md Abu Ayub Ansari ◽  
Kazi Mazharul Islam ◽  
Md Aminur Rahman ◽  
ABM Abdul Matin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Social Impact ◽  
Gastroesophageal Junction ◽  
Treatment Protocol ◽  
Armed Forces ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Cancer Data ◽  
Her2 Positivity

Background: Carcinoma of the stomach is a major cause of cancer mortality worldwide. Due to social impact of gastric carcinoma (GC), there is a need to stratify patients into appropriate screening, surveillance and treatment programs. Although histopathology remains the most reliable and less expensive method, numerous efforts have been made to identify and validate novel biomarkers to accomplish the goals. In recent years, several molecules have been identified and tested for their clinical relevace in GC management. Among the biomarkers with the exception of HER2, none of the biomarkers is currently used in clinical practice, and some of them were described in single studies. Materials and Methods: This prospective type of observational study was performed in the Department of Surgery, Dhaka Medical College Hospital, Dhaka, 6 months from approval of protocol. Total 45 consecutive patients aged 18 years and above without consideration of gender were selected purposefully. Every patient was evaluated by clinical examination, appropriate investigations and after a confirm diagnosis of the tissue from the cancer. All patients have undergone operative intervention and Gastrectomy specimens were subtotal (including cardiac and pylorus), subtotal (including the pylorus), total radical gastrectomy and oesophago-gastrectomy sample. All specimens obtained were immersed in 10% formalin. Samples of whom were sent to the department of pathology, DMCH for histopathology examination. Portion of representative tissue/block was sent to AFIP (Armed Forces Institute of Pathology, Dhaka) for immunohistochemistry to find out the HER2 expression in gastric cancer and gastro-oesophageal cancer. Data was collected in a pre-designed questionnaire by face to face interview. Result and observation: In this study when 45 cases were categorized according to WHO grading system it was observed that majority (30) patients were found in grade II, among them 3(10%) were HER2 positive. But with grade III tumour the HER2 positivity were found more i,e; 37.5% (3/8). Grade- I tumor show HER2 neu expression 28.57% (2/7) and according to location most of the cases with HER2 positive expression was located in the gastro-esophageal junction which is 27.27% (3/11) than gastric carcinoma which is 14.70% (5/34). Conclusion: Most of the patients of gastric and gastrooesophageal junction adenocarcinoma are diagnosed at a very late stage, so they require special attention in treatment protocol, including chemotherapy and immunotherapy for increasing their survivability. The study showed with poorly differentiated (high grade) tumour, the HER2 positivity were found more. Journal of Surgical Sciences (2018) Vol. 22 (2) : 79-82

scholarly journals Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 400 ◽  
Author(s):  
Seiichiro Mitani ◽  
Hisato Kawakami
Keyword(s):  
Gastroesophageal Junction ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Drug Conjugates ◽  
Gastroesophageal Junction Cancer ◽  
Development Of Resistance ◽  
Epidermal Growth ◽  
Antibody Drug

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody–drug conjugates that are under development and have shown promising antitumor activity in early studies.

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

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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