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Published in: Surgery Today 12/2013

01-12-2013 | Original Article

Human epidermal growth factor receptor 2 (Her-2) and S-1 adjuvant chemotherapy in stage 2/3 gastric cancer patients who underwent D2 gastrectomy

Authors: Toru Aoyama, Takaki Yoshikawa, Yohei Miyagi, Yoichi Kameda, Junya Shirai, Tsutomu Hayashi, Haruhiko Cho, Takashi Oshima, Norio Yukawa, Yasushi Rino, Munetaka Masuda, Akira Tsuburaya

Published in: Surgery Today | Issue 12/2013

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Abstract

Purposes

The trastuzumab for Gastric Cancer study newly defined tumors that were positive for human epidermal receptor-2 (Her-2) and created a Her-2-oriented treatment strategy that is also applicable in the adjuvant setting for stage 2/3 cancers. However, there is currently no information available on the rate of Her-2 positivity and the relapse-free survival (RFS) stratified by Her-2 status in stage 2/3 patients.

Methods

The Her-2 status, defined by the current standard method, was examined in 100 gastric cancer patients who underwent curative D2 surgery, who were pathologically diagnosed with stage 2/3 cancer, and received adjuvant S-1 chemotherapy between June 2002 and December 2011.

Results

Ten of the 100 patients were Her-2 positive. Her-2-positive status was more frequently seen in tumors with a differentiated histology. The 5-year RFS rate was 56.3 % in Her-2-positive cases, and 48.8 % in Her-2 negative cases, which was not significantly different (P = 0.786).

Conclusions

The Her-2-positive rate for stage 2/3 gastric cancer patients was low, at only 10 %. Although the RFS was not significantly different based on the Her-2 status, the low positive rate made interpretation difficult. A multi-center study with a large sample size is necessary to clarify the prognostic impact of Her-2 in stage 2/3 gastric cancer patients.
Literature
1.
go back to reference Ohtsu A, Yoshida S, Saijo N. Disparities in gastric cancer chemotherapy between the East and West. J Clin Oncol. 2006;24:2188–96.PubMedCrossRef Ohtsu A, Yoshida S, Saijo N. Disparities in gastric cancer chemotherapy between the East and West. J Clin Oncol. 2006;24:2188–96.PubMedCrossRef
2.
go back to reference Okines A, Verheij M, Allum W, Cunningham D, Cervantes A; ESMO Guidelines Working Group. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(suppl 5):v50–4. Okines A, Verheij M, Allum W, Cunningham D, Cervantes A; ESMO Guidelines Working Group. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(suppl 5):v50–4.
4.
go back to reference Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.PubMedCrossRef Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.PubMedCrossRef
5.
go back to reference Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;28(379):315–21.CrossRef Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;28(379):315–21.CrossRef
6.
go back to reference Hudis CA. Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med. 2007;357:39–51.PubMedCrossRef Hudis CA. Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med. 2007;357:39–51.PubMedCrossRef
7.
go back to reference Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.PubMedCrossRef Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.PubMedCrossRef
8.
go back to reference Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.PubMedCrossRef Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.PubMedCrossRef
9.
go back to reference Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, for the HERA study team, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomized controlled trial. Lancet. 2007;369:29–36.PubMedCrossRef Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, for the HERA study team, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomized controlled trial. Lancet. 2007;369:29–36.PubMedCrossRef
10.
go back to reference Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet. 2010;376:687–97.PubMedCrossRef Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet. 2010;376:687–97.PubMedCrossRef
11.
go back to reference Tsujitani S, Saito H, Wakatsuki T, Ikeguchi M, Shirabe K, Morita M, et al. Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer. Surg Today. 2012;42:225–32.PubMedCrossRef Tsujitani S, Saito H, Wakatsuki T, Ikeguchi M, Shirabe K, Morita M, et al. Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer. Surg Today. 2012;42:225–32.PubMedCrossRef
12.
go back to reference Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14:101–12.CrossRef Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14:101–12.CrossRef
13.
go back to reference Tsuburaya A, Sakamoto J, Morita S, Kodera Y, Kobayashi M, Miyashita Y, et al. A randomized phase III trial of post-operative adjuvant oral fluoropyrimidine versus sequential paclitaxel/oral fluoropyrimidine; and UFT versus S1 for T3/T4 gastric carcinoma: the Stomach Cancer Adjuvant Multi-institutional Trial Group (Samit) Trial. Jpn J Clin Oncol. 2005;35:672–5.PubMedCrossRef Tsuburaya A, Sakamoto J, Morita S, Kodera Y, Kobayashi M, Miyashita Y, et al. A randomized phase III trial of post-operative adjuvant oral fluoropyrimidine versus sequential paclitaxel/oral fluoropyrimidine; and UFT versus S1 for T3/T4 gastric carcinoma: the Stomach Cancer Adjuvant Multi-institutional Trial Group (Samit) Trial. Jpn J Clin Oncol. 2005;35:672–5.PubMedCrossRef
14.
go back to reference Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res. 1991;51:1034–8.PubMed Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res. 1991;51:1034–8.PubMed
15.
go back to reference Tanaka T, Matsuoka M, Sutani A, Gemma A, Maemondo M, Inoue A, et al. Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer. 2010;126:651–5.PubMedCrossRef Tanaka T, Matsuoka M, Sutani A, Gemma A, Maemondo M, Inoue A, et al. Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer. 2010;126:651–5.PubMedCrossRef
16.
go back to reference Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16:273–8.PubMedCrossRef Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16:273–8.PubMedCrossRef
17.
go back to reference Shitara K, Yatabe Y, Matsuo K, Sugano M, Kondo C, Takahari D, et al. Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment. Gastric Cancer. 2012. doi:10.1007/s10120-012-0179-9. Shitara K, Yatabe Y, Matsuo K, Sugano M, Kondo C, Takahari D, et al. Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment. Gastric Cancer. 2012. doi:10.​1007/​s10120-012-0179-9.
18.
go back to reference Aoyama T, Yoshikawa T, Watanabe T, Hayashi T, Ogata T, Cho H, et al. Macroscopic tumor size as an independent prognostic factor for stage II/III gastric cancer patients who underwent D2 gastrectomy followed by adjuvant chemotherapy with S-1. Gastric Cancer. 2011;14:274–8.PubMedCrossRef Aoyama T, Yoshikawa T, Watanabe T, Hayashi T, Ogata T, Cho H, et al. Macroscopic tumor size as an independent prognostic factor for stage II/III gastric cancer patients who underwent D2 gastrectomy followed by adjuvant chemotherapy with S-1. Gastric Cancer. 2011;14:274–8.PubMedCrossRef
19.
go back to reference Aoyama T, Yoshikawa T, Hayashi T, Kuwabara H, Mikayama Y, Ogata T, et al. Risk factors for peritoneal recurrence in stage II/III gastric cancer patients who received S-1 adjuvant chemotherapy after D2 gastrectomy. Ann Surg Oncol. 2012;19:1568–74.PubMedCrossRef Aoyama T, Yoshikawa T, Hayashi T, Kuwabara H, Mikayama Y, Ogata T, et al. Risk factors for peritoneal recurrence in stage II/III gastric cancer patients who received S-1 adjuvant chemotherapy after D2 gastrectomy. Ann Surg Oncol. 2012;19:1568–74.PubMedCrossRef
Metadata
Title
Human epidermal growth factor receptor 2 (Her-2) and S-1 adjuvant chemotherapy in stage 2/3 gastric cancer patients who underwent D2 gastrectomy
Authors
Toru Aoyama
Takaki Yoshikawa
Yohei Miyagi
Yoichi Kameda
Junya Shirai
Tsutomu Hayashi
Haruhiko Cho
Takashi Oshima
Norio Yukawa
Yasushi Rino
Munetaka Masuda
Akira Tsuburaya
Publication date
01-12-2013
Publisher
Springer Japan
Published in
Surgery Today / Issue 12/2013
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-013-0544-2

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