Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer

Sep 21, 2026

Helicobacter pylori is a common worldwide cause of chronic gastric infection and a leading carcinogenic factor for gastric cancer (GC). While H. pylori can drive GC in most East Asian patients, only specific GC subtypes are linked to the bacterium. Cytotoxin-associated gene A may disrupt DNA damage repair by inhibiting BRCA1/2 nuclear translocation, linking hereditary breast and ovarian cancers (HBOCs) to GC development. Using hereditary cancer genomic information, the study finds high GC incidence in HBOC families and suggests PARP inhibitors can be safe and effective for hereditary GC with BRCA1/2 mutations.

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Brief Report Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer Takuma Hayashi 1, *, Kenji Sano 2, Mako Okada 1, Manabu Muto 3 and Ikuo Konishi 1,4 Citation: Hayashi, T.; Sano, K.; Okada, M.; Muto, M.; Konishi, I. Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer. Curr. Oncol. 2024, 31, 6723–6734. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/curroncol31110496](10.3390/curroncol31110496) Received: 3 September 2024 Revised: 24 October 2024 Accepted: 25 October 2024 Published: 29 October 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Cancer Medicine, National Hospital Organization Kyoto Medical Center, Fushimi-ku, Kyoto 612-8555, Kyoto, Japan 2 Pathological Division, Shinshu University Hospital, Matsumoto 390-0877, Nagano, Japan 3 Medical Oncology, Kyoto University Hospital, Kyoto 612-8555, Kyoto, Japan 4 Department of Medical Oncology, Kyoto University School of Medicine, Kyoto 606-8507, Kyoto, Japan * [Correspondence: yoyoyo224@hotmail.com](Correspondence: yoyoyo224@hotmail.com) Abstract: Helicobacter pylori, a gram-negative, flagellated, helical bacterium, is a common cause of chronic gastric infection worldwide. According to the World Health Organization, H. pylori infection, a specific carcinogenic factor, was the leading cause of gastric cancer (GC) in 2014 worldwide (80%) . H. pylori infection causes GC in >98% of patients in East Asian countries, including Japan. However, only some types of GCs are associated with H. pylori infection. Previous clinical studies have revealed that the bacterium secretes cytotoxin-associated gene A antigen, which inhibits the nuclear translocation of the breast cancer susceptibility gene 1 and 2 (BRCA1/2), a factor involved in DNA damage repair. This indicated an association between hereditary breast and ovarian cancers (HBOCs) and the development of GC. However, the detailed mechanisms underlying the development of GC caused by H. pylori infection remain unclear. Using the information on hereditary cancers obtained based on cancer genomic medicine, this study revealed that the incidence of GC was high in families with HBOC, with a preponderance for men from families with HBOC. Furthermore, the use of polyadenosine diphosphate-ribose polymerase inhibitors in patients with hereditary GC is considered safe and effective. This study provides substantial evidence for guiding the establishment of early treatment for patients with advanced-stage/metastatic GC who harbored BRCA1/2 mutations. Keywords: gastric cancer; Helicobacter pylori; BRCA1; BRCA2; hereditary breast and ovarian cancer 1. Introduction Gastric cancer (GC) involves the uncontrolled neoplastic transformation of the mucosal epithelial cells lining the stomach wall that leads to the formation of malignant tumors, which may recur or metastasize [1] . Cancer cells proliferate and gradually invade deeper into the gastric submucosa, muscularis propria, and serosal layers. Eventually, these cancer cells may cross the serosa, spread to the surrounding areas, and invade the surrounding organs, such as the large intestine, pancreas, diaphragm, and liver. In cases of advancedstage GC, cancer cells can spread beyond the outer serosa and scatter throughout the abdomen; this phenomenon is known as peritoneal dissemination. In addition, distant metastasis can occur via lymphatic or blood flow. The common symptoms of GC include stomach pain, discomfort, heartburn, nausea, and loss of appetite [2] . Moreov

FAQs

What link does the document describe between Helicobacter pylori and hereditary breast and ovarian cancer-related gastric cancer?

The document explains that H. pylori secretes CagA, which inhibits nuclear translocation of BRCA1/2 involved in DNA damage repair. This mechanism is proposed to connect hereditary breast and ovarian cancers (HBOCs) to gastric cancer development.

What does the study report about gastric cancer incidence in hereditary breast and ovarian cancer families?

It reports a high incidence of gastric cancer in families with HBOC, with a preponderance of men from these families.

How does the document assess olaparib-based therapy for hereditary gastric cancer?

It states that polyadenosine diphosphate-ribose polymerase inhibitors are considered safe and effective, providing evidence to guide early treatment for advanced or metastatic gastric cancer with BRCA1/2 mutations.

Sep 21, 2026

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