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Rates of Occult Gastric Carcinoma in Patients With Hereditary Lobular Breast Cancer Due to CDH1 Genetic Variants


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In a single-institution prospective cohort study reported in JAMA Surgery, Gamble et al found that patients with hereditary lobular breast cancer due to CDH1 variants also had a high prevalence of occult signet ring cell gastric carcinoma.

Study Details

The study involved 283 patients from 151 families with germline CDH1 pathogenic or likely pathogenic (P/LP) variants enrolled at a quaternary medical center (National Cancer Institute Center for Cancer Research) between October 2017 and January 2021. Analyses were performed in three patient groups: 1) patients with a family history of breast cancer and no gastric cancer in a hereditary lobular breast cancer group (n = 44); 2) patients with a family history of gastric cancer and no breast cancer in a hereditary diffuse gastric cancer group (n = 46); and 3) patients with a family history of both breast and gastric cancers in a mixed group (n = 193). The primary outcome measure was prevalence of occult signet ring cell gastric carcinoma in patients with hereditary lobular breast cancer.

Key Findings

The hereditary lobular breast cancer group included 31 distinct families with 19 CDH1 variants; 10 of these variants were also identified in the hereditary diffuse gastric cancer and mixed groups.

Of 32 patients in the hereditary lobular breast cancer group who underwent surveillance endoscopy, 11 (34.4%) had occult signet ring cell carcinoma (median age = 33 years, range = 27–79 years). Among 16 patients who underwent risk-reducing total gastrectomy due to underlying CDH1 P/LP, 15 (93.8%) were found to have gastric carcinoma (median age = 50 years).

In the hereditary diffuse gastric cancer group, occult carcinoma was identified in 13 (43.3%) of 30 patients who underwent surveillance endoscopy (median age = 43 years) and in 18 (94.7%; P = .98 vs hereditary lobular breast cancer group) who underwent risk-reducing gastrectomy (median age = 33 years).

In the mixed group, occult carcinoma was found in 55 (38.2%) of 144 patients who underwent surveillance endoscopy and in 83 (89.2%) of 93 who underwent total gastrectomy.

The investigators concluded, “Carriers of CDH1 P/LP variants with no family history of gastric cancer exhibited high rates of occult signet ring cell gastric cancer. Germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history. These data may prove useful for counseling families with CDH1 variants presumed to have hereditary lobular breast cancer.”

Jeremy L. Davis, MD, of the Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, is the corresponding author for the JAMA Surgery article.

Disclosure: The study was funded by the Intramural Research Program of the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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