Breast cancer as part of Cowden syndrome

Cowden syndrome is a rare disease characterized by multiple hamartomas and increased breast, thyroid, kidney and uterine neoplasm risk. The lifetime breast cancer risk for patients with Cowden syndrome is 85%, with an average age of diagnosis between 38 and 46 years. The diagnostic criteria for Cowden syndrome have been established by the International Cowden Consortium (ICC) and the National Comprehensive Cancer Network (NCCN), and are regularly revised, but the diagnosis of Cowden syndrome remains difficult due to the variety of phenotypic and clinical features of the disease. At the same time, the genetic variants associated with Cowden syndrome analysis is not a standard for patients with breast cancer. Objective: To demonstrate the non-BRCA hereditary breast cancer detection using whole genome sequencing on the Cowden syndrome clinical case example. Materials and methods: The article describes a clinical case of a 37-year-old female patient with breast cancer, normal intelligence and phenotype, structural abnormalities of the thyroid gland (multinodular goiter). Whole genome sequencing was used to identify clinically significant genetic variants associated with hereditary tumor syndromes. Clinical case: The article presents a brief literature review on the clinical presentation of Cowden syndrome and indications for its molecular diagnosis. Also, the presented clinical case describes patient R., 37 years old female with breast cancer, who underwent treatment in the City Clinical Oncological Hospital № 1 of the Moscow City Health Department in 2021. The patient was fully examined and enrolled in the whole genome sequencing project under the Order № 69 of Moscow Healthcare Department dated February 1, 2021 «Oncogenetic research organization in Moscow». The results revealed a pathogenic variant in the PTEN gene, previously associated with Cowden syndrome. Conclusion: The use of whole genome sequencing allows to identify hereditary tumor syndromes, the clinical manifestation of which may be breast cancer.