Hints from a Female Patient with Breast Cancer Who Later Presented with Cowden Syndrome / 한국유방암학회지

A 51-year-old woman presented with metachronous tumor development in bilateral breasts, thyroid, and endometrium. Additional signs and symptoms fulfilled the National Comprehensive Cancer Network criteria for Cowden syndrome. Immunohistochemistry showed loss of PTEN expression in all tumors. Single nucleotide variants, 647 germline variants (including one each in PTEN and MSH3), and 21 somatic mutations within exons were detected in all tumors after whole-exome sequencing. There were 0, 11, and 46 specific somatic mutations in bilateral breasts, thyroid, and endometrial cancers, respectively.Although PTEN mutation is key to the development of Cowden syndrome, DNA repair dysfunction might be the initial driver of mutations. Fewer mutations were required to induce initial bilateral breast carcinomas, with subsequent thyroid and endometrial carcinomas requiring more mutations for induction. When genetic screening is unavailable, breast cancer patients with clinical manifestations of Cowden syndrome must be carefully assessed for secondary malignancies, such as thyroid and endometrial carcinomas.

Hints from a Female Patient with Breast Cancer Who Later Presented with Cowden Syndrome / 한국유방암학회지

A 51-year-old woman presented with metachronous tumor development in bilateral breasts, thyroid, and endometrium. Additional signs and symptoms fulfilled the National Comprehensive Cancer Network criteria for Cowden syndrome. Immunohistochemistry showed loss of PTEN expression in all tumors. Single nucleotide variants, 647 germline variants (including one each in PTEN and MSH3), and 21 somatic mutations within exons were detected in all tumors after whole-exome sequencing. There were 0, 11, and 46 specific somatic mutations in bilateral breasts, thyroid, and endometrial cancers, respectively.Although PTEN mutation is key to the development of Cowden syndrome, DNA repair dysfunction might be the initial driver of mutations. Fewer mutations were required to induce initial bilateral breast carcinomas, with subsequent thyroid and endometrial carcinomas requiring more mutations for induction. When genetic screening is unavailable, breast cancer patients with clinical manifestations of Cowden syndrome must be carefully assessed for secondary malignancies, such as thyroid and endometrial carcinomas.

The phase I trial

Los objetivos del estudio del estudio Fase 1 en el desarrollo de drogas anticancer son: determinar la dósis más alta tolerada, programas de administración, patrones de toxicidad, propiedades farmacoquinéticas, y si fuera posible, potencial terapéutico. Su diseño depende grandemente de datos obtenidos en el desarrollo preclínico. Muchos protocolos requieren una dósis inicial a nivel de 1/10 de la dósis letal en ratones (en mg/m2), escalando por etapas, siguiendo un esquema tipo Fibonacci, y administrando la droga una vez o diariamente por cinco días cada tres o cuatro semanas. Los estudios Fase 1 se limitan a pacientes con función hepática y renal relativametne buena y con neoplasias clínicamente estables que han sido confirmadas histológicamente y son resistentes a teapia convencional. Los hallazgos correlacionados dósis/programa con niveles plasmáticos/toxicidad son incorporados en el diseño de estudios terapéuticos subsiguientes