Is there an association between a genetic syndrome for breast cancer and medullary nephrocalcinosis in a patient with a strong family history of breast cancer and recently diagnosed medullary nephrocalcinosis?

From the Guidelines

There is a potential association between breast cancer and medullary nephrocalcinosis through hyperparathyroidism-jaw tumor syndrome (HPT-JT), a rare autosomal dominant disorder caused by mutations in the CDC73/HRPT2 gene, and patients with a strong family history of breast cancer and recently diagnosed medullary nephrocalcinosis should be considered for genetic testing for CDC73/HRPT2 mutations. The connection between breast cancer and medullary nephrocalcinosis is thought to be related to the disruption of the tumor suppression function of the CDC73 gene, which produces parafibromin, a protein that plays a crucial role in regulating cell growth and division 1. Patients with HPT-JT typically present with primary hyperparathyroidism, which can lead to medullary nephrocalcinosis due to hypercalcemia and hypercalciuria, and they also have an increased risk of developing various tumors, including parathyroid tumors, ossifying fibromas of the jaw, renal tumors, and uterine tumors 1. Importantly, female patients with HPT-JT have an elevated risk of developing breast cancer compared to the general population, and genetic testing for CDC73/HRPT2 mutations can help identify individuals at risk 1. Management of patients with medullary nephrocalcinosis and a strong family history of breast cancer should include monitoring calcium levels, renal function, and appropriate cancer surveillance, including regular breast imaging, as well as evaluation for hyperparathyroidism with serum calcium, phosphorus, and PTH levels 1. It is essential to note that genetic testing should be performed in the context of pre- and post-test genetic counseling, and the results should be interpreted in the context of the patient's family history and medical history 1. Additionally, the American Society of Clinical Oncology (ASCO) recommends that patients with a strong family history of breast cancer or other cancers should be referred for genetic counseling and consideration of genetic testing for hereditary cancer syndromes 1.

Key Points

• Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disorder caused by mutations in the CDC73/HRPT2 gene.
• Patients with HPT-JT have an increased risk of developing various tumors, including breast cancer.
• Genetic testing for CDC73/HRPT2 mutations can help identify individuals at risk.
• Management should include monitoring calcium levels, renal function, and appropriate cancer surveillance.
• Genetic testing should be performed in the context of pre- and post-test genetic counseling.

Recommendations

• Consider genetic testing for CDC73/HRPT2 mutations in patients with medullary nephrocalcinosis and a strong family history of breast cancer.
• Monitor calcium levels, renal function, and perform appropriate cancer surveillance, including regular breast imaging.
• Evaluate for hyperparathyroidism with serum calcium, phosphorus, and PTH levels.
• Refer patients with a strong family history of breast cancer or other cancers for genetic counseling and consideration of genetic testing for hereditary cancer syndromes.

From the Research

Association Between Genetic Syndrome for Breast Cancer and Medullary Nephrocalcinosis

There is limited research directly linking a genetic syndrome for breast cancer and medullary nephrocalcinosis. However, some studies provide insight into the relationship between genetic syndromes, breast cancer, and other conditions.

• The study 2 discusses various genodermatoses with malignant potential, including Birt-Hogg-Dube syndrome, which is associated with medullary carcinoma of the thyroid and renal cell carcinoma. This suggests a possible link between genetic syndromes and kidney-related conditions.
• The study 3 outlines recommendations for genetic testing to assess hereditary risk for breast cancer, including testing for BRCA1/BRCA2 and PALB2. While this study does not specifically address medullary nephrocalcinosis, it highlights the importance of genetic testing in assessing cancer risk.
• Studies 4 and 5 focus on the association between family history and breast cancer risk, with 4 finding a >60% increased risk of breast cancer in women with a first-degree family history of breast cancer. These studies do not directly address medullary nephrocalcinosis but emphasize the significance of family history in assessing cancer risk.
• The study 6 discusses the familial atypical multiple mole melanoma (FAMMM) syndrome, which is associated with an increased risk of melanoma and pancreatic cancer. While this study does not address medullary nephrocalcinosis, it illustrates the complexity of genetic syndromes and their associations with various cancers.

Key Findings

• Genetic syndromes can increase the risk of various cancers, including breast cancer and kidney-related conditions.
• Family history is a significant factor in assessing breast cancer risk.
• Genetic testing can help identify individuals at risk for hereditary breast cancer and other conditions.
• There is limited research directly linking genetic syndromes for breast cancer and medullary nephrocalcinosis, suggesting a need for further study in this area.