Authors' objectives: Breast cancer is the most common malignancy and the second most common cause of cancer-related death among women. It is estimated that, in the United States alone, more than 232,000 women will be diagnosed with breast cancer in 2014, and that approximately 40,000 will die from the disease. Currently, the 5-year survival rate for breast cancer localized to the breast is more than 98%. However, this rate drops to approximately 86% for women with breast cancer that has spread to the lymph nodes and to approximately 25% for women with distant metastases. Overall, the lifetime risk for a woman to develop breast cancer is approximately 12%, although this risk increases significantly for individuals with a family history of the disease. Despite the strong links between family history and breast cancer risk, it is estimated that only 5% to 10% of breast cancer cases are the result of gene variants associated with high-risk cancer predisposition syndromes. Indications that a patient may have a heritable form of breast cancer (and would be a candidate for genetic testing) include a strong family history of breast cancer and potentially related malignancies (such as ovarian or pancreatic cancer), an early disease onset (age < 45 years), bilateral breast cancer, multiple primary tumors, a personal or family history of male breast cancer, and an ethnicity associated with a higher risk of hereditary breast cancer (such as Ashkenazi Jewish ancestry). Inherited variants in the breast cancer susceptibility 1 (BRCA1) and breast cancer susceptibility 2 (BRCA2) genes, which are associated with a high risk of breast and ovarian cancer, account for up to 40% of familial breast cancer cases. For those cases in which no BRCA1/2 gene variant can be identified, it is believed that genetic alterations in low- to moderate-risk susceptibility genes may play a role. One of the recently identified moderate-risk breast cancer susceptibility genes is the partner and localizer of BRCA2 (PALB2) gene. The PALB2 gene, located on chromosome 16 at band p12.1, encodes an essential protein that interacts with both BRCA1 and BRCA2 proteins during the process of DNA repair. PALB2 sequence variants are transmitted in an autosomal dominant manner (i.e., only 1 of the 2 gene copies needs to be altered in order to develop breast cancer) and are characterized by incomplete penetrance (i.e., not all PALB2 carriers will develop breast cancer). At the present time, it is estimated that variants in the PALB2 gene are present in 1% to 2% of BRCA1/2-negative patients affected with familial breast cancer, and that the lifetime risk of breast cancer for PALB2 carriers is between 20% and 40%. In addition, PALB2 gene variants have been linked to an increased risk for pancreatic cancer, and some carriers have been reported with malignancies of the ovaries, stomach, and prostate gland. Currently, there are no specific recommendations regarding PALB2 gene testing, although it has been suggested that BRCA1/2-negative patients with characteristics of hereditary breast cancer may be appropriate candidates. There are also no published guidelines regarding medical management of PALB2 carriers.

Project Status: Completed

Year Published: 2014

URL for published report: The report may be purchased from: http://www.hayesinc.com/hayes/crd/?crd=16932

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

Contact Name: saleinfo@hayesinc.com

Contact Email: saleinfo@hayesinc.com

Copyright: 2014 Winifred S. Hayes, Inc