Your Cancer Answers: Which genetic syndromes increase the risk of breast cancer?

In In The News by Barbara Jacoby

By: Dr. Kevin Lin 


Question: Which genetic syndromes increase the risk of breast cancer?

Many risk factors for breast cancer have been identified, including genetic, environmental, and lifestyle factors. Some are modifiable and others are not. A family history of breast cancer in a first-degree relative is the most widely recognized breast cancer risk factor, but only 5-10% of women diagnosed with breast cancer have a known genetic predisposition. Women with a family history of breast cancer in a mother or sister have a 1.5-3 fold increase in the risk of developing breast cancer.

Multi-panel genetic testing for hereditary breast cancer syndromes is currently not standard for all women diagnosed with breast cancers due to insufficient data regarding interpretation accuracy and its utility. For now, BRCA1/2 testing accounts for half of the detected genetic breast mutations and is recommended in a women with: Personal history of breast cancer diagnosed before the age of 50, multiple female relatives with breast cancer on same side of the family or family history of male breast cancer, multiple breast cancers, both breast and ovarian cancer,with Ashkenazi Jewish heritage.

Those with BRCA mutation are at risk for developing breast cancer (50 to 80%) by age 70 and developing ovarian cancer (40-60%) by age 85. Since 2014, PALB2 (partner and localizer of BRCA2 gene) testing is frequently added to BRCA due to its inherent breast cancer risk of 5 to 9 times the average.

Optional genetic panel testing includes PTEN, TP53, ATM, CDH1, CHEK2, NBN, NF1, STK11, and PMS2/MSH2 — Lynch syndrome, also known as hereditary non-polyposis colorectal cancer, is a hereditary cancer syndrome, and is associated with multiple types of cancers, particularly colon, ovarian and endometrial/uterine, as well as breast cancers.

Women with these mismatch repair genetic mutations (Lynch) may also have a 2-3 fold increase risk of breast cancer compared to the general population. Additionally, the personal and family cancer history suggests crossover in eligibility for breast specific genetic testing in a significant number of patients (16.5–24.4%). If positive for breast cancer specific genetic mutations such as BRCA these women are eligible for enhanced breast surveillance which would otherwise not be offered.

Thus, risk reducing prophylactic mastectomy can be considered for women with hereditary pathogenic mutations in BRCA, PTEN (Hamartoma Tumor Syndrome or Cowden disease) and TP53 (Li-Fraumeni). Other rare genetic disorders, such as Peutz-Jeghers syndrome and hereditary nonpolyposis colorectal carcinoma (HNPCC), are associated with an increased risk of breast cancer. For women with BRCA1 mutation, current expert guidelines also recommend bilateral prophylactic oophorectomy between ages 35 to 40 or after childbearing is completed.