Wednesday, July 13, 2016

Treating and Managing Future Risk in Women with Hereditary Breast Cancer

Cancer News in Context is excited to publish four posts this week on high-risk breast and ovarian cancer.  These posts will provide insight for women (and their families) from Washington University School of Medicine physicians on unique aspects of high-risk disease -- from genetic testing and treatment to prevention and risk management.  
July 11 - Overview: High-Risk Breast Cancer - Prevention and Risk Management
July 12 - High-Risk Ovarian Cancer: Identifying, Preventing, and Managing Risk
July 13 - Treating and Managing Future Risk in Women with Hereditary Breast Cancer
July 14 - Genetic Risk of Breast Cancer and Your Options
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by
Cynthia Ma, MD
Associate Professor, Division of Hematology & Oncology, Department of Medicine, 

Washington University School of Medicine

Most women with breast cancer are without an inherited genetic mutation. However, about 10 percent of breast cancers are hereditary that can pass along in blood relatives. A number of genes, including BRCA1/2, TP53, PTEN, PALB2, STK11, CDH1 and others, could cause hereditary breast cancer. Among these, BRCA1/2 mutation is most common, representing about 20 percent of the hereditary cases. These genes are often tumor suppressor genes that normally protect cells from cancer formation, mutations of which lead to loss of tumor suppressor function. For example, BRCA1 or BRCA2 is important for the accurate repair of any damages occurring in the DNA, the genetic code in the cell, to prevent cancer formation. When BCRA1 or BRCA2 is mutated, cells accumulate damaged or mutated DNA, leading to cancer.

It is important to identify hereditary breast cancer as it increases the chance of developing a second breast cancer or other cancer types in the patient. Family members could be carriers of the same mutation that predispose them to breast and other cancers. For example, breast cancer patients who are BRCA1/2 mutation carriers have a much higher risk of developing a second breast cancer, exceeding 60 percent if the first cancer was diagnosed at a young age. In addition, BRCA1/2 mutation carriers are at a significantly increased risk of ovarian cancer (40 percent in BRCA1 and 15 percent in BRCA2 mutation carriers) and other cancers such as prostate and pancreatic cancer.

As hereditary breast cancer tend to occur at a young age, in other family members and high risk ethnic groups (such as Ashkenazi Jewish descents), a detailed personal and family cancer history is important. In addition, breast cancer diagnosed in male should raise the possibility of hereditary breast cancer. Since breast cancer in BRCA1 mutation carriers are often triple negative (negative for estrogen receptor, progesterone receptor, and HER2), any patients with triple negative breast cancer diagnosed at age 60 or younger should be evaluated for BRCA1/2 mutations.

Breast cancer patients who are BRCA1/2 mutation carriers are recommended to proceed with bilateral mastectomies rather than lumpectomy surgery when treating the initial breast cancer to reduce the risk of a second breast cancer and bilateral salpingo-oophorectomy to reduce ovarian cancer risk. This is often the preferred approach as it is highly effective, although some patients may elect with bilateral salpingo-oophorectomy alone which reduces the risk of ovarian cancer by at least 80 percent but also risks of breast cancer by about 50 percent when performed before menopause by reducing estrogen levels. Alternatively, hormonal therapy with either tamoxifen or aromatase inhibitors, which is often recommended to treat the breast cancer after surgery, could reduce the subsequent primary breast cancer diagnosis by 50 percent.

Other implications in the treatment of breast cancer in BRCA1/2 mutation carriers include the sensitivity of their breast cancers to platinum class chemotherapy and investigational Poly (ADP-ribose) polymerase (PARP) inhibitors. Although PARP inhibitors have not received food and drug administration (FDA) approval, pending large phase III studies, patients could potentially receive these drugs through participation in clinical trials.

In summary, effective prevention and treatment are available for breast cancer patients with inheritable mutations and their family members. All breast cancers, particularly if early onset, triple negative, in high risk ethnic group, in male, or with family history, should be evaluated for potential genetic causes of breast cancer. In addition to BRCA1/2, other genes could be in play. Genetic risk assessment is an integral part of cancer care for breast cancer patients.

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