PGT for Hereditary Breast and Ovarian Cancer Syndrome

by | Oct 10, 2019
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What is Hereditary Breast and Ovarian Cancer syndrome?

While most cancer happens by chance (i.e. sporadic), about 5-10% of cancers are caused, in part, by inheriting a genetic variant from a parent that increases the risk for certain cancers over a person’s lifetime. Hereditary breast and ovarian cancer syndrome (or HBOC) is an adult-onset inherited cancer predisposition that affects about one out of every 300-500 people in the general population. However, HBOC is more common among certain ethnic groups. Individuals of Ashkenazi Jewish ancestry, for example, have up to a 1 in 40 risk for HBOC.  

As the name suggests, HBOC is associated with breast and ovarian cancer. While there are several genes that can increase the risk to have these cancers, the two most common and well-studied genes are BRCA1 and BRCA2. These genes serve as “caretakers”, correcting sporadic DNA errors due to faulty cell division or environmental exposures. Individuals who are “BRCA-positive” have a pathogenic variant (also called a genetic mutation) in the BRCA1 or BRCA2 gene which can cause DNA damage and lead to cancer. 

Women who are BRCA-positive have up to a 72% chance of developing breast cancer, and up to a 44% chance of developing ovarian cancer by the age of 80. Males who are BRCA-positive are at an increased risk for male breast cancer and prostate cancer. Also, males and females who are BRCA-positive are at a slightly increased risk for other cancers, such as pancreatic cancer and melanoma.    

How is HBOC syndrome inherited?

HBOC is an autosomal dominant condition. There is a 50% chance that someone with a pathogenic variant could pass it on to each of their children. Pathogenic variants can be inherited from either the mother or the father.

How is HBOC syndrome diagnosed?

HBOC is diagnosed through genetic testing. A genetic counselor or other healthcare provider familiar with genetics will review a patient’s personal and family history to see if there is an increased risk to have HBOC. 

There are professional guidelines that help providers determine whether or not a patient is appropriate for testing. According to recent guidelines published by the American Society of Breast Surgeons, genetic testing should be made available to all patients with a personal history of breast cancer. The National Cancer Center Network guidelines also recommend that genetic testing be offered to patients with a personal history of male breast cancer, ovarian cancer, pancreatic cancer or metastatic prostate cancer. Patients without a personal history of cancer may be appropriate for genetic testing if they have a family history suspicious of HBOC.  Furthermore, a new statement from the US Preventive Services Task Force recommends that primary care providers use a family history tool to assess all women who have an ancestry associated with a higher risk for BRCA1/2 gene mutations (such as Ashkenazi Jewish).

When offering genetic testing for HBOC, most providers suggest testing for a panel of genes that can cause HBOC that extends beyond just the BRCA genes. If the result reveals a pathogenic (clearly disease-causing) variant in one of these genes, the provider will discuss the associated cancer risks as well as the published medical management guidelines available for carriers of the pathogenic variant. 

There is a difference between at-home genetic tests and diagnostic tests in the information they provide. Therefore, patients should consult with a genetic counselor or other healthcare provider familiar with inherited cancer testing before they submit a sample to make sure they are getting the best test for their situation. 

How is HBOC syndrome treated?

There may be alternative medical management options available for patients with cancer who have HBOC. For example, breast cancer patients who are BRCA-positive may choose to have a total bilateral mastectomy instead of a lumpectomy since their risk to develop a second primary breast cancer is up to 40%. Also PARP inhibitors may be prescribed, which are a type of FDA-approved therapy designed specifically for patients with pathogenic variants in BRCA or other genes who have metastatic breast or ovarian cancer. Ongoing clinical trials are also showing promise for patients with pancreatic or metastatic prostate cancer who are BRCA-positive.

“Previvors” or “unaffected carriers” are individuals who have a hereditary predisposition to cancer, but have not developed the disease. Identifying a pathogenic variant in a cancer predisposition gene may enable preventative options that can catch cancer at an earlier, more curable stage or prevent cancer altogether. For example, women who are BRCA-positive are encouraged to have an annual mammogram with an annual breast MRI often scheduled six months apart. Alternatively, they can significantly reduce their risk for both breast and ovarian cancer by choosing prophylactic surgeries.  

Is preimplantation genetic testing available for HBOC syndrome? 

Both men and women who have a known pathogenic variant in a gene that causes HBOC can pursue preimplantation genetic testing (also called PGT-M) since they have a 50% chance of passing the disease to their children. 

Brandi Preston, Founder and Chief Volunteering Officer of the Kamie K. Preston Hereditary Cancer Foundation, first learned about PGT-M for HBOC at a conference a few years ago. “I do believe women should hear about PGT-M prior to starting a family,” says Preston.

“So many of us are given options for cancer early detection and prevention during genetic counseling. In a way, PGT-M is the ultimate cancer risk-reduction for the next generation.”

Yet many young patients who carry a hereditary cancer predisposition are unaware of PGT-M as a family planning option. “So many of us wonder if we want to have children, because we fear losing our life to cancer before the children grow up,” says Preston. “We also fear passing on a cancer-causing mutation to children, especially if we know about the gene prior to having children. Giving PGT-M as an option allows patients to decide if they want children, and if they do, there is an option to ensure their children will not carry the same mutation that has often caused so much suffering and heartache within the family.” 

Whitney, a male previvor who is BRCA-positive, has an extensive family history of breast cancer and discussed his and his wife’s decision to pursue PGT-M with his family. Whitney has seen and felt the impact of breast cancer. He says, “Just countless cases of breast cancer throughout the family. Being able to eliminate that from our lineage is something that my mom was just thrilled to know was going to happen.” He and his wife Brittney gave birth to a healthy baby boy in the summer of 2016.

If you believe you may be at risk for HBOC and would like to speak with a genetic counselor either in person or by phone, the National Society of Genetic Counselors or a fertility clinic with genetic counseling expertise can help. Identifying a mutation in a gene that causes a hereditary predisposition to cancer is the first step to pursuing PGT-M for the disease.

Leslie is a board-certified clinical genetic counselor and former Program Manager for the preimplantation genetic testing (PGT) program of the ORM Genomics team and former Project Manager for SharingHealthyGenes.com. She completed her Bachelor’s degree at DePauw University and her Master’s degree in Genetic Counseling at the University of Texas Graduate School of Biomedical Sciences at Houston. Since graduating in 2000, she has worked as a clinical genetic counselor in several specialties including prenatal, pediatric and cancer genetics and has been very involved with the National Society of Genetic Counselors.

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