Genetic testing can find BRCA1 and BRCA2 mutations — then what?

By Linda Liu, MD

Although most breast cancers aren't caused by a genetic mutation, it's important to identify the small percentage that are. The most common and well-known mutations associated with breast and ovarian cancers are the BRCA1 and BRCA2 mutations. Finding these mutations — or, in fact, any genetic mutation linked to tumor formation — is a powerful weapon to prevent additional cancers in these patients, their relatives and future generations.

What is a genetic mutation?

genetic mutation - BRCA 2 and BRCA 3 - HonorHealth

The BRCA1 and BRCA2 genes normally function as tumor suppressor genes. They help repair DNA damages that could lead to cancer formation. When there's a harmful mutation — an alteration in either of these genes — the ability to defend against cancer formation is greatly weakened. Individuals with one of these mutations are more likely to get a cancer at a much earlier age than expected and develop multiple tumors, sometimes in different organs.

These faulty genes are then inherited by their children, and a characteristic pattern of hereditary cancer arises in these families — numerous relatives with cancers, often occurring at young ages, with the same individual sometimes having several different kinds of cancers.

Identifying the presence of the BRCA mutation empowers individuals to understand their chance of getting future cancers. Most importantly, it allows prevention or detection much earlier. This knowledge can help patients recently diagnosed with cancer and family members who do not have cancers but are concerned about their risk.

Who should consider genetic testing?

History that should prompt genetic testing in patients diagnosed with cancer includes:

  • Breast cancer in patients less than 50 years of age.
  • Triple negative breast cancer, a more aggressive form that's not responsive to estrogen or progesterone and does not have extra HER2/neu protein markers.
  • Multiple breast tumors in the same patient, either simultaneous, distinctly different tumors, or a history of multiple episodes of breast cancer occurring at different times.
  • Ashkenazi Jewish ancestry.
  • Ovarian cancer: Either a personal history of ovarian cancer in the past or a relative with ovarian cancer.
  • Male breast cancer diagnosed in the patient or in a family member.
  • Pancreatic cancer: A personal history or in family members.
  • A strong family history of breast cancer with multiple relatives on the same side or an unusual pattern with relatives who developed cancer at an early age — less than 50 — or multiple times.

Patients who have not had a breast or ovarian cancer, but who have a concerning family history, should have genetic testing based on the following criteria:

  • A relative with a confirmed BRCA mutation.
  • A strong family history of breast cancer that is striking in:
    • The number of relatives — at least three on the same side of the family.
    • An unusual history of breast cancer at less than 50 years of age or individual relatives who had multiple cancers. "Red flag" cancers are uncommon cancers that should also raise a suspicion to test — a relative with ovarian cancer, male breast cancer or pancreatic cancer.
  • It's best to first test a family member who has been diagnosed with a cancer, but that's not always possible. The next best person to test is an unaffected family member higher in the family tree. A negative result in that person clears all of his or her children from having a mutation.

Risk elevation from BRCA mutations

Increased cancer risks with BRCA mutations cover a broad range. Risks are influenced by the particular mutation, family history and other complex factors.

Cancer risk over lifetime General population BRCA1 or 2 mutation
Breast (female) 12% 45-80%
Second breast cancer 5-15% 30-50%
Male breast cancer 0.1% 2-8%
Ovarian cancer <2% 20-40%
Pancreatic cancer <1% 1-7%

Effective strategies for prevention or early detection can reassure individuals with a BRCA mutation that they don't need to feel vulnerable and anxious. For patients diagnosed with breast cancer, awareness of an underlying BRCA mutation can more precisely guide their surgery choice, treatment path and future screenings.

When to have a mammogram, other tests

Earlier and more thorough examinations are encouraged in patients with hereditary breast and ovarian cancer genes, even if they don't have cancer. For women, these exams include:

  • Monthly breast self-exams starting at 20.
  • Examination by clinicians every six months.
  • Breast MRI, if available, for greater detection starting in the 25-29 age range. Ultrasound is also helpful if MRIs are difficult. 
  • Mammograms starting at 30. 
  • Screening for ovarian cancer is difficult and of questionable value. Transvaginal ultrasound and measuring tumor markers (found in the blood or body tissue of some people with cancer) can be considered. Pelvic exams should begin by age 30.

Men should perform breast exams by age 35, but they don't necessarily need mammograms unless they have large amounts of breast tissue. Men should undergo earlier prostate screening.

Medications and surgery can reduce your risk of breast cancer

Risk reduction involves the use of medication to decrease the chance of cancer formation or prophylactic (preventive) surgery to remove tissue before it can develop a cancer. Available options include:

  • Taking tamoxifen for five years blocks estrogen activation of breast cancers, reducing them by 40-50%. 
  • Oral contraceptives may reduce the risk of ovarian cancer.
  • Oophorectomy, surgical removal of ovaries and fallopian tubes, is strongly recommended because ovarian cancer is difficult to detect. The surgery reduces the risk of ovarian cancer by 90% and is recommended when the patient is done with childbearing, between the ages of 35 and 44 — earlier for BRCA 1 carriers. When this surgery is performed when a woman is in her 30s or 40s, the estrogen reduction can effectively decrease breast cancer by 30-60%.
  • Mastectomies, the surgical removal of both breasts, reduce breast cancer risk by 90-95%. Reconstruction is often done during the same surgery, sometimes keeping the nipple and areola for the best cosmetic effect. Patients should receive thorough counseling to help guide the decision for surgery versus the option of continued close surveillance. 

With greater understanding of the many genetic mutations that can cause hereditary breast and ovarian cancer, doctors can order full panels of genetic tests to detect less common mutations, in addition to the BRCA mutations. This allows us to create an early detection and prevention plan designed with your unique risk factors in mind. 

Ready to take control of your journey?

If you have a personal history of cancer or if cancer runs in your family, consider taking an important and potentially lifesaving step — genetic counseling. For more information or to schedule an appointment, call 623-434-6138.

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