BRCA Mutations and Breast Cancer

BRCA1 and BRCA2 affect breast cancer risk and survival

puzzle pieces interaction of breast cancer, brca mutations, and survival
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Several genes have been linked to breast cancer, the most common of which are BRCA mutations (BRCA1 and BRCA2). To give you a sense of their significance, the overall lifetime risk of breast cancer in women without a BRCA mutation is around 12%. For those with such a mutation, the average lifetime risk of developing breast cancer is around 70%. BRCA mutations increase the risk of several other types of cancer as well.

Since a BRCA mutation is such a significant risk factor, many women with a family history of the disease are encouraged to get genetic testing to see if they have one. Such testing is not routine and requires thoughtful consideration about potential next steps should results be positive. The possibility of discovering a such a predisposition to breast cancer can be frightening, but new research about long-term survival of people with these mutations may help temper some of your fears.

The Role of BRCA Genes

Genes, which are inside each cell in your body, are made of DNA molecules. They are a blueprint—coding for the proteins that your body builds. BRCA genes are normal genes that function as tumor suppressor genes. Each of your cells contains two copies of each BRCA gene (BRCA1 and BRCA2)—one copy from your mother and one copy from your father.

Given the risk of cancer tied to mutations of these genes, some are surprised to learn that normal BRCA genes code for proteins that prevent the growth of tumors such as breast cancer and ovarian cancer. Specifically, these proteins are responsible for repairing cancer-causing damage to DNA in your cells.

You may hear some people refer to these as B-R-C-A mutations, while others may call them "braca" mutations.

BRCA Genes Mutations

Mutations are genetic errors. There are a number of different BRCA gene mutations, and they can be located on different chromosomes. The most common ones are BRCA1 and BRCA2.

BRCA gene mutations are autosomal recessive, meaning that both copies of the gene must be abnormal for a person to lose the normal anti-cancer effect.

It is far more common to inherit only one mutated gene (this is written as BRCA1/2) than two of them. Having one BRCA mutation gives you a genetic predisposition to cancer, but it does not mean that you will definitely develop cancer.

In order for cancer to occur, the other copy of the gene needs to undergo a mutation, which makes your DNA repair system inadequate for preventing cancer. You can have two abnormal copies of a BRCA gene if you have an inherited mutation and develop an acquired mutation.

  • Inherited (germ-line) BRCA mutations are passed from a mother or father to a child at conception.
  • Acquired mutations occur as a result of DNA damage related to the environment, lifestyle factors (like smoking), or even normal metabolic processes in cells. These can occur at any time during a person's life.

Breast Cancer Risk

BRCA mutations are associated with hereditary breast cancer, but not all hereditary breast cancers are due to BRCA mutations.

Overall, BRCA mutations account for 20% to 25% of hereditary breast cancers and 5% to 10% of breast cancers. Again, the average lifetime risk of developing breast cancer if you have a BRCA mutation is about 70%.

Hereditary breast cancers not related to BRCA mutations are referred to as non-BRCA familial breast cancer or BRCAX. Gene mutations that are linked to breast cancer include those in ATM CDH1, CHEK2, PALB2, PTKN, STK11, and TP53. There are likely many more awaiting discovery, but research is still in the early stages.

In those under age 40, about 10% of breast cancers are associated with being BRCA-positive. In contrast, the number is closer to 5% in older women with the disease.

How BRCA Mutations Affect Breast Cancer Treatment

BRCA mutations tend to be associated with cancers that have a higher tumor grade, a measure of the aggressiveness of the tumor. Tumor features make treatment difficult.

In addition, breast cancers in women with BRCA mutations (especially BRCA1) are less likely to have estrogen or progesterone receptors, proteins on the surface of breast cancer cells that cause tumors to grow when they bind with these hormones. These breast cancer cases are also less likely to be HER2-positive.

While this sounds like a positive, it means that medications that are effective for hormone receptor-positive and HER2-positive breast cancers are likely not options for women with BRCA mutations.

Triple-negative breast cancers—which don't have HER2 receptors, estrogen receptors, or progesterone receptors—are more common in women with BRCA mutations than in women without the mutation. In general, triple-negative breast cancers are more challenging to treat, as neither hormonal therapies nor HER-targeted agents will be effective.

On a more welcomed note, breast cancers in women with BRCA mutations tend to respond better to neoadjuvant chemotherapy (chemotherapy prior to surgery) than those in women without these mutations.

Genetic Testing for BRCA Mutations

Overall, genetic testing for breast cancer genes is not standard. However, it is often recommended for women who have a family history of breast cancer or who have personally had breast cancer at a young age.

If you are thinking about getting tested for breast cancer genes, you should speak with your doctor and/or a genetic counselor before your test. You may be faced with some major decisions if you test positive for BRCA genes or other breast cancer genes (often called non-BRCA gene mutations).

While there may be clear medical indications as to why such testing could be beneficial to you, there is no denying that this is an emotionally-charged decision. Many women want to get tested in every way possible, while others prefer to avoid knowing about their risk given that nothing may ever come of it.

If you're struggling with the decision to move ahead with BRCA testing, you may benefit from having a conversation with your loved ones about how you might handle your results. If you feel some support could help you pursue testing, you might consider asking some immediate family members, who could also benefit from doing this, to get tested with you.

Regardless of your decision, you certainly need to get your recommended mammograms.

While your health insurance carrier might not cover the cost of genetic testing if you are not considered high risk, you still can get tested and pay for it out of pocket, if you desire.

Keep in mind that a negative test result (no identified breast cancer genes) does not mean that you will not get breast cancer. Likewise, testing positive doesn't mean you will absolutely get breast cancer.

If You're Positive

Having a positive result (an identified breast cancer gene) may mean that you need to have screening mammograms at a younger age (before age 40).

There are no clear-cut recommendations regarding treatment for positive genetic tests because many women with these results don't develop breast cancer. There is no right or wrong decision. Whether or not to pursue treatment at this stage, however, is a very personal decision that you have to make carefully after learning about your case and all of your options.

Breast Cancer Prevention

At this stage, it is important that you think about breast cancer prevention. While eating healthy and exercising isn't guaranteed to prevent breast cancer, experts suggest that avoiding preservatives, consuming antioxidants (found in fresh fruit and vegetables), and not smoking can decrease your risk of all cancers. Discussing your use of hormone therapies (such as those in oral contraceptives) with your doctor is important too.

Some women who have BRCA mutations opt to use hormone therapy that is normally used to treat breast cancer. Hormone treatment is not without risks, however, and might not prevent cancer.

Another option: prophylactic mastectomy. This is the surgical removal of the breasts (usually followed by reconstruction) when there is a high risk of breast cancer. Prophylactic mastectomy is a very personal choice that you have to weigh with your doctor.

BRCA Mutations and Other Cancers

Ovarian cancer occurs in roughly 1.3% of women in the general population. For those with BRCA1 mutations, 39% are expected to develop ovarian cancer, while 11% to 17% of those with a BRCA2 mutation will develop the disease.

There are other cancers that can be associated with BRCA mutations as well, such as prostate cancer, pancreatic cancer, and even lung cancer.

Psychological Effects of a Positive Test

If you or a relative have tested positive, you may become overwhelmed with worry about breast cancer. This reaction is not usual, but you owe it to yourself to sort out your feelings about the issue. If you are pre-occupied with the risk of breast cancer, it can help to talk to a therapist who can listen to you and provide you with strategies to cope with your feelings and apprehensions.

A Word From Verywell

Once you have your BRCA results, you can work with your doctor and genetic counselor to decide on your next steps, which will include breast cancer screening and potentially other therapies, such as hormone therapy or surgery. Voice your concerns. Ask your questions. It's important that you feel confident about what you do following BRCA testing.

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