BRCA Mutations and Breast Cancer

How these mutations can lead to breast cancer

puzzle pieces interaction of breast cancer, brca mutations, and survival
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Several genes have been linked to breast cancer, and the most common are BRCA mutations. If you carry BRCA mutations, this can significantly increase your risk of developing the condition.

Most women do not routinely get tested for breast cancer genes. But if you have a family history of the disease, or if you have opted to have a genetic test, you may discover that you carry genes that predispose you to breast cancer. It can be terrifying for most women to learn that they have a breast cancer gene.

If you do carry a BRCA mutation, it can mean many extra tests and difficult decisions—for you and for other women in your family. But new research about long-term survival with these mutations may reduce some of your fears.

BRCA Genes

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

BRCA genes code for proteins that prevent the growth of tumors such as breast cancer and ovarian cancer. Specifically, the proteins coded by normal BRCA genes are responsible for repairing cancer-causing damage to DNA in our cells.

BRCA Mutations

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

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 does not mean that you will definitely develop cancer.

In order for cancer to occur, the other copy of the gene will need 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.

  • Germ-line or inherited 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— and can occur at any time during a person's life.

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

The overall lifetime risk of breast cancer in women without a BRCA mutation is around 12 percent. For those who have a BRCA1 or BRCA2 mutation, the average lifetime risk of developing breast cancer is around 70 percent.

Younger women who develop breast cancer are more likely to have these mutations than older women who develop breast cancer. For those under the age of 40, about 10 percent of breast cancers are associated with being BRCA positive. In contrast, the number is closer to 5 percent in older women with the disease.

BRCA Mutations and Other Cancers

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

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

How BRCA Mutations Affect Breast Cancer

Breast cancers in women with BRCA mutations tend to respond better to neoadjuvant chemotherapy (chemotherapy prior to surgery) than those without these mutations. But there are also challenges associated with these mutations. Women who have BRCA mutations often have more aggressive breast cancer, which is characterized by features that make it difficult to treat.

BRCA mutations tend to be associated with cancers that have a higher tumor grade. Tumor grade is a measure of the aggressiveness of the tumor.

Breast cancers in women with BRCA mutations (especially BRCA1 mutations) are less likely to have estrogen or progesterone hormone receptors. Hormone receptors are proteins on the surface of breast cancer cells, When these receptors bind to hormones, this causes the tumors to grow. Hormone receptor-positive breast cancers can be treated with medications that counteract the hormone effect.

Breast cancers in women with BRCA mutations are also less likely to be HER2 positive. HER2 positive breast cancers can be treated with certain medications.

And triple-negative breast cancers—which don't have HER2 receptors, estrogen receptors, or progesterone receptions— 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.

BRCA Mutations and Familial Breast Cancer

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 percent of hereditary breast cancers and 5 to 10 percent of breast cancers overall.

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 waiting for discovery, but the research is still in the early stages.

Getting Tested for BRCA Mutations

Overall, genetic testing for breast cancer genes is not standard. However, women who have a family history of breast cancer or who have personally had breast cancer at a young age are often given a recommendation for genetic testing. And while your health insurance carrier might not cover the cost of genetic testing if you are not high risk, you still can get tested and pay for it out of pocket.

Keep in mind that a negative test result (no identified breast cancer genes) does not mean that you will not get breast cancer. Rather, having a positive result (an identified breast cancer gene) may mean that you need to have screening mammograms at a younger age (normally they are recommended yearly starting at age 40).

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, is 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.

A Word From Verywell

If you are thinking about getting tested for breast cancer genes, you should speak with your doctor and/or a genetic counselor before and after 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).

Once you have the information, 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.

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