women with breast cancer pink ribbon puts her hand on a breast cancer patient with a pink scarf on her head.

Alyssa (not her real name) came to see me as a new patient for her annual exam. Her insurance changed and she was looking for a new provider. As we reviewed her family history, the word “cancer” kept coming up. Her mom had breast cancer, as did her maternal grandmother and one of her mom’s sisters. In addition, one of her mom’s brothers had prostate cancer. 

Surprisingly, Alyssa had not been offered genetic testing for her family history of breast cancer, and now that she was in her 50s with teenagers, she was interested in finding out if she and her kids were also at risk. As I explained to her, there were genetic tests available to help her make more informed choices about screening tests, like mammograms, ultrasounds, and MRIs. And also, to consider whether other preventive treatments would be appropriate.

Let’s start with a quick review of how genetic mutations are related to cancer.

Our genes are pieces of DNA (deoxyribonucleic acid) that hold our genetic “blueprint” in each cell. We inherit our height, hair, and eye color from our parents through our genes. Mutations or errors in our genes can affect a cell’s proteins and how it grows and divides. When cells grow abnormally, that can lead to cancer.

Gene Mutations – Inherited or Environmental?

But it’s important to remember that only about 5% to 10% of all cancers are thought to be strongly related to an inherited gene mutation. Cancers more commonly start with gene mutations that occur over time with exposure to harmful chemicals such as those found in cigarettes, or too much sun exposure. A poor diet, lack of exercise, and stress can also affect the health and resilience of our cells. Mutations like these that come from outside only appear in the cancer cells themselves. An inherited genetic mutation will show up in all the cells of the body and can be passed on to the person’s children. 

Predictive Genetic Testing 

This is the term used for medical tests that look for certain inherited gene mutations 

that might increase the risk of someone getting certain kinds of cancer.

The following family history factors suggest a possible increased risk for hereditary cancer:

  • Family history of cancer. Having 3 or more relatives on the same side of the family with the same or related forms of cancer.
  • Cancer at an early age. Having 2 or more relatives diagnosed with cancer at an early age. This factor may differ depending on the type of cancer.
  • Multiple cancers. When one relative develops 2 or more types of cancer.
  • Rare cancers. Some types of cancer, such as ovarian cancer, adrenocortical cancer, or sarcoma, are linked to inherited genetic mutations.
  • Some types of prostate, pancreatic, and colon cancer that have similar genetic mutations as breast cancer. Women with a family history that includes these types of cancer, may want to consider genetic testing for an increased risk of breast or ovarian cancer.

What are BRCA1, BRCA2, and PALB2 Genes?

BRCA stands for “breast cancer gene” 1 or 2, and  PALB2 is short for “partner and localizer of BRCA2” because it partners with another gene, called BRCA2 – breast cancer gene two.

A genetic counselor will go over your family history and discuss your level of risk and what testing might be advisable. You might have heard of the BRCA1, BRCA2, and PALB2 genes, they are the ones that can raise the risk of breast and/or ovarian cancer if they become abnormal. 

They can be inherited from the mother or father, and men with BRCA mutations are considered to have a higher lifetime risk of male breast cancer, especially if the BRCA2 gene is affected. It is suspected that abnormal PALB2 genes raise the risk of ovarian cancer, but this has not been confirmed by large studies. 

I Was Tested for BRCA

My mom was BRCA1 positive, had breast cancer at age 32, and survived. I knew that women with a BRCA1 or BRCA2 mutation can have a 45 – 65% chance of being diagnosed with breast cancer by age 70. I decided to get tested as soon as the tests were available. Before my test, let me tell you, I was worried that I would be positive and had already started to think about what I would do if the tests showed a mutation. Luckily, I didn’t have to face those decisions, but for women who are positive, here are the choices to consider:

  • Increased screening– An early detection plan for someone with a BRCA or PALB2 gene mutation will likely involve more frequent breast cancer screenings starting at a younger age. Ultrasound or MRI scans might be used.
  • Preventive surgery– A preventative double mastectomy (bilateral prophylactic mastectomy) is the surgical removal of both breasts so there is little chance of cancer developing. 
  • Removal of the ovaries and fallopian tubes– a procedure known as a preventative salpingo-oophorectomy, is often recommended to reduce breast cancer risk.

Lynch Syndrome

Named for Henry T. Lynch, MD, who first reported in detail on familial clusters of cancers in 1966-67, Lynch syndrome is the most common inherited genetic condition that increases your risk of colon cancer, endometrial cancer, and several other cancers. It is estimated that around 3 out of every 100 colon cancers or endometrial cancers are caused by Lynch syndrome. It can be detected using a blood test.

People with Lynch syndrome are more likely to get colorectal cancer and other cancers, and when younger, before age 50. Other cancers include:  

  • Uterine (endometrial)
  • Stomach
  • Liver
  • Kidney
  • Brain
  • Certain types of skin cancers
  • Possibly breast cancer

Lynch syndrome causes about 4,000 colorectal cancers and 1,800 uterine (endometrial) cancers per year. It is due to inherited mutations in genes that affect how our DNA is repaired and maintained when copied. These genes, MLHL, MSH2, MSH6, PMS2, and EPCAM, normally protect you from getting certain cancers, but mutations can prevent them from working as they should. 

Recent evidence has shown a possible association between PMS2 in Lynch syndrome and an increased risk of breast cancer. 

A person has two copies of each of the genes involved in Lynch syndrome, one from their father and one from their mother. Even if a person inherits a mutation in a Lynch syndrome gene from their mother, they still have the normal copy of the gene from their father. Cancer occurs when a second mutation affects the normal working copy of the gene, so that the person no longer has a healthy copy. This mutation might occur from a non-inherited cause, such as smoking. So, the second mutation would not be present throughout the person’s body, but would be present in the cancer tissue. 

I have many patients like Alyssa who are tested for genetic mutations. If they have positive results, we recommend genetic counseling and a consult with the appropriate specialist.

I also have a patient in her early 20’s who recently discovered she was BRCA2 positive. After feeling overwhelmed and fearful, and reviewing what she could take control of now, she has started making positive lifestyle changes to reduce her risks. She losing weight, restricting alcohol, and exercising. I’ve made a referral to UCSF’s hereditary cancer clinic for more in-depth advice.

If you do decide to have genetic testing, make sure you talk to your health care provider about next steps and a follow up plan if the results are positive.

For more on hereditary cancers, you can visit Survivor.net, I recently volunteered to film videos on many aspects of survivorship and genetic testing for cancers. 

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