Cancer genetics and women’s health
Cancer genetics and women’s health
Kerry Kingham, MS, CGC, is a senior genetic counselor and clinical assistant professor (affiliated) of pediatrics working in the Cancer Genetics Clinic at Stanford Health Care. BeWell spoke with Kingham to gain a better understanding of genetic testing and its role in women’s health and cancer screening.
What is sporadic cancer vs. hereditary cancer?
“Hereditary cancer” is a bit of a misnomer as most people are not born with cancer. We would refer to “hereditary cancer” as a gene mutation, or hereditary cancer syndrome, that causes an increased risk for a particular cancer or spectrum of cancers in a family.
“Sporadic cancer” is cancer that does not appear to be due to someone’s family history or a particular risk factor. For instance, 12% of women in the US develop breast cancer; it is a common disease. Yet, only 5-10% of these women will develop breast cancer because of a hereditary gene mutation.
What are the features of a family with a hereditary cancer syndrome?
In general, we look for an early age of cancer diagnosis (often defined as <50 years of age), more than one primary cancer in one individual, and multiple generations affected in a pattern of specific cancer types. These are not mutually exclusive. For instance, some hereditary cancer syndromes are due to a de novo mutation — a mutation in a hereditary cancer gene that occurs at the time of that individual’s conception. Thus, in these individuals, the clue that there may be a gene mutation present is their young age, or a diagnosis of more than one cancer type in their life, rather than a family history. Early age of diagnosis is often a key factor.
How do I decide whether to get genetic testing? What steps would I take if I’m worried I have a family history of cancer?
The best step to take prior to deciding whether or not to proceed with genetic testing is to meet with a genetic counselor. Your doctor can provide a referral. The genetic counselor will take a three generation family history, discuss the testing that might be indicated for you or a family member, and explain the risks and benefits of the testing. They also discuss the potential outcomes of the testing: whether a mutation is found, a mutation is not found, or there are uncertain results. Even when a genetic test is negative, this may not mean that the individual or their family is not at risk for cancer.
How common are the mutations that can cause breast and/or ovarian cancer? How much of an increased risk is there for someone with a certain mutation?
Some of the gene mutations are more common than others; mutations in the BRCA1 and BRCA2 genes are present in approximately 1/300 – 1/800 individuals in the general population, and 1/40 individuals of Ashkenazi (Eastern European) Jewish descent. Lynch syndrome, a hereditary colon and gynecologic cancer syndrome, is equally as common. However, inherited TP53 gene mutations that cause Li Fraumeni syndrome are estimated to be present in 1/20,000 individuals and people with Cowden syndrome (PTEN gene mutations) are estimated at 1/100,000.
Each gene has a specific spectrum of risk. For instance, individuals who carry mutations in the MLH1 gene — one of the causes of Lynch syndrome — have up to an 80% lifetime colon cancer risk. Women who carry mutations in this gene have an additional 60% lifetime risk for endometrial cancer. Women and men can both carry BRCA mutations; however, the cancer risks are highest for female carriers. Female BRCA1 mutation carriers have a 65% lifetime breast cancer risk and a 40% lifetime ovarian cancer risk.
Why would someone who had a cancer want to know if they have a genetic mutation?
Our goals are cancer prevention and early detection. The early detection of cancer is associated with a better prognosis. Knowing whether or not an individual carries a hereditary cancer gene mutation may change their medical care. BRCA1 and BRCA2 mutation carriers are advised to undergo high risk breast screening starting in their mid -20s, which includes an annual breast MRI. This is significantly earlier than age 40, which is when most women in the US are recommended to begin mammogram screening. Due to the high risk for ovarian cancer, BRCA mutation carriers are recommended to undergo surgical removal of their ovaries and fallopian tubes at the age of 40 to prevent ovarian cancer — so that a woman is not diagnosed with an ovarian cancer that could be potentially life-threatening.
The other goal of genetic testing is to inform the family. If a father or mother carries a BRCA mutation, there is a 50% chance that the mutation would be passed each time he or she has a child. It also often means that one of the grandparents carries the mutation as well, and that it could have been passed on to other family members such as aunts, uncles and cousins. Knowing this information, and sharing it with the family, allows others to make these decisions for themselves. Some members of a family might approach this information in different ways; some will want to talk about it while others do not. We always advocate for telling the family members, and then allowing them to make the decision for themselves on what they choose to do. We do want family members to understand that genetic testing can help reduce the impact that cancer can have on their lives.
Should my children undergo genetic testing for cancer?
Most of the syndromes and genes for which we test do not cause cancer risk in childhood; thus, we recommend that the children of a person who carries a hereditary cancer gene mutation consider genetic testing in their early 20s, or just before cancer screening would begin, should they be found to be a carrier. There are rare exceptions for syndromes where cancer screening may be recommended to begin in childhood.
I already did genetic testing and I don’t have a mutation. Does this mean I don’t have hereditary cancer risk?
Many of our patients previously underwent testing of their BRCA1 and BRCA2 genes in the past, but no mutations were identified in these two genes despite a strong personal or family history of cancer. At that time, we had no other genetic tests to offer. While mutations in the BRCA1/2 genes explain many of the families with hereditary breast and ovarian cancer, they do not explain all of them. We stated to these patients in the past that this could be due to a mutation in another as-yet-unknown hereditary cancer gene that we did not have the ability to test. In 2013, a change of testing technology in addition to a patent loss on the BRCA1/2 genes allowed us to test multiple genes at once. This significantly increased the number of gene mutations we were finding which ultimately is leading to more individuals with known risk and more individuals undergoing early detection and prevention.
What can women do if they test positive for a gene mutation?
We recommend talking to a breast specialist. In our clinic, this is a medical oncologist who specializes in treating breast cancer as well as in screening women at high risk. This expert would sit down with a patient and explain the cancer risks in detail and offer screening and prevention options.
What are screening options for women at high risk for breast cancer? Why don’t we do that screening for everybody?
Women considered at high risk for breast cancer typically have a lifetime estimated risk of 20 – 25% or greater, as estimated by a risk model that incorporates personal risk factors such as hormonal status as well as family history, and women who carry hereditary cancer gene mutations that cause a risk for breast cancer in this range or higher. The gold standard of high risk screening includes annual mammogram, annual breast MRI, clinical breast exam twice per year and monthly self-breast exams. Some women also consider taking medications that reduce the lifetime breast cancer risk, such as Tamoxifen.
Why is early detection so important in the treatment of breast cancer?
Early detection of breast cancer, such as at a stage 0 or stage I, is associated with a better prognosis (better survival). Women who carry BRCA mutations— and who are undergoing this high level of screening and stay on time with their screenings — are more likely to have breast cancer identified at this early stage.
Who should consider preventive surgery for breast or ovarian cancers? How many people choose preventive surgeries?
Preventive surgery of the breasts (bilateral prophylactic mastectomy) is discussed with women who carry hereditary cancer gene mutations, such as BRCA1 or BRCA2 mutations, that place them at considerable risk for future breast cancer. The guidelines of the National Comprehensive Cancer Network recommend discussing this with these women, as removing the breasts with a surgery can reduce the risk for a woman to develop breast cancer by 90 -95%. Early detection using breast screening is considered to be a very reasonable option. Not every woman who carries a BRCA mutation undergoes prophylactic mastectomy. In fact, a majority of women do not choose this surgery. In contrast, preventive surgery to remove the ovaries and fallopian tubes (prophylactic bilateral salpingo oophorectomy) is recommended for women who carry BRCA mutations. This is because there are no proven early detection methods for ovarian cancer. This cancer is typically not detected until it is at a later stage and more difficult to cure.
What are preventive medications for breast and ovarian cancer? Who should take these?
Preventive medications for breast cancer are Tamoxifen and Raloxifene. Taken for five years, these medications reduce the risk for a breast cancer by 1/3 – 1/2. These medications are discussed with women who carry gene mutations that cause considerable lifetime breast cancer risk and are also discussed as an option with women with a strong family history of breast cancer where the gene mutation is not identified in their family. Women in these categories can have a discussion with their doctor, who can outline the risks and benefits of these medications.
… any final thoughts?
I would say that your genes don’t change – they are what they are, and knowing what is in our genes can often help us learn how to take better care of our health. This is particularly true in cancer genetics.