I’d always assumed my breast cancer risk was average and, weighing the risks and recommendations, had decided to wait until age 50 for my first mammogram.
My paternal grandmother had died of breast cancer, as had my maternal great-grandmother, but both were diagnosed postmenopause and weren’t immediate relatives. However, my risk profile changed dramatically this year when my mother was diagnosed with Stage 1 breast cancer at age 74, when I was 49.
Even still, I stubbornly stuck to my plan and waited a few months, until after my 50th birthday, to get my first mammogram. As part of the procedure, the radiation technician asked me a series of questions to assess my breast cancer risk. The formula — based on such factors as family history, age of menarche, use of birth control pills, my age and the fact that I was childless — spit out a lifetime breast cancer risk of 20%, or one in five. This, to my surprise, put me in the “high risk” category.
Within a few days, I received a letter in the mail telling me my mammogram was normal. However, the technician had recommended I receive yearly breast cancer screening tests, including an annual breast MRI as well as an annual mammogram, and suggested genetic testing might be a good idea.
My Cancer 'Pedigree'
Since I work at City of Hope®, I decided to inquire about genetic risk assessment testing here. The Women’s Center scheduled an appointment for me with genetic counselor Bita Nehoray, M.S., L.C.G.C. Before our appointment, I was sent a questionnaire that asked me to detail all of the cancers in my family tree going back three generations. Admittedly, there was a lot: Aside from her breast cancer, my mom had been treated for endometrial and thyroid cancer; my dad had died of prostate cancer; my paternal grandmother and maternal great-grandmother had died of breast cancer; three of mom’s first cousins, all sisters, had died of childhood leukemia, lung and ovarian cancer, respectively; and dad’s aunt and uncle had both died of lymphoma.
When I met with Nehoray, she showed me the family tree she had put together (called a “multigenerational pedigree”) listing all of my relatives, those with and without cancer. She told me that based on the tree, I qualified for genetic testing per national guidelines. In particular, my mother’s cancers pointed to a disorder called Cowden syndrome, caused by a mutation in the PTEN gene — her endometrial, thyroid and breast cancers are the exact trifecta associated with this rare but dominant disorder (meaning that it tends to persist in families).
She explained that they would be testing for the main genetic mutations associated with breast cancer, BRCA 1 and 2, as well as other breast cancer-related mutations and mutations associated with other forms of cancer. One of the nastiest of these is mutation of the P53 gene, implicated in ovarian, esophageal, colorectal, head and neck, larynx, lung and other cancers.
Assessing Polygenic Risk Score
In addition, they would be looking for more widespread genetic variations called SNPs that, while not mutations, may affect cancer risk. My SNPs would give me what’s called a polygenic risk score. All it would take is a simple blood test sent off to a specialty lab.
Nehoray called me when she received my test results and emailed me a copy. She said she had “good news,” which was that I carried zero known mutations associated with cancer — including no Cowden syndrome. However, my new calculated risk, based on an assessment called the Tyrer-Cuzick empiric risk estimate, yielded a remaining lifetime chance of getting breast cancer of 30.9%. The next step was to meet with one of our genetic division’s doctors to go over my results in more detail and discuss preventive options.
I next met with Jeffrey Weitzel, M.D., a clinical geneticist and director of the Division of Clinical Cancer Genomics in the Department of Population Sciences at City of Hope. He said that my genetic test results were considered “uninformative” overall because they identified no pathogenic variants and no “clinically actionable genes” that could account for my family history of cancer. This means that the cancers in my family are considered “sporadic” (not due to an inherited gene; about 80% of cancers are classified this way) and “multifactorial” in origin.
Weitzel, the Dr. Norman & Melinda Payson Professor in Medical Oncology, added that the SNP data actually gave me a slight favorable edge in terms of my cancer risk and that while my risk was high (mostly because of family history), it was difficult to quantify. He estimated my lifetime breast cancer risk of somewhere between 16% and 40%, although my chance of being diagnosed with it in the next five years was only 1.7% (while this seems small, it is double the average risk and typical for a woman 10 years older than me — breast cancer risk increases with age).
Breast Cancer Screening Recommendations
He recommended annual mammograms and MRIs done six months apart, based on National Comprehensive Cancer Network guidelines, and mentioned that some women with my risk profile choose to take tamoxifen. He also advised me to reduce other breast cancer risk factors by maintaining a healthy weight and regular exercise program, eating healthy foods and refraining from excessive alcohol consumption. In addition, he and Nehoray suggested that other family members, such as my sister, consider genetic testing, since just because I didn’t inherit any mutations, it doesn’t mean there aren’t any present in my family.
On a practical level, I plan to follow his screening recommendations, and have my first breast MRI scheduled. (Tamoxifen, no.) Emotionally, I am still trying to wrap my head around the fact that in just a few short months I went from thinking my breast cancer risk was average to learning it was high. But I am relieved to have the genetic information, as well as a screening plan in place. One thing I have learned working at City of Hope is that the best cancer treatment is prevention.
Samantha Bonar (pictured above left) is senior manager of content at City of Hope.