Early-onset cancers, defined as those diagnosed in people between the ages of 18-39, occur with surprising frequency and include breast, colon, kidney, pancreatic, and ovarian cancer. In young adults with early-onset cancers, 21% harbor germline mutations, with the most frequent being mutation of the BRCA1 or BRCA2 gene. Upon learning of a BRCA2 mutation haunting her family for generations, Mia Leslie, a young woman from Toronto, insisted and pressured her doctors to take preventive measures.
BRCA (for BReast CAncer) are genes that encode tumor suppressors; when functioning normally, they help repair damaged DNA that may occur during DNA replication. The population frequency of pathogenic BRCA mutations is 1:400. If either parent has a BRCA1 or BRCA2 mutation, there is a 50% chance of passing the mutation to their child. Mutant BRCA2 carriers are at higher risk of developing certain cancers relative to the general population and having a BRCA mutation accounts for 3-10% of all breast, pancreatic, and ovarian cancers.
In 2015, Mia, 18 at the time, had a routine breast exam during a doctor’s appointment along with a discussion about her family history of cancer. In 2009, Mia’s father had passed away suddenly eight weeks post-diagnosis with liver cancer, which raised a red flag. “It came out of nowhere,” Mia recalls. “An aggressive liver cancer with spots in his lungs. He didn’t drink or have hep B.” Mia discussed her dad’s medical history with her doctor, who posited that her father’s symptoms and rapid decline aligned with pancreatic cancer. The primary site of pancreatic cancer spread is within the abdomen to the liver; likely, the aggressive liver cancer that took her father was a metastatic lesion. Unfortunately, an investigation into the cause of cancer was not performed.
Upon her doctor’s recommendation, Mia underwent genetic screening, uncommon for a person her age. Genetic counselling recommends testing if there is any family member with pancreatic cancer, a family history of breast, ovarian or prostate cancer in multiple relatives on the same side of the family, a family history of breast cancer diagnosed at a young age, a male relative diagnosed with breast cancer, or a known genetic mutation in the family. Meeting many of the criteria on this list, in 2015, Mia was tested and diagnosed as a BRCA2 carrier.
“The genetic mutation is prevalent on my dad’s side,” Mia says. Mia’s grandmother got breast cancer when she was 42 and developed ovarian cancer 12 years later. In 2012, Mia’s aunt, her dad’s sister, was diagnosed with stage III breast cancer.
In 2015, Mia’s aunt’s daughter was diagnosed with stage II breast cancer. Both women are mutant BRCA2 carriers. Mia’s cousin from her grandmother’s side, passed away from pancreatic cancer and three others on her dad’s side are mutant BRCA2 carriers. Discovering a familial genetic mutation predisposing their family to cancer was shocking, yet some family members chose not to be screened.
Inherited susceptibility to cancer exposes young adults to unique challenges. Proactive testing is critical given the risk of primary cancer, the need for appropriate long-term surveillance, and the potential for reproductive complications. “Cancer is being detected in younger and younger people; I did not want to take the risk.” Following genetic screening, Mia had routine breast exams every few months for 3 years. In Ontario, breast screening mammography services are only provided for screening women aged 30 and older.
Mia had decided that she wanted a double mastectomy. “It is marginal to what I could be faced with,” she says. “I was trying to make a proactive decision. But the doctors said I was being naive or irrational.” In May 2018, Mia found a plastic surgeon and had a preventive bilateral double mastectomy at age 21. “My risk was reduced by 87-95 percent, which meant I only have a 1-2 % risk of breast cancer after the mastectomy.” In 2019, Mia also decided to have her tubes removed as a preventative measure to reduce her risk of developing ovarian cancer. Current research suggests the fallopian tubes are the tissue of origin for high-grade serous ovarian cancer, the deadliest subtype.
Mia is confident the surgeries have improved her situation, and she advocates for genetic testing in people with a family history of cancer. “Putting things off is not the best choice,” she says. “I don’t want to get cancer; my dad was young when he was diagnosed. I wanted to get out in front of the cancer. I did not want it to get in front of me.”