Amira,* 53, hurried from her day job of teaching high school math to pick up her granddaughter from nursery school. When her daughter arrived to take the toddler home Amira took a welcome shower. Soaping herself under the hot water, she felt an unfamiliar swelling in her left armpit. At first, she thought it might be a bug bite, but she couldn’t remember being bitten.
This felt different from a bug bite. She was scared.
Her mother had died of breast cancer. What if she had breast cancer, too? If so, are her daughter and her granddaughter doomed to breast cancer?
Had Amira been a Jewish woman of Ashkenazi descent, she might have known if she has the infamous BRCA 1 or 2 mutations, and her mother’s oncologists would have recommended her being tested. The test is covered by all the Israeli national insurance plans.
But Amira isn’t Jewish. She’s a Muslim woman whose family originates from Hebron.
What Amira learned from her own oncologist is that recent discoveries at the Hadassah Medical Organization have revealed genetic mutations common in Arab women, not on the BRCA gene, but on a gene called TP53.
Amira would be tested, and so could her daughter, in her late 20s. The doctor recommended that Amira’s sisters undergo genetic testing as well. With so many large traditional Jewish and Arab families in Israel, Hadassah researchers were able to move ahead more quickly than colleagues in many countries in identifying cancer-causing genetic mutations.
Despite the shock of being diagnosed with breast cancer, there was more encouraging news. A blood test developed at the Hebrew University and the Hadassah Medical Organization could help show how effective her own treatment is and also monitor her daughter for the first signs of possible cancer.
Says senior oncologist at Hadassah’s Sharett Institute of Oncology Dr. Aviad Zick. “Treatment of early breast cancer is critical. It leads to a cure in more than 90% of patients.”
Inherited Traits
“Hereditary cancer comprises more than 10 percent of all breast cancer cases. Identification of [hereditary] mutations enables the initiation of preventive programs that can include early detection or preventive treatment,” says Dr. Zick.
Hadassah physician researchers are at the forefront of the search for the genes or parts of genes that make a woman vulnerable to breast cancer. Hadassah research confirmed decades ago that there is at least a 10 times greater prevalence of BRCA1 gene mutations among women of Ashkenazi descent. Hadassah then identified a founder mutation in Sephardic Jews and, subsequently, in Kurdish Jews.
They discovered that part of gene TP53, which helps repair damaged DNA, makes Arab women vulnerable to developing breast cancer if it is mutated.
Breakthrough in Diagnosis
Amira’s daughter should undergo DNA sequencing to see if she has the TP53 mutation. But whether she has it or not, because of her family history, she should undergo blood tests every few months to find the very first threads of cancer, should she develop it.
Hadassah’s oncology team is collaborating with members of the pathology department as well as Prof. Yuval Dor of Hebrew University to detect breast cancer in a person’s circulating tumor DNA (ctDNA). This DNA, which is derived from the tumor, floats in the blood and thus becomes a specific marker that can be detected, measured and tracked. In addition, it is tissue/organ specific so researchers would know which type of cancer is present
“We are hoping these blood tests with liquid diagnosis of cancer will eliminate painful biopsies and even the need for surgery,” says oncologist Dr. Josh Moss, a developer of the test. His patent for a multi-cancer blood test is being developed by the California-based company GRAIL,
But Dr. Moss stresses that the blood test will be an essential tool in cancer treatment, too, allowing quick evaluation of treatment protocols, be they chemotherapy, radiation or immunotherapy.
Low-risk women who have no genetic factors and who show no cancer signs in their blood may soon be able to forgo mammograms, reducing X-ray exposure and medical costs.
Profiling Each Tumor
“Because patients are treated with chemotherapy based on statistical models, rather than their individual tumor’s molecular makeup, some women don’t benefit from standard chemotherapy. We hypothesize that ctDNA can serve as a predictive biomarker for chemotherapy success in early breast cancer," says Dr. Zick.
In addition, the specific genetics of each tumor are different from patient to patient, and different from a woman’s own genetic makeup. Hadassah clinicians include universal genetic testing of breast tumors as an essential part of the treatment program.
Hadassah investigators are working to identify the specific and nefarious ERBB2 gene mutations that are connected to an aggressive form of breast cancer.
Says Dr. Zick, “Understanding what part inherited traits play in an individual’s chance of developing breast cancer; analyzing the specific biology of each tumor to better tailor therapy for each patient; and diagnosing cancer through blood samples, rather than performing biopsies, are the directions that are shaping the approach the we’re taking for cancer research and treatment.”
For Amira and her family, as well as breast cancer patients worldwide, the exciting breakthroughs at the Hadassah Medical Organization clinics and laboratories provide new hope for detection and cure.
*Amira’s name and details of her story have been changed to protect her privacy.