Genomic Intelligence Improves Cancer Care

Sylvester physician-researchers weigh in on the transformational role genetic testing has in oncology.

Cancer survivorship starts on the day of diagnosis and continues throughout a patient’s life. But the work on cancer and its prevention can begin well before that day.

Photo of researcher in lab looking into microscope
Genetic testing can identify cancer “previvors” and establish a care plan before the actual diagnosis.

Advances in the genomic era are producing unprecedented progress. Physician-researchers are learning more about how cancer develops, who is affected and what works best, via the patient’s DNA. Moreover, the development of molecular-targeted therapies has improved cancer outcomes.

In the mission to find cancer cures, efforts are aimed not only at treating the disease, but reducing risk and increasing prevention. Along those lines, centers like Sylvester Comprehensive Cancer Center, a part of the University of Miami Miller School of Medicine, are evolving care with programs to identify “previvors.”

Cancer Previvors

Today, previvors—people who do not have cancer but are at increased risk for developing cancer due to genetic mutations—have an opportunity to intercept the disease at its earliest stages, when outcomes are the best.

Previvor needs and concerns are separate from the general population because of their increased cancer risk, and different from cancer survivors, who already have a diagnosis. As a National Cancer Institute-designated center, Sylvester understands this.

The evolution taking place in transformational care through genomics, translational research and team science speaks to Sylvester’s commitment to delivering world-class cancer care. Teams of experts across different site groups collaborate to help survivors and previvors reduce their chances of developing cancer. At the same time, they are also working with family members to manage their cancer risks.

Cancer Preparation Starts with Genetic Testing

The first step is predictive genetic testing, which looks for inherited gene mutations that might put a person at higher risk of getting certain kinds of cancer. Germline testing, which is done via cheek swabs, saliva samples or a blood draw, has important implications for patient diagnosis, prognosis, treatment and screening. It also helps determine risk-reducing interventions and identify the need for further genetic counseling and testing for patients and families.

Testing is often suggested for a person already diagnosed with cancer or who has a strong family history of certain types of cancer. In a person diagnosed with cancer, genetic information can inform treatment. Testing is also recommended to the family members of those who are known to have an inherited gene mutation that increases their risk of cancer.

Many genetic mutations may cause cancer, but two of the most well-known genes—Breast Cancer Gene 1 (BRCA1) and Breast Cancer Gene 2 (BRCA2)—can mutate and raise the risk of breast cancer. Despite their names, both are also associated with ovarian and prostate cancer, as well as other cancers. Fortunately, many medical options are available for managing cancer risk in previvors with BRCA mutations, such as increased surveillance, chemoprevention and preventive surgeries.  

Women Can Reduce Cancer Risk

According to the National Cancer Institute, about 13% of women will develop breast cancer and 1.2% will develop ovarian cancer. By contrast, 55% to 72% of women who inherit a harmful BRCA1 variant and 45% to 69% of women who inherit a harmful BRCA2 variant will develop breast cancer.

Sylvester Comprehensive Cancer Center's Abdulrahman K. Sinno, M.D.
Abdulrahman K. Sinno, M.D., directs surgical research and education at Sylvester Comprehensive Cancer Center.

With ovarian cancer, 39% to 44% of women who inherit a harmful BRCA1 variant and 11% to 17% of women who inherit a harmful BRCA2 variant will develop ovarian cancer.

“The most effective option for preventing breast and ovarian cancer in women with BRCA mutations is a double mastectomy and removal of the ovaries and fallopian tubes,” said Abdulrahman K. Sinno, M.D., director of surgical research and education at Sylvester and associate professor of clinical obstetrics, gynecology and reproductive sciences for the Miller School. “There are other options that are less invasive, but they may not be as effective or are only offered as part of a clinical trial.”

Actress Angelina Jolie, who tested positive for BRAC1, decided to document her choice to have an elective double mastectomy and removal of her ovaries and fallopian tubes. Her New York Times opinion piece in 2015 offered a very personal look at the surgery, her reasons and the fact that her mother, grandmother and aunt all carried the genetic mutation, developed cancer and passed away because of the disease.

Current guidelines suggest that the gynecological groups that benefit most from testing include anyone who has a personal history of ovarian cancer or a first-degree relative who has ovarian cancer, as well as those with a family history of breast cancer or other cancers, like Jolie. Individuals of Ashkenazi Jewish ancestry or who have Lynch syndrome are also at high risk.

Dr. Sinno noted, however, the SOROCk clinical trial, which compares fallopian tube removal to fallopian tube and ovary removal in women with the BRAC1 mutation, offers patients an alternative. The study examines whether just removing the fallopian tubes is inferior to removing both the tubes and ovaries.

“Given that the overwhelming majority of ovarian cancer that is BRCA-related starts in the fallopian tube, we are able to offer patients with BRCA1 mutations a risk-reducing salpingectomy (removal of the fallopian tubes) in lieu of a complete oophorectomy (removal of the ovaries), which avoids the risk of surgical menopause and at the same time reduces the risk of developing ovarian cancer.”

BRCA Gene a Cancer Risk for Men, Too

Most research and awareness efforts for BRCA have focused on women, but men are also at risk. Men who carry the BRCA gene mutation have a higher risk of developing breast, prostate and other cancers, as well as the same 50% chance of passing that mutation on to their children.

Sylvester Comprehensive Cancer Center researhcer Marijo Bilusic, M.D., Ph.D.
Marijo Bilusic, M.D., Ph.D., says early detection is crucial for prostate cancer patients.

Most studies show that patients with a BRCA2 mutation have a 20% to 40% chance of developing prostate cancer. For some, the odds may be as high as 60%.

“Prostate cancer in patients with the BRCA gene mutation is more common and aggressive, and can happen at an earlier age,” said Marijo Bilusic, M.D., Ph.D., Sylvester medical oncologist and lead of the Genitourinary Site Disease Group. “The cure rate for prostate cancer is very high if detected early, even with a BRCA mutation.”

Dr. Bilusic says that men whose mothers or grandmothers have cancer because of a BRCA mutation should consider genetic testing.

Genetic Cancer Predisposition Testing

At Sylvester, the Eileen Youtie Hereditary Predisposition Initiative helped establish the Sylvester Genetic Predisposition Syndrome (GPS) Clinic, which treats survivors and previvors with genetic mutations that increase cancer risk.

“The program provides specialized, coordinated and multidisciplinary care that includes emotional and psychosocial support, genetic testing, personalized care plans, navigation through high-risk clinics, access to cutting-edge research and more,” said Carmen Calfa, M.D., Sylvester medical co-director, Cancer Survivorship and Translational Behavioral Sciences, associate director of community outreach, and associate professor of clinical medicine at the Miller School. “It encompasses the expertise of all of the specialists at Sylvester and it’s offered in person or virtually.”

Genetic Counseling

On the surface, the concept of genetic testing seems simple – a sample of blood or saliva allows recipients to be proactive about their health and to help determine if other family members are at risk. When put into practice, it’s more complicated.

Sylvester Comprehensive Cancer Center's Carmen Calfa, M.D.
Sylvester medical co-director Carmen Calfa, M.D., stresses the importance of genetic counseling for cancer previvors.

The results might not reveal what patients want to hear, becauses carrying an inherited mutation that puts themselves or their kids at risk can increase stress and damage relationships.

“Patients with a positive mutation should speak with a genetic counselor to gain a clear understanding of the risk associated with the gene, as well as the recommended surveillance and risk reduction measures,” said Dr. Calfa.

The decision to move forward with prophylactic measures to manage cancer risk is a personal one. In Jolie’s case, she mentioned how she felt empowered to take control. Education made the difference. Through knowledge and action, she gained peace.

The key to making a good decision is to have not only the information but a team of experts available for consultation. This is where Sylvester physician-researchers are transforming cancer care.

Tags: BRCA1, BRCA2, cancer genetics, Dr. Abdulrahman K. Sinno, Dr. Carmen Calfa, Dr. Marijo Bilusic, Eileen Youtie Predisposition Syndrome Initiative, previvorship, Sylvester Comprehensive Cancer Center, USNWR Oncology