Cancer science today: Knowing your family’s cancer risk
On March 15, as I entered the John Theurer Cancer Center at the Hackensack University Medical Center, I was greeted by sounds of a live pianist playing soothing music in the artfully decorated, soaring atrium. I walked down a bright corridor off the lobby, passing medical offices and patient services, as I headed to the conference center to attend the “Cancer Science Today” community talk offered by the Memorial Sloan Kettering — Hackensack Meridian Health partnership.
More than 100 people — most of them women — filled the conference center for the program, called “Knowing your family’s cancer risk,” the first in a series of complimentary talks on cancer treatment.
The partnership between New Jersey’s Hackensack University Medical Center and New York’s Memorial Sloan-Kettering Cancer Center is designed to “combine the expertise of two world-class organizations to work toward more cures for cancer and increase patient access to the highest-quality cancer care available,” according to the partners’ press release. One eventual goal that its founders hope will result from linking the two centers is the opening of joint treatment facilities.
The cancer genetics panel included moderator Joanna Gagis, the host of NJTV’s “Life & Living with Joanna Gagis,” and experts from the two institutional partners: Dr. Elizabeth Jewell, director of surgery at MSK Monmouth and MSK Basking Ridge, and Dr. Deena Mary Atieh Graham, breast and gynecologic medical oncologist at Hackensack’s John Theurer Cancer Center.
One of the most rapidly moving fields in 21st-century medicine involves the discovery of cancer genes and the new technologies that permit genetic screening for cancer linked genetic mutations. Since the human genome project was completed formally in 2003, the analysis of human genes has led to the identification of a multitude of human genes linked to such diseases as cancer.
Cancer genes can be passed from parents to offspring, or they can arise from sporadic, unpredictable mutations that occur throughout life. “We’re constantly evolving,” Dr. Jewell said. “We heal, we recover, we change, and sometimes we don’t heal correctly. We are exposed to smoke or chemicals or UV radiation. Or we are born with genes that are already mutated, as opposed to sporadic mutations. You don’t pick your mom, you don’t pick your dad. That’s what you’re left with — your inherited mutations.” She reported that “most cancers are sporadic. Only five to ten percent of cancers are related to inherited mutations.”
Dr. Jewell explained that although you cannot control what you have inherited, to some extent you can reduce your exposure to environmental triggers that lead to cancer. “By not smoking, by eating well, exercising, and wearing sunscreen, you reduce the risk of the genes mutating,” she said.
Dr. Graham gave examples of cancer genes, noting that the genes associated with breast and ovarian cancer, BRCA1 and BRCA2, typically are inherited as germ-line mutations that impede the ability of cells to repair themselves. “The risk of breast cancer [due to BRCA genes] can be upward of 70 percent, and up to 40 percent for ovarian cancer,” Dr. Graham said.
She explained that another type of inherited cancer, Lynch syndrome, also involves faulty genes that affect DNA repair. That kind of genetic glitch disrupts cells’ ability to perform mismatch repair. When the letters of the DNA code are mismatched, healthy cells can cut and repair errors before they affect cell function. But cells with certain mutations cannot perform those operations leading to abnormal cell growth, and in the case of Lynch syndrome, a high risk for colon cancer as well as cancers of the ovary, uterus, stomach, brain, skin, and other organs.
Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer — or more approachably HNPCC —was named for Henry T. Lynch, who many consider to be the father of cancer genetics. In the 1960s and ‘70s, when most of the medical establishment was convinced that environmental factors caused cancer, Dr. Lynch stubbornly continued his research on the familial and genetic basis of cancer, demonstrating that some cancers run in families and are transmitted from generation to generation. His work encouraged others to study specific genes, and this led to the identification of BRCA1 and BRCA2 and many other cancer-associated genes.
It is important to note that inherited mutations do not necessarily develop into cancer, Dr. Graham said. “Even if you inherit, it’s not a guarantee to get cancer,” she said. “There are things you can do to lower risk. It doesn’t have to be a fearful thing; it is better to have the knowledge.”
“Family history is critical and provides clues for yourself or your healthcare provider,” Dr. Jewell said. Some flags for hereditary cancer include: “If you develop cancer prior to age 45, or have several different cancers, such as breast and colon, or have several family members on one side [of the family] with cancer, or a clustering of disease types, [such as] three cousins on one side with colon cancer or melanomas,” those are indications that inherited cancer genes may be involved.
Heritage can also be a factor, she continued. “There are distinct populations at higher risk for carrying these mutations. Ashkenazi Jews are at a higher risk for BRCA mutations. Icelandic populations and Mexican Hispanic populations have elevated risks as well.” About one in 50 Ashkenazi Jews carry mutations in BRCA1 or BRCA2 that are associated with an elevated risk of cancer. About 1 in 200 Icelandic people have a unique BRCA2 mutation.
Ms. Gagis, who moderated the discussion, asked if there is a misperception that only women can pass hereditary cancer genes to their children. Dr. Jewell answered that both men and women can transmit the genes to their offspring. She said that sometimes patients will say with relief, “I’m safe, I have three sons, I’m OK,” thinking erroneously that the problem genes end with them. “They’re not OK,” Dr. Jewell said. “They can pass down the genes to sons and daughters. BRCA and Lynch syndrome are not just a lady problem.” The cancer genes can increase risk of breast, ovarian, prostate, pancreatic, and colon cancer, and both men and women have to be aware of that. “There are males with BRCA, and there is breast cancer in males,” Dr. Jewell said.
The Federal Drug Agency recently approved the sale of genetic tests direct to consumers without a physician or genetic counselor being involved, she continued. The FDA lists about 100 different approved genetic tests on its website, tests that dozens of different companies offer to consumers. Those tests screen for genes associated with breast and ovarian cancer, melanoma, lung cancer, prostate cancer, acute myeloid leukemia, and others. The variety and complexity of what is available would make it very difficult for even a genetics expert to decipher.
Dr. Jewell offered an example of a direct-to-consumer genetic testing company, 23andMe, which got its start designing tests to reveal genealogical roots and heritage. (The company’s name is based on the 23 unique pairs of chromosomes in all our cells that serve as the repository of our genes.) “You can get all the clues about your gene,” she said. “For about $200 all the mysteries of your life are answered, what percent of you came from here and there.”
The first commercial tests for cancer genes were developed by Myriad Genetics, which patented the process of screening for cancer genes. The patent was challenged based on the fact that DNA is a natural material, not an invention or innovation. “The court system decided that genes are not patentable,” Dr. Jewell said. This court decision opened the floodgates to other companies to develop their versions of genetic tests.
Ms. Gagis asked the two doctors how DTC testing differs from clinical testing. How does genetic testing work at Hackensack Hospital and Memorial Sloan-Kettering?
Dr. Graham said that clinical testing is broader and includes other genes, as well as genetic counseling. She recommends that genetic testing be done under the auspices of a genetic counselor. “Genetic testing is not black and white,” she said. “It’s not cut and dry. When you meet with a genetic counselor you will know what the test will tell you and what the test will not tell you. Perhaps DTC testing is useful for people who don’t otherwise have access to testing. But in this area there are resources.” Most importantly, she added, “a genetic counselor can tell you what to do with these results.”
Dr. Jewell concurred, noting that 23andMe tests for only a few versions of the mutated genes. “It requires expertise to decide what to test you for.” If the test comes out negative for mutations, the patient “may feel false reassurance that they have not inherited the gene to be concerned about.”
In other words, the testing that private DTC companies do may be inadequate and result in incomplete information to the detriment of the patient.
“In the 1990s there were just two tests,” Dr. Jewell said. “Now it’s an alphabet soup.” She was referring to the fact that genetic tests are labeled with an odd array of code letters and acronyms. “There are so many genes. It is the medical community’s responsibility to keep the public educated. It becomes a bigger problem as we find more genes. We are concerned and excited about the future, and how it will inform the public.”
Ms. Gagis asked the panelists “If you have an inherited mutation, what preventative measures are there?”
Dr. Jewell responded by summarizing the vast scope of medical practice in cancer treatment in just a few sentences: Tamoxifen can reduce risk for women with BRCA mutations; so can surveillance through frequent mammograms and MRIs. In addition, “risk-reducing surgeries for the more serious cancers,” she said, can prevent cancers. “There are no good screening tests for ovarian cancer. CA125 [blood test] and ultrasound do not detect ovarian cancer at an early stage. But you can remove the fallopian tubes and ovaries.” There is also a new approach that is being tested called the WISP trial — WISP stands for Women Choosing Surgical Prevention. Women at high risk due to BRCA mutations are assigned into two groups. The women in the first groups undergo hysterectomy and oophorectomy at the same time — that removes the uterus, uterine tubes, and ovaries. The second group has their Fallopian tubes removed first; years later, their ovaries are removed. The intention of the second protocol is to delay menopause and permit fertility, while still reducing risk. This ongoing study still is enrolling volunteer subjects. The outcome of the study may change the approach to prophylactic surgery and give women more choices in treatment.
Another promising therapy Dr. Graham reported is the PARP inhibitor olaparib (Lynparz), which the FDA approved in January 2018 for patients with certain types of BRCA-associated breast cancers. Research on this drug, conducted in the “OlympiAD trial” on 302 patients from 19 countries, showed a 42 percent reduced risk of cancer progression or death. Dr. Graham explained that “targeted drug options … are mostly oral medications that target the error in BRCA and cells. They prevent cancer from happening in the first place.”
Immunotherapy is another approach that “revs up the immune system to fight the cancer,” Dr. Graham said. “Cancers sometimes do not look foreign, and the immune system doesn’t recognize it as foreign.” Immunotherapy already has changed the outcome for many cancer survivors, extending their lives and improving the quality of those lives.
Marsha Eisen of Hackensack attended the program to learn what she can do about her family’s cancer risk. “I’m thinking about where I’m coming from,” she said. “Three out of three of my primary relatives had cancer.” Ms. Eisen’s father died of bladder cancer when he was 73; her brother, who had esophageal cancer, died at 58, and her mother was treated for breast cancer at Hackensack Hospital. Although she was negative for BRCA mutations, Ms. Eisen’s mother was part of a national study on the BRCA genes.
Ms. Eisen, who retired after a more than 35-year career as a dietician at Hackensack Hospital, said that “you don’t have to cross the [Hudson] river” for high-quality cancer treatment. She remarked on the growth of treatment options in the past few years, noting that “the hospital has mushroomed since I retired.”
Information on the John Theurer Cancer center is at www.hackensackumc.org/services/cancer-care. MSK-HMH Partnership activities and services are at msk-hmhpartnership.org.
Dr. Miryam Z. Wahrman of Teaneck is a professor of biology at William Paterson University in Wayne. Her book, “The Hand Book: Surviving in a Germ-Filled World” provides insight and advice for healthcare workers and the general public on how to reduce the risk of infectious disease.
comments