James Cancer-Free World Podcast

James Cancer-Free World Podcast

“We used to call ovarian cancer the disease that whispers and now we say, let’s break that silence,” said David O’Malley, MD, director of the OSUCCC – James Division of Gynecologic Cancer. In Episode 69 of the James Cancer-Free World Podcast, O’Malley and Leigha Senter, an OSUCCC – James genetics counselor, help break the silence and talk about advances in the treatment of this type of cancer, and how more widespread genetic testing will save lives.

Population-wide testing could prevent many ovarian and breast cancer deaths

Population-wide testing could prevent many ovarian and breast cancer deaths

Blood testLarge-scale BRCA screening of women in the United States and around the world would help prevent a great many deaths from breast and ovarian cancers. In high-income and upper-middle-income countries, testing would be highly cost effective, according to a modeling study published in Cancers.

“General population BRCA testing can bring about a new paradigm for improving global cancer prevention,” author Ranjit Manchanda, MD, PhD, of the Queen Mary University of London, said in a press release.

Approximately 10% to 20% of ovarian cancers and 6% of breast cancers are attributable to heritable BRCA1/BRCA2 mutations. Women with harmful BRCA mutations have a 17% to 44% risk of developing ovarian cancer and a 69% to 72% risk of breast cancer before age 80. With several prevention options available, many of these cancers can be kept at bay. But for a variety of reasons, few women access BRCA testing. In the United States, only 20% of eligible women have been tested.

Currently, BRCA testing is guided purely by family history or clinical symptoms, which may leave out numerous carriers of the harmful gene. Manchanda and his colleagues sought to determine the cost effectiveness of universal BRCA testing in women from different nations with varying health systems.

The team compared lifetime costs and the impact of BRCA1/BRCA2 testing of the general female population with testing based on family health and clinical symptoms. They stratified different countries in the study according to income:

  1. High-income countries such as the United States, Netherlands and United Kingdom
  2. Upper-middle-income countries such as China and Brazil
  3. Lower-middle-income countries such as India

The research team included all women who were at least 30 years of age and modeled various scenarios of population-wide testing from the viewpoints of both the payer and society for countries in different income brackets.

The researchers found that population-based BRCA testing was cost saving in high-income countries and cost effective in upper-middle-income countries but not in lower-middle-income countries. In order to be cost effective in countries such as India, BRCA testing costs would need to fall below $172 per test. Further, from a payer perspective, population-based BRCA testing was highly cost effective in high- and upper-middle-income countries but not in lower-middle-income countries.

Moreover, the team reported that population-based testing would prevent an additional 2,319 to 2,666 breast cancer cases and 327 to 449 ovarian cancer cases per million women compared with the current testing plan.

“With increasing use of telehealth and a transformed health care system that guarantees health insurance for every American without discrimination, then we may achieve the promise of genomics to improve population health in the U.S.,” Olufunmilayo Olopade, MD, of the University of Chicago, who was not involved in the study, told MedPage Today. However, universal screening is not practical in the United States given the current state of the health care system.

“Strategies and pathways for population testing must be developed to enable population genomics to achieve its potential for maximizing early detection and cancer prevention,” Manchanda said.


Identifying Biomarkers for Ovarian Cancer

Identifying Biomarkers for Ovarian Cancer

NEW YORK – Researchers from Inova, Roswell Park Comprehensive Cancer Center, the Mayo Clinic, and MD Anderson Cancer Center have partnered with the Department of Defense to form an ovarian cancer consortium focused on the discovery of biomarkers for early detection of the disease.

The initiative, known as the DoD and SPORE Ovarian Cancer Omics Consortium, is part of the National Cancer Institute’s Specialized Programs of Research Excellence (SPORE) initiative. It has received a $544,360 grant from the DoD for the first phase of its work, which will focus on setting up the infrastructure and teams to enable its work.

The Consortium will be comprised of researchers from the DoD’s Gynecologic Cancer Center of Excellence (GYN-COE) and Women’s Health Integrated Research Center at Inova; Roswell Park Comprehensive Cancer Center in collaboration with the University of Pittsburgh Cancer Institute; the Mayo Clinic Cancer Center; and MD Anderson Cancer Center.

Using recent omics discoveries about the origins of ovarian cancers, the researchers are aiming to gather biospecimens, and discover and validate biomarkers to inform early detection and screening for serous tubal intraepithelial carcinoma (STIC) and ovarian cancer. STIC lesions are precursors of the majority of ovarian cancers. They take about seven years to develop but are rarely found before they develop into cancer.

“Recent research has implicated the fallopian tubes as the source of many ovarian cancers. Cells toward the end of the fallopian tube take on malignant features, then drop these mutated cells on the surface of the ovary and within the abdominal cavity, where they have the opportunity to develop into aggressive and hard-to-detect cancers,” Roswell Park Deputy Director Kunle Odunsi, the consortium’s principal investigator, said in a statement.

“We’re asking the question, ‘Can we identify STIC lesions long before they become cancer as a form of early detection, similar to a PAP smear?'” Odunsi added. “There’s a window of opportunity where, if we can identify STICs, we can potentially prevent ovarian cancer, and that’s the challenge these accomplished teams are coming together to tackle.”

Odunsi also noted that the research will take several years, and will rely on the participation and biospecimens of hundreds of people.


New ovarian cancer tests and treatments start to emerge

New ovarian cancer tests and treatments start to emerge

For the past few years, as part of the University of Chicago Pritzker medical school obstetrics-gynecology rotation, med students at an optional lunchtime seminar hear from ovarian cancer survivors who share stories about the shock of diagnosis, painful treatments and constant worries about whether their cancer will come back.

Last year, listening to the women’s experiences became a mandatory part of their medical education. The hope is that by humanizing the disease, this relatively rare cancer will be on the radar of a new generation of doctors and will change this common patient narrative: “My doctor didn’t take my symptoms seriously until it was too late.”

Medical info photo“We felt it was important that students shouldn’t just learn about the biology of ovarian cancer, but we wanted them to know that every patient is a whole person with a story behind them,” University of Chicago gynecologic oncologist Nita K. Lee says.

The medical school curriculum change is a sign that the subject of ovarian cancer is being taken more seriously. It’s part of a surge of hopeful recent advances, including new research on blood tests to detect the disease at an early stage, new genetic understandings of dozens of cancer subtypes and new treatments. This year, in an effort to raise public awareness, the Centers for Disease Control and Prevention beefed up its consumer website on ovarian cancer and has plans to launch broadcast ads.

Compared to other cancer success stories, ovarian cancer historically has had a shortage of good news. It is deadlier and underfunded. Until recently, the disease has not benefited from new treatments for more than 40 years. About 22,240 U.S. women were diagnosed with ovarian cancer in 2018, and 14,070 women died the same year, according to government surveillance data. The reason: More than three-fourths are diagnosed when the cancer has advanced, and survival rates are low: Just 47 percent of patients survive five or more years.

That means that unlike the 3.4 million pink-clad U.S. breast cancer survivors who make up an army of activists marching for research money and attention, there are starkly fewer women living with ovarian cancer — just 225,000 in the United States — who are around to represent their cause.

Even their signature color — teal — is understated.

“Sometimes it’s hard feeling like a stepchild in a teal dress,” says activist Ellen Engle, a project manager from Potomac, Md., who was diagnosed with Stage 4 ovarian cancer four years ago at age 47. She’s an administrator of the Ovarian Cancer Support Group on Facebook. “We hear so many stories of women having their symptoms dismissed,” she says. “They’re told they’re going through menopause or have irritable bowel syndrome.”

Engle leaves educational cards warning women about the often-overlooked symptoms of ovarian cancer — abdominal bloating, changes in appetite, pelvic pressure, lower back pain or frequent urination — in women’s bathroom stalls at airports, fast-food restaurants, even a recent Elton John concert.

Another common story is that women chalk up persistent stomach bloating symptoms to gluten or lactose sensitivities that they try to treat with probiotics or elimination diets, says Bobbie Rimel, a gynecologic oncologist at Cedars-Sinai Medical Center in Los Angeles. “I see so many people in my practice who let this ride out for five or six months because they thought they could figure it out,” she says. “But I end up figuring out it’s cancer, and it’s really sad.”

Yet the onus isn’t only on patients and doctors to be more vigilant. The field has lacked good diagnostic tools. The most commonly used test, developed in the early 1980s to measure a protein called CA 125, finds only 80 percent of cases and is subject to false-positives since the protein can also rise during menstruation and pregnancy.

Yet the onus isn’t only on patients and doctors to be more vigilant. The field has lacked good diagnostic tools. The most commonly used test, developed in the early 1980s to measure a protein called CA 125, finds only 80 percent of cases and is subject to false-positives since the protein can also rise during menstruation and pregnancy.

It’s more effective when paired with a transvaginal ultrasound, which can detect an ovarian mass. But since the current imaging technology can’t reveal whether that mass is cancerous, women usually are diagnosed after undergoing surgery to remove part of or the whole ovary.

“I do anywhere from three to six surgeries for every cancer I find,” Rimel says. “And I often don’t find them early enough to make a difference in the survival of patients.”

In search of the screening breakthrough that would dramatically improve mortality rates, scientists are looking for clues in women’s blood to see if they detect the cancer before it becomes lethal. In February, University of Kansas researchers announced they had developed a low-cost method of finding cancer markers in cell byproducts called exosomes in a drop of blood.

At the University of Texas MD Anderson Cancer Center in Houston, ovarian cancer researcher Robert Bast, who co-discovered the CA 125 test, is working on developing a different blood test that could measure multiple markers simultaneously and shave off at least a year from the time when patients traditionally have been diagnosed.

“We want to be able to detect a smaller amount of cancer earlier rather than wait for the tumor to shed enough cells into the abdominal cavity,” Bast says.

Other researchers are exploring new genetic sequencing techniques to understand how micro RNA, short molecular segments that turn off part of a person’s genome, is expressed differently in women with ovarian cancer. The team of Kevin Elias, a gynecologic oncologist who runs a lab at Brigham and Women’s Hospital in Boston, is designing a clinical trial to study blood samples of women that were collected before they noticed symptoms and were diagnosed with cancer. The goal is to see whether micro RNA patterns could have predicted who would get the disease later and estimate the magic moment when to intervene surgically to remove tumors.

“We’re trying to figure out the lead time to catch women when they’re high risk and curable,” Elias says. He says a resulting test will first be offered to the 20 percent of women who have a hereditary risk for ovarian cancer and then to the general population.

There’s also hope that new biological understandings of ovarian cancer will lead to more effective personalized treatments and prolong survival.

“We’re learning that ovarian cancer isn’t just one disease. It’s made up of many subtypes with distinct pathways and risk factors,” says Beth Karlan, a gynecologic oncologist at the David Geffen School of Medicine at the University of California at Los Angeles. For example, one kind of ovarian cancer tumor might be the size of a grapefruit that doesn’t spread, while another pea-sized subtype will quickly metastasize.

“We can’t continue to treat women as ‘one-size fits all,’ ” she says.

Recently, the Food and Drug Administration has approved targeted oral therapies, called PARP inhibitors, which kill off cancer cells. Although their intended use is for ovarian cancer patients with BRCA genetic mutations, which account for 15 percent of cases, researchers are exploring whether they can help women with other subtypes of ovarian cancer.

And another drug called bevacizumab — sold under the name Avastin — that stops the growth of blood vessels that nourish cancer cells has been successful when combined with chemotherapy for women with recurrent ovarian cancer. (Last summer, it was approved as a first-line treatment following surgery.)

Other targeted agents and immunotherapies that activate the immune system to fight cancer are in clinical trials. Still, the range and success rates of current treatment options are depressingly limited.

In the meantime, women should take advantage of new genetic sequencing tools to identity their cancer subtype and ask their doctor about getting into the right clinical trial instead of “going from chemotherapy to chemotherapy regimen hoping that something works,” says San Diego biotech executive Laura Shawver, who in 2008 founded the Clearity Foundation. The nonprofit group helps women with ovarian cancer get their tumors genetically profiled so they can be better matched to appropriate treatments.

“Women need to be aware that this technology exists and is usually covered by insurance,” she says.

What’s frustrating, Shawver says, is that by the time many women cycle through multiple chemotherapy regimens — the current standard of care for recurrent ovarian cancer — they might not be eligible for a clinical trial of new drugs. Also, their tumors might have changed over multiple treatments, so the drugs that might have worked initially for their subtypes are less effective.

“Your best chance for a cure is your first treatment and not when you’ve failed five other options,” Shawver says.

Before Liz Laats died of ovarian cancer three years ago at age 46, the mother of three from the San Diego area had suffered through 88 rounds of chemotherapy during 10 treatment regimens over six years that left her exhausted with chronic bone pain.

“At first, doctors gave her the treatments they said had done the most good for the most people, but they didn’t know how to treat her specifically,” says her husband, Andy Laats, who took her to more than two dozen doctors around the country.

“We kept thinking, ‘There must be a smarter doctor somewhere who knows.’ But you’re left trying to connect those dots,” he says, adding that Liz tried the “best of a lot of crappy options,” including drugs being tested in clinical trials that had worked in mice or patients with lung cancer.

“It felt like the game Chutes and Ladders. You get small steps of hope and then you fall down,” Laats says.

Despite the uneven progress, Lee at the University of Chicago wants the next generation of doctors to know that the story of ovarian cancer is changing for the better in small and meaningful ways.

“I don’t want to sugarcoat this terrible disease, but I also want students to see that women are living longer,” she says of the school’s collaboration with the Survivors Teaching Students program run by the Ovarian Cancer Research Alliance. “I want them to see the pictures of their families and the trips they’re taking. I want them to know that women are thriving. And I want them to know they might have the opportunity to identify the disease early enough to save a life.’


Genetic testing underutilized in ovarian cancer

Genetic testing underutilized in ovarian cancer

Only a minority of women with ovarian or breast cancer undergo recommended genetic testing, a new study suggests.

Researchers examined data for about 77,000 women diagnosed with breast cancer and 6,000 diagnosed with ovarian cancer in 2013 and 2014. Only about 24% of breast cancer patients and 31% of ovarian cancer patients had genetic test results, the research team reports in the Journal of Clinical Oncology, online April 9.

“We initiated this study – the largest population-based study of multigene testing in breast and ovarian cancer patients – because we wanted to see what cancer genetic testing and results looked like in the real world,” Dr. Allison Kurian of Stanford University in California said in a news release.

“Our major finding was substantial under-testing of ovarian cancer patients: fewer than one third were tested, while guidelines advise that nearly all should be tested. For breast cancer, guidelines have not recommended testing all patients and thus a rate of 24.1% is less concerning,” Dr. Kurian told Reuters Health by email.

“It is crucial that doctors seeing ovarian cancer patients discuss genetic testing with them and facilitate their obtaining it, and that ovarian cancer patients and their relatives advocate for appropriate genetic counseling and testing in their care,” she added.

When genetic tests were performed, 7.8% of women with breast cancer and 14.5% of those with ovarian cancer had pathogenic variants, information that “could be used to drive care decisions and influence family members’ health care and screening choices,” Dr. Kurian said in the release.

The study also found “concerning” disparities in genetic testing by race/ethnicity and insurance status.

For example, nearly 34% of non-Hispanic white women had genetic testing, compared with only about 22% of black women and 25% of Hispanic women. About 20% of Medicare patients were tested compared with about 34% of those with other forms of health insurance.

The prevalence of genetic was around 20% in areas where 20% or more of residents were poor compared with about 38% in regions with less poverty.

“More research is needed to understand all the factors contributing to this gap in care quality and how best to fix it,” Dr. Kurian told Reuters Health.

The study did not have commercial funding. Dr. Kurian has received research funding from Myriad Genetics and has other relationships with Ambry Genetics, Color Genomics, GeneDx/BioReference, Invitae and Genentech.