Although nine out of ten had experienced symptoms prior to diagnosis, fewer than half of those women visited a doctor within a month of noticing symptoms.

The World Ovarian Cancer Coalition Every Woman Study is the largest ever review of the experiences of women with ovarian cancer and includes contributions from the clinical community. It presents a bleak picture of the challenges faced by women with ovarian cancer, and those who care for them.

ovarian cancer ribbon

Around the world approximately 239,0001 women are diagnosed with ovarian cancer each year and less than half will survive to five years2. Studies3 have shown that around 15% of women die within 2 months of their diagnosis, with age, emergency presentation and co-morbidities placing them at increased risk. Incidence is rising and is expected to reach 371,000 women a year by 2035 – a 55% increase4.

The survey of over 1,500 women in 44 countries, reveals:

• Low levels of awareness of ovarian cancer as a global problem resulting in delays in women seeking medical attention
• Lack of awareness among doctors may also be a significant factor when it comes to delays in diagnosis
• Variations in access to genetic testing pre and post diagnosis where there is a family history of ovarian cancer
• Variations in access to specialist treatment – despite this being a vital step that can improve outcomes
• Variations between countries in terms of what is done well and what is most challenging

Nine in ten of the women in the Every Woman Study experienced symptoms prior to diagnosis and of these, eight in ten consulted a doctor – though less than half within a month and one in ten waited six months.

Across the world, diagnosis took an estimated average of 31 weeks from a woman experiencing symptoms to her diagnosis; for one in ten women diagnosis came more than a year after visiting a doctor.

There are examples of best practice in prevention, diagnosis and treatment of ovarian cancer across the world, but no one country does well in all three areas. This means there are opportunities right now to transform survival in ovarian cancer, simply by learning from what others do well.

Germany, for example has the fastest diagnosis, yet it is estimated that half of women are unlikely to receive specialist care. The UK, by comparison, has the lowest proportion of women diagnosed within a month of visiting a doctor, yet almost universal access to specialist clinicians. Similarly, Australian women had a longer time to diagnosis – but high rates of surgery.

In Canada awareness is high and women seek medical support yet diagnosis is slow. By contrast in Japan, although awareness is very low and fewer women consult their doctors than elsewhere, women who do visit their doctor about symptoms are diagnosed faster than in other countries surveyed.

“We wanted to find out more about the experiences of women with ovarian cancer and identify what needs to be done right now to tackle this marginalized cancer. The results show that this is a global challenge that can only be taken on by the whole community,” said Elisabeth Baugh, Chair of the Coalition, and CEO of Ovarian Cancer Canada,

Annwen Jones, CEO of Target Ovarian Cancer in the UK and Co-Chair of The Every Woman Study said: “This study, for the first time, provides powerful evidence of the challenges faced by women diagnosed with ovarian cancer across the world, and sets an agenda for global change. We were especially shocked by the widespread, woeful lack of awareness of ovarian cancer. It is vital that urgent steps are taken in every country to raise awareness of the disease and speed up diagnosis so that we can transform the outlook for the increasing numbers of women and their families affected by ovarian cancer around the world.”

Dr. Neerja Bhatla, Chair of the FIGO Gynecologic Oncology Committee, Professor at the All India Institute of Medical Sciences, and clinical Co-Chair of the Study said: “We are pleased to have completed this study, which gives us an idea of the changes that can be made to help women with ovarian cancer. We need to build support and funds for action to achieve profound and long-lasting change for women with ovarian cancer.”

A survey participant in Australia said “Governments need to do more regarding GPs [family doctors] and their lack of diagnosis and interest in women with ovarian cancer. After diagnosis I googled and all my symptoms were mentioned. GPs were not interested enough and made me feel like a hypochondriac. This went on for months!”

The Every Woman Study is an initiative of the World Ovarian Cancer Coalition that aims to transform survival and wellbeing of women diagnosed with ovarian cancer wherever she lives in the world. The study was undertaken to establish a body of evidence that speaks to the global state of affairs of ovarian cancer. This new and unique evidence base will inform the World Ovarian Cancer Coalition’s future work and support advocates all around the world to secure the changes in their countries that women so urgently need and deserve.

###

The full Every Woman Study was launched on October 18th 2018, ahead of the European Society for Medical Oncology (ESMO) 2018 Congress, Munich.

On January 5th 2006, almost a full decade ago, the National Cancer Institute issued a strongly worded Clinical Advisory alerting the medical field to the importance of “the preferred method of treatment for advanced ovarian cancer”. Yet nearly ten years later, the Advisory has gone largely unheeded. A multi-university study published online ahead of print on Monday, August 3rd 2015 in the Journal of Clinical Oncology found that fewer than 50% of eligible patients received the recommended life-saving combination treatment. In an article the same day in The New York Times by Denise Grady, Dr. Maurie Markman, the president of medicine and science at Cancer Treatment Centers of America, is quoted as saying, “The word ‘tragic’ would be fair.”

A release sent out in 2006 from NCI’s Division of Cancer Treatment and Diagnosis noted that the Clinical Advisory was timed to coincide with the publication in the New England Journal of Medicine of the results of a large clinical trial led by Deborah Armstrong, M.D., medical oncologist and an associate professor at Johns Hopkins Kimmel Cancer Center in Baltimore, Md. that reported the finding that after surgery, the use of both intravenous (IV) chemotherapy and intraperitoneal (IP) chemotherapy delivered into the abdominal cavity significantly improved survival for patients with the disease.

In the 2006 Clinical Advisory, NCI Director Andrew C. von Eschenbach, M.D. was quoted as saying that “we have firm data showing that we should use a combination of IP and IV chemotherapy in most women with advanced ovarian cancer who have had successful surgery to remove the bulk of their tumor.”

The reason for the appalling heel-dragging on the part of the medical establishment in spite of that “firm data” probably lies in this pronouncement from Dr. Eschenbach in the 2006 Clinical Advisory: “IP therapy is not a new treatment approach, but it has not been widely accepted as the gold standard for women with ovarian cancer. There has been a prejudice against IP therapy in ovarian cancer because it’s an old idea, it requires skill and experience for the surgery and for the chemotherapy, and it’s more complicated than IV chemotherapy.”

IP therapy is not without side effects, including bloating and hair loss. However, according to a multi-university study published in May 2015 in The Journal of Clinical Oncology, the reward is a longer life. The authors concluded: “The advantage of IP over intravenous chemotherapy extends beyond 10 years.”

Here at ThirdAge.com, we hope that this information will encourage you to request a second opinion if you or your loved ones are diagnosed with ovarian cancer and are not offered the combination therapy. Denise Grady ended her article in The New York Times with a powerful statement from Dr. Deborah Armstrong who led the original 2006 study: “I think it’s going to have to be the advocate community, since they’re the ones who have the most skin in the game, and can put the money where the mouth is, and say, ‘If you can’t give me the best treatment I’ll go someplace else.’ ”

Sondra Forsyth is Co-Editor-in-Chief of Thirdage.com.

Inherited mutations in the BRCA1 gene and closely related BRCA2 gene account for about 5 to 10 percent of all breast cancers and 15 percent of ovarian cancers [1]. For any given individual, the likelihood that one of these mutations is responsible goes up significantly in the presence of  a strong family history of developing such cancers at a relatively early age. Recently, actress Angelina Jolie revealed that she’d had her ovaries removed to reduce her risk of ovarian cancer—news that follows her courageous disclosure a couple of years ago that she’d undergone a prophylactic double mastectomy after learning she’d inherited a mutated version of BRCA1.

As life-saving as genetic testing and preventive surgery may be for certain individuals, it remains unclear exactly which women with BRCA1/2 mutations stand to benefit from these drastic measures. For example, it’s been estimated that about 65 percent of women born with a BRCA1 mutation will develop invasive breast cancer over the course of their lives—which means approximately 35 percent will not. How can women in this situation be provided with more precise, individualized guidance on cancer prevention? An international team, led by NIH-funded researchers at the University of Pennsylvania, recently took an important first step towards answering that complex question.

In a study published in the journal JAMA, the researchers analyzed genetic data and health information from more than 31,000 women with mutations in BRCA1/2. They found that among such women, the answer to whether a particular individual will develop breast cancer, ovarian cancer, both types of cancer, or neither cancer appears to vary considerably depending upon two factors: the precise type of mutation inherited and the locations of these mutations in the DNA sequences of the genes [2].

We’ve known about the roles of BRCA1 and BRCA2 in inherited breast and ovarian cancer for some time. The tumor suppressor genes, which code for proteins involved in DNA repair, were first isolated 20 years ago. However, over the years, we’ve also learned that each of these genes can contain different types of inherited mutations that vary among the individuals/families being studied. Until we understand with far greater precision how each of these many mutations (or even groups of mutations) affects individual cancer susceptibility, the best that health-care professionals can do is to offer BRCA1/2 carriers prevention guidance based on general risk calculations.

The new work by Penn’s Timothy Rebbeck, Katherine Nathanson, and their colleagues represents a significant step toward more precise and individualized risk calculations. In their study, the researchers teamed up with the Consortium of Investigators of Modifiers of BRCA (CIMBA), a collaboration that spans 33 nations on six continents. CIMBA’s database contains vast troves of genetic and health data on BRCA1/2 carriers from a wide range of races and ethnicities.

Of 19,591 women in the CIMBA database with BRCA1 mutations, 46 percent were diagnosed with breast cancer, 12 percent with ovarian cancer, and 5 percent with both cancers by the age of 70. It’s important to note that 37 percent of women with BRCA1 mutations had not developed cancer by the age of 70. The picture was similar for the 11,900 women with BRCA2 mutations: 52 percent were diagnosed with breast cancer, 6 percent with ovarian cancer, and 2 percent with both cancers by the age of 70. About 40 percent had not developed cancer by the age of 70.

To gather information that may help to refine the timing of prevention strategies, the Penn team also looked closely the age at which BRCA1 and BRCA2 carriers were diagnosed with cancer. For BRCA1, the average age at diagnosis for breast cancer was 39.9 and 50 for ovarian cancer, while for BRCA2, the average age for breast cancer diagnosis was 42.8 and 54.5 for ovarian cancer.

Then, the researchers went on to identify BRCA1/2 mutations associated with significantly different risks of breast and ovarian cancer. For example, mutations located near the ends of BRCA1 were associated with a greater risk for breast cancer, while mutations located near the middle—specifically, in a long protein-coding sequence called exon 11—appeared to confer a higher risk of ovarian cancer. Interestingly, mutations located in or near BRCA1’s exon 11 also tended to be associated with earlier onset of both types of cancer than mutations elsewhere in the gene.

While the new findings represents encouraging progress towards more precise prevention of cancer among BRCA1/2 carriers, researchers caution that much follow-up work is needed before such information can be used to guide the very difficult decisions currently faced by such women. Ultimately, our hope is not only to spare women with BRCA1/2 who are at low risk of cancer from needless surgery, but to use this newfound knowledge to develop drugs and other less-invasive strategies for cancer prevention in high-risk women.

Developing more individualized ways to prevent inherited cancer is just one of many things we at NIH are doing to realize the full promise of precision medicine. Check out the Precision Medicine Initiative to learn more about the research needed to move such innovation into virtually all areas of health and disease.

Reference:

Links:

Basser Research Center for BRCA, University of Pennsylvania, Philadelphia

Decision Tool for Women with BRCA Mutations, Stanford University, Palo Alto, CA

Timothy Rebbeck, University of Pennsylvania, Philadelphia

Katherine Nathanson, University of Pennsylvania, Philadelphia

The Consortium of Investigators of Modifiers of BRCA1/2, University of Cambridge, England

Precision Medicine Initiative (NIH)

NIH Support: National Cancer Institute

This article first appeared on the NIH Director’s Blog, http://directorsblog.nih.gov/. Reprinted with permission from the National Institutes of Health (NIH).

Francis Collins, M.D., Ph.D., is Director of NIH.

A release from the university quotes Dr. Pramod Srivastava, director of the Carole and Ray Neag Comprehensive Cancer Center at UConn Health and one of the principal investigators on the study, as saying, “This has the potential to dramatically change how we treat cancer. This research will serve as the basis for the first ever genomics-driven personalized medicine clinical trial in immunotherapy of ovarian cancer, and will begin at UConn Health this fall.”

UConn bioinformatics engineer Ion Mandoiu, associate professor of computer science and engineering, collaborated as the other principal investigator for the study, which has been in development for the past four years. The results appear online in the 22 September issue of the Journal of Experimental Medicine.

Dr. Angela Kueck, a gynecological oncologist at UConn Health, will run the initial clinical study, once it is approved by the FDA. The research team will sequence DNA from the tumors of 15 to 20 women with ovarian cancer, and use that information to make a personalized vaccine for each woman.

The researchers focused their clinical trial on patients with ovarian cancer because the disease usually responds well to surgery and chemotherapy in the short term, but often returns lethally within a year or two. That gives researchers the perfect window to prepare and administer the new therapeutic vaccines, and also means they may be able to tell within two years or so whether the vaccine made a difference. If the personalized vaccines prove to be safe and feasible, they’ll design a Phase II trial to test its clinical effectiveness by determining whether they prolong patients’ lives.

Identifying tiny differences
In order for the immune system to attack cancers, it first has to recognize them. Every cell in the body has a sequence of proteins on its exterior that acts like an ID card or secret handshake, confirming that it’s one of the good guys. These protein sequences, called epitopes, are what the immune system ‘sees’ when it looks at a cell. Cancerous cells have epitopes, too. Since cancer cells originate from the body itself, their epitopes are very similar to those of healthy cells, and the immune system doesn’t recognize them as bad actors that must be destroyed.

But just as even the best spy occasionally slips up on the details, cancer cell epitopes have tiny differences or mistakes that could give them away, if only the immune system knew what to look for.

“We want to break the immune system’s ignorance,” Srivastava says. For example, there could be 1,000 subtle changes in the cancer cell epitopes, but only 10 are “real,” meaning significant to the immune system. To find the real, important differences, Mandoiu, the bioinformatics engineer, took DNA sequences from skin tumors in mice and compared them with DNA from the mice’s healthy tissue.

Previous researchers had done this but looked at how strongly the immune system cells bound to the cancer’s epitopes. This works when making vaccines against viruses, but not for cancers. Instead, Srivastava’s team came up with a novel measure: they looked at how different the cancer epitopes were from the mice’s normal epitopes. And it worked. When mice were inoculated with vaccines made of the cancer epitopes differing the most from normal tissue, they were very resistant to skin cancer.

Theoretically, this approach could work for other cancers, although the research has yet to be done.

Researchers in cancer biology, immunology, and computational bioinformatics had to work together to discover these connections. This type of collaboration is the engine driving UConn’s personalized medicine and genomics research, according to UConn’s vice president for research, Jeffrey Seemann.

“This research is a great example of how diverse disciplines create synergy under the umbrella of genomics,” Seemann says. “UConn aims to capitalize on such synergies to make progress in many areas that tap into the genomics realm.”

UConn researchers have applied for two patents for their new technique, and a Connecticut start-up company, Accuragen Inc., in which Srivastava has a financial interest, has obtained an option to license the patents.

Creating a safe, effective cancer vaccine is one of the major long-term goals of personalized medicine. Using a different approach than the one described in this paper, Srivastava’s research has already created a vaccine against kidney cancer, which is in clinical use and commercially available in Russia.

“It is known that patients have genetic sequences that make them better candidates for some drugs than others. And we can figure that out much more easily now than five years ago,” Srivastava says. The novelty of Srivastava’s approach in this new research is that it results in a drug specifically designed for a single person. If the approach proves safe and effective, it would be the ultimate in individualized medicine.