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Highlights of Ovarian Cancer Science from ASCO

Dr. Rivkin and I attended the annual meeting of the American Society of Clinical Oncology (ASCO)—a gathering of 38,000 oncology experts from all over the world—in early June in Chicago, Illinois. In addition to oncologists, the attendees included researchers, educators, advocates, research funders, survivors and representatives from genetic testing, drug and other services companies. Our aims of attending ASCO were to learn about the latest findings in the prevention, early detection and treatment of ovarian cancer, meet with ovarian cancer researchers, and to meet with leaders from organizations focused on ovarian cancer research, education and advocacy from around the world. This year there were developments in two hot areas pertinent to ovarian cancer that were at the center of discussion at ASCO: PARP inhibitors and surgical treatment of ovarian cancer (see below for highlights). We left ASCO optimistic and inspired—both from learning about new scientific advances and about opportunities for collaboration with other ovarian cancer focused organizations. We have a lot of work to do and we’re determined to do it!

 

Here are the highlights of ovarian cancer science and discussions from ASCO:

 

PARP Inhibitor Highlights

Our cells have a large array of proteins that are mobilized to detect and correct damage that can occur on DNA to prevent mutations and cancer. PARP inhibitors are effective for the treatment of tumors that have defects in proteins needed for response to DNA damage. BRCA1, BRCA2 and many other ovarian and breast cancer genes are components of the cell’s DNA damage response program. Tumors in women with BRCA and other gene mutations have a defective DNA damage response; therefore, PARP inhibitors have been effective in treatment for those women. Some PARP inhibitors are approved for treatment of women who have had several other therapies prior to their use. Other PARP inhibitors are approved for maintenance, meaning that women who have finished treatment take the PARP inhibitor to delay recurrence. A key challenge to PARP inhibitor effectiveness is that even in women who do respond, the duration of the response is limited and the tumor comes back. There was a lot of discussion at ASCO of what combination therapies can be used to increase PARP inhibitor response, initially to increase time before recurrence but, of course, with the goal of eliminating the cancer completely.

  • Status of approval of different PARP inhibitors in the US by the FDA and in Europe by the EMA:
    • Maintenance Therapy: Niraparib is approved by the FDA for maintenance therapy for all patients regardless of histology, BRCA & DNA damage response status. Olaparib approval for maintenance therapy is awaited in US. Olaparib is approved in Europe for maintenance therapy for BRCA mutation carriers only. Niraparib approval is awaited in Europe
    • Treatment: Rucaparib and Olaparib are approved by the FDA as therapy for women with BRCA mutations who’ve received several rounds of other chemotherapy.
  • The quality of life on olaparib is no different than on placebo for patients with ovarian cancer
  • Testing of tumors for DNA damage repair status may be key to identifying more patients who can benefit from PARP inhibitor therapy, including those who do not carry BRCA mutations
  • There is a need to identify new biomarkers to identify tumors that have defective DNA repair to extend use of PARP inhibitors. Genomic scarring and other tests currently used to identify DNA repair defective tumors may not be able to tell if certain chemoresistance mechanisms may be at play which would prevent PARP inhibitor.
  • There was significant discussion on identifying components of the DNA damage repair and response pathways as targets for combination therapy with PARP inhibitors. Currently at least ten targets (ATR, ATM, WEE1, etc) with known inhibitors exist and await results for testing in combination with PARP inhibitors.
  • There was also discussion of targeting the environment of the tumor to increase efficacy of PARP inhibitors. One example is to create hypoxic (low in oxygen) local environment which been shown to decrease DNA damage response.

 

Surgery related developments

Surgery remains an important component of ovarian cancer treatment. Here are reports of some studies that examine different surgery related practices.

  • The LION trial finds that removing lymph nodes during cancer surgery in women who do not have cancer positive lymph nodes does more harm than good.
  • The DESKTOP III trial shows that women with platinum sensitive cancer who have surgery (with no residual disease), after first recurrence, before chemo have better outcomes without increasing adverse events

 

Other Highlights

  • We need to refine the way we classify ovarian cancer to better define treatments and prognosis.
  • Patient engagement improves survival: Patients with advanced cancer who used an online tool to report side effects & symptoms lived 5 months longer than those who did not and also had reduced ER visits.
  • Discussion on testing of germline (inherited) and somatic (non-inherited, usually from the tumor) mutations and different practices of genetics clinics, including a focus on testing non-BRCA genes

You can follow the conversations we had as ASCO with #ASCOvarian.

Talk to your Family

Talking to your family and identifying cancer in your family tree can be a good indicator of your health risks. Download our Family Tree Worksheet here.  Be sure to include yourself, children, parents, siblings, aunts, uncles, and grandparents.

Get Educated

Know your body and be proactive about your health. Learn about your breast and ovarian health. Learn about the risk factors and signs & symptoms for breast and ovarian cancer.

Trusted Healthcare Provider

Having a relationship with a health care provider you know and trust is one of the most important decisions you’ll make about your health care. Click here to find a provider

Higher Risk in the Ashkenazi Jewish Population

In the general population, around 1 in 400 people carry a BRCA1 or BRCA2 mutation. People of Ashkenazi Jewish ancestry have a 1 in 40 chance of carrying a BRCA mutation, making them 10 times as likely to carry a BRCA mutation as someone in the general population. Whether you’re a man or a woman, if you have a BRCA mutation then there is a 50% chance of passing the mutation on to your children, whether they are boys or girls. It’s important to note that these mutations significantly increase risk, but are not a guarantee a person will get cancer.

Why is the Ashkenazi Jewish population at higher risk?

Over 90% of the BRCA mutations found in the Jewish community are one of three “founder mutations”. A founder mutation is a specific gene mutation in a population that was founded by a small group of ancestors that were geographically or culturally isolated. Because the population was isolated, the rate of founder mutations in descendants is much higher than it would be if the population were larger and co-mingling with more genetically diverse populations. A large expansion in the population caused the current high frequency of the mutations in the Ashkenazi Jewish population. If you are of Ashkenazi Jewish ancestry, the chance of carrying a BRCA gene mutation compared to the general population is increased tenfold. BRCA mutations can be passed down from either your mother’s or father’s side, and may be associated with any of the following cancers:
  • Breast cancer
  • Ovarian cancer, fallopian tube, peritoneal cancer
  • Male breast cancer
  • Prostate cancer
  • Pancreatic cancer
  • Colon Cancer

Ready to take action? Knowledge is power. Take this short quiz to be proactive about your health.

Genes 101

Our bodies are made of many tiny building blocks called cells. Our cells contain a copy of our genome – all of the DNA genetic code we inherited from our parents. Our genome is organized into 46 chromosomes, 23 inherited from mom and 23 from dad. Each chromosome has hundreds or thousands of genes. Each gene has the instructions to make a protein that may control the structure or function of cells, can determine many things including how tall we are or the color of our eyes. Genes also contain instructions for many things inside of us that we cannot see, such as how our bones are formed or how our heart works. Each gene is made up of molecules called nucleic acids (A, T, C, and G). The specific sequence of the nucleic acids holds the instructions that control all the components and their functions in cells.

If the DNA sequence is changed, like a spelling mistake, the instructions may not make sense. The technical term for this change is “mutation,” meaning there is a change to the usual genetic code that may change the instructions stored in the gene. A mutation in a gene that repairs DNA damage or controls cell growth can increase the risk of developing cancer.

Sporadic vs Hereditary Cancers:

Ovarian and breast cancer can be either sporadic or hereditary. Sporadic cancers make up the vast majority (85-90%) of ovarian and breast cancers and are not associated with family history of either cancer or inherited cancer-associated mutations. Sporadic cancers arise from genetic mutations acquired in some cells of the body by events part of normal metabolism and environmental factors. This type of cancer can happen to anyone. Most acquired gene mutations are not shared among relatives or passed on to children.

Hereditary (also known as inherited, or familial) cancers are those that occur due to genetic mutations that are inherited from mom or dad. Other blood relatives may also share these same gene mutations. Parents give one copy of each gene to their children. If a parent has a genetic mutation in a gene, each of their children have a 50% chance of inheriting that mutation. Therefore, even in families with hereditary cancer, not all family members inherit the mutation that is causing cancer, and their risk of cancer is similar to the average person in the general population. Individuals who are suspected to have a family history with high incidence of ovarian, breast, and other cancers may be offered genetic testing to try to find the specific genetic mutation that may put them at risk. Importantly, individuals who do not have a known genetic mutation but have high incidence of ovarian, breast, or other cancers in their families are still considered at higher risk for developing those cancers.

Hereditary cancers often occur at an earlier age than the sporadic form of the same cancer, so experts often recommend starting cancer screening at a younger age for individuals at high risk for hereditary cancer. Hereditary cancers can also be more aggressive than the sporadic form of the same cancer. Individuals who have inherited a gene mutation may be at a higher risk for more than one type of cancer.

BRCA 1 and BRCA 2: Most Common hereditary breast and ovarian cancer

The genes that are most commonly involved in hereditary breast and ovarian cancer (HBOC) are BRCA1 and BRCA2. These genes are named for their link to breast (BR) cancer (CA), but they are also linked to ovarian cancer risk as well as other cancers. Both women and men can inherit mutations in these HBOC genes. BRCA1 and BRCA2 are tumor suppressor genes that have a usual role in our body of providing instructions on repairing DNA damage and preventing cancer. When a family has an inherited mutation in BRCA1 or BRCA2, this leads to an increase in cancer risk. Not every man or woman who has inherited a mutation in the BRCA1 or BRCA2 gene will develop cancer, but people who have a mutation do have a significanlty increased chance of developing cancer, particularly cancer of the breasts or ovaries.

While breast and ovarian cancers are the most common cancers diagnosed in people with BRCA1 and BRCA2 mutations, the risk of some other cancers is also increased. Men with BRCA1 and BRCA2 mutations have a higher risk of early-onset prostate cancer than men without mutations in either gene. Other cancers seen at increased rates, particularly in individuals with BRCA2 mutations, include pancreatic cancer and melanoma. Researchers are continuing to find new genes that are involved in hereditary breast and/or ovarian cancer so it is important to follow up with a genetic counselor on a regular basis if hereditary breast and ovarian cancer is likely in your family.

Talk to your family about your health history and take the Assess Your Risk quiz here

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