cancer risk wasn’t always a major topic in health care.

Barriers to the discussion included lack of family history details, cost of genetic testing and a full understanding of genetics’ role in cancer development. However, evolving research has shown that history and risk can go hand in hand.

Health care providers are starting conversations with patients, and patients are speaking up among their relatives. Advocacy organizations such as Facing Our Risk of Cancer Empowered, more commonly known as FORCE, have helped bridge the gap and serve as a starting point for women who face hereditary breast and ovarian cancer.

More women are also taking steps to discuss genetics with their children. For instance, the book “Proactive Genes,” written by Shannon Pulaski and published by MJH Life Sciences 

, uses age-appropriate language to help children understand their risk, establish healthy lifestyle behaviors and grow into pro- active patients.

Decades ago, some families relied solely on experts in the genetics field to tell them if they carried certain mutations, such as in the BRCA1 and BRCA2 genes, that put them at higher risk of cancer. Described as “the father of hereditary cancer detection and prevention,” Dr. Henry Lynch founded and directed the Hereditary Cancer Center at Creighton University, which opened in 1984, and studied thousands of families to track the links between genetics and cancer.

Decades later, at least two women whose families were part of his research found flaws, each received a misdiagnosis for the BRCA gene. One was told she was BRCA1 positive but was really negative; the other was told she was BRCA2 negative when in fact she was positive. Within these pages, both women describe how they learned about the mistake and the steps they are taking to regain control of their health.

also delves into the basics of uterine sarcoma, a rare cancer that occurs in about 1,200 women each year in the United States. We also share the innovative research in biological advancements that are helping patients with cervical cancer and explain how palliative care can reduce the severity of the disease’s physical and psychological symptoms.

Also inside: the power of PARP inhibitors, immunotherapy for cervical cancer and women’s willingness to take on treatment side effects.

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From the Chairman

Make sure to prioritize your family health history to understand your risk of cancer.
 

Prioritizing Family Health History

challenges in ovarian cancer involves early detection. The disease often presents with vague symptoms that can be overlooked not only by a patient but also by health care providers.

A swollen abdomen, increased urination, pelvic pain and difficulty eating can be confused with other medical conditions, such as ovarian cysts and irritable bowel syndrome. That’s why women often wait to see a physician or the ones who do go for an examination are misdiagnosed — and why ovarian cancer is usually found at a more advanced stage.

This complexity has researchers looking for better screening options, which are still not up to par. For example, testing for cancer antigen 125 (CA 125), a potential biomarker for

the disease, is oncologists’ best tool at this point, but its reliability is debatable.

Physicians are doing their best to use CA 125 to assist as many women as possible by looking at the protein’s rate of change over time, which is often used in cases of patients facing disease recurrence, something you will read about within the pages of this special issue of 

Although advances in imaging, such as ultrasounds and scans, can play an important role in detecting the often-silent disease, it’s imperative that, to help spread awareness, physicians and patients alike be vocal about these symptoms that persist without an easy explanation.

Research is also leading to treatment advances in ovarian cancer, especially following recurrence. Although still being investigated, hyperthermic intraperitoneal chemotherapy, or “hot chemotherapy,” plus surgery has been shown to improve survival. Interest is also growing in neoadjuvant chemotherapy — giving chemotherapy before surgery. Typically, chemotherapy has been given after surgery, but using it prior may give women time to help shrink the tumor before undergoing radical surgery, and the reduced tumor helps lower surgical morbidity.

New medication options, such as Avastin (bevacizumab), a monoclonal antibody approved by the Food and Drug Administration two years ago, can be used to treat advanced disease or recurrence and help prevent ovarian cancer progression. Used as maintenance therapy, PARP inhibitors are showing promise for women who have a BRCA gene mutation.

These drugs can treat patients after progression on chemotherapy or help maintain a remission after a response to chemotherapy. And instead of just relying on BRCA mutations, researchers have also begun studying DNA repair deficiency to determine who might benefit from a PARP inhibitor even without BRCA mutations.

Innovations like these build on one another and lead to advancements for women who may not see gains from current available therapies. For instance, because physicians can use chemotherapy preoperatively, maybe they can try using new biological drugs the same way. If patients don’t respond, per- haps that’s when new drugs are employed.

Refining existing treatments and adapting the regimen sequence may allow women to derive a benefit much earlier in their treatment course. Ongoing studies to better understand the basic mechanisms of ovarian cancer will help bring about new and more precise treatments.

Editor's Page

CURE®’s Editor-in-Chief weighs in on how the treatment and detection landscape needs to be refined to help patients with ovarian cancer.
 

Refine and Retry, Getting Ovarian Cancer Treatment Right for Patients

PARP inhibitor to treat certain patients with ovarian cancer was approved by the Food and Drug Administration (FDA). Since then, two more PARP inhibitors have come to market for ovarian cancer, and the types of cancers they can treat have expanded.

These agents block a cellular enzyme called PARP, which helps repair damaged DNA. In cancer treatment, using PARP inhibitors to prevent this process may cause cancer cells to die.

“Typically, what happens is if one pathway doesn’t work, a cell just uses another one,” explains Dr. Shannon Westin, a gynecologic oncologist at The University of Texas MD Anderson Cancer Center in Houston.

“For example, people with BRCA mutations ... have dysfunction of a different DNA-damage repair pathway, which is actually called the homologous recombination pathway. Their homologous recombination pathway doesn’t work. It’s deficient. Their cells really rely on PARP to repair DNA damage. And so if you’ve already got a problem in homologous recombination and then you block PARP, that cell is going to die because it can’t fix its problems.”

The three FDA-approved PARP inhibitors include Lynparza (olaparib), Rubraca (rucaparib) and Zejula (niraparib), all oral medications. If given upfront in the treatment course, patients usually take a PARP inhibitor for two years. However, many women with ovarian cancer face recurrence. In this case, whether a PARP inhibitor is used to re-treat cancer or as maintenance therapy after response to chemotherapy, a patient will be on the medication until the cancer grows or side effects become intolerable.

“One of the common misconceptions, especially when people are coming off chemotherapy, is ... ‘Oh, I’m going to be taking a pill, and it’s going to be easy peasy.’ But these drugs have side effects,” Westin says. Importantly, they can be mitigated with appropriate management.

Toxicities of PARP inhibitors include gastrointestinal issues such as nausea, diarrhea, reflux and feeling full early; headaches and dizziness; and fatigue. They can also affect the bone marrow, Westin says, causing anemia, neutropenia and thrombocytopenia — conditions that affect blood counts.

“I tell patients that we just have to find your sweet spot,” she says. “We’re starting your dose here, but that may not be the best dose for you. We have to manage it and make changes as needed.”

The drugs’ response primarily depends on the tumor; they’re most effective in tumors that have a BRCA gene mutation or another abnormality in a member of the homologous recombination pathway, according to Westin. For patients with no biomarker, there is some efficacy, but combination therapies may work better.

“PARP inhibitors work on their own, but there is not 100% efficacy, and they don’t work forever,” Westin says. “There is a lot of interest around combining PARP inhibitors with other targeted therapies or immunotherapy to try to improve upon the benefit and make it work better for more people.”

Researchers are also examining two other PARP inhibitors, ABT-888 (veliparib) and Talzenna (talazoparib).

In a phase 3 clinical trial that included more than 1,100 women with advanced ovarian cancer, first-line treatment of ABT-888 combined with chemotherapy reduced the risk of disease progression or death. Talzenna, which is FDA approved to treat certain patients with advanced

or metastatic breast cancer, is now being explored in the ovarian cancer space.

“Patients need to talk to their doctor to see if a (PARP inhibitor) is an option for them,” Westin says. “They also must understand that (PARP inhibitors) can’t benefit every single patient that has ovarian cancer, and this is why clinical trials are critical.”

Features

These targeted therapies fight disease by stopping the fix-it process in damaged cancer cells.
 

Women's Cancers | CURE

Prioritizing Family Health History

Refine and Retry, Getting Ovarian Cancer Treatment Right for Patients

How PARP Inhibitors Work In Women

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