Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Ovarian Cancer

What is Ovarian Cancer?

• Ovarian cancer is when abnormal cells in the ovary begin to grow and divide in an uncontrolled way, and eventually form a growth (tumor).​​
• First-line treatment for ovarian cancer includes surgery followed by a chemotherapy regimen combining a platinum-based (usually carboplatin) and a taxane-based (usually paclitaxel) treatment. This course of treatment leads to a complete response in approximately 80% of patients. ​
• While significant advances have been made in surgical and chemo-based treatments for ovarian cancer, the survival rates have only modestly improved. ​
• The American Cancer Society estimates for ovarian cancer in the United States for 2019 are:​
  • About 22,530 women will receive a new diagnosis of ovarian cancer.​
  • About 13,980 women will die from ovarian cancer.​
• Approximately 70% of women will experience their first recurrence within just 3 years, and with each recurrence, their prognosis gets progressively worse.​
• With an estimated 5-year survival rate of less than 50%, this amounts to the highest mortality rate of all gynecological cancers.​
• Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. ​
  • A woman’s risk of getting ovarian cancer during her lifetime is about 1 in 78. ​
  • Her lifetime chance of dying from ovarian cancer is about 1 in 108.​
• Ovarian cancer usually begins in the part of the fallopian tube closest to an ovary and then spreads to that ovary. ​
• The disease may also sometimes begin in the peritoneum, the membranes the surround the contents of the abdomen, and then spread to an ovary. For that reason, ovarian cancer, cancer of the fallopian tubes, and primary peritoneal cancer are often grouped together when discussing these cancers.​
• There are more than 30 different types of ovarian cancer, which are classified by the type of cell from which they start. ​
  • Cancerous ovarian tumors start from three common cell types:​
    • Surface Epithelium – cells covering the outer lining of the ovaries​
    • Germ Cells – cells that are destined to form eggs​
    • Stromal Cells – cells that release hormones and connect the different structures of the ovaries​

How Do You Get It?

• We don’t yet know exactly what causes most ovarian cancers. We do know some factors that make a woman more likely to develop epithelial ovarian cancer. Much less is known about risk factors for germ cell and stromal tumors of the ovaries.
• There are many theories about the causes of ovarian cancer. Some of them came from looking at the things that change the risk of ovarian cancer. For example, pregnancy and taking birth control pills both lower the risk of ovarian cancer. Since both of these things reduce the number of times the ovary releases an egg (ovulation), some researchers think that there may be some relationship between ovulation and the risk of developing ovarian cancer.​
• Another theory is that male hormones (androgens) can cause ovarian cancer.​
• A small portion of ovarian cancers occur in women with inherited mutations linked to an increased risk of ovarian cancer. ​
• These include mutations in the BRCA1 and BRCA2 genes, as well as the genes related to other family cancer syndromes linked to an increased risk of ovarian cancer, such as PTEN (PTEN tumor hamartoma syndrome), STK11 (Peutz-Jeghers syndrome), MUTYH (MUTYH-asociated polyposis, and the many genes that can cause hereditary nonpolyposis colon cancer (MLH1, MLH3, MSH2, MSH6, TGFBR2, PMS1, and PMS2).​
  • The BRCA gene test is a blood test that uses DNA analysis to identify harmful changes (mutations) in either one of the two breast cancer susceptibility genes — BRCA1 and BRCA2.​
  • Women who have inherited mutations in these genes are at an increased risk of developing breast cancer and ovarian cancer compared with the general population.​
  • The BRCA gene test is offered only to people who are likely to have an inherited mutation based on personal or family history, or who have a specific type of breast cancer. The BRCA gene test isn’t routinely performed on women at average risk of breast and ovarian cancers.​
  • A BRCA gene test determines whether you carry an inherited BRCA mutation.​
  • Having a BRCA gene mutation is uncommon. Inherited BRCA gene mutations are responsible for about 5 to 10 percent of breast cancers and about 15 percent of ovarian cancers.​​
• Other risk factors include:
  • Old age
  • Hormone replacement therapy (estrogen therapy)
  • Late menopause
  • Infertility
  • Talcum powder
  • Endometriosis
  • Childbirth after age 35

What Are The Symptoms?

• Symptoms of ovarian cancer may be confused with less serious, noncancerous conditions. ​If you experience persistent symptoms for more than a few weeks or notice a change in your ovarian health, consult a doctor for follow-up.
• Common symptoms may include:
  • Abdominal bloating, indigestion or nausea​
  • Changes in appetite, such as a loss of appetite or feeling full sooner​
  • Pressure/pain in the pelvis or lower back​
  • A more frequent or urgent need to urinate and/or constipation​
  • Changes in bowel movements​
  • Increased abdominal girth​
  • Tiredness or low energy​
  • Changes in menstruation​
  • ​Painful sex

How Is It Treated?

• The goal of treatment for ovarian cancer is to surgically remove as much of the cancer as possible through the debulking and then to provide what is called adjuvant, or additional therapy, such as chemotherapy, to kill any possibly remaining cancer cells in the body. ​
• Treatment for ovarian cancer usually involves a combination of surgery and chemotherapy.​
• A Gynecologic oncologist—a doctor who was trained to treat cancers of a woman’s reproductive system—often plays a central role.​
• Many ovarian cancer patients experience side effects from their disease or its treatment, including gastrointestinal symptoms, sexual function impacts, and neuropathy. ​
• Surgery
  • Surgery is typically performed to decrease the size of the tumor as much as possible.
  • In stage 1 and 2 ovarian cancer, removal of the cancerous tumor and diseased organs may be adequate treatment. During surgery, your doctor may perform biopsies to check for spread to your lymph nodes or surrounding tissues.
  • In stage 3 or 4 ovarian cancer, surgery may be performed prior to chemotherapy in order to remove the tumor, both ovaries, and affected organs and lymph nodes throughout the body.
  • Surgical procedures used for ovarian cancer include:
    • Surgery to remove one ovary. For very early stage cancer that hasn’t spread beyond one ovary, surgery may involve removing the affected ovary and its fallopian tube. This procedure may preserve your ability to have children.​
    • Surgery to remove both ovaries. If cancer is present in both your ovaries, but there are no signs of additional cancer, your surgeon may remove both ovaries and both fallopian tubes. This procedure leaves your uterus intact, so you may still be able to become pregnant using your own frozen embryos or eggs or with eggs from a donor.​
    • Surgery to remove both ovaries and the uterus. If your cancer is more extensive or if you don’t wish to preserve your ability to have children, your surgeon will remove the ovaries, the fallopian tubes, the uterus, nearby lymph nodes and a fold of fatty abdominal tissue (omentum).​
    • Surgery for advanced cancer. If your cancer is advanced, your doctor may recommend chemotherapy followed by surgery to remove as much of the cancer as possible.​
• Chemotherapy
  • For ovarian cancer, chemotherapy is typically delivered orally (by mouth), intravenously (through a vein) or directly into the abdomen through a catheter, in a treatment called intraperitoneal chemotherapy.
  • Chemotherapy may be suggested for high-risk stage I patients, as well as stage II patients.​
  • After surgery, the majority of patients will start a personalized chemotherapy plan, including one or more chemotherapy drugs. Sometimes, once a diagnosis of ovarian cancer has been made by a biopsy, a few cycles of chemotherapy are given first in order to make surgery more successful and less complicated. ​
  • ​Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. ​
    • Carboplatin, Platinol (cisplatin), Eloxatin (oxaliplatin)​
    • Taxol (paclitaxel), Taxotere (docetaxel)​
    • Abraxane (paclitaxel liposome injection)​
    • Alimta (pemetrexed)​
    • Doxil (doxorubicin liposome injection)​
    • Camptosar (ironotecan)​
    • Gemzar (gemcitabine)​
    • Hexalin (altretamine)​
    • Hycamtin (topotecan)​
    • Xeloda (capecitabine)​
• Hormone therapy
  • Hormone therapy deprives ovarian cancer cells of the hormones they need to grow, including estrogen.​
• Targeted therapy
  • Targeted therapy drugs called PARP inhibitors, which are designed to stop cancer cells from repairing themselves, are often used to treat ovarian cancer.
    • PARP Inhibitors: The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. A new class of precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of cancer cell growth.​
    • PARP inhibitors have the greatest effect in women with mutations of the BRCA genes but may benefit additional patients with different genetic profiles as well. BRCA genes are involved with repairing damaged DNA and normally work to prevent the development of cancer. The best way to incorporate PARP inhibitors into the overall management of ovarian cancer is being determined however they already have been shown to improve outcomes when used as maintenance therapy following completion of chemotherapy.​
    • Examples include olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula)
      • Olaparib and rucaparib can be used to treat advanced ovarian cancer that has come back after treatment, and then shrank in response to chemotherapy containing cisplatin or carboplatin.​
      • Olaparib and rucaparib can help extend the time before the cancer comes back or starts growing again.
      • Niraparib (Zejula) is typically used to treat recurrent ovarian cancer, after chemotherapy has been tried. ​
      • Side effects of these drugs can include nausea, vomiting, diarrhea, fatigue, loss of appetite, taste changes, low red blood cell counts (anemia), belly pain, and muscle and joint pain. ​
      • Rarely, some patients treated with these drugs have developed a blood cancer, such as myelodysplastic syndrome or acute myeloid leukemia. ​
    • These drugs have been shown to help shrink or slow the growth of some advanced ovarian cancers for a time. So far, though, it’s not clear if they can help women live longer.​
    • PARP enzymes are normally involved in one pathway to help repair damaged DNA inside cells. ​
    • The BRCA genes (BRCA1 and BRCA2) are also normally involved in a different pathway of DNA repair, and mutations in those genes can block that pathway. ​
    • By blocking the PARP pathway, these drugs make it very hard for tumor cells with a mutated BRCA gene to repair damaged DNA, which often leads to the death of these cells.​
    • All of these drugs are taken daily by mouth, as pills or capsules.​
  • Targeted therapy uses medications that target the specific vulnerabilities present within your cancer cells. Targeted therapy drugs are usually reserved for treating ovarian cancer that returns after initial treatment or cancer that resists other treatments. Your doctor may test your cancer cells to determine which targeted therapy is most likely to have an effect on your cancer.​
  • ​Targeted therapy is an active area of cancer research. Many clinical trials are testing new targeted therapies.
  • Avastin® (bevacizumab: A targeted therapy that is effective in the treatment of ovarian cancer is Avastin®. ​
    • Avastin slows or prevents the growth of new blood vessels by inhibiting a protein known as VEGF; this deprives the cancer of oxygen and nutrients. Avastin may also improve the delivery of chemotherapy to cancer cells by normalizing blood supply.​
    • ​Approved in 2018 by the FDA
• Ovarian cortex cryopreservation
  • Ovarian cortex cryopreservation is the process of freezing ovarian tissue before cancer treatment begins so women may be able to have children later.
• Radiation therapy
  • Radiation therapy is a cancer treatment that uses high-energy X-rays or other types of radiation to eliminate cancer cells or stop cancer growth.​
  • Radiation therapy is used to treat select cases of ovarian cancer. While most ovarian cancer patients are not treated with radiation therapy, it may be used for patients with certain types of ovarian cancer, those who have isolated and/or minimal recurrence, or to control symptoms such as pain. In rare or recurrent cases, these radiation treatments may be performed:​
    • 3D imaging radiation therapy called intensity-modulated radiation therapy (IMRT). Radiation is externally delivered and aimed at the tumor, firing thin radiation beams from different angles. This reduces the damage to the surrounding healthy tissue.​
    • ​In brachytherapy or interstitial brachytherapy, radioactive material is directly implanted in or near the tumor via a tiny needle, wire, or other device.
• The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Because of the poor prognosis with current treatment, all patients with stage IV ovarian cancer should consider participation in a clinical trial. ​
• Complementary therapies are diverse practices and products that are used along with conventional medicine. ​
• There are questions about most complementary therapies that have not yet been answered through well-designed scientific studies, such as clinical trials. ​
• Before beginning any complementary therapy, it is important to discuss the approach with your healthcare team and complementary therapy practitioner.​
• Examples include:
  • Acupuncture​
  • Aromatherapy​
  • Herbal Medicine​
  • Massage​
  • Meditation​
  • Qi Gong ​
  • Stress Reduction​
  • Yoga, Tai Chi​

Where Can I Learn More???

• Learn more about this disease from the Ovarian Cancer Research Alliance.
• Check out our cornerstone on this disease here.