37 Ovarian Cancer

Ovarian Cancer – the “silent cancer”

Fortunately, ovarian cancer is less common than breast cancer, however, it has a much higher mortality rate.  Approximately 3 thousand Canadian women are diagnosed with ovarian cancer each year and over half of diagnosed women will die from the disease.  The main reason for the high mortality rate is due to the fact that only 25% are diagnosed in an early stage of the disease, which is why it is sometimes called the “silent killer”.    

There are five different types of ovarian carcinoma, with high-grade serous epithelial ovarian carcinoma being the most common.  This cancer is thought to originate from fallopian epithelial cells that implant on the ovary.  Cells become cancerous through the accumulation of DNA mutations.  A small percentage of ovarian cancers are related to inherited genetic mutations in either Breast Cancer Gene 1 (BRCA1) or Breast Cancer Gene 2 (BRCA2), though not eveyone that has BRCA1/2 mutations will develop ovarian cancer.

Unfortunately, ovarian cancer spreads easily through lymphatics and the peritoneal and can become metastatic before symptoms appear, leading to poor prognosis.  The lack of reliable screening is a key factor in late detection.

Ovarian Cancer – Risk Factors and Prevention Strategies

Risk factors include age and genetics, including a family history of first-degree relative.  Family history suggests a greater chance of inheriting BRCA1 or BRCA2.  Longer exposure levels to estrogen due to early menarche (before 12yrs old), late menopause (after 55yrs old), nulliparity (never been pregnant) or hormone replacement therapy (HRT) for longer than 5yrs are all risk factors.  Tall adult height is also thought to be a risk factor due to levels of or duration of exposure to growth and puberty hormones.  Conversely, birth control pills that contain both esterogen and progesterone are thought to lower the risk of developing ovarian cancer.  Sedentary behaviour, obesity, and low intake of vegetables are considered risk factors.  As well, exposure to carcinogens and immunosuppression are risk factors for all cancers.

Prevention strategies include: healthy diet following Canada’s Food Guide, healthy lifestyle following the Canadian Physical Activity Guidelines.  Other prevention strategies include limiting one’s exposure to alcohol, tobacco products, ionizing radiation and other known carcinogens.  Vaccinations and precautions against infections with oncoviruses (e.g., HPV, HBV, HCV, EBV) including viruses that can be immunosuppressive (e.g., HIV) is recommended in preventing cancers that can harm in primary organs and then by metastasizing.

Some individuals that have a family history may choose to have DNA tests performed to determine whether they carry BRCA1 or BRCA2 mutations and therefore have an increased risk of developing ovarian cancer.  BRCA1 mutations are noted to increase the risk of ovarian cancer before the age of 50 and BRCA2 mutations increase the risk after the age of 60.  Hereditary Breast and Ovarian Cancer (HBOC) is inherited in an autosomal dominant manner, meaning that if just one of the two copies of either BRCA1 or BRCA2 is mutated, there is an increased risk of both breast and ovarian cancers.  Females with BRCA1 or BRCA2 mutations may choose to have their fallopian tubes and ovaries removed (bilateral salpingo-oophorectomy) in addition to prophylactic (preventative) mastectomy.

Ovarian Cancer – Signs & Symptoms

As the tumor grows, several conditions may appear including: abnormal vaginal bleeding or discharge, urinary frequency, indigestion, heartburn, nausea, constipation, feel full, loss of appetite, weight loss, pain in lower back. legs, or pelvis, pain during intercourse, and a swelling, lump, and/or pain in abdomen.

Ovarian Cancer – Diagnosis

Often, diagnosis begins with physical exams (e.g., palpation of the abdomen, pelvic and rectal exams) and blood tests to check for levels of hormones (estrogen, testosterone, inhibin) and cancer markers (i.e., proteins that are often elevated in cancer cells).

The following serum cancer markers can be higher when ovarian cancer is present.  Notice that many are normally produced by immature, foetal cells, which reminds us that cancer cells have de-differentiated and become abnormally immature.

• Alpha-fetoprotein (AFP)
• Cancer antigen 125 (CA125)
• Carcinoembryonic antigen (CEA)
• Human chorionic gonadotropin (HCG)

Imaging (e.g., trans-vaginal ultrasound, MRI, CT scan, PET scan) and laparoscopic biopsies are used to diagnose ovarian cancer.  At times cells are collected using paracentesis if there has been a build up of fluid in the peritoneal cavity (ascites).  The collected cells are examined for signs of cancer (i.e., morphological changes indicative of cancer).  Biopsy and microscopic analysis of cells is the only definitive way to diagnose ovarian cancer.

Ovarian Cancer – Treatment

There are several types of ovarian cancers.  Treatments typically include surgery, chemotherapy (e.g., anti-mitotic drugs), radiation therapy, hormone therapy (e.g., anti-estrogens), and immunotherapy.  Surgery most often involves a total hysterectomy and bilateral salpingo-oophorectomy and removal of any affected surrounding tissue when possible.

Some ovarian cancers can benefit from targeted therapies against specific enzymes that some cancerous cells rely on for survival.  For example, cancers with BRCA1 and BRCA2 mutations rely on PARP (poly ADP ribose polymerase) for survival, so are sometimes treated with PARP enzyme inhibitors.  Some cancers are treated with anti-angiogenesis medications such as anti-VEGF-A antibodies that blocks a vascular growth factor that cancer cells often produce (i.e., vascular endothelial growth factor A).