Early detection and prevention of ovarian cancer has long been considered an enigma. The disease bears the dubious moniker “the cancer that whispers,” because it tends to develop with vague symptoms that are often dismissed as being associated with getting older: back pain, bloating, decreased appetite, and changes in bowel and bladder habits among others.
Ovarian cancer, although rare, is a deadly disease because it is often diagnosed at a late stage. It is the fifth leading cause of cancer death among women, claiming more than 14,000 lives in the U.S. each year.
Recent research around the origins of ovarian cancer may lead to future advances in prevention. Research published in Nature Communications and highlighted in The Wall Street Journal has confirmed what we’ve suspected for more than 20 years: Ovarian cancer might actually originate in the fallopian tubes, not the ovaries.
Furthermore, researchers found that cancer cells form much more slowly in the fallopian tubes – some for as long as seven years – before spreading to the ovaries. When it does, the cancer grows quickly and can spread to other tissues and organs within a year or less.
How did we arrive at the tubal origin hypothesis?
Studies initially found early cancer and even cancer precursors in the fallopian tubes of patients with mutations in the BRCA genes who’d had their fallopian tubes and ovaries removed to prevent cancer in those organs. The research highlighted in The Wall Street Journal was an extension of the work that has been done since that initial finding.
For part of the project, researchers examined tissue samples of the fallopian tubes, ovaries, and peritoneum (the lining of the abdominal wall) from two populations of women: healthy women and women with ovarian cancer. They then compared cancer cells retrieved from the second group with healthy tissue samples from the first. Nearly all of the cancerous tissue was similar to the fallopian tube tissue. This lent credence to the hypothesis that ovarian cancer develops in the fallopian tubes and travels to the ovaries
The next steps will be to confirm these findings on a larger scale. These findings could change how we approach early detection and prevention of ovarian cancer.
What are the current options for early detection and prevention?
Removal of fallopian tubes and ovaries has been the standard of prevention for many years for patients with mutations of the BRCA genes. The procedure to remove both is called risk-reducing salpingo-oophorectomy (RRSO). This preventive procedure typically is recommended for women ages 35 to 40 if they are done having children, or 10 years before the age of youngest ovarian cancer death in the family.
RRSO is incredibly effective for reducing the incidence of ovarian cancer. It can reduce the risk from as high as 40 percent, depending on the type of BRCA mutation, to around 3 percent. However, there are subsequent risks involved. The major drawback to RRSO is that when we remove the ovaries in a young woman, she goes into menopause. There are multiple health implications related to decreased estrogen production in menopause, including:
● Heart health concerns
● Hot flashes and night sweats
● Vaginal dryness
Doctors must discuss of the risks and benefits of the procedure with patients. For women who choose not to undergo RRSO, doctors might recommend transvaginal ultrasound combined with a blood test for a tumor marker called serum CA-125 that often is present in women with certain types of ovarian cancer.
It’s important to note that this screening is for patients known to be at high risk for ovarian cancer and is generally limited to patients with mutations in the BRCA genes, along with a few others. The U.S. Preventive Services Task Force agrees that current screenings are ineffective for women at average risk of ovarian cancer because screening too often results in false positives that lead to unnecessary stress or surgeries.
Screening ineffectiveness can be boiled down to two specific concerns. First, serum CA-125 often is elevated in women with a number of noncancer conditions, such as endometriosis, pancreatitis, and even gastroenteritis.
Second, ultrasound does not reliably differentiate between cancerous and benign ovarian masses. The ovaries are located in the upper pelvis. If we happen to see a mass on ultrasound, we can’t biopsy it. If the mass is cancerous, doing a biopsy might seed the abdomen and pelvis with cancer cells. In order to make a diagnosis, we must remove the entire ovary. Many of these masses are not cancer, and screening with ultrasound leads many women to undergo procedures that they may not have needed. In other words, the risk of routine screening outweighs the benefits for average-risk women.
"Clearly, we need to find safer, more effective tactics to detect and prevent ovarian cancer."
Potential future benefits for women
These findings have changed the way gynecologists approach hysterectomy. If a woman undergoes hysterectomy, gynecologists should routinely remove the fallopian tubes as well to theoretically reduce the risk of ovarian cancer. And if it were deemed safe to do so, they should leave the ovaries to continue producing female hormones and avoid early menopause.
Dr. Doug Levine, senior author of one of the studies published in Nature Communications, is conducting research in conjunction with researchers at MD Anderson. The goal is to determine whether removing just the fallopian tubes in patients who are genetically predisposed to ovarian cancer can effectively decrease the rate of those cancers while still maintaining ovarian function. Women in the study are encouraged to undergo removal of the ovaries at age 40-50.
Risk factors for ovarian cancer include:
● BRCA1 or BRCA2 mutations, which account for about 20 percent of ovarian cancers
● Eastern European or Ashkenazi Jewish heritage
● Family history of breast or ovarian cancer.
● History of breast, uterine, or colorectal cancer survivors
● Difficulty conceiving, or having never given birth
Women with these risk factors, particularly those with a family history of breast or ovarian cancer, should talk to their doctor to see if referral to a genetic counselor and genetic testing is appropriate.
UT Southwestern is participating in a clinical trial for a potential ovarian cancer screening protocol. The trial involves having routine ultrasounds and regular blood sampling to test for serum CA-125. Women interested in enrolling can call 214-648-7874 for information.
Clearly, we need to find safer, more effective tactics to detect and prevent ovarian cancer. The recent findings regarding the origins of ovarian cancer might help us save more lives in the future with less radical surgery and fewer side effects.
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