varian cancer is known as the “silent” killer because so often the diverse and varied nature of its symptoms leads to a diagnosis in late stage when it is very difficult to control and almost impossible to cure.

That could all be changing now.  Earlier this year, research concluded that there IS a constellation of symptoms that has significance in the early detection of ovarian cancer.  According to Patricia Goldman, ovarian cancer survivor and President of the Ovarian Cancer National Alliance, clinical support for this concept is “the most encouraging thing we’ve seen” in the last year.

Even though symptoms vary by patient, physicians can now be on the lookout and may be less likely to dismiss symptoms that could point to early disease.  

“The text books have historically informed practitioners that there are no symptoms until advanced stage, therefore when a frontline practitioner sees a woman who manifests the subtle signs of ovarian cancer, they have been sometimes dismissed, ” Goldman tells cancerpage.  

Symptoms 

Common symptoms are abdominal cramping, bloating, and distension, early satiety, constipation or diarrhea, gas, indigestion, and changes in bladder habits.

Prevention - many questions, few answers

In the area of prevention, Goldman is encouraged by work being done with oral contraceptives as chemo-preventative agents against the fifth leading cause of cancer death in U.S. women.

There’s a growing body of evidence that oral contraceptives reduce the risk of developing ovarian cancer. The question is why.  Theories have suggested the process of repeated ovulation offers many opportunities for something to go wrong on the cellular level that can develop into ovarian cancer. Does the pill lower risk because it stops women from ovulating? Recent research may be pointing to another explanation.

New research suggests that oral contraceptives that contain higher levels of the hormone progestin have “twice the protective effect of the low-progestin pills” according to Gustavo C. Rodriguez (MD) of Duke University Medical Center who delivered his findings in March to the annual meeting of the Society of Gynecological Oncologists.  Progestin may increase the production of a substance associated with cell death Rodriguez hypothesizes.

Unfortunately, the data suggests women who may have a genetic predisposition to develop ovarian cancer aren’t helped by oral contraceptives. (New England Journal of Medicine 2001;345:235-240) For some of them – those with the BRCA1 gene mutation – getting their fallopian tubes tied appears to have some protective value according to Dr. Steven Narod of the University of Toronto and the Hereditary Ovarian Cancer Clinical Study Group.  He and his co-workers concluded that his research data supports “the recommendation that tubal ligation be offered to women with BRCA1 mutations as a means of reducing ovarian cancer risk.” (Lancet 2001;357:1467-1470.)

Evidence that aspirin use is linked to lower ovarian cancer risk was also reported this year. Researcher Arsian Akhmedkhanov of the New York University of Medicine was not ready to recommend that women take aspirin as a prophylactic but his 12-year study of 748 women concluded women who took aspirin at least three times a week over six months had a 40% lower risk of developing one type of ovarian cancer - epithelial ovarian cancer - that is cancer that starts in the thin membrane surrounding each ovary.

It’s thought that inflammation may have a role to play in the development of ovarian cancer thus explaining the benefits of aspirin and NSAIDs (non-steroid anti-inflammatory drugs) such as ibuprofen.  Another report this past year found lower ovarian cancer risk among women who used various barrier methods of birth control including condoms and diaphragms leading one of the researchers to suggest studying whether sperm contains inflammation-causing substances that are blocked by barrier method contraceptives. (Epidemiology 2001; 12:307-312)

Though researchers don’t know why this is the case, a report in the Journal of the American Medical Association this year concluded that use of estrogen replacement therapy by postmenopausal women “increased risk of fatal ovarian cancer.”  They also concluded that risk decreased “with length of time since last use.”(JAMA 2001; 285:1460-1465)  Dr. Rodriguez of Duke believes his progestin findings, if confirmed in larger trials could point to the benefits of increasing progestin levels in Hormone Replacement Therapies.

Detection – developing tests, improving the odds

Early detection is key to long-term survival in most cancers including ovarian cancer. There are no tests such as mammography for breast cancer, pap smear for cervical cancer, colonoscopy for colon cancer or PSA for prostate cancer that have proven cost effective or reliable for early stage ovarian cancer.

Testing for elevated CA125 protein levels in the blood has proved ineffective because for pre-menopausal women levels may be elevated for many reasons.  It’s thought this test could be useful for post-menopausal women however and a clinical trial being conducted by the National Cancer Institute is currently enrolling patients to assess whether CA125 tests coupled with transvaginal ultrasound is an effective detection tool for women between the ages of 55 and 74.

In January, a study published in the journal Cancer found that women with malignant ovarian tumors had significantly higher vascular epithelial growth factor (VEGF) levels in their blood than did women who had non-malignant or borderline tumors.

A clinical trial being sponsored by the National Cancer Institute is currently enrolling up to 6,000 women to help "identify and develop highly sensitive and specific tumor markers for the detection of early rather than advanced stage ovarian cancer” and to determine if performing “Ovarian Pap Tests” on high risk women makes sense.  “Ovarian Pap Test" is a new diagnostic test to detect pre-cancerous or early changes on the ovaries. Using minimally invasive office laparoscopy, the "Ovarian Pap Test" involves direct visualization of the ovaries and collection of cells from the surface of the ovary and from the peritoneal cavity by the use of a laparoscopic cytologic sampling instrument.

Treatment – new ways of administering old drugs

Once diagnosed, ovarian cancer has proved difficult to treat. This is primarily true because most ovarian cancers are diagnosed in late stage after the disease has spread to surrounding tissues.   Cancer that has spread is always harder to treat. The first line of treatment for early stage ovarian cancer is surgery. Later stage disease is usually treated with surgery and platinum-based chemotherapy.

The problem is that many ovarian cancers develop a resistance to the platinum based chemo agents and recur.

A University of Wisconsin researcher found that raising the patient’s body temperature in a process called hyperthermia to 107  before administering the drug carboplatin helps break through some of that platinum resistance. H. Ian Roberts (MD) has treated 14 patients in his phase I trial and achieved one complete response, four partial responses and four cases of stable disease.

Policy - funding research

Research provides hope and according to Patrician Goldman of the Ovarian Cancer National Alliance increasing research funding is the top priority.

“Our concern with more research is to get a screening test which could be routinely applied as a pap smear is or a mammogram, that would go a long way toward wiping out the problem of late diagnoses,” she says.

The National Alliance has asked Congress to increase the budget for the Department of Defense Ovarian Research Program from $12 million to  $20 million.  The National Cancer Institute’s budget for ovarian cancer research has jumped from $20 million in 1992 to about $65 million dollars, Goldman says.  The Alliance wants to see a Centers for Disease Control program to track population differences in ovarian cancer expanded from its current funding level of $1 million to the $2.6 million proposed for FY 2001. The CDC program, Goldman says, will shed light on a number of interesting issues such as race differences in the incidence of ovarian cancer – African and Asian Americans appear to have lower risk. Goldman also wants to know what’s happening among younger women.

“There are a lot of questions about the age women are getting this disease. Anecdotally, the age appears to be getting younger, is there something in the life style of younger women?  The thought would be that with more women on oral contraceptives, the rate would decrease,” Goldman says.

Clinical Trials – on the front lines

There are more than 60 clinical trials related to ovarian cancer sponsored by the National Cancer Institute currently enrolling patients or preparing to do so.  For a list, click here for NIH sponsored clinical trials currently recruiting.

To read more about the research mentioned above, look to the news list in the column on the right hand side of this page.

Written By 
Rachael Myers Lowe, editor
cancerpage.com

Reviewed by
Katie Mullaly, RN, MSN
Jane Quigley, RN, BSN
cancerpage.com