User:Ovarian cancer

Ovarian cancer

General Information
Estimated new cases and deaths from ovarian cancer in the United States in 2006:

New cases: 20,180. Deaths: 15,310.

Several malignancies arise from the ovary. Epithelial carcinoma of the ovary is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women, with 50% of all cases occurring in women over age 65. Approximately 5% to 10% of ovarian cancers are familial and 3 distinct hereditary patterns have been identified: ovarian cancer alone, ovarian and breast cancers, or ovarian and colon cancers. The most important risk factor for ovarian cancer is a family history of a first-degree relative (e.g., mother, daughter, or sister) with the disease. The highest risk appears in women with 2 or more first-degree relatives with ovarian cancer. The risk is somewhat less for women with one first-degree and one second-degree relative (grandmother or aunt) with ovarian cancer.

In most families affected with the breast and ovarian cancer syndrome or site-specific ovarian cancer, genetic linkage has been found to the BRCA1 locus on chromosome 17q21. BRCA2, also responsible for some instances of inherited ovarian and breast cancer, has been mapped by genetic linkage to chromosome 13q12. The lifetime risk for developing ovarian cancer in patients harboring germline mutations in BRCA1 is substantially increased over the general population. Two retrospective studies of patients with germline mutations in BRCA1 suggest that these women have improved survival compared with BRCA1-mutation–negative women. [Level of evidence: 3iiiA] When interpreting these data, it must be considered that the majority of women with a BRCA1 mutation probably have family members with a history of ovarian and/or breast cancer; therefore, these women may have been more vigilant and inclined to participate in cancer screening programs that may have led to earlier detection.

For women at increased risk, prophylactic oophorectomy may be considered after the age of 35 if childbearing is complete. In a family-based study among women with BRCA1 or BRCA2 mutations, of the 259 women who had undergone bilateral prophylactic oophorectomy, two (0.8%) developed subsequent papillary serous peritoneal carcinoma, and six (2.8%) had stage I ovarian cancer at the time of surgery. Of the 292 matched controls, 20% who did not have prophylactic surgery developed ovarian cancer. Prophylactic surgery was associated with a higher than 90% reduction in the risk of ovarian cancer (relative risk [RR] = 0.04; 95% confidence interval [CI], 0.01–0.16), with an average follow-up of 9 years; however, family-based studies may be associated with biases due to case selection and other factors that may influence the estimate of benefit. (Refer to the Evidence of Benefit 6 section in the PDQ summary on Prevention of Ovarian Cancer 2 for more information.) After a prophylactic oophorectomy, a small percentage of women may develop a primary peritoneal carcinoma, similar in appearance to ovarian cancer. The prognostic information presented below deals only with epithelial carcinomas. Stromal and germ cell tumors are relatively uncommon and comprise less than 10% of cases. (Refer to the PDQ summaries on Ovarian Germ Cell Tumor Treatment 7 and Ovarian Low Malignant Potential Tumor Treatment 8 for more information.)

Ovarian cancer usually spreads via local shedding into the peritoneal cavity followed by implantation on the peritoneum and via local invasion of bowel and bladder. The incidence of positive nodes at primary surgery has been reported to be as much as 24% in patients with stage I disease, 50% in patients with stage II disease, 74% in patients with stage III disease, and 73% in patients with stage IV disease. In this study, the pelvic nodes were involved as often as the para-aortic nodes. Tumor cells may also block diaphragmatic lymphatics. The resulting impairment of lymphatic drainage of the peritoneum is thought to play a role in development of ascites in ovarian cancer. Also, transdiaphragmatic spread to the pleura is common.

Prognosis in ovarian cancer is influenced by several factors, but multivariate analyses suggest that the most important favorable factors include:

Younger age. Good performance status. Cell type other than mucinous and clear cell. Lower stage. Well-differentiated tumor. Smaller disease volume prior to any surgical debulking. Absence of ascites. Smaller residual tumor following primary cytoreductive surgery. For patients with stage I disease, the most important prognostic factor is grade, followed by dense adherence and large-volume ascites. DNA flow cytometric analysis of stage I and stage IIA patients may identify a group of high-risk patients. Patients with clear cell histology appear to have a worse prognosis. Patients with a significant component of transitional cell carcinoma appear to have a better prognosis.

Although the ovarian cancer-associated antigen, CA 125, has no prognostic significance when measured at the time of diagnosis, it has a high correlation with survival when measured 1 month after the third course of chemotherapy for patients with stage III or stage IV disease. For patients whose elevated CA 125 normalizes with chemotherapy, more than one subsequent elevated CA 125 measurement is highly predictive of active disease, but this does not mandate immediate therapy.

Most patients with ovarian cancer have widespread disease at presentation. This may be partly explained by relatively early spread (and implantation) of high grade papillary serous cancers to the rest of the peritoneal cavity. Conversely, symptoms such as abdominal pain and swelling, gastrointestinal symptoms, and pelvic pain, often go unrecognized, leading to delays in diagnosis. Partly as a result of this, yearly mortality in ovarian cancer is approximately 65% of the incidence rate. Long-term follow-up of suboptimally debulked stage III and stage IV patients had a 5-year survival rate of <10% with platinum-based combination therapy prior to the current generation of trials including taxanes. By contrast, optimally debulked stage III patients treated with a combination of intravenous taxane and intraperitoneal platinum plus taxane achieved a median survival of 66 months in a Gynecologic Oncology Group trial that accrued patients between 1998 and 2001. Numerous clinical trials are in progress to refine existing therapy and test the value of different approaches to postoperative drug and radiation therapy. Patients with any stage of ovarian cancer are appropriate candidates for clinical trials.

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