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 The pathogenesis of ovarian carcinoma remains unclear. [22,24] Several theories have been proposed to explain the epidemiology of ovarian cancer. [24] 
Theory 1—Incessant OvulationFathalla’s theory of “incessant ovulation” maintains that repeated ovulation traumatizes the ovarian epithelium, increasing the likelihood of errors during DNA repair. The epithelial cells are also exposed to the estrogen-rich follicular fluid present during ovulation, making the cells more susceptible to malignant change. In this theory, preventing ovulation can protect against ovarian cancer. The decreased risk associated with multiparity, pregnancy, lactation, and oral contraceptive use support Fathalla’s theory.Theory 2—Persistent Elevation of GonadotropinsThe ovarian epithelium repeatedly invaginates throughout life to form clefts and inclusion cysts. Under excessive stimulation by gonadotropins (FSH and LH) and estrogen, the ovarian epithelium may undergo malignant transformation. This theory would explain the decreased risk associated with pregnancy and oral contraceptive use.Theory 3—Excess Androgenic StimulationFactors associated with excess androgenic stimulation of ovarian epithelial cells may be decreased by factors related to greater progesterone stimulation. This third theory is supported by findings that higher levels of DHEA were associated with an increased risk of ovarian cancer.Family history/genetic factorsThe most important risk factor for ovarian cancer is a family history of a first-degree relative (for example, mother, daughter, or sister) with the disease. The risk is highest in women with 2 or more first-degree relatives with ovarian cancer. [24]The BRCA1 and BRCA2 gene mutations were originally found in women with breast cancer. They are also responsible for 9% of ovarian cancers. These genes typically prevent cancer by producing proteins to keep cells from growing abnormally. However, the mutated gene causes the cancer-preventing protein to be less effective. The lifetime ovarian cancer risk for women with BRCA1 or BRCA2 mutations has been estimated to be between 40% and 50% by age 70. [22] The lifetime risk for the general population of women is only 1.7%. Two retrospective studies of patients with germline mutations in BRCA1 suggest these women have improved survival compared with BRCA1-negative women. [24]. It is important to note the majority of women with this mutation most likely have family members with a history of cancer. This history may have led them to be more vigilant and inclined to participate in screening programs leading to earlier diagnosis—and, therefore, an improved survival prognosis. [24] Most DNA mutations related to ovarian cancer occur during a woman’s lifetime rather than having been inherited. The causes of most acquired mutations remains unknown. [22] AgeMost ovarian cancers develop after menopause and half are found in women over the age of 63.ObesityObesity is associated with an increased mortality from ovarian cancer. In a study from the American Cancer Society, the risk was increased by 50% in the heaviest women. In cohort studies, height and body mass index, including high BMI during adolescence, were associated with an increased risk of ovarian cancer.Reproductive historyResearchers have found an apparent relationship between the number of menstrual cycles in a woman’s lifetime and her risk of developing ovarian cancer. Specific factors include [12]
Fertility drugsSome research studies have found that prolonged use of the fertility drug clomiphene citrate (especially when pregnancy is not achieved) may increase your risk of developing ovarian tumors, particularly LMP tumors. [22]Personal history of breast cancerA patient with breast cancer has an increased risk of developing ovarian cancer. In addition, a strong family history of breast cancer may also mean the patient has inherited the BRCA1 or BRCA2 gene. [22]Talcum powderMost studies, but not all, suggest a slight increase in the risk of ovarian cancer in women who used talc on the genital area. [22] An analysis of 6 case-control studies of talc and ovarian cancer found a statistically significant increase in risk (odds ratio=1.3, 95% CI 1.1-1.6). A cohort study among nurses did not observe a risk of ovarian cancer associated with perineal talc use. (RR=1.09; 95% CI=0.86-1.37). [24]ERT/HRTThe results of studies done regarding the ovarian cancer risk from estrogen replacement therapy and hormone replacement therapy have not been consistent. Some studies suggest that women using estrogens after menopause have an increased risk, while others have not found any such effect on ovarian cancer risk. [22]For more information regarding the causes and risk associated with ovarian cancer, visit the Web sites of the National Cancer Institute and the American Cancer Society. DisclaimerThese sites are not part of Hycamtin.com, a GlaxoSmithKline Web site. The content and materials in these third-party Web sites are not produced or endorsed by GlaxoSmithKline.Some of these third-party Web sites may refer to uses of our products that are not recommended by GlaxoSmithKline. You should always consult with your physician or health care professional before using any GlaxoSmithKline prescription product. Important Safety InformationContraindicationsHycamtin is contraindicated in patients who have a history of hypersensitivity reactions to topotecan or to any of its ingredients. Hycamtin should not be used in patients who are pregnant or breast-feeding, or those with severe bone marrow depression.WarningsHycamtin should be used only in patients with adequate bone marrow reserves, including baseline neutrophil counts of at least 1,500 cells/mm3 and platelet counts of at least 100,000/mm3. Frequent monitoring of blood counts should be instituted during treatment with Hycamtin.Patients should not be treated with subsequent courses of Hycamtin until neutrophils recover to >1,000 cells/mm3, platelets recover to >100,000 cells/mm3, and hemoglobin levels recover to 9.0 g/dL (with transfusion if necessary). Hycamtin may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Hycamtin. Drug InteractionsConcomitant administration of G-CSF can prolong the duration of neutropenia, so if G-CSF is to be used, it should not be initiated until day 6 of the course of therapy, 24 hours after completion of treatment with Hycamtin.Myelosuppression was more severe when Hycamtin was given in combination with cisplatin in phase I studies. In a reported study on concomitant administration of cisplatin 50 mg/m² and Hycamtin at a dose of 1.25 mg/m²/day x 5 days, 1 of 3 patients had severe neutropenia for 12 days, and a second patient died with neutropenic sepsis. There are no adequate data to define a safe and effective regimen for Hycamtin and cisplatin in combination. Adverse EventsFrequently reported nonhematologic adverse events associated with use of Hycamtin included nausea (64%), vomiting (45%), diarrhea (32%), alopecia (49%), fatigue (29%), and dyspnea (22%). Most nonhematologic toxicities were grade 1 or 2. |
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