[Show abstract][Hide abstract] ABSTRACT: This article aims to cover current concepts and controversies in the surgical management of ovarian cancer. While there have been significant advances in the surgical management of vulval, cervical and even endometrial cancer there have been few developments in the surgical management of ovarian cancer. This situation is likely to continue until we get a clearer understanding of the natural history of this disease and better therapeutic options become available.
Cancer Treatment Reviews 05/2001; 27(2):111-8. · 6.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Residual disease following primary debulking surgery is a recognized prognostic factor in ovarian cancer. Few studies have looked at the effect of initial ovarian tumor diameter on survival. As larger tumors are more likely to be detected by ultrasound, this information may be important in determining a survival benefit in screen-detected cancers. We reviewed the case notes and pathology of 168 consecutive cases of primary debulking surgery in epithelial ovarian cancer. We examined the influence of ovarian tumor diameter on survival and its relationship to CA125 levels and stage. For the purposes of analyses, we divided subjects into two groups: those with tumors < 6 cm and those with tumors > 6 cm. There were significant differences between the groups, with smaller tumors having more advanced stage disease compared to larger tumors (chi23 = 15.7, P = 0.0013) The median survival for tumors less than or equal to 6 cm was 17months (95% confidence interval [95% CI], 12 to 22), while for tumors greater than 6cm, the median survival was 36 months (95% CI, 13 to 59; logrank test = 8.61, P = 0.003). However, stage is also an important predictor of survival, and in a multivariate analysis, tumor size was not found to be an independent prognostic factor. There was no significant difference between the groups for CA125 levels. As larger diameter ovaries are more likely to be detected by ultrasound, it may be that screen-detected ovarian cancers will show a survival benefit simply because they detect a subset of ovarian cancers that are associated with a better prognosis.
International Journal of Gynecological Cancer 12/2000; 10(6):449-451. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated risk models for the inherited susceptibility of breast and ovarian cancer, using data from both high-risk families and a population based series of ovarian cancer. The first data set consisted of 112 families containing two or more relatives with epithelial ovarian cancer. BRCA1 and BRCA2 germline mutations were detected in 50% of these families. The second study involved 374 ovarian cancer cases, unselected for family history, who had DNA samples analyzed for BRCA1 mutations. Twelve women were found to be carriers. We constructed genetic models for ovarian and breast cancer using the computer program MENDEL. In the first study, we modeled the effects of BRCA1 and BRCA2 simultaneously and allowed for a third gene predisposing to ovarian cancer. None of the models fitted gave significant evidence for a third gene. Population frequencies of BRCA1 and BRCA2 mutations were estimated to be 0. 00128 and 0.00172, respectively. Our results suggest that BRCA1 and BRCA2 may be sufficient to explain the majority of familial ovarian cancer and that families without mutations can be explained by sensitivity of mutation testing and chance clusters of sporadic cases. Using data on the families of the 12 mutation carriers in the second study, we estimated age-specific ovarian and breast cancer risks for BRCA1 mutation carriers. Under the best-fitting model, the cumulative ovarian cancer risk was 66% by age 70, and the corresponding breast cancer risk was 45%. The high penetrance estimate for ovarian cancer, compared with other studies, suggests that modifying genetic or environmental factors may be important determinants of risk.
[Show abstract][Hide abstract] ABSTRACT: We conducted a population-based study to determine the contribution of germline mutations in known candidate genes to ovarian cancer diagnosed at age <30 years. Women with epithelial ovarian cancer were identified through cancer registries. DNA samples were analyzed for mutations in BRCA1, the "ovarian cancer-cluster region" (nucleotides 3139-7069) of BRCA2, and the mismatch-repair genes hMSH2 and hMLH1. Probable germline mutations in hMLH1 were identified in 2 (2%; 95% confidence interval 1%-8%) of 101 women with invasive ovarian cancer diagnosed at age <30 years. No germline mutations were identified in any of the other genes analyzed. There were no striking pedigrees suggestive of families with either breast/ovarian cancer or hereditary nonpolyposis colorectal cancer (HNPCC). There was a significantly increased incidence of all cancers in first-degree relatives of women with invasive disease (relative risk [RR] = 1.6, P=.01) but not in second-degree relatives or in relatives of women with borderline cases. First-degree relatives of women with invasive disease had increased risks of ovarian cancer (RR = 4.8, P=.03), myeloma (RR = 10, P=.01), and non-Hodgkin lymphoma (RR = 7, P=.004). Germline mutations in BRCA1, BRCA2, msh2, and mlh1 contribute to only a minority of cases of early-onset epithelial ovarian cancer. Our data suggest that early-onset ovarian cancer is not associated with a greatly increased risk of cancer in close relatives.
The American Journal of Human Genetics 12/1999; 65(6):1725-32. · 11.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The natural history of ovarian cancer is not well understood and, to date, there is conflicting evidence as to whether or not there is a demonstrable precursor lesion. Some women at high risk of developing ovarian cancer because of their family history elect to have a prophylactic oophorectomy. To determine whether or not a recognizable premalignant lesion could be defined in familial ovarian carcinogenesis, we reviewed ovarian tissue specimens from women whose ovaries were removed prophylactically before gene testing became available and who were tested subsequently for BRCA1 or BRCA2 gene mutations.
We analyzed ovarian tissue specimens from 37 women. The specimens were examined for the presence of the following four features: inclusion cysts, clefts and fissures, ovarian epithelial metaplasia, and the presence of papillae on the ovarian surface epithelium. The specimens were also examined closely for the presence of dysplasia and occult neoplasia. Furthermore, the occurrence of endometriosis and benign ovarian tumors was documented in these women. The protein truncation test, nonradioactive single-stranded conformation polymorphism analysis, and heteroduplex analysis, followed by DNA sequencing, were used to identify BRCA1 or BRCA2 mutations in either blood samples or ovarian tissue specimens.
Eleven women had inherited a mutated BRCA1 or BRCA2 gene; 26 women had not. There was no difference between these groups for any of the features studied.
Our data suggest that many of the histologic "abnormalities" described in "normal" ovaries are, in fact, variations of the normal and are not associated with the development of cancer.
JNCI Journal of the National Cancer Institute 05/1999; 91(7):626-8. · 14.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective To estimate the relative risk and lifetime risk of ovarian cancer in women with various categories of family history.Design A meta-analysis of all published caseecontrol and cohort studies.Methods Pooled relative risk estimates were calculated for the caseecontrol studies, using the Mantel-Haenzel method. These estimates were combined with the relative risks from the cohort studies. The pooled estimates of relative risk were used to estimate lifetime risks of ovarian cancer from age 15 Up to age 75, for various categories of family history.Main outcome measures Relative risks and lifetime risks of developing ovarian cancer were calculated for the categories of women with 1. an affected first degree relative; 2. an affected mother; 3. an affected sister; and 4. women with more than one affected relative.Results The relative risk to first degree relatives is 3.1 (95% CI 2.6–3.7). There is some evidence that this relative risk declines with age. The relative risk to mothers of cases 1.1 (95% CI 0.8–1.6) was lower than the relative risks to sisters: 3.8 (95% CI 2.9–5.1), and daughters: 6.0 (95% CI 3.0–11.9); the explanation of this difference is unclear.Conclusions Women with a family history of ovarian cancer have a substantially higher risk of developing ovarian cancer compared with women without such a history. However the risk is small for most categories of family history, except for the small number of individuals who have more than one affected relative.
BJOG An International Journal of Obstetrics & Gynaecology 04/1998; 105(5):493 - 499. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The recent identification of two breast and ovarian cancer susceptibility genes--BRCA1 and BRCA2--has received a lot of publicity. Public and professional expectations of the availability and utility of genetic testing have been raised and the importance of a family history of breast cancer overemphasized. In this chapter, we examine the significance of a family history of breast or ovarian cancer in determining individual risk. A strategy for management is proposed, based on stratifying women with such a history into three different categories of risk for breast cancer: high, moderate and low. Some of the more controversial aspects of screening for breast and ovarian cancer are reviewed, including the issue of management of women who are at increased risk of these cancers by virtue of a family history, genetic predisposition, or both. There is a need for further research to clarify the most appropriate management of those at moderate risk of developing these cancers. A management strategy for women at high risk is proposed. We believe that adoption of this strategy will strengthen consistent information giving from primary to tertiary care.
British Medical Bulletin 02/1998; 54(4):823-38. · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inherited mutations in the BRCA1 gene confer a high risk of breast and ovarian cancer in some families. To determine the contribution of BRCA1 mutations to ovarian cancer in the general population, we analyzed DNA samples from a consecutive series of women with ovarian cancer seen at one center.
We studied 374 women who received a diagnosis of epithelial ovarian cancer before the age of 70 years and were treated at the Royal Marsden Hospital between July 1993 and September 1995. Genomic DNA was analyzed by multiplex heteroduplex analysis. Variants were further identified by sequencing.
Probable germ-line BRCA1 mutations were identified in 13 of the 374 women (3 percent; 95 percent confidence interval, 2 to 6 percent). Six of the variants have not been described previously. Of the 13 mutations, 12 are predicted to result in a truncated protein product. An additional variant results in an in-frame deletion just outside the putative zinc-finger domain. Nine of the 12 women with truncating mutations had family histories of breast or ovarian cancer or both.
Assuming that our method has a sensitivity of 70 percent, mutations in BRCA1 occur in approximately 5 percent (95 percent confidence interval, 3 to 8 percent) of women in whom ovarian cancer is diagnosed before the age of 70 years.
New England Journal of Medicine 05/1997; 336(16):1125-30. · 54.42 Impact Factor