Personal History Of Ovarian Cancer Research Articles

Abstract B08: Predictors of delay to single-site confirmatory testing for familial BRCA1/2 mutations

Abstract Background: Genetic testing for cancer predisposition genes like BRCA1/2 allows the quantification of future cancer risks and the adoption of preventive measures such as chemoprevention, screening, and prophylactic surgeries to mitigate risks. First-in-family mutations in BRCA1/2 are generally identified in a proband via full-sequence analysis. Once a familial mutation is identified, probands may share test information with family members to alert them of risks. Family members may then pursue single-site testing (SST) to determine if the familial mutation was inherited. Despite the high cancer risks associated with BRCA1/2 mutations, research suggests many family members remain untested or experience delays to confirmatory SST. Few studies have characterized the diverse factors influencing transmission of risk information and uptake of SST within families. Methods: Probands undergoing full-sequence BRACAnalysis by Myriad Genetic Laboratories (MGL) who were found to have unique mutations in BRCA1/2 were randomly selected across 6 years (~50 per year, 2007-2012) from the MGL BRCA1/2 database. In the same time frame, putative “relatives” were identified by linking the proband unique mutation to all downstream requests for SST at the same site. Clinical characteristics for probands and putative relatives were extracted from the MGL Test Request Form (TRF). Pedigrees were independently constructed by two members of the research team for each family based on personal/family history data. Disputed family structures were resolved through group consensus after input from a third member of the research team. Results: Linked data for 298 probands and 701 linked relatives undergoing SST were included in analyses. Overall ≥1 relative was tested in 265/298 (89%) families. Probands were primarily women (97%) of Western/Northern European ancestry (56%). Proband mean age of testing was 49.6 years [range 22-87], and over 90% had a personal history of cancer: [breast (73%) or ovarian (12%), multiple cancers (22%)]. A median 2 relatives were tested per proband [range 0-13]. Median number of days between proband and first relative tested was 75 (2.5 mos). Median time until first test decreased by an average of 11 days per year from 2007-2012 (p=0.01) and there was a trend toward increased SST testing in year one (39% families had ≥1 SST in the first year of follow-up in 2007 vs 78% in 2012, p=0.001). Siblings (n=275/701, 39%) were overall the most frequently tested relative followed by children (22%), parents (11%) and cousins (11%), while delay was shortest for parents (mean 136 days) and longest for cousins (mean 460 days). Univariate analyses found that relationship to proband (p<0.0001), sex (p=0.05), and age (p=0.01) were associated with SST delay. A linear multivariable model found, compared to siblings, parents had significantly shorter times to testing (p<0.001) and cousins (p=0.02) and nieces/nephews (p<0.001) significantly longer. Male sex was associated with longer delay (p=0.03), and a personal history of ovarian cancer (compared to breast) with a shorter delay (p=0.005). Conclusion: Uptake of SST in BRCA1/2 families peaks in year 1 but occurs over many years and primarily among first-degree relatives. Testing delays have decreased over time (2007-2012) and may indicate more frequent sharing of high risk information in families, greater access (e.g. insurance, geographic) to BRCA1/2 SST for relatives, and/or greater awareness of the options for risk reduction once BRCA1/2 status is determined. Over an observation period ≥1 and ≤5 years, a striking 11% of positive BRCA1/2 tests were not followed by a SST. Citation Format: Michael J. Hall, Kim Rainey, Allison Davis, Elizabeth Handorf, Rajesh Kaldate, Kelsey Moyes, Mary B. Daly. Predictors of delay to single-site confirmatory testing for familial BRCA1/2 mutations. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B08.

Identification of breast cancer (BC) patients (pts) fulfilling NCCN criteria for genetic risk assessment.

e12537 Background: Five to 10% of BC pts develop the disease due to an inherited predisposition syndrome; BRCA1/2 germline mutations are most commonly associated. NCCN guidelines help identify a somewhat broad group of pts requiring further genetic evaluation and a narrower one, for whom genetic testing is specifically recommended. Aims: The identification of pts requiring genetic guidance and the description of subgroups fulfilling NCCN criteria for genetic testing, according to family history (FH), demographic and clinical features, in a group of unselected Greek BC pts. Methods: This is a retrospective, medical records analysis of all histologically confirmed, unselected BC pts who who visited our department (Medical Oncology Unit, Hippocratio Hospital) between 2009 and 2012. Demographic, histopathologic and family history data was extracted and analyzed. Results: Among 690 pts eligible for analysis, 682 of which (98.8%) of Greek ethnicity, 233 (33.7% ) had a HER2+ subtype, 311 (45%) ER/PR+, and 69 (10%) triple-negative. Information was incomplete for the remaining 76 (11.1%). General criteria for furthr genetic evaluation were fulfilled by 301 patient (43.6%). Two hundred and eighty-six of them (41.44% ) were diagnosed with BC at age ≤50 and 15 (2.17%) at age older than 50; 12 (1.7%) had at least 2 close relatives with BC and 3 (0.43%) had a personal history of ovarian cancer (OC). BRCA1/2 testing criteria were fulfilled by 259 pts (37.5%). 172 (24.9%) were diagnosed at age ≤45. Seventy-five (10.8%) were diagnosed at age 46-50, 22 of which (3.1%) had one close relative with BC or OC and 16 (2.3% ) had two close relatives with BC or OC. Thirty-six pts (5.2%) with triple negative BC were diagnosed at age <60, 16 of which (2.3%) < 45 years old. No pts had a personal or FamHx of sarcoma, thus did not fulfill the relevant TP53 testing criteria. However 7 (1%) were diagnosed under age 30. Only 11 patients (1.6%) underwent genetic testing, revealing 5 (0.7%) carriers of a deleterious BRCA1 mutation. Conclusions: Almost half pts with BC require further genetic evaluation. The need for genetic counseling services and insurance coverage of genetic testing is highlighted by this study.

OC23.02: Which histologies limit the ability of CA-125 to characterize adnexal masses? An observational study of 3511 patients

simple rules were not applicable. 649 of these masses had CA-125 results available. The malignancy rate was 31% (203/649). The data were randomly divided into a development set (70% of the data, n = 457) and a test set (30% of the data, n = 192). Results: In the development set, the following variables were retained as predictors of malignancy: age, personal history of ovarian cancer, largest diameter of the lesion, largest diameter of the largest solid component, presence of blood flow in papillary projection and CA125. The area under the ROC curve (AUC) was 0.86 (95% CI, 0.82–0.90) in the development set and 0.83 (0.76–0.89) in the test set. Expert’s subjective assessment and RMI had an AUC in the test set of 0.88 (0.82–0.94) and 0.69 (0.60–0.77), respectively. To be able to compare the performance of the new model with LR1 and LR2, we excluded from the test set the 53 cases that were part of the original development set for LR1 and LR2 (IOTA phase 1, 1999–2004). On the reduced test set of 139 cases, the AUC of the new model, subjective assessment, RMI, LR1 and LR2 were 0.83 (0.76–0.91), 0.87 (0.80–0.94), 0.72 (0.63–0.81), 0.79 (0.71–0.87) and 0.72 (0.63–0.82), respectively. Conclusions: In adnexal masses where the simple rules are not applicable, our new mathematical model might be useful, but its performance must be prospectively validated.

Abstract A25: Public and provider awareness and use of a CA-125 test for ovarian cancer

Abstract Introduction: CA-125 is a serum marker approved for detecting recurrent ovarian cancer in women with a personal history of ovarian cancer. Several large trials have investigated the use of CA-125 (alone or in combination with transvaginal ultrasound [TVU]) as a screening test for ovarian cancer. However, this test has generally been associated with a low positive predictive value and trials have concluded that screening asymptomatic women in the average risk population with CA-125 is not beneficial. Still, there remains widespread discussion and marketing of ovarian cancer screening tests that include CA-125. Since little is known about public and provider awareness of CA-125, the objective of this study was to measure women's familiarity with the CA-125 test, and clinician beliefs about the effectiveness of screening for ovarian cancer with CA-125 in the United States. Methods: In 2008, CDC funded the collection of data as part of its national awareness campaign, Inside Knowledge: Get the Facts About Gynecologic Cancer. Several questions related to CA-125 were included as part of a standardized, survey administered annually in the contiguous United States by Porter Novelli. The HealthStyles survey included 2,991 female respondents age ≥ 18 years, and the DocStyles survey included 1,250 physician respondents of family/general practitioners (n=510), internists (n=490), and obstetrician/gynecologists (n=250). Participant responses to CA-125-related questions for the HealthStyles survey were weighted to match the demographic distribution of the general population. Chi-square tests were used to assess differences with the p-value set to 0.05. Results: Overall, most women (56%) had not heard of the CA-125 test, 29% had heard of it, and 15% were unsure. Demographic characteristics generally were similar for women who had not heard of the CA-125 test, except that women who had heard of the test more often were over age 45 (58% vs 37%) (p<0.0001) and were peri- or post-menopausal (54% vs 35%) (p<0.0001), compared to women who had not heard of CA-125. Few women (12%) had ever had a CA-125 test. About 15% of women who reported being “very concerned” about getting ovarian cancer also reported having had a CA-125 test. In the DocStyles results, the majority (53%) of physicians said that both CA-125 and TVU are effective screening tests for ovarian cancer. A greater proportion of OB/GYNs (57%) reported neither CA125 nor TVU were effective as screening tests for asymptomatic women in the average risk population than family/general practitioners (34%) or internists (30%) (p<0.0001). Conclusions: The large percentage of physicians who believe CA-125 is an effective screen for ovarian cancer signals the need for improved education. Educational efforts geared toward the public and providers that include both lack of evidence for screening with CA-125, as well as the potential harms of false-positive CA-125 tests should be a priority for public health programs and awareness campaigns. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A25.

Ovarian Cancer Metastatic to the Breast Presenting as Inflammatory Breast Cancer: A Case Report and Literature Review

Background. Primary ovarian carcinoma with metastasis to the breast is rare, with only 39 cases reported in the current literature. Ovarian metastasis to the breast presenting as inflammatory breast carcinoma is even more infrequent, with only 6 cases reported.Case. We present a patient who developed metastatic inflammatory cancer of the breast from a stage IIIC papillary serous ovarian adenocarcinoma approximately 1 year after the original diagnosis. Pathologic analysis confirmed the origin of the tumor: a high-grade adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. In addition, the tumor was strongly positive on immunohistochemistry for CA-125, identical to the ovarian primary. The patient died of diffuse metastasis 5 months after the breast tumor was noted.Conclusion. Although ovarian metastasis to the breast presenting as inflammatory breast cancer is rare, it should be included in the differential diagnosis for any patient with a personal history of ovarian cancer. Accurate differentiation is necessary because treatment differs significantly for patients with ovarian metastasis to the breast, as compared with patients with primary inflammatory breast cancer. Ovarian metastasis to the breast confers a poor prognosis: patient survival ranged from 3 to 18 months, with a median survival of 6 months after the diagnosis of the breast metastasis.

Background Enhancement Patterns on Screening Breast MRI – Impact on Biopsy Rate and Short Interval Follow Up.

Abstract Introduction:Marked background enhancement is one of the perceived limiting factors on breast MRI possibly obscuring suspicious lesions and reducing both the sensitivity and specificity of detection of small cancers. Background enhancement on MRI refers to the normal physiological enhancement of the woman's fibroglandular tissue and varies with age, hormonal status, menstrual cycle and breast glandularity. Patterns of enhancement vary greatly and marked enhancement can occur even when the MRI is performed in week 2 of the menstrual cycle or in postmenopausal women.Aim:To determine what impact background enhancement has on biopsy rate and short interval follow up rate.Method:231 consecutive baseline screening MRIs, in women aged between 16 -79 (average age 48) performed between Jan 2003 and Oct 2004 were selected. Indications for screening included significant family history (46.3%), personal history of contralateral mastectomy (25.1%), personal history of atypia (19.5%), other (3.0%), personal history of mantle radiation (2.2%), personal history of breast cancer > 5 years previously (2.2%), personal history of ovarian cancer (1.7%).The background enhancement in each case was described as minimal (< 25% glandular tissue showing enhancement), mild (25-50% enhancement), moderate (50-75% enhancement) and marked (> 75% enhancement).The BIRADS category, positive predictive value of biopsy and false positive rate was determined and compared for enhancement patterns.Results:Of 231 screening studies 26.6% demonstrated minimal enhancement, 32.8% mild enhancement, 22.7% moderate enhancement and 17.9% marked enhancement. Patients with minimal/mild enhancement had significantly higher rate of normal (BIRADS 1/2) examinations than those with moderate/marked enhancement (47.8% vs. 30.5%, p = 0.008). Patients with minimal/mild enhancement had significantly lower rate of six month followup (BIRADS 3) (38.97% vs. 53.68%, p = 0.02). No significant difference in biopsy rate was noted (11.7% minimal/mild enhancement vs. 14.7% moderate/marked enhancement, p = 0.5). No significant difference in positive predictive value of biopsy between the groups was noted (35.7% for moderate/marked enhancement vs. 25% for minimal/mild enhancement, p = 0.52).Conclusion:No significant association was found between background enhancement pattern and biopsy rate or false positive rate. However, patients with moderate/marked enhancement were significantly more likely to be given a category of BIRADS 3 and assigned to short interval follow up. The increased rate of BIRADS 3 in patients with moderate/marked background enhancement may be related to reduced reader confidence in these patients. Recognition of normal background enhancement patterns is important to limit the number of patients undergoing short interval followup. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4020.

Socioeconomic Factors Influencing BRCA 1/2 Mutation Carriers To Choose Risk Reduction Surgery in Community Cancer Genetics Program.

Abstract Background: Mutations in the BRCA 1/2 genes predispose women to increased risk of breast and ovarian cancer. Prophylactic mastectomy (PM) reduces the risk of breast cancer by approximately 90% while prophylactic salpingo-oophorectomy (PSO) reduces the risk of both breast and ovarian cancer. Yet, there is a paucity of data to determine if mutation carriers avail themselves of these risk reducing surgeries in the community setting.Purpose: This study evaluates if particular socioeconomic factors influence BRCA 1/2 mutation carriers to elect risk reduction surgery (RRS), either PM or PSO or both.Method: Of 129 BRCA1/2 positive patients identified by a community-based cancer genetics program outside Philadelphia from 1998 to 2008, 44 were excluded due to personal history of ovarian cancer, loss of follow-up, male gender, or deceased status. The 85 remaining patients were asked to complete a questionnaire addressing: age at diagnosis, ethnicity, religion, parity, education level, marital status, occupation, number of first degree relatives with breast or ovarian cancer, personal history of breast cancer, and use of oral contraceptives, tobacco, and alcohol. A chart review was performed on all responders.Results: Forty-nine patients (58%) completed the questionnaire. Of these, 68% (34/49) had RRS. Of those who did not have RRS, 63% (10/15) stated they definitely plan for RRS in the future. More than half of the women planning RRS in the future (6/10) were younger than 30 years old. Therefore, of all responders, 90% (44/49) stated they had or definitely plan to have RRS. The mean age of women with RRS versus those without was 43.9 and 35.6 years, respectively (p=.0102). Women age 40-64 had the highest rate of RRS (26/34; 84%; p=0.004). Most women (88%) with RRS had children (30/34; p=0.0493). Sixty-five percent (32/49) of women responders were college graduates; 24% were high school graduates (12/49). Of women who had RRS, 68% were college graduates. College graduates age > 40 were the group most likely to have RRS (17/18; 94%; p= .00029). Only 63% of high school graduates age > 40 (5/8; p=1.0) had RRS. Eight-five percent (11/13) of Ashkenazi Jewish women had RRS versus 67% (18/27) of non-Jewish Caucasian women. This was not statistically significant (p=0.2925). There was also no statistical difference for women choosing RRS with respect to occupation, birth control pill use, history of breast cancer, or family history of breast or ovarian cancer. Only 3/49 smoked cigarettes (>more than 1 pack per week) and none drank alcohol (>1 drink/day).Discussion: Women who presented to this community based genetics program had a high rate of RRS, were likely to be college educated, non-smokers, and non-drinkers. Age older than 40, completion of child bearing, and attainment of a college degree were the most significant factors associated with BRCA 1/2 mutation carriers having RRS. Further studies should explore barriers to genetic testing services, as well as evaluate reasons why BRCA1/2 mutation carriers decline RRS. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4076.

Preoperative diagnosis of ovarian tumors using Logistic model

Objective To assess the diagnostic value of Logistic model in differentiating between malignant and benign ovarian lesions. Methods Thirty-five indexes of clinical and ultrasound data were recorded in 601 ovarian lesions confirmed by surgical pathology. The Logistic model was developed on a training set( n - 400) and tested on a test set( n = 201). Results Variable selection resulted in a set of 10 variables for the models: personal history of ovarian cancer, maximal diameter of the lesion, maximal diameter of the solid component, multilocular-solid tumor, solid tumor, ascites, flow within papillation, irregular walls, very strong intratumoral blood flow (i. e. color score 4) and acoustic shadows. Test set area under the receiver-operating characteristics curve was 0.963 with a sensitivity 93.9% and a specificity 93. 1 %. Conclusions Logistic model can accurately separate malignant from benign ovarian masses. Key words: Ultrasonography; Ovarian neoplasms; Diagnosis, differential; Logistic model

Preoperative diagnosis of ovarian tumors using Bayesian kernel‐based methods

To develop flexible classifiers that predict malignancy in adnexal masses using a large database from nine centers. The database consisted of 1066 patients with at least one persistent adnexal mass for which a large amount of clinical and ultrasound data were recorded. The outcome of interest was the histological classification of the adnexal mass as benign or malignant. The outcome was predicted using Bayesian least squares support vector machines in comparison with relevance vector machines. The models were developed on a training set (n=754) and tested on a test set (n=312). Twenty-five percent of the patients (n=266) had a malignant tumor. Variable selection resulted in a set of 12 variables for the models: age, maximal diameter of the ovary, maximal diameter of the solid component, personal history of ovarian cancer, hormonal therapy, very strong intratumoral blood flow (i.e. color score 4), ascites, presumed ovarian origin of tumor, multilocular-solid tumor, blood flow within papillary projections, irregular internal cyst wall and acoustic shadows. Test set area under the receiver-operating characteristics curve (AUC) for all models exceeded 0.940, with a sensitivity above 90% and a specificity above 80% for all models. The least squares support vector machine model with linear kernel performed very well, with an AUC of 0.946, 91% sensitivity and 84% specificity. The models performed well in the test sets of all the centers. Bayesian kernel-based methods can accurately separate malignant from benign masses. The robustness of the models will be investigated in future studies.

Association between clinical characteristics and risk‐reduction interventions in women who underwent BRCA1 and BRCA2 testing

Women who are at increased risk for breast and ovarian cancers, especially BRCA1 and BRCA2 mutation carriers, face a myriad of risk-reduction options, including increased surveillance, chemoprevention, prophylactic oophorectomy, and prophylactic mastectomy. However, little is known about which clinical, demographic, or cancer-related factors are associated with risk-reduction interventions. The authors conducted a retrospective review of records for 554 women who had undergone testing at The University of Texas M. D. Anderson Cancer Center between 2000 and 2006 for deleterious BRCA1 and BRCA2 gene mutations. Data were collected on the risk-reduction interventions these women adopted after they underwent genetic testing. These data were tested for associations with demographic and clinical characteristics. Among the 554 women who underwent genetic testing for BRCA mutation, 78 were found to have a deleterious mutation in the BRCA1 gene, and 54 had a mutation in the BRCA 2 gene. Of the 554 women, 85 underwent prophylactic mastectomy, 30 prophylactic oophorectomy, and 52 both surgeries; 387 women opted for surveillance. Women who had BRCA mutations, a history of breast cancer or ductal carcinoma in situ (DCIS), or previous breast biopsies were more likely to have prophylactic surgery. Women with a family history of ovarian cancer were more likely to undergo prophylactic oophorectomy. Women with a personal history of ovarian cancer or advanced breast cancer were more likely to undergo surveillance only. Women with breast cancer who had had a total mastectomy as part of their prior breast cancer treatment underwent prophylactic mastectomy more frequently than women who either had breast-conserving surgery or no history of breast cancer. In multivariate analysis, only positive BRCA mutation carrier status was associated with having had prophylactic surgery. In addition, breast cancer history was significantly associated with prophylactic mastectomy. Women who were BRCA carriers, women who had a history of breast cancer, DCIS, or breast biopsy, or had a family history of ovarian cancer were more likely to have undergone surgery for cancer risk reduction. Women with ovarian cancer or advanced breast cancer were more likely to have undergone surveillance.

Prevalence of BRCA1 mutations in triple negative breast cancer (BC)

508 Background: 90% of BCs in women with germline BRCA1 mutations are ER, PR and HER2 negative (so-called “Triple Negatives”), and 80–90% of triple negative BCs are “basal-like” by DNA microarray and IHC analysis. Prevalence of germline BRCA1 mutations among women with triple negative BC may therefore, be elevated, and underestimated by available calculation models, which do not take tumor features into account. Methods: We randomly identified 200 women from the Dana-Farber/Harvard Cancer Center SPORE annotated specimen bank with histologically confirmed primary invasive, ER, PR and HER2 negative BC. Myriad prevalence tables for BRCA1 were used to estimate the probability that each subject carried a BRCA1 mutation according to age at BC diagnosis, family and personal history of breast and/or ovarian cancer, and Ashkenazi Jewish ancestry. Full sequencing analysis for BRCA1 germline mutations is in progress. Results: The median age at diagnosis of triple negative BC was 49 years (range 26–79). The majority of tumors were high grade (89%) ductal (95%) carcinomas; median tumor size was 2 cm, 50% had positive nodes. 3 patients had a personal history of ovarian cancer and 13 reported Ashkenazi Jewish ancestry. 44% had at least one first or second degree relative with BC; 12% had at least one relative with ovarian cancer. The estimated probability of detecting a BRCA1 mutation according to the Myriad tables ranged from 0.019 to 0.386 (median 0.039): the total expected number of BRCA1 mutations was 11. In a subgroup of 23 patients (12%), who had undergone clinical testing, 2.7 BRCA1 and 1.4 BRCA2 mutations were expected according to the Myriad tables. However, 9 deleterious BRCA1 mutations (39.1%) were found; 2 patients had a BRCA2 mutation (8.7%). Conclusions: The relative excess of BRCA1 mutations in a small group of patients with triple negative BC suggests that established risk factors alone may underestimate the prevalence of BRCA1 mutations among women with this BC subtype. We anticipate that complete BRCA1 analysis of our entire group will more definitively estimate the prevalence BRCA1 mutations among women with triple negative BC. No significant financial relationships to disclose.

Clinical factors that affect breast cancer risk reduction decisions in high risk women tested for the BRCA1/2 genetic mutation

1013 Background: Women with an increased risk for breast cancer have many risk reduction options including: prophylactic mastectomy, prophylactic oophorectomy, chemoprevention, and screening. Women without breast cancer make such decisions in a purely preventive setting and factors that affect their decisions are unclear. Method: We performed an IRB approved retrospective review of the medical records on women who underwent BRCA testing. We evaluated the women without a history of breast cancer to assess clinical characteristics and their relation to decision making. The risk reduction categories analyzed were: prophylactic mastectomy, prophylactic oophorectomy, tamoxifen, increased surveillance with MRI, and standard screening (clinical breast exam and mammography). Patient characteristics were tabulated by clinical decision group and the chi-square test or Fisher’s exact test was used. Results: From 2001, 627 patients have undergone genetic testing. 202 of these women did not have a history of breast cancer among whom 58 were mutation carriers. Most patients chose standard screening (47%) or increased surveillance (38%). 4% chose tamoxifen, 7% chose prophylactic mastectomy, 3% chose both prophylactic mastectomy and oophorectomy, and 5% chose oophorectomy. The tamoxifen group was too small to do further analysis. Increased surveillance did not show any significant association with any of the clinical factors that we evaluated. The majority of women who chose standard screening had a personal history of ovarian cancer (p<0.0001) and had no family history of ovarian cancer (p=0.02). Prophylactic surgeries were significantly associated with positive BRCA status (p=0.01). Women with a family history of ovarian cancer tended to have prophylactic surgery (p=0.02). Women who had DCIS or a breast biopsy tended to have prophylactic mastectomies (p=0.0001 and p<0.001 respectively). Conclusion: In breast cancer free women, BRCA status, family history of ovarian cancer, DCIS, and breast biopsy were associated with prophylactic surgeries. Having ovarian cancer or no family history of ovarian cancer were associated with standard screening. We are performing a questionnaire study to determine the reasons behind these women’s choices. No significant financial relationships to disclose.

Logistic Regression Model to Distinguish Between the Benign and Malignant Adnexal Mass Before Surgery: A Multicenter Study by the International Ovarian Tumor Analysis Group

To collect data for the development of a more universally useful logistic regression model to distinguish between a malignant and benign adnexal tumor before surgery. Patients had at least one persistent mass. More than 50 clinical and sonographic end points were defined and recorded for analysis. The outcome measure was the histologic classification of excised tissues as malignant or benign. Data from 1,066 patients recruited from nine European centers were included in the analysis; 800 patients (75%) had benign tumors and 266 (25%) had malignant tumors. The most useful independent prognostic variables for the logistic regression model were as follows: (1) personal history of ovarian cancer, (2) hormonal therapy, (3) age, (4) maximum diameter of lesion, (5) pain, (6) ascites, (7) blood flow within a solid papillary projection, (8) presence of an entirely solid tumor, (9) maximal diameter of solid component, (10) irregular internal cyst walls, (11) acoustic shadows, and (12) a color score of intratumoral blood flow. The model containing all 12 variables (M1) gave an area under the receiver operating characteristic curve of 0.95 for the development data set (n = 754 patients). The corresponding value for the test data set (n = 312 patients) was 0.94; and a probability cutoff value of .10 gave a sensitivity of 93% and a specificity of 76%. Because the model was constructed from multicenter data, it is more likely to be generally applicable. The effectiveness of the model will be tested prospectively at different centers.

Prevalence of <EMPH TYPE="ITAL">BRCA1</EMPH> and <EMPH TYPE="ITAL">BRCA2</EMPH> Mutations in Women Diagnosed With Ductal Carcinoma In Situ

The distribution of BRCA1 and BRCA2 mutations in women diagnosed with noninvasive breast carcinoma is unknown. To estimate the BRCA1 and BRCA2 mutation prevalence in women with ductal carcinoma in situ (DCIS), unselected for age, family history, or ethnicity. The data were 369 DCIS cases diagnosed among female residents aged 20 to 79 years from the state of Connecticut between September 15, 1994, and March 14, 1998. These women were participants in a large population-based case-control study of breast carcinoma in situ. Telephone interviews were used to collect risk factor information and blood or buccal specimens were collected for BRCA1 and BRCA2 mutation testing. Prevalence of disease-associated mutations of BRCA1 and BRCA2 in women diagnosed with DCIS. Three (0.8%) and 9 (2.4%) of 369 DCIS cases had disease-associated mutations in BRCA1 or BRCA2, respectively. One woman had a mutation in both genes (BRCA1 W321X and BRCA2 3398del5). Carriers were significantly more likely than noncarriers to report a first-degree (mother, sister, or daughter) family history of breast cancer (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.1-12.4), as well as a personal history of ovarian cancer. In addition, carriers were more likely than noncarriers to be diagnosed at an early age (<50 years) (OR, 3.4; 95% CI, 1.0-11.7), as well as to report at least 1 first-degree relative diagnosed with breast cancer before 50 years (OR, 10.6; 95% CI, 3.0-37.0). Ductal carcinoma in situ is a part of the breast/ovarian cancer syndromes defined by BRCA1 and BRCA2, with mutation rates similar to those found for invasive breast cancer. These findings suggest that patients with breast cancer with an appropriate personal or family history of breast and/or ovarian cancer should be screened and followed according to high-risk protocols, regardless of whether they are diagnosed with in situ or invasive breast cancer.