An economic analysis of cisplatin alone versus cisplatin doublets in the treatment of women with advanced or recurrent cervical cancer.

PURPOSE OF INVESTIGATION: Randomized trials have demonstrated improvements in overall survival when using platinum doublets com- pared to single agent platinum in the treatment of women with advanced or recurrent cervical cancer. The authors sought to evaluate the cost effectiveness of these regimens. METHODS: A decision model was developed based on Gynecologic Oncology Group (GOG) protocols 179 and 204. Cisplatin alone was compared to cisplatin/paclitaxel (CP), cisplatin/topotecan (CT), cisplatin/gemcitabine (GC), cisplatin/vinorelbine (CV), and a hypothetical novel agent. Parameters included overall survival (OS), cost, and complications. One way sensitivity analyses were performed. In further sensitivity analysis, a hypothetical agent that added 3.7 months survival to CP's survival was studied. RESULTS: The chemotherapy drug costs for six cycles of cisplatin was 89 USD while for cisplatin/paclitaxel it was 489 USD. The highest chemotherapy cost was for GC at 18,306 USD. The average total cost of six cycles CP was 13,250 USD while the average cost of cisplatin alone was 14,573 USD. The highest average cost for six cycles was for GC at 33,559 USD. With cisplatin/paclitaxel being the most effective, the cost effectiveness analysis showed that cisplatin, CT, GC, and VC were all dominated by CP. Because of the regimens being dominated, no baseline ICERs compared to CP were calculable. Sensitivity analyses demonstrate that even all of the chemotherapies were given for free, CP would still be the regimen of choice. CONCLUSIONS: In this model, CP is the most cost effective regimen for the treatment of these patients with an average cost of 13,250 USD. With the fact that GOG 204 also showed statistically significantly improved survival for CP, CP should be considered the regimen of choice.

Vascular endothelial growth factor (VEGF) and cyclooxygenase 2 (COX 2) immunostaining in ovarian cancer.

PURPOSE OF INVESTIGATION: Vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX 2) are markers of angiogenesis and potential therapeutic targets. Previous studies demonstrate that VEGF is upregulated in some ovarian cancers. The purpose of this study was to determine the correlation of VEGF and COX 2 staining with survival in ovarian cancer patients. MATERIALS AND METHODS: One hundred forty-three consecutive patients with ovarian carcinoma underwent primary staging or cytoreduction prior to platinum-based chemotherapy. Their tumors were immunohistochemically stained for expression of VEGF and COX 2. FIGO stage, grade, cytoreduction status, and histology were also analyzed as prognostic factors. RESULTS: Twenty-seven patients had Stage I tumors, three Stage II, 87 Stage III, and 26 Stage IV. Median follow-up was 74 months (mean 79 months). One hundred nineteen patients (83.2%) had tumors that were positive for VEGF and 110 patients (76.9%) had tumors that were positive for COX 2. Patients with tumors staining positive for both VEGF and COX 2 (68.5%) had a significantly increased risk of dying from their ovarian cancer (Chi-square p = 0.011, Log rank p = 0.037). Multivariate logistic regression analysis revealed FIGO stage, grade, cytoreduction status, and VEGF/COX 2 expression to be independent prognostic indicators of survival. Conclusion: VEGF and COX 2 staining are frequently positive in ovarian cancer. Patients whose tumors are positive for both VEGF and COX 2 have a decreased survival. These patients may benefit from anti-angiogenesis targeted therapy.

Cyclin E is overexpressed by clear cell carcinomas of the endometrium and is a prognostic indicator of survival.

OBJECTIVE: Upregulation of cyclin E and cyclin D1-6 accelerates the transition from G1 to S phase. The objective of this study was to determine if cyclin D1 and E are prognostic indicators in endometrial cancer. MATERIALS AND METHODS: Surgically-treated patients with endometrial carcinoma had their tumors stained for nuclear expression of cyclin D1 and E. Quantification of staining and measurement of growth phase fraction were performed using image analysis. FIGO stage, grade, and histology were also analyzed. RESULTS: Cyclin D1 and E expression was unrelated to DNA index (p = 0.93). While cyclin D1 expression did not correlate with S+G2M phase fraction (p = 0.69), increased cyclin E expression was directly correlated with increased S+G2M phase fraction (p = 0.002). Cyclin E expression was highest in clear cell carcinomas (p = 0.042) while cyclin D1 expression was highest in adenosquamous carcinomas (p = 0.028). Patients dying from cancer had significantly higher expression of cyclin D1 (p = 0.042) and E (p = 0.02) as compared to patients surviving their disease. Multivariate logistic regression revealed FIGO stage, grade, and lack of cyclin E overexpression to be independent prognostic indicators of survival. CONCLUSION: Cyclin E expression is related to increased growth fraction, clear cell histology, and decreased survival in patients with endometrial cancer.

Total colectomy in primary ovarian cytoreduction.

OBJECTIVE: To review the indications, procedure, and complications associated with total colectomy with ileorectal anastamosis in women undergoing primary debulking of ovarian cancer. METHODS: Charts were reviewed to determine all patients undergoing total colectomy with ileorectal anastamosis during primary debulking of ovarian, peritoneal, or fallopian tube cancer. Charts were also reviewed for perioperative morbidity and mortality, as well as rates of fecal incontinence. RESULTS: Nine patients underwent the above procedures during primary debulking of ovarian cancer. The mean age was 61 years with a mean BMI of 31 kg/m2. The average postoperative hospital stay was 11 days with an average estimated blood loss of 700 ml. There was no perioperative mortality. Although all patients had greatly increased frequency of stools, no patients had incontinence of stool after eight weeks. CONCLUSIONS: Radical surgery, including total colectomy, can be performed in select patients with primary ovarian cancer. Acceptable morbidity, mortality, and rectal continence can be obtained.

Robotically-assisted laparoscopic radical parametrectomy and radical vaginectomy.

BACKGROUND: Radical parametrectomy is a technically challenging operation used for women found to have occult cervix cancer after a hysterectomy for benign reasons. A similar operation, radical vaginectomy, is rarely performed because of the its technical difficulty in getting adequate margins without an attached uterus. CASE REPORTS: A 41-year-old woman was found to have a presumed surgical Stage IB1 squamous cell carcinoma of the cervix at time of surgery for uterine prolapse. The patient was offered multiple options of surgery and chemoradiation. A second case, a 55-year-old woman, was found to have 1 cm vaginal cancer nine years after a total vaginal hysterectomy for carcinoma in situ of the cervix. She was also offered chemoradiation versus surgery. For the robotically-assisted laparoscopic radical parametrectomy operating time was 186 minutes with an estimated blood loss of 250 ml. For the robotically-assisted laparoscopic radical vaginectomy operating time was 154 minutes with an estimated blood loss of 150 ml. Neither patient had a hospitalization over 24 hours. There were no intraoperative or postoperative complications. CONCLUSIONS: Robotically-assisted laparoscopic radical paremetrectomy and vaginectomy are both technically feasible procedures.

Estrogen receptor alpha and beta expression in a case matched series of serous and endometrioid adenocarcinomas of the ovary.

OBJECTIVE: The purpose of this study was to analyze estrogen receptor alpha and beta (ERalpha, ERbeta) expression in a stage and grade matched cohort of patients with serous and endometrioid adenocarcinoma of the ovary. METHODS: Forty-two patients from 1991 to the present were found to have the diagnosis of endometrioid adenocarcinoma of the ovary and have tissue available for analysis. Of these 42, ten were selected for analysis. These were stage and grade matched with ten patients having serous adenocarcinoma of the ovary during the same time period. ERalpha and ERbeta mRNA was detected by a multiplex RT-PCR and amplification of random hexamer generated cDNA using a housekeeping gene (G3PD) as a control for mRNA quality and quantity. Methylation specific PCR (MS-PCR) was used to correlate methylation of the ERalpha and ERbeta CpG islands with mRNA expression status. RESULTS: ERalpha expression was present in ten of ten endometrioid adenocarcinomas but in only five of ten serous carcinomas (chi2, p = 0.01). ERbeta expression was present in six of ten endometrioid adenocarcinomas and in four of ten serous caricinomas (chi2, p = 0.65). Methylation of the ERalpha and ERbeta CpG islands was found in tumors without mRNA expression but not in the tumors with mRNA expression (p = 0.005). CONCLUSIONS: ERalpha expression, but not ERbeta expression, is significantly more common in endometrioid than serous adenocarcinomas of the ovary when controlled for stage and grade. The role of methylation in ER silencing may lead to potential therapeutic interventions.

Tunneled central venous catheters in a gynecologic oncology service: operative and short-term complications.

PURPOSE: To determine the difference in the immediate complication rate between placement of long-term central venous catheters (LTCVCs) by the percutaneous versus jugular venous cutdown method. METHOD: Case lists were examined to determine the number of LTCVCs placed during the designated time period. Medical records, operative reports, and chest roentgenograms were examined to extract pertinent information. Immediate complications included complications occurring in the operating room until 30 days postoperatively. Complications included misplacement of the catheter requiring an adjustment or a repeat procedure, pneumothorax, hydrothorax, or hemothorax, operative site or tunnel infection, and line migration requiring removal. RESULTS: Five hundred and one patients had LTCVCs placed during the period of this study. This included 399 totally implantable venous access devices (TIVADs) and 102 free access venous access devices (FAVADs) with 163 placed percutaneously into subclavian veins and 338 placed by cutdown into jugular veins. There was a significant increased risk in the overall immediate complication rate for the percutaneous placement compared to venous cutdown (p < 0.001). Also, pneumothorax was more common with the percutaneous approach compared to the venous cutdown approach (p < 0.001). CONCLUSIONS: Immediate complications, especially pneumothorax, were more common when placing catheters by the percutaneous approach as compared to the venous cutdown approach.

5-Fluorouracil cardiotoxicity complicating treatment of stage IIB cervical cancer--case report.

A 31-year-old female was found to have FIGO Stage IIB squamous cell carcinoma of the cervix. The patient began her prescribed radiation therapy and 5-fluorouracil radio-sensitizing chemotherapy. During the first day of infusion, she began having severe shortness of breath. Cardiac evaluation revealed acute congestive heart failure with a cardiac ejection fraction of 19%. Radiation was continued without chemotherapy. Four years later, the patient is alive and well with an ejection fraction of 53%.

Pelvic and para-aortic lymphadenectomy in patients with endometrioid adenocarcinoma of the endometrium.

BACKGROUND: The purpose is to determine the rate of lymph node metastases in women with endometrioid adenocarcinoma of the endometrium (EAE) undergoing systematic lymphadenectomy. METHODS: Patients (349) underwent a complete pelvic and para-aortic lymphadenectomy from caudal to the median circumflex to the level of the renal vessels. RESULTS: Grade 1 tumors accounted for 32.7% of the tumors and 31.0% of the positive nodes, grade 2 accounted for 47.3% of the tumors (37.9% of positive nodes), and grade 3 accounted for 20.1% of the tumors and 31.0% of the positive nodes (P>0.05). Positive nodes were found in 15.8% of grade 1 tumors, 13.3% of grade 2 tumors and 25.7% of grade 3 tumors (P>0.05). Isolated para-aortic involvement without pelvic nodal involvement occurred in 29% of patients with positive nodes. CONCLUSIONS: When complete lymphadenectomies are performed in EAE, positive lymph nodes (including isolated para-aortic lymph nodes) are common in all grades.

CAG repeat length in exon 1 of the androgen receptor gene is related to age of diagnosis but not germ line BRCA1 mutation status in ovarian cancer.

It has been postulated that androgens, through their interaction with androgen receptors (AR), may play an important role in the development of ovarian cancer. Exon 1 of the AR gene contains three highly polymorphic trinucleotide repeats. The length of the (CAG)n repeat segment 1 is inversely correlated with the transactivation function of the AR. Recent studies have shown that BRCA1 may function as an AR coregulator or coactivator and play positive roles in androgen-induced cell death in cancer cells as well as other androgen/AR target organs. We hypothesize that the AR gene, involved in endocrine signaling, may modify BRCA1-associated ovarian cancer risk. To test this hypothesis, potential associations between the (CAG)n repeat length, germ line BRCA1 mutation status, and age of diagnosis for ovarian cancer were investigated. One hundred and eleven ovarian cancer patients (27 hereditary and 84 sporadic) were included. All the cases were allelotyped for CAG repeat length and genotyped for mutations in the BRCA1 gene by direct sequencing. No association between CAG repeat length and BRCA1 mutation status was identified. Furthermore, there were no differences between hereditary and sporadic ovarian cancer in the number of (CAG)n repeats of the short allele (P= 0.336), long allele (P= 0.875), or average allele length (P= 0.550). However, ovarian cancer patients from both groups (hereditary and sporadic) who carried any AR allele of (CAG)n < or = 22 repeats were diagnosed on average 8.17 years (95% confidence interval [1.3, 15.0]) earlier than the patients whose shortest AR allele (CAG)n was >22 (P= 0.020). In conclusion, it is suggested that the CAG repeat length in AR exon 1 may affect the age of diagnosis of ovarian cancer but does so independent of germ line BRCA1 carrier status.

Evaluation of DNA methylation in the human genome: why examine it and what method to use.

PURPOSE: Since its discovery 50 years ago, DNA methylation has been found to be an important part of gene regulation. Newer methods of analysis over the last decade have helped further the understanding of this epigenetic phenomenon. The purpose of this article is to describe current methods of analysis and discuss advantages and disadvantages of each and their possible roles in gynecologic malignancies. RESULTS: The methods for analysis of DNA methylation are divided into two major categories: 1) methods which utilize chemical methods or restriction enzymes to differentially cleave at cytosine versus 5-methylcytosine sites, 2) methods which utilize sodium bisulfite (NaHSO3) to specifically convert unmethylated cytosines to uracil (thymine after PCR). This recently developed method appears to be more sensitive and allows the investigator to specifically delineate the study site(s). CONCLUSION: DNA methylation is important in the human genome. Its role in tumorigenesis is just beginning to be understood. While relying upon newly designed methods of analysis, further understanding of this epigenetic phenomenon and its role in gene expression and tumorigenesis will be forthcoming.

HSP27 in patients with ovarian carcinoma: still an independent prognostic indicator at 60 months follow-up.

OBJECTIVE: Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The authors have previously shown that HSP27 is an independent prognostic indicator in patients with ovarian carcinoma. The present study was performed to see whether HSP27 remained an independent prognostic indicator with longer follow-up. METHODS: One hundred and three consecutive patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. HPS27 staining was performed as previously described. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction and survival. RESULTS: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO Stage I disease, four Stage II, 59 Stage III, and 20 Stage IV. Immunohistochemical (IHC) staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant decrease in HSP27 staining was found to correlate with increased FIGO stage (p = 0.008). Using cox-regression analysis, HSP27 staining (p = 0.025), stage (p = 0.0012), and level of cytoreduction (p < 0.0001) were independent predictors of survival in these patients. CONCLUSION: Cox-regression analysis found HSP27 to be an independent indicator of prognosis and survival in patients with ovarian carcinoma who had longer follow-up. Decreased HSP27 staining was related to decreased survival. This study confirms the authors' earlier report on the importance of HSP27 as a prognostic indicator in ovarian carcinoma.

Heat shock protein 27 in the placentas of women with and without severe preeclampsia.

BACKGROUND: Although not fully understood, heat shock proteins (HSP) are well known stress response proteins. The purpose of this analysis was to determine whether staining for HSP27 was different between placentas from pregnancies complicated by severe pre-eclampsia with intrauterine growth restriction (IUGR) as compared to controls. METHODS: Sterile placental tissue was collected from ten women whose pregnancies were complicated by severe preeclampsia with IUGR and from ten women with uncomplicated by severe pre-eclampsia with IUGR and from ten women with uncomplicated term pregnancies. The tissue was then stained for HSP27. RESULTS: The median age of the patients was 27 years (mean 27, range 17-37). The median estimated gestational age at delivery was 38 weeks (mean 37, range 29-41). Overall 12 of 20 placentas stained positively for HSP27 (nuclear and/or cytoplasmic). Eight of ten placentas from women with pre-eclampsia and IUGR stained positively for HSP27 (p = 0.046). CONCLUSION: HSP27 staining of the placenta is twice as common in patients with severe preeclampsia as compared to patients with normal term gestations. These preliminary results warrant the inauguration of a similar but larger study to examine the significance of these findings.

Nuclear and cytoplasmic c-myc staining in endometrial carcinoma and their relationship to survival.

OBJECTIVE: The role of the c-myc proto-oncogene in genomic instability is just becoming more fully understood. However, its role in endometrial cancer is essentially unknown. The objective of this study was to determine the relationship between cytoplasmic and nuclear c-myc staining, DNA index, and survival in patients with endometrial carcinoma. METHODS: One hundred and twenty-one patients with endometrial carcinoma were studied. Image analysis was used to determine DNA index. In addition to cytoplasmic and nuclear c-myc staining and DNA index, histologic type, stage, grade, depth of invasion, lymphvascular space invasion, and peritoneal cytology were evaluated as prognostic indicators. Univariate and multivariate analyses were performed. RESULTS: One hundred and twenty-one patients were followed for over 5 years. c-myc cytoplasmic staining was present in 75.2% of the patients' tumors, and nuclear staining was present in 66.9% (P = 0.99). DNA index was significantly higher in patients with nuclear c-myc staining and no cytoplasmic staining (DNA index 1.38) as compared to those patients whose tumors displayed cytoplasmic c-myc staining but no nuclear c-myc staining (1.18) (P = 0.016). Patients whose tumors stained positively for nuclear c-myc and negatively for cytoplasmic c-myc had significantly worse survival by Kaplan-Meier analysis (P < 0.0001). Seventeen patients died during the follow-up period of this study. By multivariate analysis, positive cytoplasmic c-myc staining with negative nuclear staining (P = 0.0076), negative cytoplasmic c-myc staining with positive nuclear staining (P = 0.011) and FIGO stage (P < 0.0001) were shown to be independent prognostic indicators predictive of survival. CONCLUSION: Nuclear and cytoplasmic c-myc staining, as well as FIGO stage, when assessed by multivariate analysis, were demonstrated to be important factors in predicting survival in the 121 patients in this study. While increasing FIGO stage was prognostic of decreased survival, the specific location of c-myc staining was also associated with prognosis. The expression of the c-myc protein is related to survival in patients with adenocarcinoma of the endometrium.

Nuclear size, shape, and density in endometrial carcinoma: relationship to survival at over 5 years of follow-up. Does analyzing only cells occupying the G0-G1 peak add useful information?

OBJECTIVE: The authors, using image analysis, previously demonstrated nuclear size and summed optical density to be independent prognostic indicators of recurrence in patients with endometrial carcinoma. The same tumors were analyzed by studying the optical features in the G0-G1 peak to see if this changed the values found as well as their importance as prognostic features at greater than 5 years of follow-up. METHODS: Tumors from 74 consecutive patients, surgically treated, with endometrial cancer, were evaluated. Survival, depth of invasion, lymphvascular space invasion, FIGO stage, grade, histology were analyzed. DNA index, progesterone receptor status, as well as nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD) were evaluated. NUSZ, NUSH, and NUSD were quantified using image analysis. RESULTS: Fifteen patients died from disease during the observation period of the study. Mean follow-up was 82 months with a median of 84 months. Forty-nine patients had stage I cancers, five stage II, 17 stage III, and three stage IV. NUSZ and NUSD were all significantly different between the original (entire cell cycle) and the re-measured (G0G1 only) values (both P < 0.001). Multivariate analysis showed both the original (P = 0.0001) and G0G1-only (P = 0.046) NUSZ and the original (P = 0.0002) and G0G1-only (P = 0.018) NUSD to be independent prognosticators of survival. CONCLUSION: Image analysis is able to quantify cellular and nuclear parameters not otherwise quantifiable. NUSD and NUSZ correlated with traditional prognostic indicators, were demonstrated independent predictors of survival at over 5 years of follow-up. Although the re-measured NUSZ and NUSD from only the G0-G1 peak were significantly different from the original NUSZ and NUSD, they were not as valuable as prognostic factors. Nuclear size and summed optical density measured from the entire cell cycle are independent prognostic indicators of survival at greater than 5 years of follow-up. Measuring nuclear morphometric features in the G0-G1 peak only does not add any new prognostic information.

Chemotherapy for ovarian cancer: an evidence-based approach.

Although cytoreductive surgery is the most influential factor in treatment for ovarian cancer, chemotherapy is needed for almost all patients diagnosed with this disease. The mainstay of chemotherapy is platinum. Different platinum compounds are used for different histologies, and different combinations are used for different histologies also. We will present the data so that each reader can understand the knowledge behind chemotherapy decisions.

Malignant mixed mullerian tumor of the ovary and bilateral breast cancer: an argument for BRCA3, or a coincidental cluster of unconnected cancers?

OBJECTIVES: Malignant mixed mullerian tumors (MMMTs) of the ovary are a rare, aggressive subtype of ovarian cancer without a clear relationship to familial breast-ovarian cancer syndromes. CASE: We present the case of a woman with bilateral breast cancers who subsequently developed a stage IIIc MMMT of the ovary. The patient had a first-degree female relative with breast and ovarian cancer (not MMMT), as well as second- and third-degree female relatives each with bilateral breast cancers. BRCA1 and BRCA2 sequencing of germline DNA revealed no evidence of a heritable mutation. CONCLUSIONS: Ovarian MMMTs may be a hallmark of breast/ovarian cancer secondary to genetic risk independent of classic BRCA1/2 pathways.

Methylation: a second hit in the two-hit hypothesis.

This case illustrates that methylation of one BRCA1 allele may serve as the second hit in a patient with a diploid locus and missense mutation on the other allele.

Papillary serous carcinoma of the uterus: increased risk of subsequent or concurrent development of breast carcinoma.

OBJECTIVE: Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. METHODS: The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. RESULTS: Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). CONCLUSION: Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus.

Ovarian cancer BRCA1 mutation detection: Protein truncation test (PTT) outperforms single strand conformation polymorphism analysis (SSCP).

Recent studies have shown that the BRCA1 tumor suppressor gene plays a role in the development of both hereditary and sporadic ovarian cancer. Since several different mechanisms may give rise to tumor gene defects, a better understanding of these mechanisms may identify BRCA1 as an attractive therapeutic target in ovarian cancer. Sequencing this large gene is not practical on a population-wide basis. The optimal screening strategy is yet to be determined. The purpose of our study is to compare two common screening techniques: the protein truncation test (PTT) and single strand conformational polymorphism analysis (SSCP). Ninety-four patients with epithelial ovarian cancer and available snap-frozen tissue were screened for BRCA1 mutations by both PTT (five individual PCR reactions with complete translation of the product in the TNT System (Promega, Madison, WI)) and SSCP (41 individual PCR reactions covering the entire coding sequence). All abnormal results were confirmed by sequencing. A paired peripheral blood DNA sample was utilized to determine if the sequence abnormality was a germline mutation. Twenty-three mutations in BRCA1 were found in 22 patients (14 germline, eight somatic, one unknown) including four novel mutations: E489X, 3558delT, 3871delGTCT, del exon 7-10. Although the predictive value of a negative test was close for the two methods (PTT 99.1%, SSCP 99.8%), the comparison of positive predictive value overwhelmingly favored PTT (100.0%, vs. 26.4%, respectively). The specificity for PTT was 100.0% while the sensitivity was 82.6%. While for SSCP, the specificity was 99.0% and the sensitivity was only 60.9%. The concordance rate for the two screening tests was 88.9%. Only SSCP can detect missense mutations. PTT is a superior screening test for truncating BRCA1 mutations that are expected to be of clinical significance.