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M S Piver

Publications and source records attributed to M S Piver.

At least 55 records · Page 3Linked to original sources

Five-year survival after second-line cisplatin-based intraperitoneal chemotherapy for advanced ovarian cancer.

BACKGROUND: To evaluate the 5-year survival rates of second-line intraperitoneal chemotherapy in advanced-staged ovarian cancer. MATERIALS AND METHODS: Between August 1985 and September 1991, 63 patients with advanced epithelial ovarian cancer received intraperitoneal cisplatin and cytarabine chemotherapy as second-line treatment. RESULTS: The median survival from the time of initiation of intraperitoneal chemotherapy (IPC) was 29.1 months. A significant advantage in 5-year survival (40%) and 5-year progression-free survival (37%) was observed among 21 patients who demonstrated a response to first-line and second-line treatment compared to those who demonstrated a response to first-line treatment only (6 and 0%, respectively) (P < 0.0001). No patient (n = 13) who failed to respond to either first-line or second-line treatment survived for 5 years. Among 42 patients with < or = 5 mm residual disease at the time of initiation of IPC, 5-year survival was 36% and 5-year progression-free survival was 31%, while no patient (n = 21) with residual disease measuring > 5 mm at the initiation of IPC survived 5 years (P < 0.0001). CONCLUSION: Given the limitation that this is not a randomized trial, the data appear to indicate that salvage platinum-based intraperitoneal chemotherapy results in significant 5-year survival and progression-free survival in selected patients who initiated therapy with small (< or = 5 mm) tumor burden. These survival rates as second-line therapy approach those achieved by first-line platinum-based intravenous chemotherapy in patients with advanced-stage ovarian cancer with similar small residual disease at the initiation of therapy.

Adult↗

Correlation between extreme drug resistance assay and response to primary paclitaxel and cisplatin in patients with epithelial ovarian cancer.

OBJECTIVE: The extreme drug resistance (EDR) assay has been correlated with failure of response to chemotherapy in greater than 99% of patients. The goal of this study is to correlate the results of the EDR assay to response to first-line paclitaxel/cisplatin among patients with epithelial ovarian cancer. METHODS: Seventy-five of 100 patients with epithelial ovarian cancer for whom EDR assay was performed were treated with weekly induction cisplatin (1 mg/kg body wt) x 4, followed by monthly paclitaxel (135 mg/m2) and cisplatin (75 mg/m2) x 6 and were evaluable for correlation of response to chemotherapy and EDR assay. Specimens for EDR assay were obtained at primary surgery and the EDR assay was performed by Oncotech, Inc. Response to chemotherapy was correlated to EDR assay results regarding paclitaxel and cisplatin. RESULTS: Among 75 evaluable patients, the prevalence of EDR to paclitaxel was 20.0% (n = 15) and to cisplatin it was 2.7% (n = 2). Only 1 patient (1.3%) exhibited EDR to both paclitaxel and cisplatin. Surgical assessment of response was performed in 42 patients; 33 patients were clinically evaluable. The overall response rate was 85.3%. The overall response rate for patients whose tumors demonstrated no EDR to either paclitaxel or cisplatin did not differ significantly from that for patients whose tumors demonstrated EDR to at least one of these two drugs (86.4% versus 81.3%, respectively, P = 0.692). Similarly, the complete surgical response rate for both groups did not differ significantly (25.4% versus 12.5%, respectively, P = 0. 34). A single patient whose tumor exhibited EDR to both paclitaxel and cisplatin had tumor progression. The sensitivity, specificity, positive predictive value, and negative predictive value of the EDR assay were 79.6, 27.0, 86.0, and 19.0%, respectively. CONCLUSIONS: EDR to paclitaxel does not preclude response to the combination of paclitaxel and cisplatin as primary therapy for patients with epithelial ovarian cancer. The role of the EDR assay in the primary management of patients with epithelial ovarian cancer remains to be determined.

Adult↗

Prolonged disease-free survival by maintenance chemotherapy among patients with recurrent platinum-sensitive ovarian cancer.

OBJECTIVE: The aim of this study was to determine the potential benefit and complications of prolonged salvage and maintenance chemotherapy among patients with recurrent epithelial ovarian cancer who achieve response to salvage chemotherapy. METHODS: Patients with recurrent platinum-sensitive epithelial ovarian cancer who were treated between 1982 and 1996 and achieved complete response to platinum-based salvage chemotherapy were offered prolonged (1 year) monthly salvage followed by maintenance (every 8 weeks) chemotherapy. Patients who accepted such treatment (n = 16) were compared to those who refused and discontinued therapy (n = 11) with regard to overall survival from time of initial diagnosis and overall and disease-free survival from time of recurrence. Chemotherapy-related toxicity in the study group was recorded. Survival curves were constructed according to the Kaplan and Meier method and survival curves were compared using the log-rank test. RESULTS: Patients in the study and control groups were similar with regard to age, stage, histology, grade, performance status, primary cytoreductive surgery, type of primary and salvage chemotherapy, and method of assessment of tumor response. The study group had a significantly longer disease-free interval from date of recurrence than the control group (median: 35.0 versus 6.0 months, respectively, P = 0.001). The study group had longer overall survival from date of recurrence than the control group. However, the difference did not achieve statistical significance (median: 119 versus 90 months, respectively, P = 0.056). There was no significant difference between the study group and the control group as to survival from date of initial diagnosis (median: 157 versus 124 months, respectively, P = 0.28). Chemotherapy-related toxicity was minimal. CONCLUSIONS: Prolonged salvage and maintenance chemotherapy is a safe method of treatment that may extend disease-free interval among patients with platinum-sensitive recurrent epithelial ovarian cancer who achieve response to salvage chemotherapy. These preliminary results need to be confirmed by a larger prospective randomized trial.

Adult↗

Complications related to indwelling caval catheters on a gynecologic oncology service.

OBJECTIVE: To assess the rate of complications of indwelling caval catheter (ICC) use on a gynecologic oncology service and to compare complication rates between subcutaneous ports and external catheters. METHODS: A retrospective analysis of 185 patients who underwent 216 ICC placements between April 1, 1987 and April 1, 1997, was performed. Patient and catheter characteristics were analyzed as they related to the rate of pneumothorax, bacteremia, and deep neck and thoracic vein thrombosis (DNVT). RESULTS: A total of 216 ICCs were placed including 152 implanted ports and 64 external catheters. Pneumothorax occurred in 2% of ICC insertions. Bacteremia complicated 16% of ICCs. Multivariate analysis demonstrated that external catheters (P < 0.01) and neutropenia (P < 0.01) were independent risk factors for bacteremia. DNVT complicated 6% of ICCs and was observed significantly (P < 0.02) more frequently among 11 catheters placed in patients with clear cell malignancies of the female reproductive tract. Unplanned catheter removal occurred significantly (P < 0.01) more frequently among patients with external catheters compared to implanted devices. CONCLUSIONS: Implantable ICCs appear to offer a significant advantage compared to external devices with regard to the development of bacteremia and unplanned catheter removal. Though catheter type, neutropenia, and TPN are associated with an increased incidence of bacteremia, multivariate analysis does not include TPN as an independent risk factor for ICC-related bacteremia. A significant increase in the rate of DNVT among a small number of patients with clear cell gynecologic malignancies warrants further study.

Antineoplastic Agents↗

Epidemiologic differences between women with extraovarian primary peritoneal carcinoma and women with epithelial ovarian cancer.

OBJECTIVE: To describe the epidemiologic features of women with extraovarian primary peritoneal carcinoma and compare them with those of women with primary epithelial ovarian cancer. METHODS: The epidemiologic features of 50 women with extraovarian primary peritoneal carcinoma were compared with those of 503 women with primary epithelial ovarian cancer. We included all women with the respective diagnoses admitted to the Roswell Park Cancer Institute between October 1982 and October 1996 who returned an epidemiologic questionnaire. Epidemiologic features of the study and control groups were extracted from a database compiled from a self-administered questionnaire that has been given to patients as part of the admission process since 1982. Individual variables between the study and control groups were compared using Student t test, chi2 analysis, and Wilcoxon nonparametric test. Two-tailed P < .05 was considered significant. RESULTS: We found few significantly different epidemiologic features between women with extraovarian primary peritoneal carcinoma and those with primary epithelial ovarian cancer. Women with extraovarian primary peritoneal carcinoma were significantly older (mean age 63.8 versus 55.0 years, P < .001), had later menarche (13.3 versus 12.8 years, P = .024), and were less likely to have used perineal talc powder (26.0% versus 48.1%, P = .003). There were no significant differences with respect to reproductive history, contraceptive use, or use of hormone replacement therapy. A larger proportion of ovarian cancer patients reported a family history of breast cancer, but the numbers were too small to reach statistical significance. CONCLUSION: The epidemiologic features of women with extraovarian primary peritoneal carcinoma compared with women with primary epithelial ovarian cancer show few differences. The observed areas of difference warrant further research to determine whether they suggest the occurrence of distinct disease entities.

Epidemiologic Factors↗

Correlation of TP53 mutations and p53 expression in ovarian tumors.

To characterize the involvement of the TP53 tumor suppressor gene in ovarian cancer, mutation analysis of exons 2-11 of TP53 and immunodetection of its protein product, p53, were done in 48 ovarian tumors. Normally, p53 is not immunodetectable. Missense TP53 mutations have been reported to result in p53 accumulation and detection, but mutations generating premature stop codons have not. Mutations were identified in 19 of 41 malignant tumors but not in 5 benign tumors and 2 tumors of low malignant potential. Fifteen of the 19 tumors with mutations also stained positively by immunohistochemistry or Western blot or both. They included 11 missense mutations, 1 in-frame duplication (474ins6), and 3 frameshift mutations generating premature stop codons. The three tumors with frameshifts also had a wild-type TP53 allele and displayed normal size but not truncated p53 by Western blot. This indicates that these tumors express wild-type p53. The significance of TP53 mutations in the development of the three tumors is questionable unless there is a mechanism for inactivating wild-type p53. Nine of the 19 mutations found here, including the 3 frameshifts, were previously not reported in ovarian cancer. Thirteen of the 19 mutations were single nucleotide substitutions with 6 transitions and 7 transversions. The ratio of transversions to transitions (1.2) was different from literature reports (0.5) (P < 0.01). Thus, the spectrum of TP53 mutations in our study differed from other ovarian tumor reports. This difference may be due to population-based differences in the molecular epidemiology of TP53 mutations.

Blotting, Western↗

Mutations in BRCA1 from fixed, paraffin-embedded tissue can be artifacts of preservation.

DNA isolated from paraffin-embedded tissues has been used for analysis of DNA alterations in disease states. Use of archival tissue can expedite the gathering of large numbers of specimens from rare disease subtypes that would take years to accumulate prospectively. Therefore, archival tissues from 70 ovarian cancer cases diagnosed before or at age 40 were retrieved for analysis of BRCA1 mutations. DNA was isolated from paraffin-embedded tissue of 70 ovarian cancer cases diagnosed before or at age 40. BRCA1 mutation analysis was conducted by single-strand conformation polymorphism analysis and DNA sequencing. Fifty-eight BRCA1 mutations were found in 34 of the 70 ovarian cancer cases. Twenty-two cases had one mutation each and 12 cases had multiple mutations. Multiple mutations found in histologically normal tissue of 2 cases were not present in matched tumor tissue. For another case, DNA from two separate blocks of normal tissue contained different mutations. These observations were anomalous and suggested that mutations detected in fixed tissues may be artifacts of tissue preservation and not present in the original unfixed tissues. To test this suggestion, blood was obtained from 2 patients for whom mutations were found in fixed, normal tissue. DNA from their unfixed lymphocytes did not contain the mutations found in fixed normal tissue. Thus, mutations found in fixed, paraffin-embedded tissues can be artifacts of tissue preservation. The reliability of DNA sequence data derived from such tissues must be questioned in the absence of corroborating data from unfixed tissues. This severely limits the use of fixed tissues as a source of DNA for retrospective research and for clinical genetic testing in families for which a disease-affected member is not alive.

Adult↗

Stage I adenocarcinoma of the cervix: does lesion size affect treatment options and prognosis?

A retrospective analysis of 93 patients with International Federation of Gynecology and Obstetrics stage I adenocarcinoma of the cervix was performed to determine the significance of tumor size, patient age, tumor grade, lymph node status, and primary treatment modality as prognostic variables of 5-year survival and 5-year progression-free survival (PFS). Multivariate analysis demonstrated that patient age and tumor grade were significant variables prognostic of survival (p < 0.01 and p = 0.01, respectively). Tumor size was a significant (p < 0.01) prognostic variable of PFS in a multivariate model that included tumor size and patient age. An important advantage in survival and PFS for patients with lesions smaller than 3 cm compared with those patients with lesions 3 cm or more was observed (92% vs. 76% and 89% vs. 67%, respectively). Among surgically treated patients, survival and PFS among patients with lesions smaller than 3 cm were significantly improved compared with patients with tumors 3 cm or more (97% vs. 77% [p = 0.03] and 90% vs. 69% [p = 0.03], respectively). Significant improvement in survival and PFS was observed among patients with lesions smaller than 3 cm who were treated with surgery compared with those who received radiation therapy (97% vs. 77% [p = 0.03] and 90% vs. 77% [p = 0.048], respectively).

Adenocarcinoma↗

Progesterone receptor status is a significant prognostic variable of progression-free survival in advanced epithelial ovarian cancer.

The purpose of this study was to determine if tumor estrogen receptor (ER) or progesterone receptor (PR) status were significant prognostic variables of survival and progression-free survival among patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV epithelial ovarian cancer. Tumor steroid receptor status was evaluated among 67 consecutive patients who underwent primary surgery from June 1983 through September 1990. Characteristics of receptor-negative and receptor-positive populations were compared by chi-square analysis. Univariate and multivariate analyses were used to identify variables prognostic of survival and progression-free survival. Fifty-one of 67 patients (76.1%) had ER-positive tumors and 31 (46.3%) patients had PR-positive tumors. Significant differences between receptor-positive and receptor-negative populations were not observed. Neither univariate nor multivariate analysis identified ER or PR status as significant prognostic variables of survival (p = 0.93 and p = 0.06, respectively). Progesterone receptor-positive status was a significant prognostic variable of progression-free survival in both univariate (p = 0.03) and multivariate (p = 0.04) analyses even after adjustment for residual disease and patient age. Estrogen receptor status was not a significant prognostic indicator of progression-free survival in either univariate or multivariate analyses. Progesterone receptor-positive tumor status is shown to be an independent prognostic variable of improved progression-free survival among patients with advanced epithelial ovarian cancer.

Adult↗

Assessment of family cancer history collection and utilization in patient care.

OBJECTIVES: This study was conducted to determine whether patients and accompanying persons visiting the Gynecologic Oncology Clinic were aware if a family cancer history was recorded and utilized in their medical care; whether they were aware of the importance of a family cancer history, and whether they would like to learn more about familial cancer. METHODS: Sixteen- and 17-item self-report questionnaires were administered to patients and their accompanying persons, respectively, who were visiting the Gynecologic Oncology Clinic. All responses were anonymous. RESULTS: Two hundred forty-four patient questionnaires and 114 accompanying person questionnaires were completed. Seventy-eight percent of the patients and 70% of the accompanying persons replied that a physician had inquired about their family history of cancer. Only 40% of those patients and 70% of those accompanying persons (31 and 49% of total patients and accompanying persons, respectively) replied that the inquiry was by their family physician. Sixty-seven percent of these patients and 63% of these accompanying persons reported that a written record was made of the family history. Thirty-one percent of the patients and 28% of accompanying persons knew that their family cancer history information had been used to aid in their medical care. Eighty-eight percent of the patients and 83% of the accompanying persons reported the occurrence of at least one relative with cancer; however, only 44% of the patients and 35% of the accompanying persons replied that a health care provider had ever provided teaching about the importance of a family cancer history. Seventy-five percent of the patients and 73% of the accompanying persons indicated that they would like to learn more about hereditary cancer and cancer genetics. CONCLUSIONS: This study demonstrates that patients desire information about cancer genetics and hereditary cancer. Therefore, health care providers should provide better education and information to their patients as well as improve their family history-taking skills.

Journal Article↗

Prospective sequential trials of induction weekly cisplatin followed by monthly cisplatin, doxorubicin, cyclophosphamide and paclitaxel and cisplatin in optimal (< or = 1 cm) stage III and IV ovarian cancer.

PURPOSE OF INVESTIGATION: This study was conduced to assess the results of paclitaxel plus cisplatin given over six months as firstline therapy in women with stage III and IV epithelial ovarian cancer with residual disease < 1 cm and compare it to our previous standard of cisplatin, adriamycin, and cyclophosphamide given over ten months in two sequential trials totaling 100 patients. METHODS: We compared induction weekly cisplatin (1 mg/kg x 4) followed by monthly cisplatin (50 mg/m2), doxorubicin (50 mg/m2) and cyclophosphamide (750 mg/m2) x 10 (n = 56) versus induction cisplatin (1 mg/kg x 4) followed by cisplatin (75 mg/m2) and paclitaxel (135 mg/m2) monthly over six months (n = 44). RESULTS: The two groups were similar in age, histologic subtypes, grade, performance status, and substage. The mean dose of cisplatin in the PAC patients was 617.1 (+/-92.7) mg/m2 as compared to 567.1 (+/-89.2) mg/m2 in the TP patients (p < 0.0001). Surgical response was assessed in 83.9% of the PAC and 86.4% of the TP patients. The incidence of nausea and vomiting, myelotoxicity and renal toxicity were similar in the two groups. Peripheral neuropathy occurred more frequently following TP (57% vs 16%; p = 0.001). Cardiac toxicity (grade 1) occurred in 39% of the PAC patients and in 4.5% of the TP patients (p < 0.001). The overall response rate (75% vs 88.7%), surgical response rate (67.9% vs 79.5%), complete surgical responses (37.5% vs 40.9%), estimated two-year survival (80.2% vs 79.6%), progression-free median survival (36 months vs 30.4 months) and two-year progression/recurrence rates (32.3% vs 46.9%), respectively, of PAC and TP patients were not statistically significant (p = NS). CONCLUSIONS: Given the discussed limitations of the study, compared with PAC, TP did not improve overall and surgical response rates, two-year survival, two year disease-free survival, or median time of recurrence in patients with optimal (< 1 cm) stage III and IV ovarian cancer and resulted in higher peripheral neuropathy rates.

Adult↗

The clinical value of digene hybrid capture HPV DNA testing in a referral-based population with abnormal pap smears.

PURPOSE OF INVESTIGATION: The hybrid capture human papillomavirus (HPV) DNA assay is offered by the manufacturer to assist clinicians with patients with ASCUS pap smear results to assess the risk factor and to potentially direct follow-up of these patients. In our practice, a gynecologic oncology practice that has a referral based population with abnormal pap smears, our purpose was to evaluate the patients referred with all grades of abnormal cervical cytology. METHODS: One hundred consecutive patients who were referred for evaluation of abnormal cervical cytology: atypical squamous cells of undetermined significance (ASCUS); low-grade squamous intraepithelial lesion (LGSIL); high-grade squamous intraepithelial lesion (HGSIL); or squamous cell carcinoma (SCC) were evaluated by repeat pap smear, hybrid capture HPV DNA analysis and colposcopy. Colposcopic findings were recorded, and if appropriate, cervical biopsies were performed. Hybrid capture results were correlated with histologic and cytologic findings. Using histopathologic diagnosis as the reference standard, the sensitivity and positive predictive value of pap smear and high risk HPV were calculated. The Kappa test was used to correlate colposcopic and histopathologic findings. RESULTS: Repeat pap smears at the time of initial consultation demonstrated 25 patients with normal results, 39 with LGSIL, 30 with HGSIL, 1 SCC and 5 ASCUS. Seventy-eight patients underwent cervical biopsy. Colposcopic findings correlated significantly with histopathologic findings (p<0.0001). Forty-four percent of patients tested positive for HPV DNA: 40 patients with high risk HPV, three patients with low risk HPV, and one patient with both high risk and low risk HPV. Sixteen of 39 patients (41%) with LGSIL on pap smear tested positive for high risk HPV; 37% of patients in this group required cervical conization because cervical biopsies demonstrated moderate/severe dysplasia. The diagnosis of moderate/severe dysplasia significantly correlated with the presence of high risk HPV [OR 78.9 (8.31-389.30)]. There was no significant correlation between the HPV DNA signal strengths and the histologic grade of dysplasia. The sensitivity and the positive predictive value of pap smear alone in identifying moderate/severe dysplasia was 62% and 96%, respectively. The combination of HGSIL pap smears and high risk HPV increased the sensitivity but not the positive predictive value for the detection of moderate/severe dysplasia to 77.7% and 95%, respectively (P=NS). CONCLUSIONS: Although in this setting, the use of hybrid capture DNA testing did not significantly improve the sensitivity or positive predictive value of the diagnosis of HGSIL cytology when compared to cytologically indicated plus colposcopically directed cervical biopsies in this population of women at high risk for the presence of disease, the combination of HGSIL pap smears and high-risk HPV did result in a clinically important increase in the diagnosis of moderate/severe dysplasia.

Adult↗

Extraovarian primary peritoneal carcinoma.

Extraovarian primary peritoneal carcinoma (EOPPC), a relatively newly defined disease that develops only in women, accounts for approximately 10% of cases with a presumed diagnosis of ovarian cancer. Characterized by abdominal carcinomatosis, uninvolved or minimally involved ovaries, and no identifiable primary, EOPPC has been reported following bilateral oophorectomy performed for benign disease or prophylaxis. Most cases are of serous histology; however, nonserous tumors have been observed. Although EOPPC is similar to serous ovarian carcinoma with respect to clinical presentation, histologic appearance, and response to chemotherapy, molecular and epidemiologic studies have indicated that it may be a separate entity. This review explores the clinical presentation, management, prognosis, and survival of EOPPC.

Adenocarcinoma↗

Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial.

PURPOSE: The value of adjuvant radiation therapy and staging pelvic lymphadenectomy in patients with low-risk, early-stage endometrial cancer is controversial. The aim of this study was to report the long-term survival, rate of recurrences, and complications in patients with Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion treated with hysterectomy (without formal staging pelvic and periaortic lymph node sampling or lymphadenectomy) and postoperative vaginal brachytherapy. METHODS AND MATERIALS: A total of 303 patients with pathologic Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion and nonmalignant peritoneal cytology, were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative vaginal brachytherapy (30 Gy to point 0.5 cm depth) in a prospective study extending from 1958 to 1994. In addition, 29 additional Stage I, Grade 1-2 patients with <50% myometrial invasion and malignant peritoneal cytology were treated with 1 year of progesterone therapy. Patients were followed for 1.2-32 years (median 8.1 y). RESULTS: Six patients had recurrences and died secondary to disease. There were no vaginal recurrences. The 5-, 10-, 20-, and 30-year disease-free survivals of the 303 patients with nonmalignant peritoneal cytology were 98.9%, 97.8%, 96.7%, and 96.7%, respectively. Patients with malignant peritoneal cytology had a 5- and 10-year disease-free survival of 100%. Significant radiation complications occurred in 2.1% of the patients. CONCLUSION: In patients with low-risk, Stage I endometrial cancer, hysterectomy and adjuvant postoperative vaginal brachytherapy provide excellent long-term survival, eliminate vaginal recurrences, and are not associated with significant complications. The addition of 1 year of progesterone therapy to patients with malignant cytology provides 100% long-term survival. Based on these results, patients with low-risk, Stage I endometrial adenocarcinoma do not need formal staging pelvic and periaortic lymphadenectomy.

Adenocarcinoma↗

Estrogen replacement therapy following oophorectomy in women with a family history of ovarian cancer.

Compliance with estrogen replacement therapy (ERT) following surgical menopause is poor. In women who have a family history of ovarian cancer, fear of the oncogenic potential of estrogen might affect compliance with ERT following oophorectomy. Compliance with ERT in such a select group of women has not been previously reported. The aim of the present study was to report on compliance with and side effects of ERT in women with a family history of ovarian cancer who underwent oophorectomy either prophylactically or for benign disease. Eighty women with a family history of ovarian cancer who underwent oophorectomy at Roswell Park Cancer Institute were followed for a median duration of 4.2 years (range, 5 months to 14 years). Of the 76 women who were given prescriptions for ERT, the rates of commencement and maintenance of ERT at 1, 2, and 5 years were calculated. Side effects related to the different modalities of ERT were recorded. Seventy-one of 76 women (93.4%) who were given prescriptions for ERT initiated treatment. The rate of commencement of ERT was higher in premenopausal than in postmenopausal women (98.3% versus 75%, respectively, P = 0.003). Except for one patient who developed breast cancer after the oophorectomy and was advised to stop estrogen, all patients said they continued to use ERT. The maintenance rates at 1, 2, and 5 years were 100% as per patients' history. The pharmacy records for ERT prescription refills were reviewed for 52 patients who were on ERT for more than 1 year. ERT compliance was confirmed in 42 patients (80.7%). Seven of 30 patients (23.3%) who retained their uterus developed irregular uterine bleeding and 4 underwent endometrial biopsies. The incidence of irregular uterine bleeding was significantly higher after continuous compared to cyclic estrogen and progestogen (37.6 and 7% respectively, P = 0.049). Four patients (5.6%) complained of hot flashes and were managed by changing the dose or formula of estrogen. Compliance with ERT among patients with a family history of ovarian cancer who underwent oophorectomy either prophylactically or for benign disease was excellent. The presence of the uterus and the incidence of irregular uterine bleeding did not affect patients' compliance with ERT.

Administration, Oral↗

Age at onset of ovarian cancer in women with a strong family history of ovarian cancer.

OBJECTIVE: To determine whether women with a strong family history of ovarian cancer develop ovarian cancer at a younger age than the general population, and to determine if the age at onset of ovarian cancer in families with multiple cases of ovarian cancer is progressively younger with successive generations. METHODS: Using a large voluntary familial ovarian cancer registry, 90 probands were identified whose grandmothers had developed ovarian cancer and for whom the age at onset was known. The distribution of age at onset of ovarian cancer in the grandmothers was compared to the expected distribution based on data from the Surveillance Epidemiology End Results (SEER) project. In addition, 131 families were identified for whom complete pedigrees were available and in whom 3 or more family members had developed ovarian cancer. Ovarian cancer-free survival curves were constructed for each aggregate generation (using the probands as the reference generation) utilizing the Kaplan-Meier method. RESULTS: Among the 90 grandmothers, 18 from families with 3 or more cases of ovarian cancer had a distribution of age of onset that was younger than expected (P = 0.02). However, the distribution of age at onset among the 72 grandmothers from families with only 2 cases of ovarian cancer was not significantly different from that expected based on the SEER data (P = 0.18). Among the 131 families with 3 or more cases of ovarian cancer, the probands' daughters developed ovarian cancer at a younger age than the probands (P = 0.018), probands developed ovarian cancer at a younger age than their mothers (P = 0.0008), and the probands' mothers developed ovarian cancer at a younger age than the probands' grandmothers (P = 0.0038). CONCLUSIONS: Ovarian cancer patients from families with 3 or more cases of ovarian cancer tend to develop their cancer at a younger than expected age. This is consistent with the phenomenon known as anticipation.

Adult↗