Germline BRCA1/2 testing of breast and ovarian cancer patients is growing rapidly as the result affects both treatment and cancer prevention in patients and relatives. Through the DNA-BONus study we ...offered BRCA1/2 testing and familial risk assessment to all new patients with breast (N=893) or ovarian (N=122) cancer diagnosed between September 2012 and April 2015, irrespective of family history or age, and without prior face-to-face genetic counselling. BRCA1/2 testing was accepted by 405 (45.4%) and 83 (68.0%) of the patients with breast or ovarian cancer, respectively. A pathogenic BRCA1/2 variant was found in 7 (1.7%) of the breast cancer patients and 19 (22.3%) of the ovarian cancer patients. In retrospect, all BRCA1/2 mutation carriers appeared to fulfill current criteria for BRCA1/2 testing. Hospital Anxiety and Depression Scale (HADS) scores showed that the mean levels of anxiety and depression were comparable to those reported for breast and gynecological cancer patients in general, with a significant drop in anxiety symptoms during a 6-month follow-up period, during which the test result was forwarded to the patients. These results show that BRCA1/2 testing is well accepted in newly diagnosed breast and ovarian cancer patients. Current test criteria based on age and family history are sufficient to identify most BRCA1/2 mutation carriers among breast cancer patients. We recommend germline BRCA1/2 testing in all patients with epithelial ovarian cancer because of the high prevalence of pathogenic BRCA1/2 variants.
Abstract Ten BRCA mutations were demonstrated to be frequent in the Norwegian population. We present maps verifying the uneven distribution of prevalences according to municipality. We tested ...incident breast cancer cases treated in Mid-Norway from 1999 onwards for these mutations. Uptake of testing was 97% and 2.5% were demonstrated to be mutation carriers. Ten (77%) were outside families previously known to carry a mutation. Ten (77%) did not meet clinical criteria to be selected for mutation testing. We tested incident ovarian cancer cases in South-West Norway from 2001 onwards. Uptake of testing was 80% and 23% were mutation carriers. Twenty-one (88%) were outside families previously known. Twelve (67%) did not meet clinical criteria to be selected for testing. All patients with mutation collaborated actively to give our offer of predictive genetic testing to their relatives. No complaint on the activity was received.
Cervical intraepithelial neoplasia grades 2-3 (CIN2-3) are usually treated by cone excision, although only 30% progress to cancer and 6-50% regress spontaneously. The aim of this study was to examine ...the influence of clinical factors like smoking habits, number of lifetime sexual partners, age at first sexual intercourse, sexual activity span and hormonal versus non-hormonal contraception type on the regression rate of CIN2-3.
In this prospective population-based cohort study 170 women aged 25-40 with abnormal cytology and colposcopy-directed biopsies showing first time onset CIN2-3 were consecutively included. The interval between biopsy and cone excision was standardized to minimum 12 weeks. Regression was defined as ≤ CIN1 in the cone biopsy.
The regression rate was 22%. Consistent condom use, defined as those women whose partners used condoms for all instances of sexual intercourse, was infrequent (n=20, 12%). In univariate analysis consistent condom use, hormonal contraception and age at first sexual intercourse significantly predicted regression. In a multivariate analysis only consistent condom use remained as an independent predictor of regression (regression rate 55%, p=0.001, hazard ratio=4.4).
Consistent condom use between punch biopsy and cone excision in first-time onset CIN2-3 patients significantly increases the regression rate.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: Inherited ovarian cancer carries a serious prognosis. Prophylactic oophorectomy has been advocated. The degree to which inherited
ovarian cancer is restricted to BRCA mutation carriers is ...not fully known. We wanted to determine the prevalence of BRCA mutation carriers in women at high risk from ovarian cancer.
Experimental Design: Healthy women who were found to be at increased risk judged by family history were followed prospectively. Full BRCA1/2 mutation analysis was conducted on all patients who contracted pelvic cancer.
Results: We identified 1,582 women at risk during 5,674 person-years. Forty infiltrating epithelial ovarian cancers, six peritoneal
cancers, and one fallopian tube cancer were diagnosed. All but one of these patients (98%) had a BRCA mutation, a frequency that was significantly higher than for the 3 patients with borderline ovarian cancers, who were all
mutation negative ( P = 0.0002). Eighty-two percent of the detected mutations belonged to one of the 10 Norwegian founder mutations previously
reported. At prophylactic bilateral salpingo-oophorectomy, cancer was found in 18 of 345 (5.2%) of mutation carriers compared
with none in the 446 mutation negative ( P = 0.0000).
Conclusions: In healthy women with a family history of ovarian cancer, high risk for ovarian cancer was restricted to BRCA1/2 mutation carriers. A woman at risk for ovarian cancer according to her family history should have access to full BRCA1/2 mutation testing before deciding on prophylactic bilateral salpingo-oophorectomy.
Objective To analyze the prognostic value of molecular biomarkers in curettages of endometrioid endometrial cancer pathologic FIGO stages 1 and 2. Study Design Population-based survival analysis in ...258 patients of classical prognostic features and molecular biomarkers of cell cycle regulation, (anti)apoptosis, proliferation, squamous differentiation, and PTEN/Akt pathway. Results With 74 months median follow-up (range, 1-209), 24 (9.3%) patients had metastases develop. Pathologic FIGO stage 2B (6% of all cases) and age > 68 years had independent multivariate prognostic value. Many molecular biomarkers were prognostic, particularly cell-cycle regulators p16, p21, p27, p53, p63, and the antiapoptosis marker survivin (which mostly stains mitoses). The strong prognostic value of a multivariate model with survivin, p21, and p53 overshadowed all other prognosticators in pathologic FIGO 1 and 2A. Conclusion In pathologic FIGO stage 1 and 2A endometrioid endometrial cancer curettages, combined biomarkers survivin, p21, and p53 expression patterns are prognostically stronger than classical feature combinations.
The major cause of cervical intraepithelial neoplasia (CIN) is persistent infection with human papillomavirus (HPV). Most CIN grade 2 and 3 lesions are treated with cone excision, although a ...substantial proportion (6-50%) of CIN2-3 lesions will regresses spontaneously. Predictors for regression of CIN2-3 are desirable in order to reduce this overtreatment.
In this prospective cohort study, 145 consecutive women with first-time onset CIN2-3 in colposcopy-directed biopsies and standardized biopsy-cone excision interval were included. The genotype of the high-risk human papillomaviruses (=hrHPV) and clinical factors including sexual behaviour, parity, contraception and smoking were assessed. Patients were divided into two groups according to lesions containing HPV16 (hrHPV16+) and high-risk non-HPV16 (hrHPV16-) genotypes.
Women whose partners consistently used condoms showed a significantly higher regression rate than women using other types of contraception (53% versus 13%, p<0.0001). However, this effect was only seen in hrHPV16- patients (73% regression rate versus 13%, p<0.0001). HrHPV16+ patients had a significantly higher number of sexual partners and more current smokers compared to hrHPV16- patients. The regression rate was not significantly different in CIN2-3 lesions containing HPV16 (hrHPV16+) versus hrHPV16- genotypes.
Heterogeneity among hrHPV genotypes excists. HPV-genotype analyses can identify women who significantly increase their chance of regression by consistent condom use.
AGO‐OVAR 12 investigated the effect of adding the oral triple angiokinase inhibitor nintedanib to standard front‐line chemotherapy for advanced ovarian cancer. At the primary analysis, nintedanib ...demonstrated significantly improved progression‐free survival (PFS; primary endpoint) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IV newly diagnosed ovarian cancer were randomised 2:1 to receive carboplatin (area under the curve 5 or 6) plus paclitaxel (175 mg/m2) on day 1 every 3 weeks for six cycles combined with either nintedanib 200 mg or placebo twice daily on days 2–21 every 3 weeks for up to 120 weeks. Between December 2009 and July 2011, 1,366 patients were randomised (911 to nintedanib, 455 to placebo). Disease was considered as high risk (FIGO stage III with >1 cm residuum, or any stage IV) in 39%. At the final analysis, 605 patients (44%) had died. There was no difference in OS (hazard ratio 0.99, 95% confidence interval CI 0.83–1.17, p = 0.86; median 62.0 months with nintedanib vs. 62.8 months with placebo). Subgroup analyses according to stratification factors, clinical characteristics and risk status showed no OS difference between treatments. The previously reported PFS improvement seen with nintedanib did not translate into an OS benefit in the nonhigh‐risk subgroup. Updated PFS results were consistent with the primary analysis (hazard ratio 0.86, 95% CI 0.75–0.98; p = 0.029) favouring nintedanib. The safety profile was consistent with previous reports.
What's new?
Primary results from the randomised phase III AGO‐OVAR 12 trial comparing nintedanib (a triple angiokinase inhibitor) with placebo given in combination with chemotherapy and then continued as maintenance therapy in patients with newly diagnosed advanced ovarian carcinoma demonstrated a significant improvement in progression‐free survival with nintedanib. However, as reported in this paper, final overall survival (OS) results showed that the addition of nintedanib had no impact on OS. These results do not, therefore, support use of nintedanib in ovarian cancer.
This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian ...cancer (OC).
Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75).
The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP).
This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities.
ClinicalTrials.gov, number NCT01379989.
Introduction
Gynecological cancer patients are routinely followed up for five years after primary treatment. However, the value of such follow up has been debated, as retrospective studies indicate ...that first recurrence is often symptomatic and occurs within two to three years of primary treatment. We prospectively investigated time to first recurrence, symptoms at recurrence, diagnostic procedures, and recurrence treatment in gynecological cancer patients after primary curative treatment.
Material and methods
Clinicians from 21 hospitals in Norway interviewed 680 patients with first recurrence of gynecological cancer (409 ovarian, 213 uterine, and 58 cervical cancer patients) between 2012 and 2016. A standardized questionnaire was used to collect information on self‐reported and clinical variables.
Results
Within two years of primary treatment, 72% of ovarian, 64% of uterine, and 66% of cervical cancer patients were diagnosed with first recurrence, and 54, 67, and 72%, respectively, had symptomatic recurrence. Of symptomatic patients, 25–50% failed to make an appointment before their next scheduled follow‐up visit. Computer tomography was the most common diagnostic procedure (89% of ovarian, 76% of uterine, and 62% of cervical cancer patients), and recurrence treatment in terms of chemotherapy was most frequently planned (86% of ovarian, 46% of uterine, and 62% of cervical cancer patients).
Conclusions
A majority of patients experienced symptomatic recurrence, but many patients failed to make an appointment earlier than scheduled. Most first recurrences occurred within two years of primary treatment; the mean annual incidence rate for years 3–5 after primary treatment was <7%. New models for follow up of gynecological cancer patients could be considered.
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