Risk Of Fallopian Tube Cancer Research Articles

Risk factors for carcinoma of the fallopian tube in women with and without a germline BRCA mutation

Objective The purpose of this study was to identify risk factors for fallopian tube cancer in women with and without a BRCA mutation. Methods Subjects with fallopian tube cancer were identified from two sources: 1) a large international registry of women who carry a BRCA1 or BRCA2 mutation ( n = 56), and; 2) a population-based study of ovarian and fallopian tube cancer conducted in Ontario, Canada ( n = 66). BRCA mutation status was established for all subjects. Each subject was matched to one or more unaffected controls, for date of birth (within four years), for BRCA mutation status (negative, BRCA1, and BRCA2), for country of residence and for past history of breast cancer (yes/no). All subjects completed a questionnaire about medical history and lifestyle factors. Odds ratios and 95% confidence intervals were calculated for parity, oral contraceptive use, tubal ligation, hormone replacement therapy and body mass index, using conditional logistic regression. Results We studied 103 women with fallopian tube cancer (48 with a BRCA1 mutation, 12 with a BRCA2 mutation and 43 with no identified BRCA mutation) and 980 matched controls. Increasing parity was associated with a decreased risk of fallopian tube cancer in non-carriers (trend per birth odds ratio 0.71 (95% CI 0.52–0.97), p = 0.03), in BRCA1 carriers (OR = 0.79 (0.62–1.02) p = 0.07) and in BRCA2 carriers (OR = 0.62 (0.34–1.15), p = 0.13), but was statistically significant only for non-carriers. Oral contraceptive use was associated with a reduced risk in BRCA1 carriers (trend per year of use odds ratio = 0.91 (0.83–0.99), p = 0.03) but not for non-carriers (OR = 0.97 (0.87–1.09), p = 0.64) or for BRCA2 carriers (OR = 0.94 (0.80–1.11), p = 0.47). Hormone replacement therapy was associated with an increased risk for fallopian tube cancer in all subjects (OR = 1.07 (1.01–1.13), p = 0.03), and in the subgroups stratified by mutation, however the association was not significant in the subgroups. Tubal ligation was associated with a decreased risk of fallopian tube cancer for all subjects (OR = 0.64 (0.31–1.28), p = 0.21), however the reduction was not significant. Conclusions Parity and oral contraceptive use are associated with reduced risks of fallopian tube cancer. In contrast, hormone replacement therapy may be associated with an increase in the risk of fallopian tube cancer.

Hereditary Breast-Ovarian Cancer Team of the University Medical Centre Groningen (UMCG) - a Report

Female carriers of a germline BRCA1 or BRCA2 mutation have a cumulative lifetime ovarian cancer risk of 39-54% or 11-23%, respectively [1,2]. Preventive health strategies for these women include gynaecological screening aiming at early cancer detection and prophylactic salpingo-ophorectomy aiming at cancer risk reduction. However, it is becoming increasingly clear that (bi) annual gynaecological screening by transvaginal ultrasonography and serum CA125 estimation in women at increased risk of ovarian cancer is ineffective in detecting presymptomatic ovarian cancer [4]. In a recent publication a positive predictive value of 17% and a sensitivity of less than 50% were found for screening for ovarian cancer in a high-risk population [3]. Preventive bilateral salpingo-oophorectomy (BSO) reduces ovarian cancer risk by 96% and breast cancer risk by 50% or less, depending on the age of preventive surgery. Preventive BSO at a premenopausal age is the most effective strategy to prolong life in the case of a BRCA1 mutation [5]. In our clinic, we therefore counsel women with a BRCA1/2 gene mutation to choose preventive surgery after childbearing age. From the age of 35-40 for BRCA1 mutation carriers and from the age of 40-45 for BRCA2 mutation carriers, these women are advised to undergo a laparoscopic BSO. Counselling is provided at our multidisciplinary outpatient clinic by an experienced gynaecologist who discusses the benefits and drawbacks of the decision for or against preventive surgery with the patient and the (contra) indications for hormonal replacement therapy (HRT). Additional psychological counselling is available from the team's psychologist. In our clinic, uptake of preventive BSO is more than 70% in the total group of counselled mutation carriers and rises to more than 90% in women by the time they reach the age of 50 years. The operation is performed in a day care setting and starts with peritoneal washing for a cytologic examination to detect subclinical (extra) ovarian or tubal cancer, followed by BSO. Atraumatic tissue handling is performed by grasping the ovarian pedicles instead of the ovarian epithelium. The fallopian tube is removed from the uterine corner by bipolar coagulation and only the intramural part of the tube is left in situ. After marking one adnex, the adnexa are taken out of the body by an endobag. The tissue is sent for histopathological examination. Since the publications of case reports linking BRCA mutations to an increased risk of fallopian tube cancer as well, preventive oophorectomy is recommended to be replaced by BSO [6]. Although the rationale for removing the total fallopian tube by removing the uterus as well is clear, we could not find any evidence that a hysterectomy adds to reducing the risk of fallopian tube cancer more than a complete BSO alone. In a large clinicopathologic study of 105 cases of fallopian tube cancer, 92% were situated in the tubal portion, most often the distal part, while 8% were confined to the fimbriae [7]. Following preventive BSO, women who are younger than 45 years of age and have no history of breast cancer are counselled to use HRT, to treat vasomotor symptoms and sexual side effects of oestrogen deprivation. In the case of prescription of HRT, we prescribe tibolone, because in contrast to oestrogen/progestogen treatment, it appears to exert little stimulation of breast tissue and does not increase the mammographic breast density [8]. Women who have been treated for breast cancer, or are older than 45-50 years of age, are advised not to use HRT. In the case of severe vasomotor symptoms, non-hormonal treatment is proposed by selective serotonin reuptake inhibitors (SSRI).