Chen Nahshon

Attitude of BRCA1/2 mutation carriers towards surgical risk reduction for breast, ovarian and uterine cancer: still much to be done

To study and quantify the attitude of BRCA1/2 mutation carriers towards surgical risk reduction procedures. This cross-sectional national study was conducted by distribution of an anonymous questionnaire on social media platforms and to BRCA1/2 carriers' medical clinic. 530 BRCA1/2 mutation carriers answered the survey. Risk reduction bilateral salpingo-oophorectomy was discussed with 447/489 (91%) of patients and performed in 260/489 (53%). Hormonal replacement therapy was discussed in 280/474 (59%) of patients. Addition of hysterectomy to risk reduction bilateral salpingo-oophorectomy was discussed in 129/481 (27%) of patients and performed in 44/443(10%). Age over 35 years at time of mutation detection was found to be significant in raising risk reduction bilateral salpingo-oophorectomy and hysterectomy performance rates. Risk reduction mastectomy was discussed in 390/471 (83%) of patients and performed in 156/471 (33%). In a multivariate analysis, BRCA1 mutation carriers (OR=1.66 (95% CI 1.07 to 2.57), p=0.024) and a personal cancer history leading to the mutation detection (OR=4.75 (95% CI 1.82 to 12.4), p=0.001) were found to be significant in increasing the likelihood of opting for risk reduction mastectomy. Additionally, highest risk reduction mastectomy performance rates were observed in the group of patients with a first-degree family history of breast cancer under the age of 50 years (OR=1.58 (95% CI 1.07 to 2.32), p=0.01). This study highlights the high performance rates of risk reduction bilateral salpingo-oophorectomy, while hysterectomy was added in 10%, and that despite high awareness and acceptance rates for risk reduction mastectomy, only 33% had the procedure. The data presented provides insights for the clinician counseling BRCA1/2 mutation carriers, with regards to adherence to recommendations, understanding their concerns towards treatment and management alternatives; and finally, to construct a personalized management medical plan.

Sentinel lymph node sampling versus full lymphadenectomy in endometrial cancer: a SEER database analysis

To assess the long term outcomes and prognosis of sentinel lymph node sampling compared with full lymph node dissection in endometrial cancer patients. We used the Surveillance, Epidemiology, and End Results (SEER) database for information on women diagnosed with endometrial cancer from 2010 to 2019. We conducted a comparison including overall survival between patients who had undergone sentinel lymph node sampling only and patients who had undergone formal lymph node dissection. Propensity score matching was performed according to the patient's age, type of endometrial cancer, grade and stage of disease, and adjuvant therapy. Subgroup analyses were performed according to type and grade of endometrial cancer. 41411 endometrial cancer patients were identified through the database. After matching, 6019 patients each were included in the sentinel lymph node and lymph node dissection groups. Median (interquartile range (IQR)) follow-up time was 16 (7-31) months in both groups. One year survival rates were longer in the sentinel lymph node group compared with the lymph node dissection group (hazard ratio (HR) 1.61 (95% confidence interval (CI) 1.17 to 2.21); p=0.004). Subgroups analysis according to grade of disease showed that 1 year survival rates were longer in the sentinel lymph node group in patients with endometrioid-type grade 1-2 endometrial cancer (HR 1.70 (95% CI 1.31 to 2.56); p=0.01), while no difference in survival was found between the sentinel lymph node and lymph node dissection groups in the subgroup of patients with high grade endometrial cancer (HR 1.40 (95%CI 0.94 to 2.24); p=0.17). In patients with low grade endometrial cancer included in the sentinel lymph node group, only 7% had lymph nodes positive for malignancy compared with 17% in the high grade group. Survival rates were not compromised in endometrial cancer patients undergoing sentinel lymph node sampling versus full lymph node dissection for all grades of disease.

Incidence and characteristics of ovarian cancer following endometrial cancer in the emerging era of conservative management of endometrial cancer—Implications for counseling—A SEER analysis

AbstractObjectiveTo assess the ovarian cancer (OC) risk following endometrial cancer (EC) in patients who underwent ovarian preservation as part of the EC staging.Study DesignWith permission of the Surveillance, Epidemiology and End Results (SEER) program of the United States National Cancer Institute, clinicopathological information of women diagnosed with EC and following OC were analyzed. Incidence of OC and survival according to the surgical approach were studied. Primary analysis was conducted in women up to and including the age of 49 years.ResultsA total of 116 patients up to the age of 49 years were diagnosed with EC and following OC. In this group of patients, no differences in incidence (IRR 0.9, CI 0.56–1.49, p = 0.66) or survival rates (p = 0.71) were found comparing ovarian preservation and bilateral salpingo‐oophorectomy (BSO) performance. In an overall analysis of women diagnosed with EC and following OC at any age, incidence of OC did not differ between groups (IRR 1.07, CI 0.83–1.39, p = 0.59) yet when including patients older than 49 years old survival rates were shorter in ovarian preservation patients compared to patients with BSO performed as part of their EC treatment.ConclusionOvarian preservation in EC patients under the age of 49 years may be considered safe, with no impact on OC incidence or survival, benefiting longer natural hormonal status.

RE: Endometrial Cancer Risk in Women With Germline BRCA1 or BRCA2 Mutations: Multicenter Cohort Study

Attitude of BRCA1/2 mutation carriers towards fertility preservation, family planning and preimplantation genetic testing for primary prevention of breast and ovarian cancer in the next generation

To study the attitude of BRCA1/2 mutation carriers regarding family planning, fertility preservation, and preimplantation genetic testing (PGT). A national cross-sectional study was conducted by the distribution of an anonymous questionnaire, from August 2022 to January 2023. The main outcomes measures were discussion, acceptance, and performance rates of fertility preservation and PGT. The questionnaire was completed by 530 BRCA1/2 mutation carriers. The mean (SD) age at mutation detection was 36.4 (9.6) years. At the time of mutation detection, 40% did not have children. Following mutation detection, 37% of responders changed their family planning, mostly choosing to have children earlier or to have less children than planned. Twenty-eight percent of BRCA carriers discussed the option of fertility preservation with a physician, 72% agreed that fertility preservation is an acceptable option for BRCA1/2 mutation carriers and finally 11% underwent oocyte/embryo vitrification before RRBSO. 44% of BRCA carriers discussed the option of PGT, 58% agreed that PGT is justified in BRCA1/2 mutation carriers and finally 8% underwent PGT to select non-carrier embryos. In a multivariate analysis, age under 35 years and the a priori need for fertility treatments were both found significant factors increasing the likelihood of performing fertility preservation and PGT. This study emphasizes that despite a substantial proportion of women admitting that mutation detection affected their family planning and high acceptance rates, performance of fertility preservation and PGT remained exceedingly low. Increasing the knowledge and awareness of these issues is important and should be included in multidisciplinary counselling.

Five-year survival decreases over time in patients with BRCA-mutated ovarian cancer: a systemic review and meta-analysis

Short-term survival rates of patients with BRCA-mutated ovarian cancer have been previously shown to be longer than those of non-carriers. We aimed to study the long-term survival rates of these patients and investigate whether the 5-year advantage decreases over time. A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyzes (PRISMA) statement. The study protocol can be assessed at PROSPERO International prospective register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO, registration number CRD42019137455). We considered for inclusion studies providing Kaplan-Meier survival curves up to and including 10 years, comparing patients with ovarian cancer with and without BRCA mutations. Our main outcome was the conditional probability of surviving an additional 5 years. A total of 13 references comprising 4565 patients was analyzed, of which 1131 BRCA1/2-mutated carriers and 3434 non-carriers were included. The expected higher 5-year survival rate in BRCA-mutated patients was observed (risk difference (RD)=14.9%, p=0.0002, risk ratio (RR)=1.36, p=0.001). Ten-year survival rates were comparatively less improved in BRCA-mutated patients (RD=8.6%, p=0.042, RR=1.25, p=0.12). After already surviving 5 years, no advantage in probability of further surviving 5 additional years was observed for the BRCA-mutated group (RD=2.9%, p=0.71, RR=0.97, p=0.78). Our results provide insight into long-term survival rates and prognosis in patients with BRCA-mutated ovarian cancer which suggest that, despite the improved 5-year prognosis, the conditional probability of surviving an additional 5 years does not show the same advantage. The relatively low long-term advantage highlights the significance of epithelial ovarian cancer recurrence prevention. In the era of poly adenosine ribose inhibitors, future studies should explore the adequate follow-up and the benefit of a longer maintenance treatment phase, aiming to prolong the long-term survival of BRCA-mutated patients.

Effect of known pathological risk factors on the incidence of metastatic lymph nodes and survival in early‐stage vulvar cancer: SEER analysis

AbstractObjectiveThe current study was performed to evaluate the incidence of positive lymph nodes (LNs) in relation to known pathological risk factors, specifically among patients with apparent low‐grade, small tumors.MethodsWe used the Surveillance, Epidemiology, and End Results (SEER) database to retrospectively identify patients with vulvar squamous cell carcinoma (SCC) diagnosed between January 1, 2000, and December 31, 2019, with known tumor size and regional LN examined. A comparison between patients who had positive and negative LNs was conducted to identify risk factors for LN metastases in relation to survival. Subgroup analysis was conducted in patients with diagnosed grade 1 vulvar SCC and tumor size up to 2 cm according to the status of LNs.ResultsMultivariate analysis found that both grade of disease and tumor size were significant factors in predicting LN status. Among patients with low‐grade small tumors up to 2 cm, the odds ratio for positive LNs was 2.5 for those with tumor size larger than 1 cm. In a multivariate survival analysis, older age, larger tumor size, and positive LNs were independently associated with decreased survival.ConclusionsThe current study confirms that among small tumors, those larger than 1 cm have a significantly increased risk for positive nodes compared with those smaller than 1 cm, and, among this specific group, patients with positive nodes have decreased survival. Future studies are needed to answer the question of whether, in the era of the sentinel node procedure, it is safe to omit LN evaluation altogether.