Search Results (44)

Background: Hereditary cancer syndromes such as BRCA1/2 and Lynch syndrome significantly increase the lifetime risk of ovarian, fallopian tube, and endometrial cancers. Risk-reducing salpingo-oophorectomy (RRSO) and hysterectomy are standard preventive strategies. Vaginal natural orifice transluminal endoscopic surgery (vNOTES) has recently emerged as a minimally invasive, scarless alternative that may enhance patient acceptance while maintaining oncologic safety. Objective: This narrative review aims to synthesize the current evidence regarding the role of vNOTES in risk-reducing gynecologic surgery for women with hereditary cancer syndromes, focusing on surgical feasibility, technical considerations, oncologic safety, and patient-reported outcomes. Methods: A structured literature search was conducted in PubMed and Web of Science for studies published between January 2000 and April 2025, using terms related to vNOTES, prophylactic gynecologic surgery, BRCA mutations, and Lynch syndrome. Inclusion criteria focused on studies reporting outcomes of vNOTES in risk-reducing or oncologic contexts. A total of eight studies were included for qualitative synthesis. Results: vNOTES has demonstrated technical feasibility and favorable surgical outcomes in risk-reducing procedures such as RRSO and hysterectomy in BRCA and Lynch syndrome carriers. Comparative studies report lower postoperative pain, faster recovery, and high patient satisfaction, with oncologic standards maintained through specimen containment, peritoneal inspection, and adherence to the SEE-FIM protocol. Limitations include the learning curve and restricted access to the upper abdomen, which may necessitate hybrid approaches in selected cases. Conclusions: vNOTES offers a promising, patient-centered surgical approach for hereditary cancer prevention, combining oncologic safety with enhanced recovery and cosmetic benefits. Further research is needed to standardize protocols, evaluate long-term outcomes, and define its role within broader personalized cancer prevention strategies. Full article

Background/Objectives: This study was designed to evaluate skin-sparing mastectomy with implant reconstruction complication rates in patients operated on due to high penetrant gene profile. All patients went to skin-sparing mastectomy with implant reconstruction and risk-reducing salpingo-oophorectomy. The effect of radiotherapy and chemotherapy on wound healing is a frequently discussed topic in the literature. However, studies on the effect of these on patients undergoing implant-based reconstruction are rare. In our clinic, two surgeries are performed under the same anesthesia and it is aimed to investigate the effect of this situation on complications in this rare patient group. In this retrospective study, we report our clinical experience regarding complication rates due to these factors among the high penetrant gene group. Methods: Between June 2022 and June 2024, 61 patients were grouped according to demographic data. Post-operative complications were defined as any of the following: major complications which were active bleeding or wound dehiscence; minor complications which were hematoma, seroma, surgical-site infection, <20% skin or nipple necrosis, and reoperation due to wound dehiscence or any other complication. Patients were compared in terms of complications according to whether they received previous radiotherapy (RT), neoadjuvant chemotherapy (CT), or underwent skin-reducing mammoplasty. Results: Patients receiving neoadjuvant chemotherapy, patients receiving preoperative RT, and patients undergoing skin-reducing mastectomy were compared in terms of major and minor complications. While neoadjuvant CT and preoperative RT only increased the risk of seroma, it was found that skin-reducing mastectomy had no significant effect on complication rates. Conclusions: Skin-sparing mastectomy with implant reconstruction and risk-reducing salphingo-oophorectomy is a comprehensive operation method in this patient group. Complication control can be achieved by performing two surgeries in a single anesthesia period, using the spy immunofluorescence device for vascularization control, and performing all surgeries with the same experienced team. Full article

Background/Objectives: Endometrial hyperplasia is a uterine pathology characterized by the abnormal proliferation of endometrial glands, resulting in an increased gland-to-stroma ratio. Complex atypical hyperplasia represents the primary precursor to endometrial cancer. Given the high risk of progression to endometrial adenocarcinoma, the accurate diagnosis and classification of endometrial hyperplasia are crucial. Since the treatment for atypical endometrial hyperplasia is the same as that for early-stage endometrial cancer (i.e., total hysterectomy and bilateral salpingo-oophorectomy), researchers have questioned whether sentinel lymph node mapping could also have a prognostic role in atypical endometrial hyperplasia. Methods: A literature search was conducted in PubMed and Scopus from 2014 to 2025. Of the 65 papers found, 31 relevant articles were selected based on inclusion criteria, focusing on sentinel lymph node staging in patients with atypical endometrial hyperplasia. This review aims to assess whether sentinel lymph node mapping can be routinely used for prognostic and therapeutic purposes in clinical practice. Results: Sentinel lymph node biopsy represents a promising diagnostic technique for patients with atypical endometrial hyperplasia, reducing the need for invasive procedures and postoperative risks. However, its application requires advanced surgical skills and access to specific technologies, raising ethical and financial concerns, while future studies could improve patient selection and the reliability of the procedure through technological innovations. Conclusions: Sentinel lymph node biopsy is a safe and effective method for staging early-stage endometrial cancer and atypical hyperplasia, with low metastasis rates, but future research should focus on identifying patients who would benefit most from this procedure, considering its costs and required expertise. Full article

The lifetime risk of breast and ovarian cancer increases substantially for individuals with mutations in BRCA1/2. The evidence indicates that BRCA1/2 mutation carriers benefit from early cancer detection and prevention strategies. However, data on the patterns of risk-reducing interventions are lacking. This study investigated the patterns of surveillance and risk-reducing interventions among unaffected BRCA1/2 mutation carriers. A cohort of unaffected BRCA1/2 mutation carriers was identified from the Korean Hereditary Breast cAncer (KOHBRA) study database, and a telephone survey was conducted. The survey included questions on the incidence of new cancers, patterns of cancer (breast, ovarian, prostate, other) surveillance, chemoprevention, risk-reducing surgery, and reasons for participating in risk-reducing strategies. Between November 2016 and November 2020, 192 BRCA1/2 mutation carriers were contacted, of which 83 responded. After excluding 37 responders who refused to participate, 46 participants (15 males, 31 females) were included in the analysis. The mean ± SD follow-up time was 103 ± 17 months (median 107, range 68~154), and the mean ± SD age was 31 ± 8 years. Ten BRCA1/2 mutation carriers developed breast cancer, one developed ovarian cancer, and three developed other cancers. Six BRCA1/2 mutation carriers (19.4%) underwent annual breast cancer surveillance as recommended by guidelines, while none underwent ovarian or prostate cancer surveillance. Three carriers (9.7%) used chemoprevention for breast cancer. Risk-reducing salpingo-oophorectomy was performed on only one BRCA1/2 mutation carrier. The rates of breast/ovarian cancer surveillance, chemoprevention, and risk-reducing surgery were low among unaffected Korean BRCA1/2 mutation carriers. Given this cohort’s relatively high risk of developing breast cancer, strategies to encourage active participation in risk reduction are needed. Full article

Hereditary breast/ovarian cancer (HBOC) syndrome is caused by the inheritance of monoallelic germline BRCA1/2 gene mutations. If BRCA1/2 mutation carriers are identified before the disease develops, effective actions against HBOC can be taken, including intensive screening, risk-reducing mastectomy and salpingo-oophorectomy, and risk-reducing medications. The Italian National Prevention Plan mandates the creation of regional BRCA genetic testing programmes. So far, however, only informal data have been reported on their implementation. We have designed a study aimed at evaluating the results of a population-based programme for risk assessment and genetic counselling and testing for BRCA1/2-related HBOC that is underway in the Emilia-Romagna region (northern Italy). The programme—which is entirely free—includes basic screening with an estimate of the likelihood of carrying a BRCA1/2 mutation using a familial risk assessment tool, a closer examination of women with suspected risk increase, an assessment of the need for further genetic counselling and, if needed, genetic testing and risk-reducing interventions. In this paper, the design of the programme and the protocol of the study are presented. The study has an observational, historical cohort design. Eligible are the women found to be at an increased risk of HBOC (profile 3 women). The main objectives are (i) to determine the precision of the programme in measuring the level of risk of HBOC for profile 3 women; (ii) to determine the characteristics of profile 3 women and their association with the risk management strategy chosen; (iii) to compare the age at onset, histologic type, tumour stage, molecular subtype, and prognosis of breast/ovarian cancers observed in the cohort of profile 3 women with the features of sporadic cancers observed in the general female population; (iv) to determine the level and the determinants of adherence to recommendations; and (v) to determine the appropriateness and timing of risk-reducing surgery and medications. Investigating the quality and results of the programme is necessary because the best practices in risk assessment and genetic counselling and testing for BRCA1/2-related cancer and the challenges they encounter should be identified and shared. The study has the potential to provide sound empirical evidence for the factors affecting the effectiveness of this type of service. Full article

Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk-reducing salpingo-oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in the increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT directly alleviated the levels of urogenital symptoms (β = −0.195, p = 0.005), which mediated its indirect significant effects on the somatic–vegetative and psychological symptoms of menopause (β = −0.046, −0.067; both p values = 0.004, respectively), especially in BRCA2 carriers and in women who were currently physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in women with a history of cancer. MBSR, on the other hand, was associated with indirect increases in the intensity of the somatic–vegetative and psychological symptoms of menopause (β = 0.108, 0.029; p = 0.003, 0.033, respectively). It exerted positive direct effects on different menopausal symptoms in multigroup analysis. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level, while their need for extensive measures to optimize their psychological wellbeing is ongoing. The adverse effects of MBSR, which are captured in the present study, imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in these women. Full article

Breast cancer (BC) risks imparted by CHEK2 c.1100delC (“1100delC”) germline pathogenic/likely pathogenic variant (GPV) are 20–30%, compared to CHEK2 c.470T>C (“I157T”) GPV with <20%, leading to different breast screening recommendations through MRI. We compared cancer risk management (CRM) across these two GPVs. Study participants were adult females with an 1100delC or I157T GPV drawn from the Inherited Cancer Registry (ICARE) across the United States. Cancer history, clinical characteristics, and CRM were compared using chi-squared tests, t-tests, and logistic regression. Of 150 CHEK2 carriers, 40.7% had BC, with a mean age of 50. Comparing 1100delC and I157T GPVs, there were no differences in rates of (1) breast MRI among those with (65.2% versus 55.6% of 23 and 9; p = 0.612) and without (44.0% versus 44.8% of 50 and 29; p = 0.943) BC; (2) risk-reducing mastectomy among those with (50% versus 38.9% of 46 and 15; p = 0.501) and without (13.8% versus 6.5% of 58 and 31; p = 0.296) BC; and (3) risk-reducing salpingo-oophorectomy among those with (24.2% versus 22.2% of 45 and 18; p = 0.852) and without (17.5% versus 16.7% of 57 and 30; p = 0.918) BC. The results suggest over-screening with breast MRI among CHEK2 I157T GPV carriers and possible overuse of risk-reducing surgeries among CHEK2 carriers. Full article

BRCA1 and BRCA2 mutations are responsible for a higher incidence of breast and ovarian cancer (from 55% up to 70% vs. 12% in the general population). If their functions have been widely investigated in the onset of these malignancies, still little is known about their role in fertility impairment. Cancer patients treated with antineoplastic drugs can be susceptible to their gonadotoxicity and, in women, some of them can induce apoptotic program in premature ovarian follicles, progressive depletion of ovarian reserve and, consequently, cancer treatment-related infertility (CTRI). BRCA variants seem to be associated with early infertility, thus accelerating treatment impairment of ovaries and making women face the concrete possibility of an early pregnancy. In this regard, fertility preservation (FP) procedures should be discussed in oncofertility counseling—from the first line of prevention with risk-reducing salpingo-oophorectomy (RRSO) to the new experimental ovarian stem cells (OSCs) model as a new way to obtain in vitro-differentiated oocytes, several techniques may represent a valid option to BRCA-mutated patients. In this review, we revisit knowledge about BRCA involvement in lower fertility, pregnancy feasibility, and the fertility preservation (FP) options available. Full article

Background: Risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) are the most effective breast and ovarian cancer preventive interventions. EQ-5D is the recommended tool to assess the quality of life and determine health-related utility scores (HRUSs), yet there are no published EQ-5D HRUSs after these procedures. These are essential for clinicians counselling patients and for health-economic evaluations. Methods: We used aggregate data from our published systematic review and converted SF-36/SF-12 summary scores to EQ-5D HRUSs using a published mapping algorithm. Study control arm or age-matched country-specific reference values provided comparison. Random-effects meta-analysis provided adjusted disutilities and utility scores. Subgroup analyses included long-term vs. short-term follow-up. Results: Four studies (209 patients) reported RRM outcomes using SF-36, and five studies (742 patients) reported RRSO outcomes using SF-12/SF-36. RRM is associated with a long-term (>2 years) disutility of −0.08 (95% CI −0.11, −0.04) (I² 31.4%) and a utility of 0.92 (95% CI 0.88, 0.95) (I² 31.4%). RRSO is associated with a long-term (>1 year) disutility of −0.03 (95% CI −0.05, 0.00) (I² 17.2%) and a utility of 0.97 (95% CI 0.94, 0.99) (I² 34.0%). Conclusions: We present the first HRUSs sourced from patients following RRM and RRSO. There is a need for high-quality prospective studies to characterise quality of life at different timepoints. Full article

Hereditary breast and ovarian cancer (HBOC) syndrome is responsible for approximately 10% of breast cancers (BCs). The HBOC gene panel includes both high-risk genes, i.e., a four times higher risk of BC (BRCA1, BRCA2, PALB2, CDH1, PTEN, STK11 and TP53), and moderate-risk genes, i.e., a two to four times higher risk of BC (BARD1, CHEK2, RAD51C, RAD51D and ATM). Pathogenic germline variants (PGVs) in HBOC genes confer an absolute risk of BC that changes according to the gene considered. We illustrate and compare different BC risk estimation models, also describing their limitations. These models allow us to identify women eligible for genetic testing and possibly to offer surgical strategies for primary prevention, i.e., risk-reducing mastectomies and salpingo-oophorectomies. Full article

Risk-reducing bilateral salpingo-oophorectomy (RRSO) is recommended for breast cancer gene 1 (BRCA1) and 2 (BRCA2) mutation carriers. A major consequence of RRSO is surgical menopause associated with severe menopausal symptoms, mostly genitourinary complaints. Due to the inherent breast cancer risk, estrogen-based therapies are generally avoided in these patients. So far, the non-hormonal approaches available are not efficient to successfully treat the disabling vaginal atrophy-related symptoms. In regenerative medicine, mesenchymal stem cells (MSC) are the most frequently used cell type due to their remarkable and regenerative characteristics. Therapies based on MSC have revealed positive outcomes regarding symptoms and signs associated with vaginal atrophy by promoting angiogenesis, vaginal restoration, and the proliferation of vaginal mucosa cells. Menstrual blood-derived stem cells (MenSC) are a novel source of MSC, with promising therapeutic potential directly linked to their high proliferative rates; low immunogenicity; non-invasive, easy, and periodic acquisition; and almost no associated ethical issues. In this review, we update the current knowledge and research regarding the potential value of previously preserved MenSC in the therapy of vaginal atrophy among BRCA mutation carriers subjected to RRSO. Full article

Background: Germline pathogenic variants (PV) in BRCA1 and BRCA2 genes, which account for 20% of familial breast cancer (BC) cases, are highly penetrant and are associated with Hereditary Breast/Ovarian Cancer Syndrome. Previous studies, mostly including higher numbers of BRCA1 BC patients, yielded conflicting results regarding BRCA1/2 BC outcomes. In the Portuguese population, BRCA2 BC is diagnosed more frequently than BRCA1 BC. We aimed to compare clinicopathological characteristics and prognosis between BC patients with BRCA1 and BRCA2 mutations and a control group without germline PV (BRCA-wt). Furthermore, we explored the frequency and outcomes of risk-reducing surgeries in BRCA-mutated patients. Methods: Prospective follow-up was proposed for patients with a diagnosed BRCA1/2 PV. For this study, a matched control group (by age at diagnosis, by decade, and by stage at diagnosis) included BC patients without germline PV. We compared overall survival (OS) and invasive disease-free survival (iDFS) within the three groups, and the use of risk-reducing surgeries among the BRCA cohort. Results: For a mean follow-up time of 113.0 months, BRCA-wt patients showed longer time to recurrence (p = 0.002) and longer OS (p < 0.001). Among patients with BRCA mutations, no statistical differences were found, although patients with BRCA2 BC had longer iDFS and OS. Uptake of risk-reducing surgeries (contralateral prophylactic mastectomy and salpingo-oophorectomy) were negative predictors of invasive disease and death, respectively. Conclusions: Testing positive for a BRCA PV is associated with a higher risk of relapse and death in patients with BC in the Portuguese population. Risk-reducing mastectomy and salpingo-oophorectomy were associated with lower incidence of relapse and longer median iDFS and OS, respectively. Full article

Ovarian cancer (OC) is Canada’s third most common gynecological cancer, with an estimated 3000 new cases and 1950 deaths projected in 2022. No effective screening has been found to identify OC, especially the most common subtype, high-grade serous carcinoma (HGSC), at an earlier, curable stage. In patients with hereditary predispositions such as BRCA mutations, the rates of HGSC are significantly elevated, leading to the use of risk-reducing salpingo-oophorectomy as the key preventative intervention. Although surgery has been shown to prevent HGSC in high-risk women, the associated premature menopause has adverse long-term sequelae and mortality due to non-cancer causes. The fact that 75% of HGSCs are sporadic means that most women diagnosed with HGSC will not have had the option to avail of either screening or prevention. Recent research suggests that the fimbrial distal fallopian tube is the most likely origin of HGSC. This has led to the development of a prevention plan for the general population: opportunistic salpingectomy, the removal of both fallopian tubes. This article aims to compile and review the studies evaluating the effect of opportunistic salpingectomy on surgical-related complications, ovarian reserve, cost, and OC incidence when performed along with hysterectomy or instead of tubal ligation in the general population. Full article

Pathogenic variants (PVs) in BRCA1 and BRCA2 increase the lifetime risks of breast and ovarian cancer. Guidelines recommend breast screening (magnetic resonance imaging (MRI) and mammogram) or risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO). We sought to (1) characterize the population of BRCA1/2 PV carriers in Newfoundland and Labrador (NL), (2) evaluate risk-reducing interventions, and (3) identify factors influencing screening and prevention adherence. We conducted a retrospective study from a population-based provincial cohort of BRCA1/2 PV carriers. The eligibility criteria for risk-reducing interventions were defined for each case and patients were categorized based on their level of adherence with recommendations. Chi-squared and regression analyses were used to determine which factors influenced uptake and level of adherence. A total of 276 BRCA1/2 PV carriers were identified; 156 living NL biological females composed the study population. Unaffected females were younger at testing than those with a cancer diagnosis (44.4 years versus 51.7 years; p = 0.002). Categorized by eligibility, 61.0%, 61.6%, 39.0%, and 75.7% of patients underwent MRI, mammogram, RRM, and RRSO, respectively. Individuals with breast cancer were more likely to have RRM (64.7% versus 35.3%; p < 0.001), and those who attended a specialty hereditary cancer clinic were more likely to be adherent to recommendations (73.2% versus 13.4%; p < 0.001) and to undergo RRSO (84.1% versus 15.9%; p < 0.001). Nearly 40% of the female BRCA1/2 PV carriers were not receiving breast surveillance according to evidence-based recommendations. Cancer risk reduction and uptake of breast imaging and prophylactic surgeries are significantly higher in patients who receive dedicated specialty care. Organized hereditary cancer prevention programs will be a valuable component of Canadian healthcare systems and have the potential to reduce the burden of disease countrywide. Full article

Hysterectomy, most often performed because of bleeding disorders or uterine leiomyoma, is one of the most common major surgical procedures in women and is usually performed during the perimenopausal period on ages 45–55 years. Hysterectomy may be combined with bilateral salpingo-oophorectomy, as a risk-reducing procedure to minimize the risk of ovarian cancer. An open question is whether concomitant oophorectomy, with cessation of ovarian androgen secretion, has any long-term effects on sexual function. In the present prospective cohort study of women undergoing benign hysterectomy, the long-term (10–12 years) effects on sexual function and changes in sex hormone levels were investigated in women having undergone perimenopausal hysterectomy, with or without concomitant bilateral salpingo-oophorectomy. Originally, 491 women (mean age around 50 years) were operated with (patient preference) either only hysterectomy (HYST) or hysterectomy plus bilateral salpingo-oophorectomy (HYST + BSO), and 441 women (90%; HYST; n = 271 and HYST + BSO; n = 170) completed a one-year survey. In the present study, 185 women (42%) of the cohort with one-year follow up participated in the long-term follow up after 10–12 years. Follow-up was with the 10-item McCoy Female Sex Questionnaire and blood analysis of levels of testosterone, estradiol and sexual-hormone-binding globulin. The results showed that specific aspects of sexual function were lower after HYST + BSO compared to HYST 10–12 years after surgery. These lowered items were frequency of sexual fantasies, enjoyment of sexual activity, sexual arousal, and orgasmic frequency. No long-term differences in sex hormone levels were found between the two groups. In conclusion, some items related to sexual function were lower after HYST + BSO in a long-term perspective study, although the levels of testosterone were unaltered. This finding may have implications for clinical recommendations concerning prophylactic salpingo-oophorectomy or for hysterectomy during the perimenopausal age. Full article