Novel approaches are needed to ensure all patients with cancer have access to quality genetic education before genetic testing to enable informed treatment decisions. The purpose of this study was to test the use of an artificial intelligence (AI) intervention for the delivery of genetic education by non-genetic providers to patients with cancer undergoing active treatment.

A conversational AI-based application was developed on the HealthFAX platform to provide tailored genetic education to patients with cancer and tested at Johns Hopkins Hospital between April 2021 and Feb 2022. Patients' responses around the adoption, use, and experience of the AI application were assessed.

Out of 64 individuals who consented to the study, 51 accessed the tool. The responding participants had a mean age of 61 years (ranging from 30-90 years) with 39 individuals undergoing active treatment for breast cancer and 12 for advanced prostate cancer. All patients chose to complete the tool at home. The median time between study enrollment and AI application initiation was 1 day, and the median time to complete the application was 24 min. All participants in their survey responses felt that the tool was secure, easy to use, liked the convenience of viewing it at home, and felt it provided valuable information. Eighteen percent of participants viewed the application with a family member. Ninety-eight percent of the participants completed their genetic education prior to receiving their test results. In 16%, a pathogenic variant was identified.

The 51 patients who adopted the AI application were highly satisfied with its usability and convenience. Our results support the continued evaluation of this cost-effective AI application in a large-scale study.

Tailored pre-test genetic education can be successfully delivered to patients with cancer undergoing active treatment via an AI application at their convenience.

Breast reconstruction following prophylactic mastectomy in women with ptotic or hypertrophic breasts often poses challenges. We describe a combined technique of large-volume fat grafting (>100 mL) and an inferior dermal flap, aiming to improve aesthetic outcomes and patient satisfaction.

We conducted a retrospective analysis of 21 patients undergoing immediate breast reconstruction with the described technique. All patients were asked to complete the BREAST-Q questionnaire preoperatively and at least 12 months postoperatively (median interval: 20 months). Statistical analysis (Wilcoxon signed-rank test) was used to assess changes in satisfaction and well-being; aesthetic outcomes were scored by an independent, multidisciplinary team.

Among 13 patients with complete BREAST-Q data, satisfaction with the breasts increased significantly from a median score of 38-85 (p = 0.002), psychosocial well-being from 57-70 (p = 0.045), and physical well-being (chest) from 68 to 81 (p = 0.045). Sexual well-being rose from 47-63 (p = 0.023). Aesthetic evaluation by an independent panel showed notable improvements in breast symmetry, shape, and overall appearance. Minimal and asymptomatic fat necroses or oil liponecrotic pseudocysts were observed.

Combining large-volume fat grafting with an inferior dermal flap appears promising for women with ptotic breasts, yielding high satisfaction and low complication rates. Despite requiring multiple operative stages, this autologous reconstruction technique may offer a less invasive alternative for high-risk patients seeking natural outcomes without implants.

Best practices for improving access to assessment of hereditary cancer risk in primary care are lacking.

To compare 2 population-based engagement strategies for identifying primary care patients with a family or personal history of cancer and offering eligible individuals genetic testing for cancer susceptibility.

The EDGE (Early Detection of Genetic Risk) clinical trial cluster-randomized 12 clinics from 2 health care systems in Montana, Wyoming, and Washington state to 1 of 2 engagement approaches for assessment of hereditary cancer risk in primary care. The study population included 95 623 English-speaking patients at least 25 years old with a primary care visit during the recruitment window between April 1, 2021, and March 31, 2022.

The intervention comprised 2 risk assessment engagement approaches: (1) point of care (POC), conducted by staff immediately preceding clinical appointments, and (2) direct patient engagement (DPE), where letter and email outreach facilitated at-home completion. Patients who completed risk assessment and met prespecified criteria were offered genetic testing via a home-delivered saliva testing kit at no cost.

Primary outcomes were the proportion of patients with a visit who (1) completed the risk assessment and (2) completed genetic testing. Logistic regression models were used to compare the POC and DPE approaches, allowing for overdispersion and including clinic as a design factor. An intention-to-treat analysis was used to evaluate primary outcomes.

Over a 12-month window, 95 623 patients had a primary care visit across the 12 clinics. Those who completed the risk assessment (n = 13 705) were predominately female (64.7%) and aged between 65 and 84 years (39.6%). The POC approach resulted in a higher proportion of patients completing risk assessment than the DPE approach (19.1% vs 8.7%; adjusted odds ratio [AOR], 2.68; 95% CI, 1.72-4.17; P < .001) but a similar proportion completing testing (1.5% vs 1.6%; AOR, 0.96; 95% CI, 0.64-1.46; P = .86). Among those eligible for testing, POC test completion was approximately half of that for the DPE approach (24.7% vs 44.7%; AOR, 0.49; 95% CI, 0.37-0.64; P < .001). The proportion of tested patients identified with an actionable pathogenic variant was significantly lower for the POC approach than the DPE approach (3.8% vs 6.6%; AOR, 0.61; 95% CI, 0.44-0.85; P = .003).

In this cluster randomized clinical trial of risk assessment delivery, POC engagement resulted in a higher rate of assessment of hereditary cancer risk than the DPE approach but a similar rate of genetic testing completion. Using a combination of engagement strategies may be the optimal approach for greater reach and impact.

ClinicalTrials.gov Identifier: NCT04746794.

Women with ovarian cancer (OC) and a pathogenic variant in the BRCA1 or BRCA2 genes are at increased risk of developing breast cancer (BC). Evidence for long term outcomes in these patients who undergo bilateral risk reduction mastectomy (RRM) after ovarian cancer is sparse. The aim of this study was to analyse the long-term breast cancer-related outcomes of patients who have been diagnosed with ovarian cancer and found to have BRCA1 or 2 pathogenic variants.

Local approval was granted. The hospital clinical genetics database was interrogated to identify women who have been diagnosed with OC and a germline BRCA1/2 pathogenic variant between January 2010-March 2020. Patient demographics, OC treatment as well as any BC related information was analysed.

148 women were diagnosed with OC and a pathogenic variant in BRCA1/2 in the study period. 47 patients were excluded as they did not have treatment at our institution. 101 patients were included. The median age at diagnosis of OC was 52 years (IQR 46-61). Eighty-four (82 %) were FIGO stage 3 or 4 OC. At a median follow-up of 63 months (IQR 39-94), 55 (54.4 %) women had been diagnosed with a recurrence of ovarian cancer and 38 (37 %) women have died. Twenty-one (21 %) women were diagnosed with BC. 13 (12.9 %) had BC before OC, 4 after and 4 synchronous with OC. Of the remaining patients who did not have BC, 6 underwent bilateral risk reduction mastectomy (RRM) after treatment for OC.

Risk of disease recurrence and death due to stage 3 and 4 ovarian cancer remained high in this time period. RRM can be undertaken in carefully selected patients, however we would recommend reserving this for women who have favourable OC disease prognosis.

Breast cancer associated with pathogenic variants of BRCA1 and BRCA2 genes requires specific management. This review examines the prognostic benefits, prophylactic surgical strategies, and impact on quality of life of patients at very high risk of breast cancer. Breast surgical prophylaxis concerns women at high risk of breast cancer with a risk assessment based on their personal and family history, or by diagnosis of pathogenic variants in high-risk genes. Personalized management is based on enhanced clinical and radiological monitoring, the use of predictive tools such as BOADICEA, and surgical options such as prophylactic bilateral mastectomy, which can reduce the risk of cancer by over 90 %. Although its impact on overall survival is still debated, advances in surgical techniques have significantly improved aesthetic results and patient satisfaction, thanks to modern reconstruction methods. The surgical strategy, whether primary or secondary, must be individualized, considering the patient's history, therapeutic needs, and preferences. Mastectomy with preservation of the skin envelope, often performed in one or two stages, offers significant psychosocial benefits, although radiotherapy may increase the risk of complications. Options include immediate reconstruction, by implant or autologous technique, adapted to the patient's morphology and any adjuvant treatments.

Prophylactic bilateral mastectomy is an effective strategy for reducing the risk of breast cancer, particularly in patients with pathogenic BRCA gene variants. Personalized assessment, detailed information on risks and impacts, and the use of decision-support tools are essential to enable informed choices tailored to individual patient needs.

To investigate the prevalence of pathological findings and clinical outcomes of risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV).

This retrospective study enrolled asymptomatic carriers with germline HR gene PV/LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea. Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed.

Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9-71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months.

Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.

BRCA1/2 genetic testing has become clinically important in breast cancer care, but increasing demand may put a burden on the shortage of healthcare professionals. We performed a single-center, pilot randomized controlled study to assess the effectiveness of employing a video educational tool that included standard pre-test genetic counseling elements related to BRCA1/2. Patients with operable breast cancer who met the criteria for genetic testing based on age, sex, subtype, and family history were recruited. Sixty consenting participants were randomized 1:1 and placed in groups that received either traditional face-to-face pre-test counseling or video-viewing and face-to-face decisional support. To assess decisional conflict in the participants, surveys based on the Decisional Conflict Scale (DCS) were administered two times, once immediately after intervention and again 2-4 weeks later. The time taken for counseling and confirmation of whether the participants had undergone testing were also recorded. The difference in the total DCS scores between the two groups was not significantly different for either of the survey periods, and there was no significant difference in the number of participants who underwent testing (23/30 [76.7%] vs. 26/30 [86.7%]; p = 0.51). However, the "effective decision" subscale score was significantly higher in the video group 2-4 weeks after counseling (31.01 ± 16.82 vs. 21.43 ± 16.09; p = 0.04 [mean ± SD]). The time taken for counseling was significantly shorter in the video group (8.00 ± 4.5 vs. 27.00 ± 7.61 min; p < 0.001 [median ± SD]). Our findings indicate the potential benefit of the video educational tool for providing BRCA1/2-related information. These tools may also enable healthcare professionals to spend more time supporting psychological issues. Notably, after some time, patients may question whether their decision was appropriate. Therefore, it is necessary to identify those in conflict and provide them with proper support.

As demand for genetic cancer risk assessment (GCRA) continues to increase, so does the sense of urgency to scale up efforts to triage patients, facilitate informed consent, and order genetic testing for cancer risk. The National Society of Genetic Counselors outlines the elements of informed consent that should be addressed in a GCRA session. While this practice resource aims to improve health equity, research on how well the elements of informed consent are implemented in practice is lacking. This retrospective and prospective mixed-methods study assessed how adequately the elements of informed consent are addressed during pre-test GCRA among 307 community clinicians (CC) and 129 cancer genetic counselors (GC), and barriers they face to addressing these elements. Results revealed that more than 90% of both cohorts consistently addressed components of at least 5 of the 10 elements of informed consent during a pre-test consultation. Technical aspects and accuracy of the test and utilization of test results were the most similarly addressed elements. Notably, GCs more often review the purpose of the test and who to test, general information about the gene(s), and economic considerations whereas CCs more often review alternatives to testing. Both cohorts reported psychosocial aspects of the informed consent process as the least adequately addressed element. Time constraints and patient-related concerns were most often cited by both cohorts as barriers to optimal facilitation of informed consent. Additional barriers reported by CCs included provider lack of awareness, experience, or education, and availability of resources and institutional support. Findings from this study may contribute to the development of alternative delivery models that incorporate supplementary educational tools to enhance patient understanding about the utility of genetic testing, while helping to mitigate the barrier of time constraints. Equally important is the use of this information to develop continuing education tools for providers.

Bilateral risk-reducing mastectomy (BRRM) is the surgical removal of both breasts to reduce the risk of cancer. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, outcomes, and risks of BRRM to update the society's 2017 statement. We held a virtual meeting to outline key topics and conducted a literature search using PubMed to identify relevant articles. After literature review, recommendations were made according to group consensus. Individuals with a high lifetime risk of breast cancer due to pathogenic variants in high penetrance breast cancer-predisposition genes, early chest or breast radiation exposure, or a compelling family history should be counseled on the option of BRRM. However, BRRM is not recommended for most patients with high-risk lesions and may be contraindicated in patients who have other competing cancers and/or a high risk of surgical complications. BRRM effectively reduces the risk of breast cancer development, although the survival benefit is unclear. For patients with low-to-moderate breast cancer risk, alternative management strategies should be encouraged, including lifestyle modifications, high-risk screening, and risk-reducing medications. Discussions of BRRM should cover: (1) breast-cancer risk estimates; (2) the procedure's degree of risk reduction and impact on survival; (3) surgical techniques, potential surgical complications and long-term sequelae; and (4) alternatives to surgery. Surgeons should encourage shared and informed decision making with patients who have an elevated lifetime risk of developing breast cancer.

Women who carry the breast cancer gene (BRCA)1/2 pathogenic variants have a higher lifetime risk of developing ovarian cancer than the general population (BRCA1, 44%; BRCA2, 17%). There is currently no reliable method for the early detection of ovarian cancer, and the prognosis of advanced ovarian cancer is poor. Therefore, risk-reducing salpingo-oophorectomy (RRSO) is recommended for patients with breast cancer who carry BRCA1/2 pathogenic variants. We retrospectively reviewed 10 cases of RRSO in such patients performed at our hospital.

This study included 10 patients with BRCA-positive breast cancer who underwent RRSO after genetic counseling between April 2021 and December 2024. The patients ranged from 39 to 72 years of age (median, 43.5 years), and of the six premenopausal patients, three had symptoms of menopause requiring medication. The surgery types were as follows: laparoscopic surgery (n = 8), laparotomy (n = 1), and conversion from laparoscopy to laparotomy (n = 1). The operative times (median) were as follows: laparoscopy, 59-91 min (85 min), and laparotomy, 76-118 min (97 min). Postoperative histopathological testing revealed no cases of occult cancer or serous tubal intraepithelial carcinoma.

It is difficult to observe the upper abdomen in laparotomic RRSO, whereas laparoscopy allows for visualization of the entire abdominal cavity and a shorter operative time; therefore, laparoscopic surgery is considered a viable option. Post-RRSO patient management requires follow-up to monitor for the development of peritoneal cancer, and in premenopausal women in particular, treatment and follow-up for any symptoms of menopause are needed; therefore, individualized care is required.

Patients who actively engage in their medical decision-making processes can experience better health outcomes. This exploratory study aimed to identify predictors of preferred and actual roles in decision-making in healthy women with BRCA1/2 pathogenic variants (PVs).

Women with BRCA1/2 PVs without a history of breast and/or ovarian cancer were recruited in six centres across Germany. Those returning the baseline questionnaires (T1) were randomly assigned to the intervention or control group (IG, CG). The IG completed a decision-coaching (DC) programme, the CG received standard care. A second survey (T2) followed after 12 weeks. Ordinal regression analyses were performed. Sociodemographic and outcome-related baseline variables were used to identify predictors of (i) desired role at T1 in the total group and (ii) actual role at T2 in the CG and the IG. Role preferences were measured with the Control Preferences Scale.

389 women completed the baseline questionnaires, 191 were randomised to the CG and 198 to the IG. At T1, high decisional conflict (OR 1.016, 95% CI 1.001-1.023, p = 0.038) and a negative self-concept (OR 1.030, 95% CI 1.008-1.054, p = 0.009) were significant predictors for preferring a more passive role. At T2, high baseline decisional conflict significantly predicted taking a more passive role in the CG, whereas in the IG, baseline decisional conflict showed no influence. Furthermore, in the IG, younger age (OR 1.049, 95% CI 1.001-1.098, p = 0.044) and a non-academic education (OR 0.46, 95% CI 0.213-0.775, p = 0.006) were identified as significant predictors for taking a more active role.

High initial decisional conflict was identified as an important predictor for preferring and taking a passive role in decision-making among women with BRCA1/2 PVs. Participating in the DC programme can counteract passivating effects of an initially high decisional conflict and particularly support younger PV carriers and those with lower educational status to take an active role. With this profile, the DC programme expands the existing counselling and care concept to include a measure that can also specifically cover the support needs of younger women and those with a lower education level.

DRKS-ID: DRKS00015527. Registered 30/10/2019.

For individuals at high risk of developing breast cancer, interventions to mitigate this risk include surgical removal of their breasts and ovaries or five years treatment with the anti-estrogen tamoxifen or aromatase inhibitors. We hypothesized that a silicone based anti-estrogen-eluting implant placed within the breast would provide the risk reduction benefit of hormonal therapy, but without the adverse effects that limit compliance. To this end, we demonstrate that when placed adjacent to mammary tissue in the 7,12-dimethylbenz[a]anthracene-induced rat breast cancer model a fulvestrant-eluting implant delays breast cancer with minimal systemic exposure. Using adult female sheep, surgical placement of fulvestrant-eluting implants was safe and did not elicit significant breast tissue pathology when placed at the base of the udder for directed elution into the mammary tissue. At 30 days of elution, fulvestrant was found to penetrate mammary tissue forming a concentration gradient beyond 15 mm from the implant. Consistent with the small animal rat study, minimal systemic fulvestrant biodistribution was found. Together, these studies provide the proof of principle that a breast indwelling fulvestrant-eluting implant can reduce the risk of breast cancer and limit systemic exposure, while penetrating and distributing through breast tissue.

Despite the association of pathogenic variants (PVs) in cancer predisposition genes with significantly increased risk of breast cancer (BC), uptake of genetic testing (GT) remains low, especially among ethnic minorities. Our prior study identified that a patient decision aid, RealRisks, improved patient-reported outcomes (including worry and perceived risk) relative to standard educational materials. This study examined patients' GT experience and its influence on subsequent actions. We also sought to identify areas for improvement in RealRisks that would expand its focus from improved GT decision-making to understanding results.

Women enrolled in the parent randomized controlled trial were recruited and interviewed. Demographic data was collected from surveys in the parent study. Interviews were conducted, transcribed, and coded to identify recurring themes. Descriptive statistics were generated to compare the interviewed subgroup to the original study cohort of 187 women.

Of the 22 women interviewed, 11 (50%) had positive GT results, 2 (9.1%) with a BRCA1/2 PV, and 9 (40.9%) with variants of uncertain significance (VUS). Median age was 40.5 years and 15 (71.4%) identified as non-Hispanic. Twenty (90.9%) reported a family history of BC, and 2 (9.1%) reported a family history of BRCA1/2 PV. The emerging themes included a preference for structured communication of GT results and the need for more actionable knowledge to mitigate BC risk, especially among patients with VUS or negative results. Few patients reported lifestyle changes following the return of their results, although they did understand that their behaviors can impact their BC risk.

Patients preferred a structured explanation of their GT results to facilitate a more personal testing experience. While most did not change lifestyle behaviors in response to their GT results, there was a consistent call for further guidance following the initial discussion of GT results. Empowering patients, especially those with negative or VUS results, with the context to internalize the implications of their results and form accurate risk perception represents a powerful opportunity to optimize subsequent risk management strategies. Informed by this study, future work will expand RealRisks to include the return of results and decision support to navigate concrete next steps.

Breast cancer (BC) screening enables early detection and timely treatment of cancer. Improving the effectiveness of BC screening can be accomplished by personalizing screening schedules according to each woman's specific risk level. However, when informing women about their risk classification, especially those at high risk, it is important to give clear recommendations on how to lower their risk. BC risk reduction comprises lifestyle modifications, preventive surgery, and chemoprevention, with the latter two being particularly applicable to high-risk individuals. Public health guidance on risk-reducing interventions is heterogeneous and context-dependent. We conducted a scoping review on BC surgical interventions and chemoprevention in East and Southeast Asia in publications between 2010 and 2024. We searched two databases and identified 23 publications relevant for inclusion. The highest number of publications came from South Korea (n = 9). More publications discussed surgical interventions compared to pharmacological interventions. The studies were largely observational and utilized data from medical records. Most studies defined high-risk individuals as BRCA carriers, many of whom previously had cancer. The field would benefit from randomized studies of BC prevention strategies focusing on Asian populations. Future research could explore women's sentiments towards chemoprevention compared to prophylactic surgery and could extend the definition of high-risk individuals beyond BRCA carriers.

We updated the Korean Society of Gynecologic Oncology (KSGO) practice guideline for the management of ovarian cancer as version 5.1. The ovarian cancer guideline team of the KSGO published announced the fifth version (version 5.0) of its clinical practice guidelines for the management of ovarian cancer in December 2023. In version 5.0, the selection of the key questions and the systematic reviews were based on the data available up to December 2022. Therefore, we updated the guidelines version 5.0 with newly accumulated clinical data and added 5 new key questions reflecting the latest insights in the field of ovarian cancer between 2023 and 2024. For each question, recommendation was provided together with corresponding level of evidence and grade of recommendation, all established through expert consensus.

ClinicalTrials.gov , NCT04251052.

Background: The effectiveness and cost-effectiveness of genetic testing for hereditary breast and ovarian cancer largely rely on the identification and clinical management of individuals with a pathogenic variant prior to developing cancer. Simulation modelling is commonly utilised to evaluate genetic testing strategies due to its ability to synthesise collections of data and extrapolate over long time periods and large populations. Existing genetic testing simulation models use simplifying assumptions for predictive genetic testing and risk management uptake, which could impact the reliability of their estimates. Our objective was to develop a microsimulation model that accurately reflects current genetic testing and subsequent care in Australia, directly incorporating the dynamic nature of predictive genetic testing within families and adherence to cancer risk management recommendations. Methods: The populatioN gEnEtic testing MOdel (NEEMO) is a population-level microsimulation that incorporates a detailed simulation of individuals linked within five-generation family units. The genetic component includes heritable high- and moderate-risk monogenic gene variants, as well as polygenic risk. Interventions include clinical genetic services, breast screening, and risk-reducing surgery. Model validation is described, and then to illustrate a practical application, NEEMO was used to compare clinical outcomes for four genetic testing scenarios in patients newly diagnosed with breast cancer (BC) and their relatives: (1) no genetic testing, (2) current practice, (3) optimised referral for genetic testing, and (4) genetic testing for all BC. Results: NEEMO accurately estimated genetic testing utilisation according to current practice and associated cancer incidence, pathology, and survival. Predictive testing uptake in first- and second-degree relatives was consistent with known prospective genetic testing data. Optimised genetic referral and expanded testing prevented up to 9.3% of BC and 4.1% of ovarian cancers in relatives of patients with BC. Expanding genetic testing eligibility to all BC patients did not lead to improvement in life-years saved in at-risk relatives compared to optimised referral of patients eligible for testing under current criteria. Conclusions: NEEMO is an adaptable and validated microsimulation model for evaluating genetic testing strategies. It captures the real-world uptake of clinical and predictive genetic testing and recommended cancer risk management, which are important considerations when considering real-world clinical and cost-effectiveness.

The Genetic Risk Assessment for Cancer Education and Empowerment Project demonstrated that tailored counseling and navigation (TCN) substantially increased the rate of genetic evaluation (GE) in women with high-risk breast or ovarian cancer (odds ratio, 8.9 [95% CI, 3.4 to 23.5] for TCN v usual care [UC]). This study sought to estimate the cost and cost-effectiveness of TCN in a clinic setting from a societal perspective.

We identified the components of the intervention and downstream outcomes which would result in resource use. We assessed time spent by staff, cost of mailings, cost of patient time, and cost of testing and counseling in 6 months. Incremental cost-effectiveness ratios were calculated for outcomes of interest. We assessed the sensitivity of our results to assumptions via one-way sensitivity analyses. In addition, we assessed how results would change if a higher volume of patients was given TCN, with a health coach working full-time.

TCN costs $68,924 in US dollars (USD) to deliver per 212 patients, or $325 USD per patient. The intervention cost was $2,154 USD per record-verified GE. Much of this was attributed to training costs for health coaches ($50,223 USD). When including testing and counseling, the incremental cost effectiveness ratio (ICER) of TCN versus UC was $3,250 USD per additional GE. This was most sensitive to TCN effectiveness (ie, GE rate in TCN patients) and cost of testing. Cost-effectiveness would be more favorable with higher coaching volume (ICER of $1,730 USD/GE).

Implementing TCN in a clinic setting would come with notable costs, and current reimbursement policies for telemedicine may not be sufficient. Cost-effectiveness of TCN can be improved if subsequent interventions are more efficacious or are delivered to greater patient volumes.

Hereditary cancer syndromes (HCS) are responsible for up to 10% of all cancers. At present, the majority of cancer susceptibility testing is initiated after a cancer diagnosis. There exists a significant opportunity for primary care providers including general obstetrician-gynecologists to engage in hereditary cancer risk assessment through adequate family history evaluation, initiation of genetic testing, and following the recommendations of national organizations. Identifying hereditary cancer genes may prompt primary prevention efforts such as enhanced screening, prevention, or personalized care strategies. We will review the literature regarding the approach and assessment of the most common gynecologic HCS.

Risk-reducing salpingo-oophorectomy (RRSO) is recommended by international guidelines in women with BRCA1/2 germline pathogenic variants (PV) to prevent ovarian cancer. Despite the solid recommendation, women frequently refuse surgery and uptake rates reported in the literature are diverse. This study analyses the uptake rate of RRSO in BRCA 1/2 PV-carriers referred to a specialised referral centre for first counselling and investigate personal factors linked to the decision.

This is a single-centre prospective study of BRCA1/2 PV-carriers referred for the first counselling to IRCCS Fondazione San Gerardo de' Tintori (Monza, Italy) between January 2010 and May 2023. Depending on individual characteristics, women were either proposed RRSO or surveillance, consisting of transvaginal ultrasound and CA125 measurement twice per year according to Regional guidelines. Women within the centre have access to a clinical psychologist, a nutritional consult and treatment of menopausal atrophy with diode vaginal laser. The primary endpoint of the study was the uptake rate of RRSO. The secondary objective was to evaluate the main reasons for refusing surgery.

Among the 287 women included, surgery was proposed to 205 women either at first counselling or during surveillance and was accepted by 197, with an uptake rate of 96.1%. 17.25% of women met the psychologist before or after surgery. The main reasons for refusing RRSO were fear of iatrogenic menopause and childbearing desire.

This study shows a high uptake rate of RRSO in BRCA PV-carriers. We believe that the presence of a dedicated outpatient clinic with a multidisciplinary team contributes decisively to our results. Gynaecologic surveillance, as though not beneficial in terms of oncological prevention, may play a significant role in encouraging women with BRCA PV to opt for risk-reducing surgery.

Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at high familial risk of ovarian cancer leads to immediate menopause. Although early natural menopause is associated with increased cardiovascular disease risk, evidence on long-term cardiovascular disease risk after early surgical menopause is scarce.

We sought to determine the long-term influence of the timing of RRSO on the development of coronary artery calcium (CAC), an established marker for cardiovascular disease risk.

We conducted a cross-sectional study (N = 733) nested in a nationwide cohort of women at high familial risk of ovarian cancer. In women aged 60-70 years (n = 328), we compared CAC scores between women with a premenopausal RRSO (age ≤45 years) and women with a postmenopausal RRSO (age ≥54 years), using multivariable Poisson analyses. Within the premenopausal RRSO group (n = 498), we also examined the effect of age at RRSO. In addition, we compared the premenopausal RRSO group with an external reference cohort (n = 5,226).

Multivariable analyses showed that the prevalence rates of any CAC (CAC >0), at least moderate CAC (CAC >100), and severe CAC (CAC >400) were comparable between the premenopausal and postmenopausal RRSO groups (relative risk [RR]: 0.93; 95% CI: 0.75-1.15 for any CAC; RR: 0.71; 95% CI: 0.43-1.17 for at least moderate CAC; RR: 0.81; 95% CI: 0.30-2.13 for severe CAC). There was no difference in CAC between the premenopausal RRSO group and a similar aged reference cohort. Timing of premenopausal RRSO (early premenopausal RRSO [<41 years] vs late premenopausal RRSO [41-45 years]) did not affect the outcomes.

Our results do not show a long-term adverse effect of surgical menopause on the development of CAC.

Recognizing individuals with Genetic tumor syndromes (GTS) in the primary central nervous system (CNS) tumors is crucial for optimizing proper genetic counseling and improving therapeutics and clinical care. We retrospectively analyzed the GTS in a Chinese CNS tumor cohort and examined the molecular characteristics and their clinical significance for diagnostic and therapeutic purposes. Our study identified 34 categories of GTS in 258 patients with CNS tumors. The gene with the highest germline pathogenic or likely pathogenic mutation frequency was TP53, followed by MSH2, NF1, and BRCA2. The top five GTS in CNS tumors showed high genetic heterogeneity GTS analysis reclassifies CNS tumors as "NEC." 53.88% of patients diagnosed with GTS harbor potential precision oncology therapy target mutations. The results of our study deepen our understanding of CNS tumors, provide a reference direction for the future design of clinical trials, and further expect to improve disease entire process management in CNS tumors.

Zona pellucida 3 (ZP3) expression is classically found in the ZP-layer of the oocytes, lately shown in ovarian and prostate cancer. A successful ZP3 ovarian cancer immunotherapy in transgenic mice suggested its use as an attractive therapeutic target. The biological role of ZP3 in cancer growth and progression is still unknown. We found that ~88% of the analyzed adenocarcinoma, squamous and small cell lung carcinomas to express ZP3. Knockout of ZP3 in a ZP3-expressing lung adenocarcinoma cell line, significantly decreased cell viability, proliferation, and migration rates in vitro. Zona pellucida 3 knock out (ZP3-KO) cell tumors inoculated in vivo in immunodeficient non-obese diabetic, severe combined immunodeficient mice showed significant inhibition of tumor growth and mitigation of the malignant phenotype. RNA sequencing revealed the deregulation of cell migration/adhesion signaling pathways in ZP3-KO cells. This novel functional relevance of ZP3 in lung cancer emphasized the suitability of ZP3 as a target in cancer immunotherapy and as a potential cancer biomarker.

Efficient and scalable solutions are needed to identify patients who qualify for germline cancer genetic testing. We evaluated the clinical validity of a brief, patient-administered hereditary cancer risk assessment digital tool programmed to assess if patients meet criteria for germline genetic testing, based on personal and family history, and in line with national guidelines.

We applied the tool to cases seen in a nationwide telehealth genetic counseling practice. Validity of the tool was evaluated by comparing the tool's assessment to that of the genetic counselor who saw the patient. Patients' histories were extracted from genetic counselor-collected pedigrees and input into the tool by the research team to model how a patient would complete the tool. We also validated the tool's assessment of which specific aspects of the personal and family history met criteria for genetic testing. Descriptive statistics were used.

Of the 152 cases (80% female, mean age 52.3), 56% had a personal history of cancer and 66% met genetic testing criteria. The tool and genetic counselor agreed in 96% of cases. Most disagreements (4/6; 67%) occurred because the genetic counselor's assessment relied on details the tool was not programmed to collect since patients typically don't have access to the relevant information (pathology details, risk models). We also found complete agreement between the tool and research team on which specific aspects of the patient's history met criteria for genetic testing.

We observed a high level of agreement with genetic counselor assessments, affirming the tool's clinical validity in identifying individuals for hereditary cancer predisposition testing and its potential for increasing access to hereditary cancer risk assessment.

To determine whether the psychostimulant lisdexamfetamine improves subjective and objective measures of cognitive functioning among women genetically at-risk for cancer who have undergone risk-reducing salpingo-oophorectomy and report new-onset executive functioning difficulties.

69 participants were assigned to a randomized controlled crossover trial with 6-week trials of active medication (lisdexamfetamine) and placebo, separated by a minimum 2-week washout in an intent-to-treat framework (clinical trial registration number: NCT03187353). At trial baseline, midpoint, and endpoint, participants completed a self-report measure of executive functioning (Brown Attention Deficit Disorder Scale). At study baseline and trial endpoint, participants completed sustained attention, attention/working memory, and verbal learning/memory cognitive tasks. Side effects were assessed at 2, 3, 4, and 6 weeks for each trial.

From trial baseline to trial endpoint, lisdexamfetamine - relative to placebo - significantly improved total scores on the self-report Brown Attention Deficit Disorder Scale (and scores on four of five subdomains) as well as attention and working memory performance. Significantly more participants endorsed side effects across the lisdexamfetamine trial versus placebo; however, trial completion rates were similar, indicating that lisdexamfetamine was nonetheless well-tolerated.

Lisdexamfetamine improved both subjective and objective measures of attention and working memory and could offer women experiencing cognitive difficulties post-risk-reducing salpingo-oophorectomy an alternative therapeutic option.

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.

The clinical utility of germline BRCA1 and BRCA2 testing is well established in patients with family history suggestive for hereditary breast and ovarian cancer syndrome. Recently, germline PALB2 pathogenic variants were also associated with an increased risk of breast and other cancers and, in the Italian population, it has been described in few studies without a systematic germline analysis of BRCA1, BRCA2 and PALB2.

In this study, we described ASST Sette Laghi cancer genetic counselling services' experience in the analysis of 402 patients with suspected breast and ovarian cancer syndrome, by using BRCA1, BRCA2 and PALB2 germline genetic test.

The frequency of PALB2 pathogenic variants was 1.2% compared to 3.5% and 3.2% for BRCA1 and BRCA2, respectively, whereas class 3 variants were detected in 0.3% and 0.5% of the BRCA1 and BRCA2 investigated patients, respectively. PALB2 pathogenic variants were identified in patients with a strong family history for breast cancer. Moreover, PALB2 variants were significantly associated with a younger age of breast cancer onset (mean age, 40.25 years) compared to wild-type patients (mean age 51.2 years, p-value = 0.0331). Similar to BRCA-associated breast cancer, the majority of PALB2 breast cancers were identified at an advanced clinical stage. Pedigree analysis revealed a family history of breast and ovarian cancer syndrome in all PALB2 pathogenic variants carriers (early breast cancer onset, bilateral breast cancer and ovarian cancer).

In conclusion, the germline analysis of BRCA1, BRCA2 and PALB2 should be included in breast cancer clinical practice as a not negligible number of PALB2 carriers could be identified and referred to specific surveillance protocols.

Female BRCA1/2 pathogenic variant (PV) carriers face substantial risks for breast and ovarian cancer. Evidence-based decision aids (DAs) can facilitate these women in their decision-making process on an individually suitable preventive strategy. However, there is a gap in previous literature exploring whether DA effectiveness varies according to women's age. This is an exploratory subanalysis with a descriptive approach from a randomised controlled study assessing the effectiveness of a German decision aid (DA) for women with BRCA1/2 PVs compared to no DA use. From the original sample, women aged 18-40 years and >40 years and the intervention and control groups (IG, CG) within each of the age groups were compared regarding decisional conflict (using the Decisional Conflict Scale DCS) and knowledge at baseline and after DA use three and six months post study inclusion. The subanalysis involved 236 women aged 18-40 and 181 women aged >40 years. At baseline, both age groups differed significantly in all socio-demographic variables, except BRCA1/2 PV distributions. The younger age group displayed higher scores in the DCS subscale informed (p = .002) and higher knowledge (p = .010). Among the 18-40-year-olds, DA use (versus no DA) led to improvements in the DCS subscale informed at three (p = .025) and six months (p = .000). In the >40-year-olds, DA use (versus no DA) led to improvements in the DCS subscales informed (p = .028), values clarity (p = .028) and support (p = .030) and increased knowledge at three months (p = .048). These results indicate that both age groups benefited from DA use, but the older ones did so to a greater extent. This suggests that it might be useful to tailor DAs more closely to age- or life stage-related needs to enable more personalised care and support for women with BRCA1/2 PVs.

Breast cancer is the most common cancer among women worldwide, and its incidence rate is still increasing, especially among younger women. Nationally, it constitutes one-fifth of all cancer cases and almost 40% of all female cancers. With a median age of 51 years, breast cancer is diagnosed at least a decade earlier, and at more advanced stages compared to Western societies. Hereditary cancers account for 10% or more of all cancer burden worldwide. With expanded indications, increased number of genes tested, and significant decline in cost of testing, such proportion will probably increase. Individuals with pathogenic variants of BRCA1 and BRCA2 are at higher risk of breast, ovarian, pancreatic and many other cancers. Over the past two decades, several highly penetrant cancer-susceptibility genes were identified across almost all tumor sites, thus increasing the need for comprehensive cancer genetic programs that address the testing process, counselling patients and at-risk family members, and then deal with all testing results and its consequences. In addition to its important role in preventing more cancers in index patients themselves and among their close relatives, identification of pathogenic or likely pathogenic variants, mostly in BRCA1 or BRCA2, may inform therapeutic decisions in common cancers including breast, ovarian, prostate and pancreatic cancers. In this manuscript, we describe the experience of a comprehensive cancer center, in a resource-limited country in establishing a comprehensive clinical cancer genetics program that can serve as an example for others who share similar demographic and financial restrains.

To study BRCA1/2 gene variants in La Rioja in the northcentral area of Spain.

We performed a molecular analysis of BRCA1 and BRCA2 in 642 individuals from 427 different families from June 2008 to December 2019.

We identified 71 families with pathogenic variants in these genes, 32 families with BRCA1 variants and 39 families with BRCA2 variants. The pathogenic variants c.959delG in BRCA1 and c.1363_1369delTCAGAGA, c.1397dupA, c.4234_4236delACTinsC and c.8387delC in BRCA2 have not been previously described. The c.81-2 A > T variant in BRCA1, detected in two unrelated families, has not been reported previously in the Spanish population. Two large genomic deletions were found in the BRCA1 gene in exons (Ex) 23-24 and Ex1A-1B-2, and one deletion was found in the BRCA2 gene in Ex2. The pathogenic variant c.5123 C > A in BRCA1 was detected in 8 unrelated families and was the most frequent pathogenic variant in our population. The c.6024dupG mutation in BRCA2 was detected in 6 unrelated families; the c.2808_2011delACAA mutation in BRCA2 was found in 5 different families; the c.211 A > G mutation in BRCA1 was found in three different families; and the c.68_69delAG, c81-2 A > T, c.4038_4039delAA, and c.5266dupC variants in BRCA1 and the c.2457delA, c.2701delC, c.5116_5119delAATA, c.6275delTT, c.7558 C > T and c.7617 + 1G > A variants in BRCA2 were found in two different families.

The spectrum of pathogenic variants in the BRCA1/2 genes in La Rioja is similar to that in other Spanish regions, with some unique characteristics. The pathogenic c.6024dupG variant in the BRCA2 gene was detected in a large number of families and could have a founding effect in the Ebro riverside areas in the regions of La Rioja and Navarra.

Not applicable.

Deep learning models for predicting variant pathogenicity have not been thoroughly evaluated on real-world clinical phenotypes. Here, we apply state-of-the-art pathogenicity prediction models to hereditary breast cancer gene variants in UK Biobank participants. Model predictions for missense variants in BRCA1, BRCA2 and PALB2, but not ATM and CHEK2, were associated with breast cancer risk. However, deep learning models had limited clinical utility when specifically applied to variants of uncertain significance.

The availability and affordability of germline genetic testing (GGT) has resulted in a broader utilization in daily clinical practice. However, adherence to testing guidelines is low, especially among older patients, where testing is often not offered.

In this study, consecutive, newly diagnosed patients with breast cancer (BC) aged ≥ 65 years and eligible for GGT, as per the National Comprehensive Cancer Network (NCCN) guidelines (version 1, 2021), were invited to participate, from March 2021 to December 2022. Patients were offered a restricted (two- or 20-gene panel), or an expanded 84-gene panel.

During the study period, 204 patients were enrolled. The mean (standard deviation (SD)) age at BC diagnosis was 70.5 (5.13) years, ranging 65 - 81 years. All patients were Arab and the majority were Jordanian. The majority (n = 188, 92.2%) had early-stage (stages I and II) disease. One hundred three (50.5%) patients were tested with a restricted two-gene (n = 13) or 20-gene (n = 90) panel, while the remaining 101 (49.5%) patients had an expanded 84-gene panel. Family history of close blood relative(s) with BC was the most common indication for testing (n = 110, 53.9%). Among the entire study cohort, 22 (10.8%) had pathogenic/likely pathogenic germline variants (PGVs) and another 97 (47.5%) had ≥ 1 variants of uncertain significance (VUS). PGV rates were significantly higher with the expanded panel (14.9%) compared to restricted testing (6.8%) (P = 0.032). Similarly, VUS rates were significantly higher with the expanded panel (64.4%) compared to the restricted panel (31.1%) (P < 0.001). The most prevalent genes with PGVs were BRCA1/2 (31.3% of all PGV-positive patients), CHEK2 (23.1%) and ATM (19.2%).

GGT should not be overlooked in older BC patients, as this study demonstrates that > 10% of patients have PGVs, largely in potentially actionable genes.