Cancer Risk Reduction Strategies Research Articles

Expanding access to genetic testing for pancreatic cancer.

Among individuals with pancreatic ductal adenocarcinoma (PDAC) 5-10% have a pathogenic germline variant (PGV) in a PDAC susceptibility gene. Guidelines recommend genetic testing among all individuals with PDAC. Additionally, at-risk relatives of PDAC patients benefit from their own genetic education, risk assessment, and testing. Multigene panel testing (MGPT) can identify individuals with inherited cancer risk who can benefit from early cancer surveillance and risk reduction strategies. This manuscript discusses various healthcare delivery models for MGPT including traditional in-person genetic counseling, novel integrated in-person infrastructures, telemedicine genetics care via telephone- or video-visits and direct-to-consumer testing. Barriers and facilitators to care on the individual, provider, and system level are also outlined including specific considerations for historically marginalized communities.

Making Informed Choices On Incorporating Chemoprevention into carE (MiCHOICE, SWOG 1904): Design and methods of a cluster randomized controlled trial

IntroductionWomen with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. Methods/designWe are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. Results/discussionWith this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. clinical settings. Trial RegistrationNCT04496739

Investigating the role of Vitamins in Prostate cancer risk among African Americans

Background & Aims: Previous studies have shown certain vitamins and minerals are associated with a reduced risk of prostate cancer. In this study, we assess whether vitamins will have an effect on prostate cancer risk among African Americans. Methods: A case-control study was conducted in Washington, District of Columbia and Nashville, Tennessee. There were 264 participants involved in the study. The participants were divided into 3 groups: prostate cancer (n=56), elevated PSA (n=377) and control (n=163). Dietary intake was measured by using a validated food frequency questionnaire. Food items rich in vitamin D, vitamin E, selenium, and lycopene were identified. Chi square tests were performed to evaluate the association between vitamins and prostate cancer risk. Results: There is a statistically significant association between the consumption of certain food items such as beef, pork, eggs and decreased prostate cancer risk (p<.05). There is also a statistically significant association between the consumption of salmon, cod liver oil, peanuts, mushrooms, orange juice and prostate cancer risk increase (p<.05). When aggregated, there was no significant correlation between the consumption of vitamin D, vitamin E, lycopene, selenium and decreased prostate cancer risk. Conclusions: Results of our case-control study suggest dietary restriction of certain meats as prostate cancer risk reduction strategy cannot be suggested. Increasing annual intake of food high in vitamin D, vitamin E, selenium, and lycopene cannot be suggested as a way to decrease prostate cancer risk. Diet modification interventions should focus on dietary moderations. Center of Excellence COE/Offce of Dean, Meharry Medical College School of Medicine, Grant Number: D34HP16299. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cancer Risk Reduction Strategies for Transgender, Non-Binary, and Gender-Diverse People With Hereditary Cancer Syndromes

Cancer Risk Reduction Strategies for Transgender, Non-Binary, and Gender-Diverse People With Hereditary Cancer Syndromes

Abstract 7332: Healthcare professionals' perceptions and educational needs in genetic counseling for cancer risk management: An integrated mixed-methods systematic review

Abstract Background: The role of healthcare professionals (HCPs) is crucial in the genetic counseling process for managing hereditary cancer risks. However, HCPs face challenges due to a lack of specialized training and confidence, particularly in communicating genetic risks to patients. Hence, it becomes paramount to identify the essential skills and expertise required by HCPs for genetic counseling. Additionally, gaining insight into their perspectives regarding the content of genetic counseling that should be provided to patients is of utmost importance. Methods: An integrated mixed-methods systematic review and content analysis were performed across five databases on 23 May 2023, employing predetermined search strategies. The quality of selected studies was assessed using the Mixed Method Appraisal Tool (MMAT), and data analysis was conducted using a deductive content analysis approach with MAXQDA 2020. Results: The review encompassed 14 studies from seven countries, revealing moderate risk of bias. It was perceived by HCPs that hereditary cancer families require information in seven specific categories including, cancer risk-reducing strategies; personalized cancer risk; family implications of hereditary cancer; psychological issues; genetic testing; the role of pathogenic genes in hereditary cancers; and social issues related to genetic testing. The study also highlighted the educational needs of HCPs, pinpointing areas such as method for supporting decision-making; clinical management in hereditary cancer families; resources for supporting hereditary cancer families; guidance to support familial communication; genetic testing; the role of each profession; and methods for supporting psychological aspects. Conclusion: The findings underscore the need for specialized training programs to equip HCPs with the necessary skills and knowledge for effective genetic counseling. Additionally, understanding HCPs’ perspectives on the content of genetic counseling is vital for tailoring educational resources and enhancing the genetic counseling process in managing cancer risks. Grants: This research was supported by a grant of the Korean Cancer Survivors Healthcare R&D Project through the National Cancer Center, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: NCC 23F1940-1) Citation Format: So-Youn Jung, Sun-Young Park, Eun-Gyeong Lee, Heejung Chae, Mi-Jin An, Yeon-Joo Kim, Yoon-Jung Choi, Kum Hei Ryu, Sun-Young Kong. Healthcare professionals' perceptions and educational needs in genetic counseling for cancer risk management: An integrated mixed-methods systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7332.

Germline testing of BRCA1, BRCA2, PALB2 and CHEK2 c.1100delC in 1514 triple negative familial and isolated breast cancers from a single centre, with extended testing of ATM, RAD51C and RAD51D in over 400

BackgroundThe identification of germline pathogenic gene variants (PGVs) in triple negative breast cancer (TNBC) is important to inform further primary cancer risk reduction and TNBC treatment strategies. We therefore investigated...

Early-Onset Ovarian Cancer <30 Years: What Do We Know about Its Genetic Predisposition?

Ovarian cancer (OC) is one of the leading causes of cancer-related deaths in women. Most patients are diagnosed with advanced epithelial OC in their late 60s, and early-onset adult OC diagnosed ≤30 years is rare, accounting for less than 5% of all OC cases. The most significant risk factor for OC development are germline pathogenic/likely pathogenic variants (GPVs) in OC predisposition genes (including BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, Lynch syndrome genes, or BRIP1), which contribute to the development of over 20% of all OC cases. GPVs in BRCA1/BRCA2 are the most prevalent. The presence of a GPV directs tailored cancer risk-reducing strategies for OC patients and their relatives. Identification of OC patients with GPVs can also have therapeutic consequences. Despite the general assumption that early cancer onset indicates higher involvement of hereditary cancer predisposition, the presence of GPVs in early-onset OC is rare (<10% of patients), and their heritability is uncertain. This review summarizes the current knowledge on the genetic predisposition to early-onset OC, with a special focus on epithelial OC, and suggests other alternative genetic factors (digenic, oligogenic, polygenic heritability, genetic mosaicism, imprinting, etc.) that may influence the development of early-onset OC in adult women lacking GPVs in known OC predisposition genes.

BRCA1/2 mutation carriers & risk reducing mastectomy: Who undergoes surgery and potential benefits

BackgroundRisk-reducing mastectomy (RRM) is the most effective breast cancer risk-reduction strategy in BRCA1/2 mutation carriers. We examined factors associated with RRM and its relationship with overall survival (OS). MethodsPatients aged 18-80y at diagnosis of their BRCA1/2 mutation were selected from our institutional database and stratified by RRM receipt. Differences were tested; unadjusted OS was estimated. ResultsOf the 306 patients, median age was 43y; median follow-up was 41.6mo. Patients undergoing RRM were more often married with a history of pregnancy (both p ​≤ ​0.05). Of female patients, 23.1% underwent RRM. Two patients had malignancy detected at RRM, and one developed breast cancer after RRM. Higher unadjusted OS was observed with RRM (p ​= ​0.02). ConclusionsOur analyses suggest that family-structure may play a role in a patient's decision to undergo RRM. We also demonstrated RRM is likely associated with improved survival, potentially underscoring the importance of this option for BRCA1/2 mutation carriers.

Lynch syndrome cancer vaccines: A roadmap for the development of precision immunoprevention strategies.

Hereditary cancer syndromes (HCS) account for 5~10% of all cancer diagnosis. Lynch syndrome (LS) is one of the most common HCS, caused by germline mutations in the DNA mismatch repair (MMR) genes. Even with prospective cancer surveillance, LS is associated with up to 50% lifetime risk of colorectal, endometrial, and other cancers. While significant progress has been made in the timely identification of germline pathogenic variant carriers and monitoring and early detection of precancerous lesions, cancer-risk reduction strategies are still centered around endoscopic or surgical removal of neoplastic lesions and susceptible organs. Safe and effective cancer prevention strategies are critically needed to improve the life quality and longevity of LS and other HCS carriers. The era of precision oncology driven by recent technological advances in tumor molecular profiling and a better understanding of genetic risk factors has transformed cancer prevention approaches for at-risk individuals, including LS carriers. MMR deficiency leads to the accumulation of insertion and deletion mutations in microsatellites (MS), which are particularly prone to DNA polymerase slippage during DNA replication. Mutations in coding MS give rise to frameshift peptides (FSP) that are recognized by the immune system as neoantigens. Due to clonal evolution, LS tumors share a set of recurrent and predictable FSP neoantigens in the same and in different LS patients. Cancer vaccines composed of commonly recurring FSP neoantigens selected through prediction algorithms have been clinically evaluated in LS carriers and proven safe and immunogenic. Preclinically analogous FSP vaccines have been shown to elicit FSP-directed immune responses and exert tumor-preventive efficacy in murine models of LS. While the immunopreventive efficacy of "off-the-shelf" vaccines consisting of commonly recurring FSP antigens is currently investigated in LS clinical trials, the feasibility and utility of personalized FSP vaccines with individual HLA-restricted epitopes are being explored for more precise targeting. Here, we discuss recent advances in precision cancer immunoprevention approaches, emerging enabling technologies, research gaps, and implementation barriers toward clinical translation of risk-tailored prevention strategies for LS carriers. We will also discuss the feasibility and practicality of next-generation cancer vaccines that are based on personalized immunogenic epitopes for precision cancer immunoprevention.

Effectiveness of Secondary Risk–Reducing Strategies in Patients With Unilateral Breast Cancer With Pathogenic Variants of BRCA1 and BRCA2 Subjected to Breast-Conserving Surgery: Evidence-Based Simulation Study

Approximately 62% of patients with breast cancer with a pathogenic variant (BRCA1 or BRCA2) undergo primary breast-conserving therapy. The study aims to develop a personalized risk management decision support tool for carriers of a pathogenic variant (BRCA1 or BRCA2) who underwent breast-conserving therapy for unilateral early-stage breast cancer. We developed a Bayesian network model of a hypothetical cohort of carriers of BRCA1 or BRCA2 diagnosed with stage I/II unilateral breast cancer and treated with breast-conserving treatment who underwent subsequent second primary cancer risk-reducing strategies. Using event dependencies structured according to expert knowledge and conditional probabilities obtained from published evidence, we predicted the 40-year overall survival rate of different risk-reducing strategies for 144 cohorts of women defined by the type of pathogenic variants (BRCA1 or BRCA2), age at primary breast cancer diagnosis, breast cancer subtype, stage of primary breast cancer, and presence or absence of adjuvant chemotherapy. Absence of adjuvant chemotherapy was the most powerful factor that was linked to a dramatic decline in survival. There was a negligible decline in the mortality in patients with triple-negative breast cancer, who received no chemotherapy and underwent any secondary risk-reducing strategy, compared with surveillance. The potential survival benefit from any risk-reducing strategy was more modest in patients with triple-negative breast cancer who received chemotherapy compared with patients with luminal breast cancer. However, most patients with triple-negative breast cancer in stage I benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy or just risk-reducing salpingo-oophorectomy. Most patients with luminal stage I/II unilateral breast cancer benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. The impact of risk-reducing salpingo-oophorectomy in patients with luminal breast cancer in stage I/II increased with age. Most older patients with the BRCA1 and BRCA2 pathogenic variants in exons 12-24/25 with luminal breast cancer may gain a similar survival benefit from other risk-reducing strategies or surveillance. Our study showed that it is mandatory to consider the complex interplay between the types of BRCA1 and BRCA2 pathogenic variants, age at primary breast cancer diagnosis, breast cancer subtype and stage, and received systemic treatment. As no prospective study results are available at the moment, our simulation model, which will integrate a decision support system in the near future, could facilitate the conversation between the health care provider and patient and help to weigh all the options for risk-reducing strategies leading to a more balanced decision.

Management of ovarian and breast cancer risk in non-BRCA HBOC pathogenic variant carriers in a large California health care system

PurposeTo describe breast and ovarian cancer risk reduction strategies in the clinical management of women who test positive for non-BRCA hereditary breast and ovarian cancer (HBOC) pathogenic variants compared to those who test positive for pathogenic BRCA variants or have negative germline panel testing. MethodsExamination of imaging and preventive surgeries in women undergoing HBOC genetic testing from 1/1/2015 to 12/31/2018, with follow up to 03/31/2020 in Kaiser Permanente Northern California. ResultsA total of 13,271 tests which included HBOC genes were identified. Rate of bilateral salpingo-oophorectomy after genetic testing were similar for BRCA and the non-BRCA moderate risk ovarian pathogenic variants (PVs) (47.4% vs 54%, p = 0.25). Rates were lower for low risk or unknownrisk non-BRCA PVs (12.8%, p < 0.001, 5.3% (p < 0.001). Rates of surveillance for ovarian cancer with ultrasound and CA 125 in the first year was 63.3% and 64.7% for BRCA PV, 37.5% and 27.1%, for non-BRCA moderate risk PVs and 13.7% and 4.6%, for low-risk PVs. Bilateral mastectomy rates were 19.7% for BRCA PV, 10.1% (p = 0.028) for non-BRCA breast high risk PVs, for moderate risk PVs 7.7% (p < 0.001) and for unknown risk 0.4% (p < 0.001). MRI surveillance rates in the first year similarly were 47.4% for non-BRCA BRCA PV, 43% for breast high risk PV, 39.4% for moderate risk and 4.9% for unknown risk PV. ConclusionSurgical and surveillance strategies are underutilized for HBOC PV, however there is concordance of uptake of preventive strategies with specific risk associated with non-BRCA PVs.

Effect of risk-reducing salpingo-oophorectomy on sex steroid hormone serum levels among postmenopausal women: an NRG Oncology/Gynecologic Oncology Group study

Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased long-term nonneoplastic sequelae, effects suggested to be mediated through reductions in systemic sex steroid hormone levels. Currently, it is unclear whether the postmenopausal ovary contributes to the systemic hormonal milieu or whether postmenopausal ovarian volume or other factors, such as body mass index and age, affect systemic hormone levels. We examined the impact of oophorectomy on sex steroid hormone levels in postmenopausal women. Furthermore, we explored how well ovarian volume measured by transvaginal ultrasound correlated with direct ovarian measures obtained during surgical pathology evaluation and investigated the association between hormone levels and ovarian volumes. Postmenopausal women who underwent risk-reducing salpingo-oophorectomy (180 cases) or ovarian cancer screening (38 controls) enrolled in an international, prospective study of risk-reducing salpingo-oophorectomy and risk of ovarian cancer algorithm-based screening among women at increased risk of ovarian cancer (Gynecologic Oncology Group-0199) were included in this analysis. Controls were frequency matched to the cases on age at menopause, age at study entry, and time interval between blood draws. Ovarian volume was calculated using measurements obtained from transvaginal ultrasound in both cases and controls and measurements recorded in surgical pathology reports from cases. Serum hormone levels of testosterone, androstenedione, androstenediol, dihydrotestosterone, androsterone, dehydroepiandrosterone, estrone, estradiol, and sex hormone-binding globulin were measured at baseline and follow-up. Spearman correlation coefficients were used to compare ovarian volumes as measured on transvaginal ultrasound and pathology examinations. Correlations between ovarian volumes by transvaginal ultrasound and measured hormone levels were examined using linear regression models. All models were adjusted for age. Paired t tests were performed to evaluate individual differences in hormone levels before and after risk-reducing salpingo-oophorectomy. Ovarian volumes measured by transvaginal ultrasound were only moderately correlated with those reported on pathology reports (Spearman rho [ρ]=0.42). The median time interval between risk-reducing salpingo-oophorectomy and follow-up for the cases was 13.3 months (range, 6.0-19.3), and the median time interval between baseline and follow-up for the controls was 12.7 months (range, 8.7-13.4). Sex steroid levels decreased with age but were not correlated with transvaginal ultrasound ovarian volume, body mass index, or time since menopause. Estradiol levels were significantly lower after risk-reducing salpingo-oophorectomy (percentage change,-61.9 post-risk-reducing salpingo-oophorectomy vs+15.2 in controls; P=.02), but no significant differences were seen for the other hormones. Ovarian volumes measured by transvaginal ultrasound were moderately correlated with volumes directly measured on pathology specimens and were not correlated with sex steroid hormone levels in postmenopausal women. Estradiol was the only hormone that declined significantly after risk-reducing salpingo-oophorectomy. Thus, it remains unclear whether the limited post-risk-reducing salpingo-oophorectomy changes in sex steroid hormones among postmenopausal women impact long-term adverse outcomes.

Cancer risk-reducing strategies: Focus on chemoprevention

Cancer risk-reducing strategies: Focus on chemoprevention

Systemic Barriers to Risk-Reducing Interventions for Hereditary Cancer Syndromes: Implications for Health Care Inequities.

Hereditary cancer syndromes result from germline genetic alterations predisposing individuals to higher lifetime cancer risk than the general population. Hereditary cancer syndromes account for 5%-10% of all malignancies and are characterized by early-onset, aggressive tumors affecting multiple tissue types.1 For example, patients with hereditary breast and ovarian cancer syndrome (HBOC) have high lifetime risk of breast (41%-90%) and ovarian (8%-62%) cancers and elevated risk for several other cancers.2 Similarly, patients with Lynch syndrome (LS) have high lifetime risk of colorectal (12%-52%) and endometrial (0%-57%) cancers, as well as other cancers.3 Reduced cost of genetic technologies4 and new guidance on collecting family history in primary care5 have enabled better detection of these syndromes, providing opportunities to reduce cancer risk. CONTEXT Key Objective Individuals with hereditary cancer syndromes are predisposed to higher lifetime cancer risk than the general population. Early diagnosis of these syndromes can lead to downstream care that greatly reduces cancer morbidity and mortality. In this narrative review, we explore the factors affecting uptake of and adherence to hereditary cancer risk reduction strategies and how these factors interact with systemic barriers to care in medically marginalized populations. Knowledge Generated We identified factors at the health system, clinician, and patient levels that interact to affect downstream hereditary cancer care and have implications for health equity. We found that several interventions designed to improve downstream care utilization did not address systemic barriers affecting marginalized populations and suggest strategies to address these barriers in future intervention design. Relevance Our review creates a template for the design of more equitable interventions to improve downstream hereditary cancer care.

Acceptability of an mHealth breast cancer risk-reduction intervention promoting risk assessment, education, and discussion of risk in the primary care setting.

Breast cancer risk assessment tools and risk reduction strategies have advanced significantly over the past few decades but are underutilized in practice, due in part to limited acceptability by patients and physicians. We implemented a tablet-based Breast Cancer Risk Education Intervention (BreastCARE) tailored towards increasing patients' knowledge about their individual risk of developing breast cancer, increasing patient-physician discussion of breast cancer risk reduction practices, and increasing participation in recommended screening. We surveyed patients and physicians who received the BreastCARE intervention and analyzed their satisfaction and acceptability of the intervention. We compared patient satisfaction measures by race/ethnicity and used multivariable logistic regression models to examine the effect of race/ethnicity on measures of patient satisfaction with the tablet-based risk assessment and with the breast cancer risk report. We also compared measures of physician satisfaction by resident vs. attending/NP status. Finally, we identified patients' and physicians' suggestions for implementation. Overall, both patients and physicians were highly satisfied with BreastCARE, with some variation by patient race/ethnicity and breast cancer risk status. The risk assessment tool and accompanying risk report helped transmit complex information in an efficient way. Patient self-administered risk assessment with a health education component at the point of care is acceptable for both patients and physicians, and represents a novel approach to facilitating health promotion. This risk assessment tool should be made routine in primary care accompanied by results that are easy for the patient to understand and actionable for the clinician.

Leveraging Clinical Decision Support and Integrated Medical-Dental Electronic Health Records to Implementing Precision in Oral Cancer Risk Assessment and Preventive Intervention.

Introduction: Precision medicine is focused on serving the unique needs of individuals. Oral and oropharyngeal cancer risk assessment identifies individual risk factors while providing support to reduce risk. The objective is to examine potential current and future strategies to broadly implement evidence-based oral and oropharyngeal cancer risk assessment and screening in dental practices throughout the United States. Methods: Feasible and effective oral cancer risk assessment and risk reduction strategies, ripe for implementation in dental practice, were identified in the published literature. Results: The Screening, Brief Intervention, Referral for Treatment (SBIRT) model is a feasible approach to assessing individual oral cancer risk and providing risk reducing interventions in the dental setting. HPV is a more recently identified risk factor that dentistry is well positioned to address. Evidence supporting the utilization of specific risk assessment tools and risk reduction strategies is summarized and future opportunities discussed. Discussion: Current knowledge of risk factors for oral and oropharyngeal cancers support the recommendation for dental providers to routinely assess all patients for risk factors, educate them about their personal level of cancer risk, and recommend actions to reduce relevant risk factors. Individuals ages 9–26 should be asked about their HPV vaccination status, educated about HPV and oropharyngeal cancer and receive a recommendation to get the HPV vaccination.

Breast Cancer Prevention: Time for Change.

Agency breast cancer prevention guidelines for other than hereditary cancers have not materially changed in 20 years; endocrine-targeted agents (then, tamoxifen; now, adding raloxifene and aromatase inhibitors) reduce good prognosis estrogen receptor (ER)-positive, progesterone receptor (PR)-positive cancers without reducing deaths from breast cancer. Across three tamoxifen placebo-controlled prevention trials (N = 23,360) begun almost 30 years ago, although there were 226 fewer breast cancer cases, there were nine more deaths from breast cancer in the tamoxifen groups. Following clinical advances, currently more than half of breast cancer cases are solved problems with extremely low risk of death. As endocrine-targeted agents commonly prevent these cancers, widespread implementation of current prevention strategies may not reduce deaths from breast cancer. Compared with other breast cancers, ER-positive, PR-negative cancers and triple-negative cancers have inferior survival (90.6% v 83.8% v 78.1%, respectively; P < .001). Against this background, in the Women's Health Initiative Dietary Modification randomized trial (N = 48,835), ER-positive, PR-negative cancers were statistically significantly reduced in the intervention group (hazard ratio, 0.77; 95% CI, 0.64 to 0.94) and deaths from breast cancer were reduced 21% (P = .02). In the Women's Health Initiative randomized, placebo-controlled trial evaluating conjugated equine estrogen (N = 10,739), ER-positive, PR-negative cancers were statistically significantly reduced in the intervention group (hazard ratio, 0.44; 95% CI, 0.27 to 0.74) and deaths from breast cancer were reduced 40% (P = .04). These findings suggest that reexamination of breast cancer risk reduction strategies and clinical practice is needed.

Abstract PS8-25: Genetic cancer risk assessment and its impact on the uptake of cancer risk reduction strategies: The experience of a Mexican center

Abstract Background: The implementation of genetic cancer risk assessment (GCRA) in resource-constrained settings is limited due to multiple factors, including insufficient access to preventive strategies. In our center, GCRA was formally established in 2014, and access to genetic testing is provided to underserved patients through a research collaboration with City of Hope's CCGCRN. The aim of this study is to determine the proportion of patients with germline mutations that underwent risk-reducing surgeries (RRS) and followed recommended breast cancer (BC) screening strategies. Methods: Patients that received GCRA in a center located in Monterrey, Mexico who met NCCN criteria for testing for BC predisposition genes were eligible. Information on mutation status, performance of RRS and BC screening strategies was prospectively collected. The patients were grouped by type of healthcare (i.e. private vs public), with differences explored using Fisher's exact or Mann Whitney U tests, as appropriate. Results: Between 2014 and 2019, a total of 437 probands and 139 of their relatives underwent GCRA. Of these, 23% and 37% were identified as mutation carriers, respectively: BRCA1/2 (72.5%), PALB2 (6.4%), CHEK2 (6.4%) and others (14.7%). The median time elapsed from disclosure of genetic test results to collection of data was 16 months. The median age was 41 years, with no statistical difference according to type of healthcare. Based on NCCN guidelines, 151 RRS were recommended according to mutational status and age, of which 52 (34%) were performed: 28 risk-reducing mastectomies (RRM) and 24 risk-reducing salpingo-oophorectomies (RRSO). A substantial proportion of these were funded by non-governmental organizations, while the rest were covered by public health insurance (as adjuvant treatment), private health insurance or the patient herself. Regarding BC screening, after excluding 78 patients because of active BC treatment, bilateral mastectomy or male sex, 92% of eligible patients followed NCCN recommendations. No differences in the performance of RRS or BC screening strategies were found according to type of healthcare delivery. Conclusion: In this cohort, an adequate adherence to recommended screening strategies was observed but only one-third of recommended RRS were performed. Notably, type of healthcare was not a determining factor for the adherence to NCCN's recommended prevention strategies, suggesting that economical barriers might not be the main limiting factor. Efforts to elucidate if sociocultural barriers limit adherence to RRS are being conducted in order to enhance standard of care at Mexican centers with GCRA programs. Characteristics according to healthcare coverage.Private insurancePublic insurancep valueMutational status- Probands: carriers/tested32/117 (27%)67/320 (21%)NS- Relatives: carriers/tested10/42 (24%)42/97 (43%)0.036RRS- RRM performed/recommended9/24 (38%)19/65 (29%)NS- RRSO performed/recommended6/18 (33%)18/44 (41%)NS- RRS covered by NGOs0 (0%)11/37 (30%)0.022Current BC screening modality- Mammogram (MMG) ± US9 (41%)33 (65%)0.033- MRI ± MMG ± US9 (41%)6 (12%)- None3 (14%)1 (2%)- Unknown1 (5%)11 (22%)Follow BC screening recommendations- Yes19 (90%)37 (93%)NS- No2 (10%)3 (8%) Citation Format: Dione Aguilar, Alejandro Aranda-Gutierrez, Ana S Ferrigno, Jeffrey N Weitzel, Kathleen N Blazer, Danielle Castillo, Josef Herzog, Rosa Mejia, Nancy L Sada-Villarreal, Servando Cardona, Mauricio Canavati-Marcos, Margarita Garza-Montemayor, Cynthia Villarreal-Garza. Genetic cancer risk assessment and its impact on the uptake of cancer risk reduction strategies: The experience of a Mexican center [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-25.

Cancer Risk Reduction Through Education of Adolescents: Development of a Tailored Cancer Risk-Reduction Educational Tool.

Growing evidence links adolescent exposures to cancer risk later in life, particularly for common cancers like breast. The adolescent time period is also important for cancer risk reduction as many individual lifestyle behaviors are initiated including smoking and alcohol use. We developed a cancer risk-reduction educational tool tailored for adolescents that focused on five modifiable cancer risk factors. To contextualize risk factors in adolescents' social and physical environments, the intervention also focused on structural barriers to individual- and community-level change, with an emphasis on environmental justice or the fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. The educational tool consisted of a 50-min module that included an introduction to cancer biology including genetic susceptibility and environmental interactions, cancer burden in the local community, and risk reduction strategies. The module also included an interactive activity in which adolescent students identify cancer risk factors and brainstorm strategies for risk reduction at both the individual and community level. We administered the module to 12 classes of over 280 high school and college students in New York City. Cancer risk reduction strategies identified by the students included family- or peer-level strategies such as team physical activity and community-level action including improving parks and taxing sugary foods. We developed a novel and interactive cancer risk-reduction education tool focused on multiple cancers that can be adopted by other communities and educational institutions.

A systematic review and meta-analysis of telephone vs in-person genetic counseling in BRCA1/BRCA2 genetic testing.

Pathogenic variants in the BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancer. Individuals with identified pathogenic variants in the BRCA1 or BRCA2 gene can benefit from cancer risk-reducing strategies. In the recent years, there has been an increase in the demand of genetic services. In light of the ongoing COVID19 pandemic, alternatives to face-to-face consultations have had to be considered and adopted, including telemedicine. Informed consent is necessary for genetic testing. Studies have suggested that increased levels of cancer-specific distress may impair the patient's ability to retain information, therefore, providing informed consent. This systematic review and meta-analysis aimed to answer if telephone genetic counseling for BRCA1 and BRCA2 genetic testing is non-inferior to in-person genetic counseling for the outcomes of cancer-specific distress and genetic knowledge. Databases of Medline, Embase, PsycINFO, CINAHL, SciELO, Web of Science, CENTRAL, ProQuest Dissertation & Theses Database, Clinicaltrials.gov, EU clinical trials register were accessed to identify any published or unpublished relevant literature. Random-effects models were used for the meta-analysis. Four studies were included in the qualitative synthesis of the results. Three studies were included in the quantitative synthesis of the results. Telephone genetic counseling was non-inferior compared to in-person genetic counseling for the outcomes of cancer-specific distress and genetic knowledge. Sensitivity analysis corroborated the main results. Telephone genetic counseling for BRCA1/BRCA2 genetic testing may be an alternative model of delivering genetic services in front of the increased demand/or when required by social context. However, the paucity of the evidence prevents from drawing strong conclusions regarding the generalizability of these results. Further research is needed to strengthen the conclusions.