In Japan, genetic testing, surveillance, and risk-reducing surgery for hereditary breast and ovarian cancer (HBOC) syndrome have been covered by the Japanese national insurance system since April 2020. On the other hand, the current situation is that medical care, including surveillance of undiagnosed (cancer-free) patients, is self-funded even for individuals with HBOC. We report a case in which breast cancer was diagnosed at an early stage during surveillance for cancer-free HBOC at the patient’s own expense, and risk-reducing surgery was performed at the same time as treatment for breast cancer.BRCA2 pathogenic variant carrier by genetic testing. The patient therefore presented to the genetic department of our hospital and underwent genetic testing (out-of-pocket). A pathogenic variant was found at the same site. During annual breast and ovarian surveillance at the patient’s own expense, a physician with sufficient expertise in contrast-enhanced breast magnetic resonance imaging (MRI) noticed a change in the contrast enhancement pattern on breast MRI and performed needle biopsy, revealing ductal carcinoma in situ. At the request of the patient, she underwent concurrent contralateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy in addition to breast cancer treatment.The patient was a 63-year-old woman. Her sister had a history of breast cancer in her 30s and was found to be a BRCA1/2 mutation carriers and expansion of insurance coverage for surgery are important future issues.We encountered a case in which cancer treatment and risk-reducing surgery were performed at the same time for a pathogenic variant carrier who was very anxious about developing cancer. Surveillance of cancer-free  BRCA1 or BRCA2 (gBRCA1/2-positive). Several studies have found that the cumulative risk of developing breast cancer by 70 years of age is 55–72% in women with BRCA1 mutations and 45–69% in women with BRCA2 mutations, whereas the cumulative risk of breast cancer in the general population is 12%. The cumulative risk of developing ovarian cancer has been reported as 39–44% for BRCA1 mutations and 11–17% for BRCA2 mutations, compared to a cumulative risk of ovarian cancer in the general population of 1–2% [BRCA1 pathogenic variant and 2.71% have some BRCA2 pathogenic variant [BRCA1/2 genetic testing and some risk-reducing surgeries, were paid for out-of-pocket by patients. A review of medical fees in Japan was implemented in April 2020. The BRACAnalysis test  was covered for breast cancer patients who met certain conditions and for all ovarian cancer patients [BRCA1/2-positive breast and ovarian cancer patients [BRCA1/2 pathogenic variant carriers not undergoing risk-reducing surgery [BRCA1/2 pathogenic variant carriers in collaboration with hospitals that have specialists with sufficient expertise in contrast-enhanced MRI of the breast and centers that can perform MRI-guided biopsies.Breast cancer is the most common cancer among Japanese women. Genetic factors are associated with the development of breast cancer in 5–10% of all breast cancer patients [However, these benefits are only available to those who have already developed breast or ovarian cancer, and the current situation is that surveillance and preventive care for HBOC remains an out-of-pocket expense for those who have not developed cancer . We repoBRCA2 pathogenic variant that had been identified in her sister (III-3). Her family tree  presented to our clinic for single-site analysis of a ree Fig.  showed t presentester III-. Her famster III-. Her famCurrently, the patient visits our hospital about once every 6 months for peritoneal cancer surveillance and postoperative wound examination. In the future, we plan to have the Department of Obstetrics and Gynecology perform peritoneal cancer surveillance, such as computed tomography, and to have the patient perform regular self-examination of the chest .BRCA1/2-positive variant carriers, RRSO has been confirmed to reduce the risk of developing cancer and prolongs overall survival [BRCA1/2-positive breast and ovarian cancer patients [BRCA1/2-positive breast and ovarian cancer patients not undergoing risk-reducing surgery [BRCA1/2 genetic testing was performed in approximately 160 cases, with the pathogenic variant found in 20 cases. More than 80% of tests have been performed in the period since insurance coverage was approved. We have also performed 8 RRSOs in our hospital. In all cases of RRSO performed, breast cancer was already present  stages III–IV [Generally, advanced ovarian cancer has a poor prognosis. In particular, HBOC-related ovarian cancer is often advanced at the time of diagnosis and shows poor prognosis , 16. Pres III–IV ), papills III–IV . At our BRCA2-positive, due to concerns about developing ovarian cancer. While the National Comprehensive Cancer Network (NCCN) guidelines recommend risk-reducing surgery for gBRCA1/2-positive variant carriers, they do not recommend ovarian surveillance. This is because no evidence suggests that such surveillance has any impact in reducing the risk of developing, or dying from, cancer. However, because the patient had not developed cancer, she would have had to pay out-of-pocket for any tests or risk-reducing surgeries. She was therefore reluctant to undergo risk-reducing surgery because of the high cost, and chose instead to undergo breast and ovarian surveillance rather than risk-reducing surgery. Surveillance and testing led to a diagnosis of non-invasive breast cancer, at which time both breast cancer surgery and risk-reducing surgery were covered by the Japanese health insurance system. Because few changes were evident on imaging and only slight changes in the kinetic curve were seen on contrast-enhanced MRI of the breast, we might not have considered core needle biopsy in the absence of a background of pathogenic mutations in gBRCA2. After the surgery, the patient was very satisfied because she had been able to undergo surgery for the cancer and RRSO and CRRM at the same time. Because this was before any ovarian cancer developed, she was able to undergo laparoscopic surgery and felt very well after the surgery. The patient has an adult daughter who does not want to be tested for BRCA1/2. In the past, she had left it up to her daughter to decide whether to undergo BRCA1/2 testing, but now that she has undergone this surgery, she is actively encouraging her daughter to undergo testing. If tested, her daughter would know her own susceptibility and could better plan for her healthcare. If she discovers she has a BRCA2 pathogenic variant that had been identified in her mother, close surveillance might detect early breast and ovarian cancer. Even with these benefits, however, cancer-free individuals may be reluctant to be tested for BRCA1/2 if surveillance and risk-reducing surgery must be self-funded. Unfortunately, this is the current state of HBOC medicine in Japan.The patient in this case had been undergoing surveillance at her own expense since she had been found to be gIn conclusion, we encountered a case of HBOC in which both RRSO and RRM were performed simultaneously in addition to breast cancer treatment at the request of the patient. When HBOC was diagnosed, the patient was concerned about developing ovarian cancer, but since she had not developed cancer, the cost of risk-reducing surgery was very high. This was therefore a case in which risk-reducing surgery could not be performed. We believe that extending insurance coverage for HBOC cases to those patients who have not yet developed cancer represents an extremely important issue for true cancer-preventive medicine in the future. In addition, if risk-reducing surgery is not covered by insurance because no cancer has yet developed, the key issue is how to detect cancer early and prevent a life-threatening status through regular surveillance performed at personal expense. To improve the accuracy of breast and ovarian surveillance, collaboration needs to be strengthened between breast oncologists and specialists with sufficient expertise in contrast-enhanced MRI of the breast and gynecologic oncologists, to create a safe environment not only for cancer patients, but also for cancer-free HBOC individuals.


Objectives: Lung cancer is a main contributor to all newly diagnosed cancers worldwide. The chemoprotective effect of the influenza vaccine among patients with hypertension remains unclear.Methods: A total of 37,022 patients with hypertension were retrospectively enrolled from the Taiwan National Health Insurance Research Database. These patients were further divided into a vaccinated group  and an unvaccinated group .Results: After adjusting for sex, age, comorbidities, medications, level of urbanization and monthly income, vaccinated patients had a significantly lower risk of lung cancer occurrence than unvaccinated patients . A potential protective effect was observed for both sexes and in the elderly age group. With a greater total number of vaccinations, a potentially greater protective effect was observed .Conclusion: Influenza vaccination was associated with a lower risk of lung cancer among patients with hypertension. The potentially chemoprotective effect appeared to be dose dependent. The pathologic mechanism underlying chronic hypertension in relation to cancer risk remains unclear, although studies have proposed that chronic hypertension is related to aberrant angiogenesis, which significantly increases the risk of tumorigenesis [Hypertension, a known risk factor for cardiovascular diseases, chronic kidney disease, cognitive impairment and dementia , is relaigenesis , 15–17. igenesis . Common Patients with hypertension have a significantly higher risk of acute viral respiratory infection and serious cardiovascular complications after infection . AlthougTaiwan’s National Health Insurance (NHI) program was established in 1995 and currently provides comprehensive health insurance for more than 98% (>23 million people) of Taiwan’s population. This study analyzed data from between 2000 and 2012 obtained from the NHI Research Database (NHIRD). No significant differences were revealed in terms of age, sex, or healthcare costs between all the participants in the study group and patients in the NHI program. Data from the NHIRD that could be used to identify patients or care providers, including medical institutions and doctors, are encrypted before being sent to the National Health Research Institutes for inclusion in the database, and records are further anonymized before being released to researchers. Theoretically, data cannot be used to identify individuals. All researchers using the NHIRD and its subsets must sign a written agreement stating that they have no intention of obtaining information that might infringe on the privacy of patients or care providers. This study was approved by the Joint Institutional Review Board of Taipei Medical University .In Taiwan, the influenza vaccination has been free of charge and recommended for high-risk adults aged ≥50 years  since 1998 and for all adults aged >65 years since 2001. The vaccination status was identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code V048 or according to the use of vaccines (confirmed through NHI Drug Codes of influenza vaccines) .The potential confounders included diabetes, dyslipidemia, medications  with different durations of usage , sociodemographic characteristics [age, sex, urbanization level , and monn = 206,077) between 1 January 2001, and 31 December 2012. Patients who had received a diagnosis of hypertension at more than two outpatient clinics or more than one hospitalization and who had recently taken two or more antihypertensive medications  were recruited for this study. The exclusion criteria were as follows: 1. patients under 55 years old ; 2. To minimize the potential confounding factors associated with previous hypertension status and treatment status of hypertension, patients who had received a diagnosis of hypertension before 2001  were excluded. 3. To eliminate the confounding effect from other types of cancer, patients who had received a diagnosis related to cancer in any inpatient or outpatient setting  were excluded. 4. Patients who had already received any vaccination within 6 months before the enrollment date  were excluded. Our final study cohort comprised 37,022 patients with hypertension who were older than 55 years in Taiwan. Of these, 15,697 had received an influenza vaccination, and 21,325 had not (The study cohort comprised patients who had received a diagnosis of hypertension (ICD-9-CM codes 401-405) at medical institutions in Taiwan over a 12 years period  method was used to reduce the selection bias in the comparison of the vaccinated group and the non-vaccinated group by accounting for the covariates with a logistic regression model . In addiTo examine the effects of the influenza vaccine among patients of different ages and sexes and with different comorbidities and medication usages, a subgroup analysis was performed. To assess the similarities and differences among the patients with hypertension in terms of receipt of the influenza vaccine and the risk of lung cancer, these data were stratified according to patient age , sex, comorbidities  and medication  use of different durations.The dose-dependent effect of influenza vaccinations on the incidence of lung cancer was also determined through a subgroup analysis, in which patients with hypertension were categorized into four groups according to their vaccination status .p < 0.05 was considered significant.All analyses were performed using SPSS 22.0 and SAS 9.4 software, and a two-tailed test result of The study cohort comprised 37,022 patients, of whom 15,697 (42.4%) had received an influenza vaccination and 21,325 (57.6%) had not . The totWe analyzed the incidence of lung cancer among patients with hypertension who had and had not received an influenza vaccination . After aAn additional subgroup analysis was performed to evaluate the association between influenza vaccination and the risk of lung cancer in different models, with stratification according to the total number of vaccinations . NotablyRegardless of sex, patients aged ≥65 years who had received ≥4 vaccinations had a significantly lower risk of lung cancer .Among patients with longer durations of diuretic agent, beta-blocking agent, calcium channel blocker, RAAS inhibitor, statin, metformin, and aspirin use, there was no significant difference in lung cancer occurrence between the vaccinated and unvaccinated groups, even after 4 influenza vaccinations .In Taiwan, in 2007, the nationwide prevalence of hypertension was 25% in men and 18% in women, increasing to 47% in individuals aged ≥60 years . CommuniLung cancer is the second most common cancer in Taiwan regardless of sex . In a reIn this cohort study, the patients with hypertension in the vaccinated group tended to be older and female compared with those in the unvaccinated group. Significantly more patients in the vaccinated group had taken antihypertensive medications, including diuretics, beta-blocking agents, calcium channel blockers, and RAAS inhibitors, and had used medications such as statins, metformin, and oral aspirin for a prolonged period. This finding indicates that, relative to those in the unvaccinated group, more patients in the vaccinated group had metabolic disorders such as hyperlipidemia and DM and were receiving treatment. The incidence of lung cancer in the vaccinated group was significantly lower than that in the unvaccinated group . To our knowledge, this is the first population-based cohort study to reveal that influenza vaccination significantly reduced the risk of lung cancer among patients with hypertension.+ T-cell-mediated antitumor immunity [The mechanisms linking metabolic syndrome and cancer risk are not fully understood. Metabolic syndrome may be a surrogate marker for other cancer risk factors, such as decreased physical activity, consumption of calorie-dense foods, high dietary fat intake, low fiber intake, and oxidative stress. Excess adiposity, particularly visceral obesity, results in a state of chronic systemic low-grade inflammation, attributed to the production of inflammatory cytokines by both adipocytes and infiltrating immune cells, creating a protumorigenic environment . Althougimmunity , which aIn a previous study conducted in Taiwan, the risk of lung cancer significantly increased after influenza virus infection . MoreoveThis population-based cohort study revealed that annual influenza vaccination significantly reduced the risk of lung cancer among patients with hypertension, demonstrating that a higher number of vaccinations was related to a stronger protective effect. Subgroup analyses were performed according to vaccination status, and we evaluated the dose-dependent effects on lung cancer events. Of the 37,022 eligible patients with hypertension, 15,697 (42.4%) had received an influenza vaccination, and 21,325 (57.6%) had not.The dose-dependent protective effect of the influenza vaccination for all ages and both sexes  was also identified in our other studies , 25. InfHowever, in the present study, the potential chemopreventive effect of influenza vaccination was not observed in patients with a longer duration of antihypertensive and other metabolic medication use. With a longer duration of medication usage, it is possible that these patients had more severe or irreversible causes of these comorbidities. In previous studies, cardiovascular disease, diabetes and dyslipidemia have been reported to be associated with a higher cancer risk –53. TherSeveral limitations to this study, similar to those in other observational studies based on clinical databases, must be considered. First, data on smoking, a key environmental risk factor for lung cancer and a cardiovascular risk factor, are not available in the NHIRD. In Taiwan, the smoking rates for men and women aged >55 years were 20.5% and 2.4% in 2002 and 14% and 1.53% in 2012, respectively . Because


This review aims to access the current state of the evidence in exercise as medicine for cardio-oncology in Hispanic and Latina breast cancer survivors and to provide our preliminary data on the effects of supervised aerobic and resistance training on cardiovascular disease (CVD) risk in this population.Breast cancer survivors have a higher risk of CVD; particularly Hispanic and Latina breast cancer survivors have a higher burden than their White counterparts. Exercise has been shown to reduce CVD risk in breast cancer survivors; however, evidence in Hispanic and Latina breast cancer survivors is scarce.Our review highlights a clear need for exercise oncology clinical trials in Hispanic and Latina breast cancer survivors targeting CVD risk factors. Moreover, our exploratory results highlight that 16 weeks of aerobic and resistance training may reduce the 10-year risk of developing CVD by 15% in Hispanic and Latina breast cancer survivors. Cardio-oncology is a subspeciality that arose from the need of detecting, monitoring, and treating cardiovascular disease occurring as a side-effect of cancer treatments . ParticuHerein, we provide a review of the current evidence on exercise interventions in Hispanic and Latina women with breast cancer targeting cardiovascular-related outcomes. Furthermore, we provide preliminary data on the effects of an exercise intervention on cardiovascular risk in Hispanic and Latina breast cancer survivor.As a prominent public health issue , cardiovCardiovascular disease and breast cancer have shared risk factors including age, diet, family history, alcohol intake, obesity/overweight, physical activity, and tobacco use . HoweverDespite the Hispanic and Latina/o population being the second largest racial and ethnic community in the USA, it is one of the most underserved populations facing numerous health disparities and inequities in access to care , 19. SpeRegarding specific risk factors for cardiovascular disease, Hispanic and Latina breast cancer survivors have higher rates of obesity compared with non-Latina/Hispanic White women , 23. ParClinical strategies have been implemented to counteract cardiovascular risk factors in breast cancer survivors including modifications in treatments, monitoring of symptoms, and pharmacological strategies -inhibitors, etc.) . While tExercise is known as a non-pharmacological strategy to reduce cardiovascular risk factors in the general population and in other clinical populations . Current2max testing, 6-min walk test, etc.) [While several clinical trials have focused on the effects of exercise in reducing cardiovascular risk factors among breast cancer survivors , Hispanit, etc.) , 50.Tab2. Exercise interventions were composed mostly of combined aerobic and resistance exercise, three exercise sessions per week for a duration of 16 weeks. Briefly, results from these studies showed that there is scarce evidence on the effects of exercise in reducing cardiovascular risk factors in Hispanic and Latina breast cancer survivors. Only two previous studies reported metabolic biomarkers and showed no differences between the exercise group and the control group [After the search, a total of 444 records were identified with only 5 studies meeting our criteria Table . On averol group , 52. Conol group , while ool group , 56. Regol group .Therefore, our review highlights the lack of exercise oncology clinical trials in Hispanic and Latina breast cancer survivors with a special emphasis on cardiovascular risk factors. The included studies have used surrogate outcomes of cardiovascular disease, but to our knowledge, no previous study has included specific outcomes of cardiovascular disease risk in this population. In this regard, one widely employed method for assessing cardiovascular disease risk is the Framingham Risk Score (FRS), which combines six risk factors—age, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), systolic blood pressure, diabetes, and smoking status . Thus, sN=100) with overweight or obesity [To fill this gap, we conducted an exploratory analysis to assess cardiovascular disease risk using the FRS in a subsample of patients from our previous clinical trial. We previously reported that aerobic and resistance exercise reduced the FRS  and the 10-year FRS-predicted risk of developing cardiovascular disease by 11% in racially/ethnically diverse breast cancer survivors . Race and ethnicity were self-reported. Participants were randomized to exercise or usual care: the exercise group performed a supervised one-on-one exercise program 3 days per week for 4 months. During the first and the third session of each week, women performed resistance (60–80% of 1-repetition maximum) and aerobic exercise (65–80% of maximum heart rate), and only aerobic exercise was done for the second session of the week. The FRS and the 10-year risk of cardiovascular disease were calculated using validated methods for women [Detailed methods from this trial have been previously published . Brieflyor women . The 6 cn=29) or usual care (n=27) groups, mean age was 46±10 years, obese (34.9±6.2 kg/m2), and a similar percentage of pre and postmenopausal women. The adherence to the exercise intervention was 96%. Post-intervention total FRS was significantly reduced in the exercise group compared to the usual care group , which corresponds to a 15%  decrease in the 10-year risk of developing cardiovascular disease  is commonly used to guide exercise interventions for breast cancer survivors , 66, andOur laboratory is currently conducting two trials with cardiovascular risk factors outcomes that are culturally tailored to Hispanic and Latina breast cancer patients where we are using the strategies mentioned above , 70. In In conclusion, most randomized exercise trials exploring cardiovascular risk factors for women with breast cancer have been composed primarily of highly educated White adults with mid-high socioeconomic status (SES) . We have


Observational studies suggest that mammographic density (MD) may have a role in the unexplained protective effect of childhood adiposity on breast cancer risk. Here, we investigated a complex and interlinked relationship between puberty onset, adiposity, MD, and their effects on breast cancer using Mendelian randomization (MR).We estimated the effects of childhood and adulthood adiposity, and age at menarche on MD phenotypes (dense area (DA), non-dense area (NDA), percent density (PD)) using MR and multivariable MR (MVMR), allowing us to disentangle their total and direct effects. Next, we examined the effect of MD on breast cancer risk, including risk of molecular subtypes, and accounting for genetic pleiotropy. Finally, we used MVMR to evaluate whether the protective effect of childhood adiposity on breast cancer was mediated by MD.Childhood adiposity had a strong inverse effect on mammographic DA, while adulthood adiposity increased NDA. Later menarche had an effect of increasing DA and PD, but when accounting for childhood adiposity, this effect attenuated to the null. DA and PD had a risk-increasing effect on breast cancer across all subtypes. The MD single-nucleotide polymorphism (SNP) estimates were extremely heterogeneous, and examination of the SNPs suggested different mechanisms may be linking MD and breast cancer. Finally, MR mediation analysis estimated that 56% (95% CIs [32% - 79%]) of the childhood adiposity effect on breast cancer risk was mediated via DA.In this work, we sought to disentangle the relationship between factors affecting MD and breast cancer. We showed that higher childhood adiposity decreases mammographic DA, which subsequently leads to reduced breast cancer risk. Understanding this mechanism is of great importance for identifying potential targets of intervention, since advocating weight gain in childhood would not be recommended. Breast cancer is the most common cancer in women worldwide . IncidenMD refers to the radiological appearance of fibroglandular vs adipose tissue in the breast and is frequently quantified in three phenotypes: dense area , non-dense area  and percent density . DA and PD are associated with an increased risk of breast cancer, whereas NDA is independently associated with a decreased risk . A high Growing evidence points to associations between childhood adiposity, puberty onset, and adult mammographic density (reviewed in ). PubertHere, we explore the mediating role of mammographic density in the protective effect of high childhood adiposity on breast cancer risk, using data from genome-wide association study (GWAS) studies of childhood body size, adult body size, age at menarche, mammographic density, and breast cancer within a Mendelian randomization framework.In this study, we aimed to investigate the mediating role of mammographic density in the protective effect of childhood adiposity on breast cancer risk. This study is reported as per the guidelines for strengthening the reporting of Mendelian randomization studies (STROBE-MR)  42]..42].We used univariable MR to evaluate the total effect of childhood and adult body sizes on each MD phenotype .To investigate potential violations of the MR assumptions and validate the robustness of the two-sample IVW MR results, we performed additional MR analyses using MR-Egger  and weigA statistics, which also were not notably large , indicating little evidence of directional pleiotropy . The Cocanalysis .2) in breast cancer rather than in MD phenotypes, and therefore, were not excluded from the analysis. Interestingly, we identified substantial heterogeneity for all MD phenotypes, suggested by very high Q-values with small p-values. High heterogeneity may be indicative of one or more variant outliers in the analysis, which was explored with additional sensitivity in the next section. The sensitivity analysis details are available in In the main IVW analysis of MD phenotypes effect on breast cancer outcomes, the evidence was present only in selected exposure-outcome pairs, as described in the previous section. Applying sensitivity methods to those results showed some inconsistency, with MR-Egger producing imprecise results. The weighted median approach, which relies on at least 50% of the variants’ total weight being from valid instruments , provideTo explore the high heterogeneity in the genetic instruments for the MD phenotypes, we applied several methods that aim to dissect heterogeneity and assess potential horizontal pleiotropy through outlier detection  analysis  on the gThe PheWAS results for the dense area phenotype are plotted in PheWAS plots for non-dense area and percent density are available in To gain some biological context for the identified outlier SNPs and distinct clusters, we mapped instrument SNPs to genes  and idenMKL1/MRTFA (rs73169097 – negative ‘null’ cluster SNP) and MTMR11 (rs11205303), both of which have dense phenotype-increasing effect but are protective against breast cancer. The potential tumour-inhibiting and tumour-promoting role of MKL1 was previously acknowledged in , , , such asedged in . MTMR11 4286946) . InteresIn the earlier sections, we reviewed the total effect of MD phenotypes on breast cancer risk  and explFrom the same MVMR analysis as the results in It is important to note that the number of MD instruments in this MVMR analysis was limited . These MWe performed mediation analysis using MR and MVMR results to assess the role of mammographic density  in the relationship between childhood body size and breast cancer. This investigation was also done focussing only on the overall breast cancer sample  area. In multivariable MR analysis, however, the independent direct effect of childhood adiposity was stronger for decreasing dense area, while adult adiposity was stronger for increasing non-dense area. The inverse effect of higher body size on density is likely explained by increasing breast adiposity, reducing the proportion of fibroglandular components, and increasing adipocyte differentiation of stromal cells, thus reducing collagen production . As breaThe previously observed association of age at menarche with breast density  was replThis finding draws attention to prior MR studies showing little evidence of effect of age at menarche on breast cancer risk , 55]. I. I55]. IThe central relationship explored in our study is that of MD and breast cancer, and whether MD helps explain the inverse association of childhood adiposity and breast cancer risk. When examining the total effect of MD phenotypes on breast cancer risk , we observed consistent trends in the direction of effects, with dense area and percent density increasing the risk and non-dense area decreasing the risk, in line with observational results 13]. We . We 13].While the total effect of MD on breast cancer was imprecisely estimated, IVW-MVMR of MD phenotypes with childhood body size showed strong evidence of a risk-increasing direct effect from the dense area on all breast cancer subtypes, with less evidence for a negative effect of non-dense area and a lack of evidence for an effect of percent density. This highlighted the possibility that dense area is the more important risk factor for breast cancer, however in observational studies , percentIn addition to the effect changes observed in MVMR, we conducted a formal mediation analysis with the dense area phenotype. Both mediation methods we applied produced very similar indirect effect estimates . Such agreement of estimates was not the case for other mediators we reviewed in our previous work . The conMLK1 in . T. T66]. T in 2020  was adjuet al . The. The9]. The analyses in this work were performed using the two-sample (univariable) MR approach, which relies on using GWAS summary statistics of two non-overlapping samples for exposure and outcome . Two-samWe used the two-step MR framework to assess whether an intermediate trait acts as a causal mediator between the exposure and the outcome of interest , 76]. M. M76]. MTwoSampleMR R package (v0.5.6) , wi, wi46],  outcome .To explore the excessive heterogeneity and potential pleiotropy identified in the effect of MD on breast cancer, we explored the genetic instruments using several outlier detection methods.MR-PRESSO R package (v1.0), using the default parameters.First, we applied MR-PRESSO , a methoRadial-MR  and andpheno v0.1.5)  to queryWe presented PheWAS results for each MD SNP grouped by clusters determined by the MR-Clust algorithm. This helped us to review the association differences between clusters of SNPs with the traits identified in GWAS databases, which might explain some of the observed heterogeneity in the MR results.enrichR R package (v3.1) [ReactomeContentService4R R package (v1.4.0) [To explore the functional relevance of the identified clusters of MD instruments, we mapped instrument SNPs of each MD phenotype to genes and identified the pathways thay are involved in. For gene mapping we used the SNP2Gene function of FUMA  platform , where we (v3.1)  (includi(v1.4.0)  to obtaiMediation analysis is used to quantify the effects of an exposure on an outcome, which act directly or indirectly via an intermediate variable  . IdentifThe total effect of exposure on outcome includes both a direct effect and any indirect effects via one or more mediators. The total effect is captured by a standard univariable MR analysis. To decompose direct and indirect effects, we used the results from two-step MR and MVMR in two mediation analysis methods: Difference method and Product method.For the Difference method, to estimate the indirect effect, we subtracted the direct effect of exposure on the outcome from MVMR  from the total effect of exposure on the outcome (univariable MR) . In ProdSupplement 1Supplement 2Supplement 3Supplement 4Supplement 5


Circadian rhythm disruptors  are risk factors for breast cancer, however studies on their association with prognosis is limited. A small but growing body of research suggests that altered sleep patterns and eating behaviours are potential mechanistic links between circadian rhythm disruptors and breast cancer. We therefore systematically summarised literature examining the influence of circadian rhythm disrupting behaviours on cancer outcomes in women with breast cancer.A systematic search of five databases from inception to January 2021 was conducted. Original research published in English, assessing the relationship between post-diagnosis sleep patters and eating behaviours, and breast cancer outcomes were considered. Risk of bias was assessed using the Newcastle–Ottawa Assessment Scale for Cohort Studies.k = 7) and, eating time and frequency (k = 1). Longer sleep duration (≥ 9 h versus [referent range] 6-8 h) was consistently associated with increased risk of all outcomes of interest (HR range: 1.37–2.33). There was limited evidence to suggest that measures of better sleep quality are associated with lower risk of all-cause mortality (HR range: 0.29-0.97). Shorter nightly fasting duration (< 13 h versus ≥ 13 h) was associated with higher risk of all breast cancer outcomes (HR range: 1.21–1.36).Eight studies published original evidence addressing sleep duration and/or quality , biomarkers, and patient-reported outcomes, in diverse populations  are warranted.The online version contains supplementary material available at 10.1007/s10549-022-06792-0. Breast cancer is the most prevalent cancer and the leading cause of cancer-related mortality in women worldwide . Due to The International Agency for Research on Cancer (IARC) classified circadian-disrupting night-shift work as a probable carcinogen for breast cancer (Group 2A) . AdditioGiven this potential role in breast cancer incidence, there is emerging research on the potential mechanistic behaviours linking circadian rhythm disruptors—sleep patterns  and eating behaviours —and disease outcomes following a breast cancer diagnosis. Evidence from the general non-cancer populations suggest, that sleep duration, nightly fasting duration, and timing of eating, are associated with metabolic  and inflammatory (C-Reactive Protein) markers –24—pathwSleep duration is the most commonly studied circadian rhythm disrupting behaviour in relation to cancer survivorship. A recent meta-analysis of sleep duration and cancer mortality in all cancer survivors reported that long sleep duration (≥ 9 h versus referent [ranging from 5–8 h]) in studies assessing either pre- or post-diagnosis was not associated with breast cancer mortality  . HoweverIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines , a systeUsing Covidence Systematic Review software  , duplicaData from eligible studies were extracted into a formatted database independently by one author (K.D.) and reviewed by three co-authors  to ensure accuracy. Data extracted included study population characteristics, exposure of interest, ascertainment of exposure , outcome(s) assessed, associations, and covariates adjusted in models. The quality of each study was appraised against the Newcastle–Ottawa Assessment Scale for Cohort Studies . Studiesk [number of studies] = 1495), 1,479 were excluded based on title and abstract, and eight were excluded based on full-text review. Ultimately, eight studies met the eligibility criteria and were included in this review   6–8 h), but not short (< 6 h) , 32, 37.Only one study assessed eating patterns, evaluating the effects of nightly fasting duration, eating episodes per day, and eating after 8PM on breast cancer outcomes Table  35]. Ea. Ea35]. This review provides a comprehensive summary on the limited evidence available on post-diagnosis behaviours that underpin circadian rhythm disruptors and breast cancer outcomes. Our updated search on sleep duration and breast cancer survival did not retrieve any additional studies and found that longer sleep duration (≥ 9 h) was associated with increased risk of breast cancer outcomes, which is consistent with the results of the meta-analysis by Stone and colleagues . SimilarFindings from our systematic review also suggest that sleep quality including sleep difficulty is associated with all-cause mortality and possibly poor progression-free survival. Gottfried and colleagues reported similar results whereby, poor sleep quality  determined via a self-reported questionnaire (standard practice on ward admission) was highly related to overall survival amongst lung cancer survivors  . ChronicOf importance to note, the observational design of the included studies makes them susceptible to reverse causation and potential confounding biases. It is currently unclear whether long sleep duration and disrupted sleep are caused by progressing or recurrent underlying disease, rather than sleep behaviour directly affecting cancer progression. In the studies that examined sleep duration across clinical cancer characteristics at diagnosis, those with more advanced disease (stage III) were only slightly more likely to report longer sleep duration (≥ 9 h) , 32, andPoor sleep quality can be explained in part by the side-effects of cancer treatment, including the occurrence or exacerbation of menopausal symptoms  and fatigue , 42. Poo1c) levels [In the single study examining meal timing, a statistically significant association was observed between short nightly fasting duration (< 13 h) and breast cancer recurrence, with small suggestive associations for all-cause and breast cancer mortality . Althoug) levels , and low) levels . Similar) levels .Our systematic review is not without limitations, inherent to the design of included studies. The results of this study are based on predominantly white, postmenopausal breast cancer survivors, limiting generalizability to ethnically diverse and younger breast cancer survivors. Additionally, all eligible studies are observational and predominantly retrospective in nature, whereby causality is not made clear. Furthermore, although most studies measured exposures using validated questionnaires and single-item questions, self-reported responses are subjective and less accurate than those using objective measurements  – but studies using objective measurements of these behaviours could still be prone to reverse causality bias. Lastly, the small number of significantly heterogeneous eligible studies limited our ability to conduct a meta-analysis to estimate the pooled effect across included studies.Our review, although narrative, comprehensively synthesizes the association between post-diagnosis behaviours reflective of circadian rhythm disruption and breast cancer outcomes, and has identified opportunities for future research. Available evidence has largely viewed women with breast cancer as a homogenous population. However, breast cancer is a heterogeneous disease characterized by different cell types and molecular subtypes . TherefoAs the number of breast cancer survivors continue to rise worldwide, the implications of circadian rhythm disrupting behaviours on breast cancer outcomes are of growing interest. This review summarized the limited literature available, suggesting post-diagnosis sleep patterns and eating behaviours reflective of circadian rhythm disruption may have adverse effects on cancer outcomes in breast cancer survivors.Supplementary file1 (PDF 129 KB)Below is the link to the electronic supplementary material.


In the US, Black women are disproportionately affected by higher breast cancer mortality rates and later-stage tumor diagnoses compared with White women. Breast density, the ratio of dense fibroglandular breast tissue to overall breast tissue area, has previously been identified as an important breast cancer risk factor. Most current genome-wide association studies for breast density have been performed in participants of European ancestry, which have yielded important insights into genetic etiology of breast density. However, little is known about the influence of common genetic variants on breast density in African ancestry populations. Our study aimed to determine genetic factors associated with breast density in African ancestry populations using a Genome-Wide Association Study (GWAS) and post-GWAS analyses on a cohort of genomic data available through the Penn Medicine BioBank. Results of this study elucidate potential genetic mechanisms associated with breast density, and thus cancer risk, among women of African ancestry.GACAT3, CTNNA3, HSD17B6, UGDH, TAAR8, ARHGAP10, BOD1L2, and NR3C2. There was significant overlap between previously identified breast cancer SNPs and SNPs identified as associated with breast density. Our results highlight the importance of breast density GWAS among diverse populations, including African ancestry populations. They may provide novel insights into genetic factors associated with breast density and help in elucidating mechanisms by which density increases breast cancer risk.Breast density, the amount of fibroglandular versus fatty tissue in the breast, is a strong breast cancer risk factor. Understanding genetic factors associated with breast density may help in clarifying mechanisms by which breast density increases cancer risk. To date, 50 genetic loci have been associated with breast density, however, these studies were performed among predominantly European ancestry populations. We utilized a cohort of women aged 40–85 years who underwent screening mammography and had genetic information available from the Penn Medicine BioBank to conduct a Genome-Wide Association Study (GWAS) of breast density among 1323 women of African ancestry. For each mammogram, the publicly available “LIBRA” software was used to quantify dense area and area percent density. We identified 34 significant loci associated with dense area and area percent density, with the strongest signals in  Black women in the US have 40% higher breast cancer mortality than White women  and are The mechanisms that underlie the association of breast density with higher breast cancer risk are poorly understood. Breast density is highly heritable, with family-based studies estimating that 50–70% of the variance in breast density is explained by genetics ,13. To dBRCA1/2 mutation . We excluded screening exams with uncertain outcomes (N = 13), screenings preceded by a breast cancer diagnosis (N = 74), and true positive and false negative screening exams (N = 153). We additionally excluded screenings where a breast implant was present (N = 429), screenings for which all four processed  DM views were unavailable (N = 406), and screenings for which breast density evaluation software failed (N = 808). Then, we removed screenings for women who did not consent to participate in the Penn Medicine BioBank (PMBB), a research biorepository where patients provide a blood sample and broadly consent to allow their biospecimens to be used for research purposes . We excluded screenings for women without a genetically-informed genotype (N = 3718), and women who did not self-identify as Black or have an African ancestry genotype (N = 1803). From this pool of screening exams, we selected the earliest exam per person, resulting in 1348 individuals.We utilized a cohort of women aged 40–85 years who underwent mammography screening  at the Hospital of the University of Pennsylvania from 1 September 2010 through 31 December 2014 and did not have a known 2 or >82 kg/m2) [Women completed a breast cancer risk factor questionnaire at the time of mammography, from which reproductive factors, age, height, and weight were pulled. Body mass index (BMI) was calculated from self-reported height and weight, supplemented with electronic health record (EHR) data by using the nearest available measurement within 1 year prior to and 6 months after the date of screening. Implausible BMI values (<12 kg/m2 kg/m2)  were setBreast Imaging Reporting and Data System (BI-RADS) 4th or 5th edition breast density was obtained from the mammography report. For each mammogram, the publicly available “LIBRA” software (v1.0.4) was used to automatically quantify breast density ,17. Brie−6, and only kept variants with minor allele frequency greater than 0.01 [p-value of 10−5 or less, we used Biofilter [We performed a GWAS on our cohort of 1333 women using PLINK 2.0 , a tool han 0.01 ,20. The han 0.01 ,22, and han 0.01 . Supplemiofilter ,25 to anp-value threshold of 10−4 and a maximum number of causal variants of 10. Then, we searched for any variants with a posterior probability of greater than or equal to 0.5 for further annotation.We used polyfun  for funcWe performed summary-based TWAS for area percent density and breast dense area . The S-Pp-value of no more than 5 × 10−8.We performed a lookup of all nominally significant SNPs and genome-wide significant genes identified from GWAS as described in We performed estimation of SNP-based heritability and genetic correlation between breast density traits, age, BMI, and menopause status using GCTA’s Haseman–Elston’s regression approach ,32. AddiThe characteristics of the study population (N = 1333) are displayed in p < 5 × 10−8) for dense area and nine significant SNPs consisting of five independent loci for area percent density, as shown in In our quantitative GWAS consisting of women of African ancestry and/or identifying as Black, we discovered sixty-five significant hits consisting of twenty-nine independent loci (p = 6.06 × 10−13), CTNNA3 (p = 1.76 × 10−12), HSD17B6 (p = 4.02 × 10−12), UGDH , TAAR8 (p = 1.08 × 10−10), ARHGAP10 , BOD1L2 (p = 4.17 × 10−10), and NR3C2 (p = 4.68 × 10−10). Two of these genes, CTNNA3 [p = 1.56 × 10−8), TLL1/SPOCK3 (p = 4.41 × 10−9), DELEC1 (p = 3.84 × 10−8), LINC00858 (p = 1.01 × 10−8), CCSER2 (p = 1.59 × 10−8), and ZIC5  were associated with area percent density. We mapped all SNPs with p-value < 1 × 10−5 to the closest genes  was reduced to only eight SNPs when we looked for an overlap with reported associations in the GWAS catalog, as shown in rs10110651), rs61895110 was associated with bone density, and rs77754964 was associated with FEV/FEC ratio (measurement of forced expiratory volume). Other SNP-trait pairings are: rs78049001, cognitive decline; rs2976530, hip bone mineral density; rs75986475, physical activity; rs78730126, sex hormone binding globulin measurement.Our set of suggestive SNPs from all three GWAS .We compared our results with effect estimates and significance reported in a recently published breast density GWAS for 27,900 European ancestry individuals  Table 4Table 4. To our knowledge, ours is the first GWAS of quantitative breast density measurements performed among women of African ancestry. Among 1333 women, we measured dense area and area percent density from digital mammograms using a validated software algorithm and found sixty-five variants in twenty-nine genes associated with dense area and nine variants in five genes associated with area percent density. Our results highlight the potential value of examining SNPs associated with breast density among women of African ancestry, emphasizing the need for diverse ancestry analyses to better understand the genetic underpinnings of breast density and its impact on breast cancer risk in underrepresented populations.Of the loci identified in this study, 13 of these regions had been previously identified as associated with breast density in studies of European ancestry populations ,14,15. FCTNNA3, catenin alpha 3, which encodes a protein involved in cell–cell adhesion in muscle cells. CTNNA3 was previously identified in breast cancer GWAS [CTNNA3 to be associated with metabolic syndrome. This is interesting given the observed differences in breast density by BMI levels [CTNNA1, which has recently been categorized as a predisposition gene for Hereditary Diffuse Gastric Cancer [Several of the identified SNPs and genes have potentially plausible mechanistic connections to breast density and breast cancer risk. Two SNPs were identified with genome-wide significance in cer GWAS . Alpha acer GWAS . AdditioI levels . In addic Cancer . Furtherc Cancer . TogetheHSD17B6, hydroxysteroid 17-beta dehydrogenase 6, is involved in androgen catabolism and has been implicated in polycystic ovarian syndrome (PCOS) [GACAT3, gastric cancer associated transcript 3 is a long non-coding RNA that has been previously implicated in gastric and other cancers, with high expression observed in breast cancer tissue [e (PCOS) , includie (PCOS) . LRP1B ee (PCOS)  and sevee (PCOS) . GACAT3,r tissue  and corrr tissue .PDE10A). PDEs have oncogenic effects, and several preclinical studies have shown that inhibition of PDEs has an anti-tumor effect [PDE10A decreased cell proliferation, induced cell cycle arrest, and increased apoptosis in ovarian cancer cells [KIFC3) encodes a member of the kinesin-14 family of microtubule motors. These motor proteins attach to microtubules and move along them to transport cellular cargo. Overexpression of KIFC3 was shown to be associated with resistance to docetaxel in breast cancer cell lines [SH3GL3 has been implicated as a tumor suppressor in glioblastoma and lung cancer, as well as in cell migration and invasion in myeloma, and has been previously identified in colorectal cancer GWAS associated with colorectal cancer [Fine-mapping results include the heterochromatin region of the phosphodiesterase 10A , is highly expressed in breast cancers [Exploratory TWAS identified two loci associated with dense area and percent density, ysosomes  and glycysosomes ,36,37,38t cancer . PRIM1, t tumors . The obsenopause . FXYD3,  cancers  and has  cancers .Despite the modest sample size, our study identified novel SNPs with plausible mechanistic connections to both breast density and breast cancer risk. Breast density was measured quantitatively using an automated algorithm with high accuracy. In addition, breast density is known to be highly heritable. In combination, the continuous quantitative trait and the high heritability may have resulted in the ability to detect moderate-to-large associations despite a relatively small sample size. However, the small sample size limits our ability to detect more modest associations. Therefore, replication in larger populations of African ancestry populations and meta-analyses are warranted to increase statistical power to detect additional SNPs with more modest associations with breast density.Given that the biological underpinnings of breast density are poorly understood, further investigation of our findings may help in identifying pathways relevant for breast density development as well as the mechanistic relationship between breast density and breast cancer risk. In this study, we investigated the overlap between our top-associated variants and those reported in previous studies of breast cancer and other related traits. We believe that this integrative approach can help in shedding light on the underlying biology of breast density and its relationship to breast cancer risk. Future research is needed to validate our preliminary findings and further explore the functional implications of the identified genetic variants.Our study highlights the value of exploring the genetic factors associated with breast density among African ancestry populations, providing proof-of-concept that additional SNPs relevant to breast density may be identified through expanding the diversity of GWAS studies. Furthermore, a strength of our study is its use of quantitative measures of breast density, which have been shown to be strongly correlated to breast cancer risk ,10 and mWe report the first GWAS of breast density among women of African ancestry, in which we identified novel SNPs associated with quantitative breast density measures, many of which had been previously identified as associated with breast cancer. Our results mark the beginning of the study of breast density among African ancestry populations and provide hypothesis generating findings that may help in clarifying the biology of both breast density and breast cancer.


Background: Lymphedema is a severe post-mastectomy complication that still causes much morbidity in breast cancer patients with axillary lymph node dissection. Therefore, after mastectomy, lymphedema prevention is crucial for long-term survival and an increase in quality of life.Aim: The study's primary objective was to determine whether pre-discharge educational intervention sessions for post-mastectomy women effectively improve the knowledge in preventing arm lymphedema.Methodology: A quasi-experimental research study, one-group pretest-posttest design, was conducted in a teaching hospital in Bangalore. The sample included 80 females who were diagnosed with breast cancer, had recently undergone mastectomy, and had chemo and radiation therapy plans. Questions were based on the knowledge of lymphedema preventive concepts, including the definition of the lymphatic system and lymphedema, its causes, symptoms, prevention, and management, and were included in a structured self-administered questionnaire. Convenience sampling was used among women who had undergone mastectomy for breast cancer. The pre-discharge educational interventions session included instructions on a self or simple lymphatic drainage technique demonstration, arm exercises, and an e-brochure on risk reduction strategies and arm lymphedema prevention. The knowledge of pre-discharge educational intervention sessions highlighting risk reduction/prevention strategies among post-mastectomy women was evaluated using the self-structured knowledge questionnaire pretest and posttest data.Results: The entire study population comprised women who had undergone mastectomy. Almost half of the subjects were older than 55 years. Prior to the intervention, the majority of patients (58) had poor knowledge (72%) about preventing lymphedema, whereas nearly all patients (80) had good knowledge (100%) after the intervention sessions. All participants felt comfortable using the treatment plan to avoid arm lymphedema. The knowledge gain was statistically significant at the 0.05 level.Conclusions: It was determined that pre-discharge educational intervention sessions enhanced post-mastectomy women's awareness and risk reduction behaviors toward preventing arm lymphedema and reducing arm morbidity. Therefore, it is suggested that women who have had breast cancer surgery participate in a pre-discharge educational intervention program. This will guarantee that all mastectomy patients have access to educational information/materials and that risk reduction strategies are followed to prevent lymphedema. The leading cause of cancer among women in India is breast cancer, followed by cervical cancer. About 6,85,000 people died in 2020 due to breast cancer worldwide, which affected 2.3 million women . The NatWhen breast cancer is detected early, treatment for the disease can be very successful, with a survival probability of 90% or higher. However, modified radical mastectomy (MRM) is still a typical surgical surgery for breast cancer, particularly in underdeveloped nations. The entire breast, including the nipple, areola, skin, subcutaneous fatty tissue, and axillary lymph nodes, must be removed . TherefoOne of the most common and dreaded side effects of breast cancer treatments is lymphedema, which has long-term physical and psychological effects on patients. It is characterized by an aberrant and localized protein-rich fluid buildup in interstitial space that can result in edema and long-term inflammation . For breComplete decongestant therapy (CDT), arm exercises, manual lymphatic drainage (MLD), skin and nail care, self-massage, compression bandages, and/or hand sleeves are some of the techniques used to treat post-mastectomy lymphedema . ThroughNeed for the studyAround 30% of women with breast cancer (BC) undergoing surgical treatment in developing countries develop lymphedema. Before being discharged, patients must receive health education regarding understanding and self-care techniques linked to lymphedema prevention since BCRL is a lifelong problem and has no known cure. After lymphedema develops, treatment is substantially less effective than prevention .BCRL risk can be reduced by patient counseling within the first week following surgery, followed by physiotherapy . In addiThe patient should be given this information timely and reminded regularly. According to one study, the optimal moment for receiving information from the patient's perspective was at the time of breast cancer diagnosis. It is a contentious topic since some medical professionals consider that informing patients about lymphedema before treatment can make them more stressed and anxious . AccordiNurses play a crucial part in preventing post-mastectomy lymphedema through patient education before symptoms and early detection. Arm training is crucial for rehabilitating post-mastectomy patients because it increases the strength and function of the upper limb muscles, lessens pain and discomfort, and enhances the quality of life and confidence .The study was conducted in the present setting as the investigator identified a need to provide information on preventing BC-related lymphedema among post-mastectomy patients before they get discharged from the hospital to create an awareness of risk reduction and prevention aspects of BCRL. The educational materials provided to the patients before discharge will enable them to have a ready reckoner for information references.Study design and settingA quasi-experimental, one-group pretest-posttest approach was used in the research. The study was conducted in the oncology division of a teaching hospital in Bengaluru, Karnataka, India.Study participants and samplingThe samples consisted of women above 35 years who were diagnosed with breast cancer, underwent a unilateral mastectomy with axillary lymph node dissection, and were expected to get radiation and chemotherapy. Eighty women were selected for the study using the convenience sampling method. The following factors were taken into consideration when selecting the patients for this study: (1) patients with unilateral breast cancer, (2) patients with breast cancer who had undergone mastectomy with axillary lymph node dissection, (3) female patients who are aged 35 years and above, (4) patients with no previous mastectomy, and (5) patients who agreed to participate in the study.Data collection tools and techniquesA structured self-administered questionnaire created based on pertinent literature served as the study method. The tool consists of sections A and B.Section AAge, education, marital status, occupation, and clinical details such as the type of surgery, the side of the surgery, the dominant arm, the type of treatment, comorbid conditions, and body mass index (BMI) are included in this section.Section BThe questionnaire on BCRL and risk reduction practices for patient knowledge is self-administered based on the pre-discharge intervention sessions covering the concepts of preventing lymphedema, including the definition of the lymphatic system and lymphedema, its causes, symptoms, and prevention and risk reduction methods.This tool had 15 questions: BCRL information (eight questions) covering definition, causes, early signs and symptoms, stages, complications, and treatment as well as risk reduction practices to reduce BCRL (seven items). Each question had two options: one point for the correct answer and zero for the wrong answer.Validity and reliability of toolsA panel of oncology specialists, including breast surgeons, medical oncologists, and radiation oncologists, evaluated the instrument's content validity to ensure its applicability and thoroughness. The necessary changes were made as a result. Reliability was calculated using the test-retest approach and was found to be 0.82. The tool was practical and trustworthy for carrying out research investigations.Scoring and interpretationCorrect and wrong responses were used to determine the score. Every correct answer received a "one" score, while every wrong answer received a "zero.”The level of BCRL knowledge was graded as follows: less than 50 - inadequate; 51-75 - moderately adequate; above 75 - adequate, and the total score was 0-100. A higher mean score reflected a higher level of knowledge.AdministrationThe post-mastectomy women used the questionnaire tool twice: once before the pre-discharge intervention session  and once after a pre-discharge educational intervention session (two weeks post-discharge during the follow-up visit to the oncology outpatient department).Pre-discharge educational intervention sessionsThe oncology department of a teaching hospital in Bangalore allowed the researcher, a nurse, and a certified lymphedema specialist to conduct the study after consulting with the appropriate authorities. First, a convenience sampling technique was used to choose the eligible samples. Then, patients who agreed to participate in the study signed a consent form. The research was carried out between December 2021 and November 2022.Data Collection MethodFigure Posttests were conducted using the same tool two weeks after the educational session during their follow-up visit to the oncology outpatient department to gauge the understanding of lymphedema and risk reduction techniques for preventing arm lymphedema.Ethical considerationThe Institutional Ethical Committee of HOSMAT Hospital Educational Institute (HHEI) accepted the present study, and official approval was taken (HHEI/HCON/S-1/02/2020).Informed and written consent was gained from participants who fulfilled the inclusion criteria, and permission was secured from the administrators of the hospital's oncology department in Bangalore. The participants were completely anonymous, and confidentiality was maintained.AnalysisThe analytical method of data calculation was carried out using SPSS version 20.0 . With the aid of descriptive statistics, the data was examined. First, demographic characteristics were determined using frequency and percentage. Next, the pre-and posttest knowledge score was computed using frequency, percentage, mean, and standard deviation. Finally, the pre- and posttest knowledge scores were compared using a paired t-test, which was significant at a p-value of 0.000 .The data were analyzed using descriptive statistics. Table Section A: Sociodemographic profile of post-mastectomy womenThe age group with the highest score, 55 years and older, comprised 51% of the 80 breast cancer samples evaluated. Eighty-five percent of the individuals were married, while 13% were widowed. Most of the samples (85%) resided in urban/metropolitan areas, while the remaining respondents (15%) lived in semi-urban areas. Furthermore, 11% of the subjects had a primary education, 40% had a secondary education, and 28% and 21% held graduate and postgraduate degrees, respectively. In addition, 92% of the subjects made more than Rs. 15,000 monthly. Seventy percent of the individuals were homemakers (housewives), and 21% were professionals.Regarding clinical characteristics, almost 99% of the samples were right-handed, and about 53% had right-side mastectomy surgery. Obesity was a comorbid condition in 36% of the samples, and radiation therapy and chemotherapy were scheduled for 94%. According to BMI values, almost 51% of the participants fell into the overweight (15%) and obese (36%) categories, while 49% were normal.Section B: Pretest and posttest knowledge scores of post-mastectomy womenTable The mean SD of the pretest score is 4.71 ± 3.98, and the mean SD of the posttest score is 13.03 ± 0.42 as shown in Table Figure BCRL is a frequent yet underreported side effect of treating breast cancer. Lymphedema (LE) impairs the general quality of life and costs patients, their caregivers, and society .According to Cancer Council, 2017, lifelong self-care and management are necessary for lymphedema. The nurse can thus support the patient in achieving self-care objectives and managing the challenges of the patient's lifetime risk and particular BCRL trajectory [Evaluation of post-mastectomy women's knowledge of lymphedema and its risk reduction techniquesThe study was done among post-mastectomy women to improve their knowledge and risk reduction measures for preventing BCRL using a pre-discharge educational intervention session. The study showed that the mean pretest score (4.71) was less than the mean posttest score (13.03). The difference between the pre- and posttest results demonstrated a statistically significant improvement in the posttest score compared to the pretest score . The study reported by Borman et al. found that breast cancer survivors, particularly in developing nations, are unaware of the BCRL or the dangers of BCRL, which supports this finding that breast cancer patients should be taught the fundamentals of preventive and prophylactic measures after mastectomy by an oncologist and nurses to avoid complications. Additionally, the study emphasized that early postoperative use of lymphedema preventive measures may lessen or delay the development of it . SimilarIndividuals' sociodemographic details and health informationThe current investigation results showed that 51% of the subjects were 55 years of age or older. Most of the subjects in the current study were married and homemakers, which may indicate the burden that married women bear in caring for their family, which causes their arms to be under more stress, increasing the risk of BCRL. According to the current study's findings regarding education level, 40% had only secondary education, and 70% were homemakers. This result aligns with that of So et al. as well as El Sayed and Badr, who discovered that almost half of breast cancer patients in their study were married, held a secondary degree, and were unemployed ,24.Taking into account the participant's clinical characteristicsAccording to the present study, most subjects were right dominant hands. This may indicate that most of the women in the study were married homemakers, which may have exposed them to household pesticides and detergents that increase the risk of LE. Research by Safwat et al. at Cairo University found that a statistically significant correlation between the development of upper arm LE following breast cancer treatment and tumor in the dominant arm supports this conclusion .The current study's findings regarding the BMI of the investigated women showed that 15% were overweight and 36% were obese. The study by Dean et al., which found that a high BMI is a risk factor for the start of upper body BCRL, supports this finding .Overall patient knowledge and sources of information about lymphedema and its risk factorsThe current study indicated that the majority of women who participated were largely unaware of breast cancer, BCRL, and LE risk reduction techniques. This finding is corroborated by a study , which fThe current study indicated that the primary sources of information for our subjects about BCRL and LE risk reduction techniques were healthcare professionals, namely, doctors, nurses, physical therapists, and others. A smaller number of our subjects also obtained information online, followed by other sources like family, friends, support groups, books, and journal articles.However, in one study, it was observed that most doctors and nurses indicated they did not frequently advise women or provide written information on BCRL prevention to their patients and the extent to which women's everyday activities were affected by BCRL following diagnosis . Hence, The current study's findings highlight that pre-discharge educational interventions session significantly improved knowledge levels and confidence among women who had undergone a mastectomy in applying the concepts of lymphedema prevention.This result aligns with the study presented by Hawash, who reported that after implementing the nursing rehabilitation program, the comprehensive knowledge improved among the studied women .Limitations and recommendationsThe study has limitations in some areas. The study was small and had one participant group, no control group, and no randomization, so it cannot be generalized. The study used multiple posttests to determine the long-term effects of the pre-discharge educational intervention that helps delay LE onset. Breast cancer survivors can maintain the post-mastectomy quality of life by holding frequent reinforcement sessions during follow-up.The following recommendations for future research and practice are made in light of the findings of the current study:In ServicesAll healthcare professionals working in breast cancer units, including nurses caring for women with breast cancer-related LE, should participate in ongoing in-service education programs to update, acquire, and develop the knowledge, performance, and attitude necessary to manage this population of patients.After breast surgery, there is a clear need for educational programs on LE and risk reduction techniques that provide the most current knowledge on breast cancer-related LE and self-care strategies to assist breast cancer survivors in effectively managing their disease.In ResearchPeriodically, it is advised that additional research be conducted to assess the outcomes of new management strategies for patients with breast cancer-related LE. In addition, extended research studies are required to assess the effect of implementing the developed self-care instructions for post-mastectomy women at risk or with BCRL.Based on this study's results, it is advised that a similar study be replicated with a bigger sample size and diverse teaching strategies, together with frequent reinforcement, which is crucial in enhancing breast cancer patients' understanding.Most study participants who had undergone a mastectomy for breast cancer either did not know BCRL or had misconceptions about it, indicating a lack of proper education regarding lymphedema. The study's findings showed that the posttest knowledge score was higher than the pretest knowledge score. The framework for delivering education, which should include teaching protocols related to disease duration, risk reduction, and lymphedema therapy, is required. An individualized BCRL educational session with live demonstration and provision of a video recording and e-brochure is effective in acquiring knowledge on the prevention of BCRL development. Early and continual education for future management is crucial among the survivors at high risk for developing BCRL. Application of lymphedema prevention concepts is a key concern to improve post-mastectomy women's functional status, shoulder, and arm functions, ultimately improving their quality of life throughout their survivorship.


Emerging data indicate that variations in quantitative epithelial and stromal tissue composition and their relative abundance in benign breast biopsies independently impact risk of future invasive breast cancer. To gain further insights into breast cancer etiopathogenesis, we investigated associations between epidemiological factors and quantitative tissue composition metrics of the normal breast.The study participants were 4108 healthy women ages 18–75 years who voluntarily donated breast tissue to the US-based Susan G. Komen Tissue Bank . Using high-accuracy machine learning algorithms, we quantified the percentage of epithelial, stromal, adipose, and fibroglandular tissue, as well as the proportion of fibroglandular tissue that is epithelium relative to stroma  on digitized hematoxylin and eosin (H&E)-stained normal breast biopsy specimens. Data on epidemiological factors were obtained from participants using a detailed questionnaire administered at the time of tissue donation. Associations between epidemiological factors and square root transformed tissue metrics were investigated using multivariable linear regression models.β ) = −0.28 ; P < 0.001] with ESP peaks at 30–40 years and 60–70 years among pre- and postmenopausal women, respectively. Pregnancy  and increasing number of live births (P-trend < 0.001) were positively associated with ESP, while breastfeeding was inversely associated with ESP . A positive family history of breast cancer (FHBC) , being overweight or obese , and Black race  were positively associated with ESP.With increasing age, the amount of stromal, epithelial, and fibroglandular tissue declined and adipose tissue increased, while that of ESP demonstrated a bimodal pattern. Several epidemiological factors were associated with individual tissue composition metrics, impacting ESP as a result. Compared with premenopausal women, postmenopausal women had lower ESP [Our findings revealed that cumulative exposure to etiological factors over the lifespan impacts normal breast tissue composition metrics, individually or jointly, to alter their dynamic equilibrium, with potential implications for breast cancer susceptibility and tumor etiologic heterogeneity.The online version contains supplementary material available at 10.1186/s13058-023-01692-7. Risk factors for breast cancer development are thought to promote carcinogenesis by inducing proliferative epithelial changes, but emerging data suggest that stromal and adipose tissue components of the breast may also play crucial roles in early stages of breast carcinogenesis –3. ResulIn support of a stromal role in breast cancer etiopathogenesis, a recent study by our group found a context-dependent role of the stroma to either prevent or promote breast cancer development in women with benign breast disease (BBD) . Among BMorphologically, non-proliferative diseases more closely resemble the normal adult female breast than proliferative diseases . AccordiThe main aim of this study was, therefore, to investigate the associations between several breast cancer risk factors and quantitative tissue composition metrics in normal breast biopsies, individually  and in combination as fibroglandular tissue (epithelium plus stroma) and ESP , among women participating in the Susan G. Komen Tissue Bank.http://komentissuebank.iu.edu/) have been described elsewhere [n = 476), we used the earliest donation corresponding to the time when questionnaires were administered. Women without hematoxylin and eosin (H&E)-stained images (n = 526) were excluded from the analytical population. In addition, we excluded women above 75 years of age (n = 51) and those without data on age (n = 3), those who were pregnant and/or breastfeeding at the time of tissue collection (n = 59), previously had breast cancer (n = 149), and those without data on menopausal status (n = 10). The final analytical population comprised 4108 women who donated tissues between 2008 and 2019 and for whom we could retrieve the corresponding digitized H&E-stained sections . Details of the KTB project , hormonal birth control use (yes vs no), menopausal status , bilateral oophorectomy (yes vs none), menopausal hormone therapy (MHT) use  and MHT type, smoking status , alcohol intake, and family history of breast cancer (FHBC) in a first degree relative (present vs absent).The methodology for exposure assessment within KTB has been described elsewhere , 18. In Up to four tissue cores were biopsied from the upper outer quadrant of the right or left breast using a standard 9-gauge (since 2010) or 10-gauge (prior to 2010) needle and one core was fixed in 10% buffered formalin , 18. The2) on each slide comprised of epithelium (42-datapoints), stroma (37-datapoints), and adipose tissue (6-datapoints) as shown on Fig. 2) by the total tissue area  on each slide and multiplying by 100. Percent fibroglandular tissue area was calculated by adding epithelial and stromal area on the slides, dividing by total tissue area, and multiplying by 100. Percent ESP was calculated by dividing the epithelial area by total fibroglandular tissue area and multiplying by 100 as we previously described [Digitized H&E-stained slides were archived using the Halo Link digital image repository  at the US National Cancer Institute (NCI). Image analysis was performed using the Halo Client computational pathology software . A custom-built, random forest, tissue classifier algorithm was trained by two pathologists (MA and MAD) to develop an optimized, 85-datapoint, tissue classifier script. By annotating regions on randomly selected representative images comprised of epithelium, stroma, and adipose tissue, the random forest algorithm was trained to identify, segment, and quantify areas , reproductive , number of live births, age at first full-term birth (AFFB), breastfeeding), and lifestyle  factors with tissue composition metrics  were assessed in linear regression models. All tissue composition metrics were square root transformed to better approximate the normal distributions for the linear regression model. Partially adjusted models included age and tissue area and fully adjusted models included all of the variables under consideration. Associations of breastfeeding, number of live births, and AFFB with tissue composition metrics were assessed in models restricted to previously pregnant women. Analyses were performed overall and stratified by menopausal status. In the overall model, bilateral oophorectomy and uterine ablation were included separately to examine their effects on tissue composition metrics. In stratified analyses, individuals who had a bilateral oophorectomy, irrespective of age, or uterine ablation after the age of 55 years, were considered postmenopausal. Locally weighted scatter plot smoothing (Lowess) functions were used to plot the residuals from multivariable linear regression models for each tissue composition metric as a function of age. Lowess plots were constructed overall, and separately for pre- and postmenopausal women, parous and nulliparous women, normal and overweight/obese women, and for Black and White women. For racial/ethnicity comparisons, plots were restricted to comparisons between Black and White women due to the very small numbers of other individual racial and ethnic groups. To explore whether BMI impacted parity and race-related curves, we conducted sensitivity analyses by stratifying Lowess plots for parity and race by BMI categories . In sensitivity analyses, we also assessed whether parity impacted the race-related curves by creating separate plots for nulliparous and parous women. The majority of the risk factors were complete for participants. For those with missing values .The characteristics of study participants are shown in Table The distributions of all the tissue composition metrics varied statistically significantly by age and menopausal status Table . With thSimilar patterns of age- and menopause-related changes in tissue composition metrics as in the regression models were seen in Lowess curves for all the tissue composition metrics, with the exception of ESP. Unlike epithelium, stroma, and fibroglandular tissue that declined with increasing age, ESP showed a bimodal age distribution, increased starting at age 18 and peaked around 40 years of age, decreased from 40 until 55 years of age, and then increased with age thereafter Fig. . SimilarIncreasing age at menarche was associated with higher stromal and fibroglandular tissue but with lower adipose tissue and lower ESP Table . CompareIn multivariable linear regression models Table , parity Separate Lowess plots for nulliparous and parous women revealed rapid increase in ESP among parous women from 20 years, peaking around 40 years, declining slightly between 40 and 60 years, increasing again after 60 years, and remaining higher for parous than nulliparous women throughout life. Among nulliparous women, epithelium decreased progressively up to around 50 years after which it began to increase, surpassing levels in parous women around 65 years. In contrast, ESP decreased progressively up to 50 years among nulliparous women and remained fairly constant afterward Fig. A.Fig. 3RThe distributions of all tissue composition metrics varied by BMI categories Table . IncreasOf the tissue composition metrics, the distributions of stroma and ESP varied statistically significantly by race and ethnicity Table . In geneThe distributions of individual tissue composition metrics varied according to several other factors, including FHBC, average number of alcoholic drinks per week, bilateral oophorectomy Tables  and 3, aBy examining breast cancer risk factors in relation to quantitative tissue composition metrics of the normal breast, we showed that joint variations in both epithelial and stromal tissue composition may be critical for breast carcinogenesis. In particular, our findings suggest that both epithelial and stromal tissues involute toward fat and that imbalance in the rate of stromal and epithelial involution can manifest as high ESP, which may represent a feature of the mammary tissue ecosystem that is conducive for carcinogenesis . The bimResults from epidemiological studies have shown that the bimodal pattern of breast cancer incidence correlates with differences in breast tumor biology , 26. TumAge-specific heterogeneity in breast cancer incidence and molecular subtype has been shown to characterize breast cancer risk relationships for parity, BMI, and race/ethnicity . For insPresumably, nulliparity might increase the risk of luminal breast cancer through an intrinsically epithelial-proliferation pathway while parity may increase the risk of basal-like breast cancer via stromal-epithelial crosstalk. The former idea is supported by results from studies showing strong associations between nulliparity and highly proliferating luminal tumors, defined by expression of the proliferation marker Ki67  and is bThe association of elevated BMI with breast cancer incidence varies by age , 50. AmoOur findings might also hold clues into differences in age-related incidence and tumor biology among racial groups . We founHaving a positive FHBC is a strong risk factor for breast cancer development. However, the tissue pathways by which FHBC influences breast cancer risk are yet to be fully defined. Results from a previous study suggested that polygenic risk scores for breast cancer development were associated with TDLU involution . Here, wThis study has several important strengths, including the application of high-accuracy machine learning algorithms for the detailed and centralized assessment of quantitative tissue composition metrics on digitized, H&E-stained, biopsy specimens from over 4000 normal breast tissue donors. To the best of our knowledge, this is the largest analysis of its kind to date to investigate associations between several questionnaire-based risk factors and quantitative tissue composition metrics of the normal breast. The large sample size allowed us to conduct analysis overall and stratified by menopausal status and other relevant characteristics. We were able to control for several potential confounders in our analyses and to conduct relevant sensitivity analyses, all of which strongly support the internal validity of our findings. Nevertheless, the current analysis is not without limitations. For instance, we were unable to examine longitudinal changes in tissue composition metrics. Also, we were unable to directly evaluate the potential impact of sociodemographic, environmental, and socioeconomic factors on our BMI and race-related findings, but all our estimates were adjusted for educational level as a surrogate for socioeconomic status. The use of questionnaire-based data may be associated with measurement error and recall bias. However, the accuracy and reproducibility of self-reports for many of the factors that were significantly associated with breast tissue composition metrics in the current study have been previously documented to be high –72. MoreIn conclusion, we investigated the relationships of host, lifestyle, and reproductive factors on quantitative tissue composition metrics of the normal breast, including epithelium, stroma, adipose tissue, fibroglandular tissue, and histologic ESP (a metric of the proportion of fibroglandular tissue that is epithelium relative to stroma). We found several established breast cancer risk factors to be associated with individual tissue metrics, including novel observations with respect to ESP. In particular, age, menopausal status, parity, breastfeeding history, BMI, race, FHBC, alcohol intake, and MHT use demonstrated heterogenous associations with ESP consistent with their documented associations with incidence of molecular breast cancer subtypes. Overall, our findings provide critical insights into the role of stromal-epithelial interactions in breast cancer etiology, with implications for our understanding of the histogenesis of breast cancer subtypes. Conceivably, variations in tissue composition metrics on biopsy, particularly ESP, could serve as intermediate markers of risk and might be used to inform breast cancer prevention strategies for women.Additional file 1. Fig. S1: Flow diagram showing the exclusion and exclusion criteria employed in this analysis.Additional file 2. Fig. S2: Magnitude of the associations between parity and epithelial composition of the normal breast according to the amount of stroma on the slides.Additional file 3. Fig. S3: Associations between race and epithelium-to-stroma proportion (ESP) by parity and body mass index (BMI).Additional file 4. Fig. S4: Distribution of BCRAT (or Gail) scores of absolute breast cancer risk for participants in this study.Additional file 5. Table S1: Frequencies of missing values for each variable included the current analysis of 4108 women from the Komen Tissue Bank Study. Table S2: Associations of host, reproductive, and lifestyle factors with epithelium-to-stroma proportion among healthy women volunteers participating in the Komen Tissue Bank project, using missing values indicators, and following multiple imputation (N = 4108). Table S3: Associations of risk factors with epithelium-to-stroma proportion among healthy women volunteers participating in the Komen Tissue Bank project, with and without adjustment for age at first full-term birth (AFFB). Table S4: Associations of host, reproductive, and lifestyle factors with quantitative tissue composition metrics among healthy premenopausal women participating in the Komen Tissue Bank project (N = 2696). Table S5: Associations of host, reproductive, and lifestyle factors with quantitative tissue composition metrics among healthy postmenopausal women participating in the Komen Tissue Bank project (N = 1412).


Breast cancer disproportionately impacts Native Hawaiian, CHamoru, and Filipino women. Few culturally informed interventions addressing breast cancer survivors exist and none have been developed or tested specifically for Native Hawaiian, CHamoru, and Filipino women. This study aimed to conduct focus groups with Native Hawaiian, CHamoru, and Filipino women previously diagnosed with breast cancer to inform future research in Guam and Hawai’i. Convenience sampling and grounded theory approaches were used. Focus group sessions were conducted during summer 2023 and included questions to understand the barriers, motivators, and implementation recommendations for lifestyle interventions aimed at reducing the risk for breast cancer recurrence among the target population. Data saturation was reached after a total of seven focus groups (an average of four survivors/group per site) were conducted (three in Hawai’i and four in Guam), which represented 28 breast cancer survivors. Themes from the focus groups emerged around developing support systems with other survivors, providing physical activity and nutrition intervention activities and materials in multiple formats, and incorporating activities and foods that accommodate the side effects of breast cancer treatments and are culturally relevant. The average desired intervention length was eight weeks. These findings will inform the development and feasibility testing of a culturally informed lifestyle intervention for breast cancer survivors in Guam and Hawai’i. Breast cancer in both Guam and Hawai’i is the second highest contributor to cancer mortality among women . Breast Obesity results from a number of social determinants of health, as depicted in the social ecological model (SEM) ,9. The SLifestyle interventions that have included cultural adaptations for Filipinos, Native Hawaiians, and/or CHamorus show promise for improved recruitment, retention, and health outcomes ,15,16. CTo address the gap in lifestyle interventions for Native Hawaiian, CHamoru, or Filipino breast cancer survivors, the Traditional and New Lifestyle Interventions to Prevent Breast Cancer Recurrence (TANICA) study was initiated in 2021. TANICA was carried out in two phases. Phase I engaged community collaborators working with indigenous populations in health and research to develop an understanding of the ideal settings to promote and support behavior changes among Native Hawaiian, CHamoru, or Filipino breast cancer survivors . The essential oils, I cannot have that. I cannot have sesame seeds anymore. …For me, I’m looking for is what things can I eat? What things do I need to avoid I really had to cut out a lot of things…”—Hawai’i Participant #7Accessibility and availability were mentioned both as barriers and facilitators. In Guam and Hawai’i, high food costs were a barrier to the accessibility and availability of healthy food. However, the availability of local  ingredients was viewed as a facilitator. External factors were both barriers and facilitators to healthy eating in Guam. Within the social structure, social obligations related to attending gatherings and eating were barriers, yet tight social networks were a support system that facilitated healthy eating. interpersonal strategies to promote physical activity as well as a healthy diet  at both sites, yet many of the facilitators and barriers identified were similar and participants agreed with others’ contributions, revealing place-based motivators and challenges unique to each site. The findings also supported having interventions for mixed groups grounded in the shared cultural values and practices and the island environment and resources.Participants in Guam and Hawai’i preferred an eight-week intervention, which aligned with a number of existing health interventions that target lifestyle changes for Native Hawaiian, Pacific Islander, or Filipino groups. Some examples included the Wahine Heart Wellness Program, which is a cardiovascular disease education program for Asian, Native Hawaiian, and Pacific Islander women , and anoGroup-based, in-person physical activities were requested by participants in Guam and Hawai’i, similar to other interventions such as the “Siglang Buhay” intervention , FilipinLastly, TANICA participants recognized the need for nutrition and physical activity interventions that address multiple facets of themselves, such their families, communities, and cultures. In Guam, Filipino participants emphasized their faith as a facet of themselves to be recognized. This was supported by Playdon et al. , who alsThe “talk story” approach has been documented in qualitative research as a culturally acceptable strategy used with Native Hawaiian and other Pacific Islanders and in this study, it was identified as a component to include in a lifestyle intervention through social support . This alThe timing of this study revealed an unexpected finding, which was the impact of the COVID-19 pandemic on establishing and maintaining healthy behaviors for breast cancer survivors. At both study sites, women reported that they started or learned a new physical activity and experienced challenges to being active due to indoor gyms or public spaces being inaccessible during the pandemic. For many, new or sustained physical activity was outdoors and related to indoor restrictions, which may have made women more likely to prefer outdoor activities during the focus group sessions. Another impact of the pandemic was the increased willingness to participate in virtual learning and openness to receive digital or online resources , which was related to the frequent use of virtual meeting platforms and digital public service announcements ,39,40,41sociocultural-level barriers and facilitators were identified at both sites and across components. These findings underscored the unique needs of each population. Together, this information reinforces the need for place-based and adapted interventions to best serve this population. This novel study investigated facilitators and barriers to lifestyle interventions across the SEM. This information provides unique insight into the women’s lived experiences and key levels of the SEM to address. Interestingly, all levels of the SEM were not represented in the facilitators and barriers mentioned by participants, which differed between the two sites and by component type . For example, in Guam, barriers and/or facilitators were identified at all levels, except the organizational level for physical activity and the community level for the nutrition component. In Hawai’i, barriers and/or facilitators were mentioned for four of six SEM levels for the physical activity  and nutrition  components. There were parallel findings between research sites in that participants did not identify barriers and/or facilitators at the organizational and community levels for physical activity and nutrition components, respectively. This demonstrated possible similarities between sites. Unsurprisingly, A strength of this qualitative study was that it addressed and met the 21 criteria of the Standards for Reporting Qualitative Research Guidelines . LimitatDeveloping support systems with other survivors, providing physical activity and nutrition intervention activities and materials in multiple formats, and incorporating activities and foods that accommodate the side effects of breast cancer treatments and are culturally relevant were key themes. The average desired intervention length was eight weeks. The findings of the study were supported by a number of published interventions that targeted similar ethnic groups but with a focus on different health conditions . These findings will be used immediately to inform the development and feasibility testing of a lifestyle intervention aimed at reducing obesity and improving the diet and physical activity of Native Hawaiian, CHamoru, and Filipino breast cancer survivors. These findings may also be of interest to others working to develop interventions within the Native Hawaiian, CHamoru, and Filipino communities in Hawai’i and Guam.