A Mediation Analysis of Obesity and Adiponectin Association with Postmenopausal Breast Cancer Risk: A Nested Cohort Study in the International Breast Cancer Intervention Study II (IBIS-II) Prevention Trial.

Obesity is a risk factor for postmenopausal breast cancer (BC), and evidence suggests a role for adiponectin in the relationship between obesity and BC. We investigated whether adiponectin or other biomarkers mediate the effect of body mass index (BMI) on postmenopausal BC risk in a cohort study nested in the IBIS-II Prevention Trial. We measured adiponectin, leptin, IGF-I, IGFBP-1, high-sensitivity C-reactive protein, glycemia, insulin, HOMA-IR index, and SHBG in baseline and 12-month serum samples from 123 cases and 302 matched controls in the placebo arm of the IBIS-II Prevention trial. We conducted the main mediation analysis considering baseline BMI as an exposure and the 12-month adiponectin increase as a mediator after adjustment for the Tyrer-Cuzick score and the lipid-lowering medications/supplements use. In the multivariable Cox model, both the 12-month adiponectin increase (HR, 0.60; 95%CI, 0.36-1.00) and BMI were associated with BC risk (HR, 1.05; 95%CI, 1.00-1.09), with a 40% reduction in women with a 12-month increase in adiponectin. A significantly higher cumulative hazard of BC events was observed in obese women (BMI > 30) with decreased adiponectin (p = 0.0087). No mediating effect of the adiponectin increase on the total effect of BMI on BC risk was observed (natural indirect effect: HR, 1.00; 95%CI, 0.98-1.02). Raising adiponectin levels might be an attractive target for postmenopausal BC prevention.

Breast cancer preventive practices and associated factors among reproductive age women in Wadila District, North East Ethiopia: community based cross-sectional study.

BACKGROUND: Cancer is one of the leading causes of morbidity and mortality worldwide. Among all cancer types, breast cancer stands out as the most common and is characterized by distinct molecular characteristics. This disease poses a growing public health concern, particularly in low and middle-income countries where it is associated with high mortality rates. Despite these challenges, there is a paucity of data on breast cancer preventive practices and associated factors among reproductive-age women in Wollo, Ethiopia. Hence, this study aimed to evaluate the level of breast cancer awareness, preventive practices, and associated factors among women of reproductive age residing in Wadila district, Wollo, Ethiopia in the year 2022. METHOD: A cross-sectional community-based study involving 352 women of reproductive age in Wadila district was carried out between May and June 2022. Participants were selected using a systematic random sampling technique, and data analysis was conducted using Statistical Package for Social Science (SPSS) version 23 software. Logistic regression analysis was utilized to determine the odds ratio for variable associations, with statistical significance set at p < 0.05. RESULT: The prevalence of breast-examination among women of reproductive age was determined to be 40.1% (95% Interval [CI]: 34.94-45.18). Factors such as educational status (Adjusted Odds Ratio [AOR]: 0.28, 95% CI: 0.13-0.6), income (AOR: 0.19, 95% CI: 0.11-0.33), and family history of breast conditions in reproductive-age women (AOR: 1.90, 95% CI: 1.08-3.34) were significantly linked to the practice of breast self-examination in this population. CONCLUSION: The study highlighted a decline in regular breast self-examination among women of reproductive age. It revealed that the reduced frequency of regular breast self-examination was a prevalent concern among women in this age group and the broader community. Educational level, monthly income, and family history of cancer among women of reproductive age were identified as significant factors linked to the practice of regular breast examination.

Cancer health awareness through screening and education: A community approach to healthy equity.

BACKGROUND: The Cancer Health Awareness through screeNinG and Education (CHANGE) initiative delivers cancer awareness education with an emphasis on modifiable risk factors and navigation to screening for prostate, breast, and colorectal cancers to residents of public housing communities who experience significant negative social determinants of health. METHODS: Residents of five communities participated. Community advisory board members were recruited and provided feedback to local environmental change projects, recruitment, and community engagement at each site. At each site, four education sessions were provided by trained facilitators on cancer risk factors and etiology, racial disparities, eligibility for cancer screening, and participation in clinical trials. Attendance, knowledge, attitudes and beliefs about cancer, and height, weight, and waist circumference were measured at baseline and 1-week post-CHANGE sessions. RESULTS: 90 residents (60% 65 and older years old, 33% male, 60% High School education, 93% AA) participated in the program. 95% completed post-intervention evaluation. Participants were eligible for breast (n = 12), prostate (n = 15), and colorectal screening (n = 25) based on American Cancer Society guidelines, and 22 for tobacco cessation; 21 participants accepted navigation assistance for these services. At post-test, participants significantly increased in knowledge and behaviors around obesity/overweight risk for cancer, nutrition, and physical activity. Colorectal, prostate, and breast cancer knowledge scores also increased, but were not significant. CONCLUSIONS: CHANGE participants demonstrated improved health knowledge and intentions to improve their modifiable health behaviors. Participants reported being motivated and confident in seeking preventive care and satisfaction with community engagement efforts. Replication of this project in similar communities may improve knowledge and health equity among underserved populations.

Mediterranean diet: Fighting breast cancer naturally: A review.

The effects and mechanisms of the Mediterranean diet (MD) on the incidence, recurrence, and prevention of breast cancer (BC) have been extensively investigated since the 1990s. Recent years have witnessed significant advancements in understanding the relationship between the components of the MD and BC, particularly in terms of their role and adherence. This comprehensive review focuses on several key aspects: the influence of the adherence of MD in cohort studies conducted across different regions on BC, the effects and mechanisms of individual component or main components as well as the supplementation of vitamins, drugs, exercise, and other factors of MD on BC; the variations in the impact of the MD on premenopausal and postmenopausal women, as well as different types in BC cases; the possible mechanisms underlying the development, recurrence, and prevention of BC in relation to the MD; and the interaction effects of individual genetic polymorphisms with the MD. Based on current research findings, this review highlights the key issues and identifies future research directions in investigating the relationship between the MD and BC. Furthermore, it suggests that healthy women of various ages and BC patients should adhere to MD in order to prevent BC or improve the prognosis.

Synergic Role of Dietary Bioactive Compounds in Breast Cancer Chemoprevention and Combination Therapies.

Breast cancer is the most common tumor in women. Chemotherapy is the gold standard for cancer treatment; however, severe side effects and tumor resistance are the major obstacles to chemotherapy success. Numerous dietary components and phytochemicals have been found to inhibit the molecular and signaling pathways associated with different stages of breast cancer development. In particular, this review is focused on the antitumor effects of PUFAs, dietary enzymes, and glucosinolates against breast cancer. The major databases were consulted to search in vitro and preclinical studies; only those with solid scientific evidence and reporting protective effects on breast cancer treatment were included. A consistent number of studies highlighted that dietary components and phytochemicals can have remarkable therapeutic effects as single agents or in combination with other anticancer agents, administered at different concentrations and via different routes of administration. These provide a natural strategy for chemoprevention, reduce the risk of breast cancer recurrence, impair cell proliferation and viability, and induce apoptosis. Some of these bioactive compounds of dietary origin, however, show poor solubility and low bioavailability; hence, encapsulation in nanoformulations are promising tools able to increase clinical efficiency.

Access to Cancer Care: Prevention and Screening for Females Post Kidney Transplantation Around the World.

Kidney transplantation offers recipients superior outcomes and improved quality of life compared with dialysis. However, the need for ongoing immunosuppression places recipients at increased risk of certain forms of cancer. Screening and early detection of precancerous lesions are one of the few proven ways to lower the risk of cancer morbidity and mortality in the transplant population. Women have additional barriers to cancer screening services globally, especially in low- and middle-income countries as well as within certain disadvantaged groups in high-income countries. There is a dearth of published data on screening guidelines and policies on post-transplant malignancy in female recipients. It is vital that health care providers and patients are educated regarding the risks of cancer at all post-transplant stages and that the recommended screening policies are adhered to in order to reduce associated morbidity and mortality in this at-risk group.

Co-development of breast cancer health promotion educational materials for ethnically diverse women working with hairdressing and beauty salons: BELONG study.

BACKGROUND: Improved screening uptake is essential for early breast cancer detection, women's health and reducing health disparities. However, minority ethnic and deprived communities often face lower breast cancer screening rates and limited access to culturally tailored educational materials. A recent review found limited culturally tailored materials for breast cancer education. AIM: To investigate the culturally appropriate interfaces and preferences of salon staff in educating their clients about breast cancer METHOD: We used a two-stage approach, following the Double Diamond framework; discover and define phases. Relevant breast cancer materials (i.e., based on cultural appropriateness, English language presentation, and alignment with the UK context) were assessed using the Suitability Assessment of Materials (SAM) toolkit. Interviews with ethnically diverse salon staff provided insights into their needs and preferences for client education materials. Thematic analysis was applied to interview transcripts. RESULTS: Cultural appropriateness was evident in 9/14 (64%) of the materials identified (e.g., targeting black ethnicities with positive representations). Of those, six of them demonstrated an overall SAM rating of 76% ("Superior"). Thematic analysis of interviews identified seven key themes, including the importance of engagement strategies, education and awareness for health promotion, salon staff's role, preferred training methods, supportive materials, inclusivity, representation, and participant satisfaction. CONCLUSION: This study highlights the SAM toolkit's role in selecting suitable educational materials for breast cancer prevention. The research offers prospects for improving breast cancer awareness in ethnically diverse communities and addressing healthcare access disparities, with salon hairdressers emerging as crucial advocates for health promotion.

Assessing nutrition-related knowledge, attitudes, and practices towards breast cancer prevention among female students at the Federal University of Oye-Ekiti, Nigeria.

BACKGROUND: Breast cancer remains a complex disease and leading cause of cancer-related death in Nigerian women. Recently, the role of nutrition has been highlighted in the etiology of breast cancer. METHODS: The aim of this research was to evaluate the nutrition-related knowledge, attitude, and practices of female university students. We also investigated the correlation between their demographic characteristics and their knowledge and attitudes of the survey participants. A descriptive cross-sectional study was carried out among female students at the Federal University of Oye (FUOYE), Nigeria. Participants completed self-administered questionnaires designed to assess their knowledge, attitude, and practices concerning cancer prevention. Statistical analysis was performed using SPSS 20, and significance was set at p < 0.05. RESULTS: Out of the 402 students who received the questionnaire, 300 completed it. The average age of the participants was 21.26 years with a standard deviation of 2.68. There was generally limited knowledge regarding breast cancer risk factors, with 45% of participants citing family history as the most recognized risk factor. Overall, knowledge level was influenced by the participants' permanent place of residence and course of study. Attitudes towards the impact of maternal and paternal nutrition on breast cancer prevention were notably low. Additionally, less than half of the participants demonstrated good dietary practices. CONCLUSION: This study revealed low levels of nutrition-related knowledge concerning cancer prevention, accompanied by poor dietary habits among the participants. These results suggest a possible link between inadequate knowledge about breast cancer prevention and the observed poor dietary practices among the participants. The frequent consumption of unhealthy foods among the participants may be a pointer to higher risk of breast cancer in the future, emphasizing a need for health education targeted at this group.

An analytical framework for breast cancer public policies in Sub-Saharan Africa: results from a comprehensive literature review and an adapted policy Delphi.

BACKGROUND: Breast cancer is the leading cause of death from cancer in women and is a major public health problem worldwide. Despite the lower incidence rates of breast cancer in resource-limited settings, especially sub-Saharan Africa, there is a higher mortality rate compared to high-resource countries where the disease has a higher incidence. This makes breast cancer the second deadliest cancer in African women. These poor results reflect the weakness in public health policies. The aim of this paper is to contribute to the effective control of breast cancer by designing a framework for a comprehensive and systemic analysis of these policies in Sub-Saharan Africa. METHODS: This research is based on a literature review that adopted a systematic approach followed by a modified policy Delphi involving breast cancer experts in Sub-Saharan Africa. We included narrative reviews and systematic reviews/meta-analyses published between 2015 and 2022 as well as official documents in the analysis. We integrated the World Health Organization's health system building blocks with Walt and Gilson's policy analysis triangle to analyse the information collected and develop our analytical framework. RESULTS: A total of 22 reviews and documents were included in the study. Sixteen breast cancer experts from Sub-Saharan Africa participated in the first Delphi round, and nine participated in the second round. The different components identified for a comprehensive and systemic analysis of effective breast cancer policies can be classified into policy content divided according to the health system building blocks and related policy processes; individual, organized national and international policy stakeholders; and policy contexts. CONCLUSION: This study enabled the design of a framework suitable for the comprehensive and systemic analysis of breast cancer control policies in Sub-Saharan Africa. This framework can be used as a checklist for stakeholders to guide the planning, implementation and evaluation of policies and specific breast cancer control programmes at the national and facility levels.

[Interest in the use of polygenic risk scores in breast cancer screening and preventive medicine]. / Intérêt de l'utilisation des scores de risques polygéniques dans le dépistage du cancer du sein et la médecine de prévention.

Despite screening programmes, numerous clinical studies and new breast imaging techniques, breast cancer incidence for women continues to rise. The arrival of predictive and personalized medicine could clearly redefine our screening recommendations. One promising approach to improving screening would be to use tools to predict the risk of developing breast cancer, including polygenic risk scores (PRS). This approach will enable us to offer women risk-based screening by adapting the frequency, type and age of screening. This article reviews some definitions of the PRS and breast cancer screening. We also explain the risk assessment models that have been developed and the various studies underway on personalized screening.

Malgré les programmes de dépistage, les nombreuses études cliniques et les nouvelles techniques d'imagerie mammaire, l'incidence du cancer du sein chez la femme continue à augmenter. L'arrivée de la médecine prédictive et personnalisée pourrait clairement redéfinir nos recommandations de dépistage. Une des approches prometteuses pour améliorer le dépistage serait d'utiliser les outils de prédiction du risque de développer un cancer du sein en incluant les scores de risques polygéniques (PRS). Cette approche permettra de proposer aux femmes un dépistage basé sur le risque en adaptant la fréquence des examens ainsi que le type et l'âge du début du dépistage. Cet article reprend quelques définitions concernant le PRS et le dépistage du cancer sein. Nous allons passer en revue les modèles de prédiction de risque qui ont été développés et les différentes études en cours sur le dépistage personnalisé.

Health literacy and mammography screening behaviors among women living in a rural area of Turkey.

INTRODUCTION: Breast cancer is the most common cause of cancer-related deaths. and early diagnosis could reduce breast cancer deaths. Therefore, health literacy is one of the most important determinants of participation in cancer screening for early diagnosis. This study aimed to determine the relationship between women's mammography screening behaviors and health literacy levels. METHODS: The cross-sectional study included 312 women aged 40-69 years living in a rural area. Data were collected through face-to-face interviews using a personal information form and the Turkish Health Literacy Scale (THLS-32). RESULTS: Of the women, 28.5% had mammography in the last 2 years. Of concern was the low health literacy levels. In addition, there were significant differences in the THLS-32 subgroup scores, including the THLS-32 total score, among the mammography screening groups. CONCLUSION: Health literacy levels of women were related to mammography screening rates. For this reason, effective intervention studies aiming to increase society's health literacy levels may contribute to an increase in breast cancer screenings.

Recommendations of Health Care Professionals on the Issue of Breastfeeding in BRCA Carriers.

Purpose: Breastfeeding is associated with numerous short- and long-term neonatal and maternal health benefits. Specifically, in BRCA1/2 female carriers, breastfeeding has been shown to reduce the considerably increased risks of breast and ovarian cancer. Nevertheless, there is paucity of data referring to the recommended postpartum surveillance of BRCA1/2 carriers. The purpose of this study was to evaluate the recommendations of health professionals regarding breastfeeding in BRCA carriers. Methods: This cross-sectional survey was conducted using an anonymous questionnaire distributed through the "Good BRCA Genes-a support and information group for BRCA carriers" association. The questionnaire included Likert scale and open-ended questions, aimed to evaluate the performance of health professionals at various aspects of the recommended follow-up. Results: Of the 388 participants, 233 (60.0%) expressed dissatisfaction with explanations provided by health professionals regarding pregnancy and breastfeeding. Women reporting dissatisfaction with explanations were younger (36.8 ± 7.0 years) compared to those satisfied with the explanations (38.8 ± 7.6 years, p = 0.0081). No significant differences were noted between women satisfied and those dissatisfied with the explanations in terms of age of genetic diagnosis, origin, religion, geographic location, and the rates of personal or familial cancer history. Of the 175 responses to an open question "please describe the reasons for unsatisfactory explanation," 76.6% stated they received no explanation on the subject, whereas 5.4% described minimal explanation or conflicting recommendations. Surprisingly, 4.7% recalled being advised to avoid, stop, or limit breastfeeding. Discussion: The results of this survey emphasize the lack of knowledge of health professionals on the issue of breastfeeding in BRCA carriers. As genetic variants in these genes involve significant proportion of the population (up to 2.5% in Ashkenazi Jewish population), raising the awareness of health care personnel to the benefits of breastfeeding in these women seems prudent.

Effects of vitamin D supplementation on a deep learning-based mammographic evaluation in SWOG S0812.

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.

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

INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.

Breast cancer awareness among women of reproductive age- a questionnaire based study.

INTRODUCTION: Breast cancer is the most frequent cancer in women worldwide, and its prevalence is rising among younger women of reproductive age. The study aims to investigate their awareness of breast cancer risk factors, warning indicators, and preventive methods. The study also aimed to assess participants' knowledge of breast self-examination (BSE) and their practices with this crucial screening method. METHODOLOGY: To achieve these goals, we used a cross-sectional survey employing a structured questionnaire. The questionnaire included multiple-choice and open-ended items about breast cancer awareness, knowledge, and practices. RESULTS: There were 400 questionnaires given out to female patients attending the out-patient department, and 290 of them were completed and returned. The majority of responders to our poll, 88 %, were aware that breast cancer is the most frequent cancer in women. The fact that 57 % of the individuals never examined their own breasts is a worrying result. There was a statistically significant difference between knowledge and family history (X2 = 13.8, P < 0.001) and knowledge and schooling (X2 = 6.4,P < 0.001). Both the practise of BSE and knowledge of BC were good in respondents under the age of 45, however they differed statistically significantly (X2-2.8,P = 0.041 and X2-2.6, P = 0.001, respectively). CONCLUSION: Understanding the extent of breast cancer awareness and knowledge gaps in this population is critical for planning targeted interventions and educational efforts. By identifying areas where knowledge is weak, healthcare practitioners and governments can implement policies to encourage early detection practices, reduce delays in seeking medical aid, and ultimately improve breast cancer outcomes.

The Women's Health Initiative Randomized Trials and Clinical Practice: A Review.

Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years. Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up. Conclusions and Relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

Influence of variables on breast self-examination: Potential barrier or enhancement of breast cancer prevention.

INTRODUCTION: Breast self-examination (BSE) is an important tool for early detection of breast cancer and can contribute to increased awareness and familiarity with breast tissue. This study aimed to review factors that influenced BSE in preventing breast cancer. METHODS: In the initial stage of searching for journal articles, 186 journals were obtained, then screening was carried out within a time span of 2019-2024 and using Indonesian and English 54 journals. Of the 12 journals reviewed, the results showed that 4 journals reviewed had conducted pre and post-BSE practices, and 8 journal reviews conducted BSE practices conducted by students and health workers. RESULTS: Several factors play an important role in implementing BSE, namely age, knowledge, history of exposure to information, family history, ethnicity, and attitude. Overall, the study shows that the need to create awareness and educate women, especially rural women, on the importance of BSE as a preventive measure for breast cancer is paramount. CONCLUSIONS: Factors influencing the implementation of BSE can be a barrier or an enhancement in breast cancer prevention.

Massage on the prevention of breast cancer through stress reduction and enhancing immune system.

INTRODUCTION: Housewives are a population at high risk of breast cancer due to repeated or chronic exposure to stress. Prevention in a simple yet evidence-based manner is needed. METHODS: This study is a narrative review of the potential of massage as breast cancer prevention through stress and immune system mechanisms. RESULTS: Massage is able to prevent chronic stress through improved sleep and fatigue and lower stress levels. Prevention of chronic stress will maximize the function of cells that eliminate cancer cells, such as B cells, T cells, and natural killer (NK) cells, and improve the balance of Foxp3 Tregulator cells. Partnered delivery massage will bring effective benefits for stress reduction. CONCLUSIONS: Massage can provide indirect prevention of breast cancer, and partnered delivery massage can be a good choice to reduce stress.

A novel combinatorial approach using sulforaphane- and withaferin A-rich extracts for prevention of estrogen receptor-negative breast cancer through epigenetic and gut microbial mechanisms.

Estrogen receptor-negative [ER(-)] mammary cancer is the most aggressive type of breast cancer (BC) with higher rate of metastasis and recurrence. In recent years, dietary prevention of BC with epigenetically active phytochemicals has received increased attention due to its feasibility, effectiveness, and ease of implementation. In this regard, combinatorial phytochemical intervention enables more efficacious BC inhibition by simultaneously targeting multiple tumorigenic pathways. We, therefore, focused on investigation of the effect of sulforaphane (SFN)-rich broccoli sprouts (BSp) and withaferin A (WA)-rich Ashwagandha (Ash) combination on BC prevention in estrogen receptor-negative [ER(-)] mammary cancer using transgenic mice. Our results indicated that combinatorial BSp + Ash treatment significantly reduced tumor incidence and tumor growth (~ 75%) as well as delayed (~ 21%) tumor latency when compared to the control treatment and combinatorial BSp + Ash treatment was statistically more effective in suppressing BC compared to single BSp or Ash intervention. At the molecular level, the BSp and Ash combination upregulated tumor suppressors (p53, p57) along with apoptosis associated proteins (BAX, PUMA) and BAX:BCL-2 ratio. Furthermore, our result indicated an expressional decline of epigenetic machinery HDAC1 and DNMT3A in mammary tumor tissue because of combinatorial treatment. Interestingly, we have reported multiple synergistic interactions between BSp and Ash that have impacted both tumor phenotype and molecular expression due to combinatorial BSp and Ash treatment. Our RNA-seq analysis results also demonstrated a transcriptome-wide expressional reshuffling of genes associated with multiple cell-signaling pathways, transcription factor activity and epigenetic regulations due to combined BSp and Ash administration. In addition, we discovered an alteration of gut microbial composition change because of combinatorial treatment. Overall, combinatorial BSp and Ash supplementation can prevent ER(-) BC through enhanced tumor suppression, apoptosis induction and transcriptome-wide reshuffling of gene expression possibly influencing multiple cell signaling pathways, epigenetic regulation and reshaping gut microbiota.