Breast cancer is a leading cause of cancer and, therefore, a major health threat for women in the United States and worldwide. We have seen over the years major advances in breast cancer prevention and care. Breast cancer screening with mammography leads to reduction in breast cancer mortality, and breast cancer prevention treatment with antiestrogens results in reduction in breast cancer incidence. More progress, however, is urgently needed for this common cancer that affects 1 in 11 American women in their lifetime. Not all women have the same breast cancer risk. A personalized approach is highly desirable as women with higher breast cancer risk may benefit from more intense breast cancer screening and/or prevention intervention while lower risk women may be spared with the cost, inconvenience, and emotional burden of these procedures. In addition to age, demographics, family history, lifestyle, and personal health, genetics is an important determinant of an individual's risk for breast cancer. Over the past 10 years, advances in cancer genomics identified multiple common genetic variants from population studies that collectively can contribute significantly to an individual's breast cancer risk. The effects of these genetic variants can be summarized as a “polygenic risk score” (PRS). We are among the first groups to prospectively evaluate the performance of these risk prediction instruments among women veterans of the Million Veteran Program (MVP). A 313-variant PRS (PRS313) predicted incident breast cancer for a prospective cohort of European (EUR) ancestry women veterans with an area under the receiver operating characteristic curve (AUC) of 0.622. The PRS313 performed less well for AFR ancestry however, with an AUC of 0.579. This is not surprising as most genome-wide association studies were conducted in people of European ancestry. This is an important area of health disparity and unmet need. The large population size and diversity of the MVP provide a unique and important opportunity to explore novel approaches to produce accurate and clinically useful genetic risk prediction instruments for minority populations. Breast cancer is a leading cause of cancer death for American women. It is also a serious issue for women veterans. Our most recent Million Veteran Program (MVP) analysis found that out of 53.5K women veterans from the MVP without prior breast cancer diagnosis (mean age at entry 48.8 and 30.0% of African [AFR] ancestry), there were 818 new breast cancer diagnoses over a median follow-up of 5.7 years, translating into a breast cancer incidence of 2.70 per 1000 per year (unpublished).1 However, the current breast cancer screening strategy is largely “one size fits all,” except for very high-risk women, such as those with BRCA mutations or prior chest wall irradiation. Appropriate risk assessment is highly desirable as higher risk women may benefit from more intense screening approaches, whereas lower risk women may do equally well with less intensity, therefore, avoiding the cost and inconvenience of screening.Breast cancer screening with mammography leads to reduction in mortality from breast cancer.3 There are a growing number of characteristics that have been validated to predict a woman's risk of developing breast cancer. This includes age; mutation status for breast cancer genes, such as BRCA1 and BRCA2; family history of cancer; personal history of benign breast biopsy; history of benign breast disease, such as atypia; exposure to hormones; breast density as seen on mammography; and more recently, background parenchymal enhancement on MRI.4In addition, tamoxifen has been approved for women above the age of 35 years for breast cancer prevention if they have an elevated risk, as seen with an average 65-year-old Caucasian woman.5) have led to a growing literature on the development and evaluation of breast cancer risk prediction models, for example Refs.6–8Harnessing these features may enable us to more precisely assess the risk of breast cancer development. Understanding individuals' risks for developing breast cancer may allow us to adopt a more appropriate breast cancer screening and/or prevention strategy. Recent successes from genome-wide association studies (GWAS) of breast cancer .10 The performance of PRS313 alone was assessed. Clinical risk models tested included a literature review and a Breast Cancer Risk Assessment Tool,12 implemented with or without PRS313. Thirty one percent of this cohort were of non-Hispanic AFR ancestry.In a prospective cohort of 35,130 women veterans without history of breast cancer (median age 49 years and median follow-up 3.9 years) in the MVP,11 literature review13 in combination with PRS313 had an area under the receiver operating characteristic curve (AUC) of 0.708  in women with European or non-AFR ancestries and 0.625 (0.539–0.711) in AFR women.9 Breast Cancer Risk Assessment Tool with PRS313 had an AUC of 0.695 (0.662–0.729) in European or non-AFR women and 0.675 (0.626–0.723) in AFR women.9Individualized Coherent Absolute Risk Estimator9 Models estimated up to 9% of European and 18% of AFR women with absolute lifetime risk >20%. Women with a lifetime breast cancer risk of >20% are generally considered to be high risk and may be appropriate for clinical studies that would examine whether these women would benefit from more intense breast cancer screening.PRS313 alone without clinical or demographic predictors yielded an AUC of 0.622 (0.580–0.664) in women of European descent and a lower AUC of 0.579 (0.522–0.636) in AFR women. Incorporation of PRS313 with clinical models improved prediction in European, but not in AFR women.14–16 This is a significant area of unmet need as African Americans have higher risk of developing early-onset breast cancer and about 40% higher breast cancer mortality than other ancestral groups in the United States.17We found that PRS313 underperformed in a prospective cohort of women veterans of AFR ancestry in the MVP. This is consistent with prior cross section or case–control studies.18 the authors performed AFR ancestry GWAS meta-analysis , and then meta-analyzed with European ancestry GWAS data  from the Breast Cancer Association Consortium. There was a 13-fold difference between the number of breast cancer subjects between European and AFR ancestries.PRS has shown great promise in improving biomedical outcomes through precision medicine. However, currently available PRS tools are much more accurate in individuals of European descent, as other ancestral groups were under-represented and understudied. In a transethnic breast cancer study,As a result of sample size and possibly different genetic architecture between the two populations, only six loci were identified from individuals of African ancestry, even after trans-ethnic analysis, in comparison with more than 200 loci reported from individuals of European ancestry. The differential performance of PRS across ancestral groups raises a significant concern about potentials to exacerbate health disparities and evokes ethical controversy surrounding the clinical implementation of PRS in general. It is, therefore, essential to include participants representing diverse populations in genomic medicine studies to ensure equitable benefit from scientific discoveries and to prevent further increase in health disparities.To circumvent this, we perform combined analysis with additional cases and controls from the MVP to increase the gain in statistical power for novel locus discoveries in different ancestral groups. Although the most straightforward solution to increase PRS performance across ancestral groups is to build well-powered GWAS resources for diverse populations, we will entertain an alternative approach by taking advantage of the observation that genetic data from different ancestral groups still share substantial information, although with differences in allele frequency, linkage disequilibrium structure, and genetic architecture.19 and PRScsx20 (that have been published), MePred and SDPRX (that are being developed by MVP researchers),21 and other methods. We believe this innovative comprehensive evaluation will offer both insights and guidance to improve risk stratifications for both European and non-European populations, expand our knowledge of disease mechanisms, and benefit disease screening and early prevention strategies.Recently, models have been developed to borrow information from European ancestral groups to help boost the power of predictions in non-European ancestral groups. We plan to conduct a comprehensive simulation and real data analyses in the MVP to evaluate these newly developed cross-population prediction models, including XPASSAll authors have contributed to the writing, editing, and approval of this publication.


Reproductive tract infections influenced a series of inflammatory processes which involved in the development of breast cancer, while the processes were largely affected by estrogen. The present study aimed to explore the associations of breast cancer risk and prognosis with reproductive tract infections and the modification effects of estrogen exposure.We collected history of reproductive tract infections, menstruation and reproduction from 1003 cases and 1107 controls and a cohort of 4264 breast cancer patients during 2008–2018 in Guangzhou, China. We used logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for risk; Cox model was applied to estimate the hazard ratios (HRs) and 95% CIs for progression-free survival (PFS) and overall survival (OS).Pinteraction = 0.015).It was found that previous reproductive tract infections were negatively associated with breast cancer risk , particularly for patients with more menstrual cycles . Patients with previous reproductive tract infections experienced better OS  and PFS . This protective effect on PFS was only found in patients with more menstrual cycles (HR = 0.52, 95% CI:0.34–0.79, The findings suggested that reproductive tract infections may be protective for the initiation and development of breast cancer, particularly for women with a longer interval of lifetime estrogen exposure.The online version contains supplementary material available at 10.1186/s12905-023-02383-3. The relationship between infections and cancer development has been of interest for many years . InfectiIn addition, it had been found that estrogen, an established breast cancer risk factor , exertedA case–control study and a cohort study were conducted to investigate the association of reproductive tract infections with and breast cancer risk and the effect of reproductive tract infections on the prognosis, respectively.Female patients with recent histologically diagnosed primary breast cancer between October 2008 and March 2012 in the First- and Second-Affiliated Hospitals and Sun Yat-sen University Cancer Center, Guangzhou, China, were consecutively included in this study. We excluded women who had metastasized breast cancer or reported a previous history of any cancers. Controls were recruited from women who attended a health check-up during the same period in the same hospitals and then frequency-matched to the cases on age (± 5 years) and. Women with major chronic disease or whose self- reported a history of cancer were excluded. A total of 1551 cases and 1605 cancer-free controls were interviewed using the same questionnaire by trained interviewers face-to-face [The subjects were recruited in the GZBCS between October 2008 and January 2018, as described in previously study . PatientAll subjects must have resided in the Guangzhou area for at least 5 years. This study was approved by the Ethics Committee of the School of Public Health at Sun Yat-sen University. Informed consent was obtained from each participant before the interviews.Candida, Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, and human papillomavirus (as defined by WHO) [Participants were interviewed by well trained investigators using a structured questionnaire in-person at baseline. The questionnaire collects the information about demographic characteristics , family history of breast cancer (yes/no), menstrual history , and reproductive history , and history of reproductive tract infections  which occurred in the fallopian tubes, ovaries, uterus, vagina, cervix and vulva and caused by invasion of pathogens such as  by WHO) . The infWe defined age at menopause as age at final menstrual period, after a 12-month of amenorrhea. Reproductive time was calculated by subtracting the age at menarche between the age at menopause. The duration of parity was defined as the sum for months of live or stillbirth. The duration of pregnancy was calculated as the sum for months of live or stillbirth, induced or spontaneous abortions. The breastfeeding duration was defined as the sum of months of breastfeeding during each birth. We calculated the number of menstrual cycles by subtracting 9 months for every pregnancy, breastfeeding duration for each live birth from the reproductive time, and then converted to years, after which it was multiplied by the reported average number of menstrual cycles per year , 24. LifThe clinicopathological characteristics were obtained from the medical records in hospitals. Immunohistochemical tests was used to determine the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) of breast cancer tissues by pathologists. Detailed definitions of ER, PR, and HER2 status were previously described in detail .We followed up the patients at least every 3 months during the first year, and every 6 months during the second and the third year; thereafter, we followed up patients once every year until death or December 31, 2020. We followed up patients by the means of phone call, and outpatient visit. The information of follow-up contained statuses of survival , updated contact information, and treatment information. Overall survival (OS) was primary endpoint for this study, defined as the time from diagnosis until the date of death; the second endpoint was progression free survival (PFS), defined as the time from diagnosis to the date of progression or death. We censored the survival status of subjects at the latest interview or December 31, 2020.We used multivariate logistic regression models to explore the association of reproductive tract infections with the risk of breast cancer were explored using, and odds ratios (OR) and confidence intervals (95%CI) were calculated. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95%CI for death and progression of breast cancer in association with reproductive tract infections. The following covariates age at diagnosis , status of menopausal , education level , marital status , status of estrogen receptor (negative or positive), human epidermal growth factor receptor 2 status , family history of breast cancer or other cancer (Yes/No), and clinical stage  were adjusted in the models.P < 0.05 was considered to be significant. We performed the above statistical analyses using SPSS, version 25.0.To explore the joint effects of female reproductive tract infections and lifetime estrogen exposure on risk and prognosis of breast cancer, we stratified patients by different lifetime estrogen exposure characteristics. We used product terms in the Cox regression models to estimate the interactions. All statistical tests were two-tailed, and Table As shown in Table We further investigated the modification effects of estrogen exposure on the associations between reproductive tract infections and breast cancer risk. As shown in Supplementary Table As shown in Table A total of 685 women (16%) reported a history of reproductive tract infections. Patients with female reproductive tract infections were more likely to be pre-menopausal, higher education level, married or cohabiting, lower parity, no family history of breast cancer, normal BMI, PR positive, and HER2 negative, while other characteristics were shown no significant associations with the infections Table . Except During the period of follow-up : 24.3–76.4 months), 897 disease progressions occurred, including 299 death and 598 recurrence or metastasis. Table Pinteraction = 0.015). Furthermore, the strength of association between breast cancer survival and reproductive tract infections was stronger in patients with more number of menstrual cycles  than those with less the cycles , though the interaction was not significant. Similar results were observed for other estrogen exposure variables .We further examined the modification effects of estrogen exposure on the associations of reproductive tract infections with prognosis of breast cancer. Shown in Table Epidemiological research on association of reproductive tract infections with development and progression of breast cancer is currently lacking. In the present study, we firstly found that reproductive tract infections were associated with a decreased risk and a better breast cancer prognosis. Furthermore, it was found that the protective effects on the risk and prognosis were stronger in patients with a longer interval of estrogen exposure than patients with the shorter interval.Shigella infection mediate depletion of macrophages and cause tumor regression in mice with breast cancer [It is known that there are an inverse association of acute infections and a positive link of chronic infections with cancer development –28. Acutt cancer . Moreovet cancer , 34. In t cancer , 36. Thet cancer –39. TherPrevious studies have yielded contradictory findings for the associations between reproductive tract infections and cancer development. Reproductive tract infections such as bacterial vaginosis and Chlamydia trachomatis infection were reported to be associated with a decreasing risk of uterine fibroids , 10; theAs for the association between infections and cancer prognosis, previous studies found similar results that infection was associated with a better prognosis of other cancers –45. For There were some limitations in this study. First, the history of reproductive tract infections was self-reported, which inevitably resulted in recall bias. Moreover, owing to the fact that some of the reproductive tract infections were asymptomatic, the infection rate might be underestimated. However, the recall bias and the underestimation occurred equally in both the case group and control group. This non-differential exposure misclassification might bias study estimators towards the null and reduce test power. Second, the hospital-based design might also lead to selection bias. However, the cases and controls were recruited from the same hospital during the same period, and all subjects must have resided in the Guangzhou area from the same catchment area and resemble each other with regard to those selective factors that led to the hospital admission and use of facilities, resulting in that the cases and controls were comparable. Thus, selection bias was minimized. Third, the frequent visits to the gynecologists for reproductive tract infections may increase the detection of early breast cancer, which would cause detection signal bias. However, breast cancer was usually diagnosed by surgeons in Department of Breast Cancer rather than gynecologists in China, suggesting that the bias was limited. Fourth, the women with long life were prone to expose to more oncogenic factors, which might lead to information bias. We performed a sensitivity analysis with the subjects whose age were younger than 65 (Supplementary Table This study firstly examined the associations of pre-diagnosis reproductive tract infections with risk and prognosis of breast cancer. Our findings did suggest that reproductive tract infections were associated with a decreased risk of breast cancer progression, particularly for patients who had a longer interval of lifetime estrogen exposure. It provided a potential predictor of risk and prognosis and a possible therapeutic regimen for breast cancer.Additional file 1.


The impact of family and personal cancer history and emotional factors, such as depression and anxiety, on disease representation has received limited attention in studies investigating the development of cancer‐related worry and risk perception within the context of genetic counseling. The current study endeavors to fill this gap by exploring the extent to which depression and anxiety influence cancer worry and risk perception, and the role of health care‐related fear as potential mediator in this relationship.A sample of 178 women who underwent their first genetic counseling for breast/ovarian cancer, 52% of whom had previous cancer diagnoses, completed questionnaires assessing sociodemographic and clinical information, emotional distress in terms of anxiety and depression, cancer‐related worry, risk perception, and health care‐related fears.Results of mediation analyses showed that cancer‐related worry and risk perception increased with rising levels of depression and anxiety, with health care‐related fears acting as a mediator in the relationship of depression and anxiety with cancer worry and risk perception. Covariate analysis revealed that previous cancer diagnosis increases cancer‐related worry but not risk perception, while the number of family members affected by cancer increases both outcomes.These findings emphasize the need for a holistic approach in genetic counseling and have implications for the clinical practice. The present study explores the extent to which depression and anxiety affect concern and risk perception, and the role of health care‐related fear as a potential mediator in this relationship. Results of mediation analyses showed that cancer‐related worry and risk perception increased with rising levels of depression and anxiety. Furthermore, health care‐related fear acted as a mediator in the relationship between depression and anxiety with cancer worry, as well as depression with risk perception. Covariate analysis revealed that the number of family members affected by cancer influenced risk perception, while previous cancer diagnosis and family cancer history affected cancer‐related worry. The BRCA1/2 mutation is associated with an increased risk of breast and/or ovarian cancer, with carriers of the mutation having a risk respectively of 72% and 44% for BRCA1 and 69% and 17% for BRCA2.Women potentially carrying the BRCA1/2 genetic mutations may have a complex psychological profile, both as a result of their family members' experiences and their own illness. Scientific evidence shows that symptoms of anxiety and depression are significantly present in those undergoing genetic counseling.The family manifestation of cancer also contributes to a specific representation of the disease, such that women with family illness experiences generate representations associated with greater concern for cancer development.In the literature, it is not sufficiently clear what the relationships are between psychological distress, illness representation, risk perception, and cancer worry. The investigation of risk perception showed that these patients may have a subjective and distorted perception of risk, but it is not clear what the influence of emotional distress is in this regard. Studies that have investigated the nature of this relationship have yielded contrasting results. In Caruso et al.,It is essential for the clinical practice to comprehend the association between family experiences, psychological distress, and risk perception. Risk perception is a relevant empirical dimension as individuals who underestimate their cancer risk are less likely to partake in health protective behaviors, while those who overestimate their risk may worry excessively and undergo unnecessary visits and checks.This study aims to investigate whether anxiety and depression affect the perception of risk and worry regarding cancer diagnosis or recurrence among those who have had cancer, and whether health care‐related fears mediate these associations. In addition, the research aims to explore how the presence/absence of the disease, considering the number of family members affected by cancer as a covariate, influences the perceived risk of carrying a genetic mutation or developing cancer and the level of cancer‐related worry.22.1This observational, single center, cohort study focuses on women attending a specialized outpatient clinic for hereditary breast and ovarian cancer. The study considers two subgroups of the population: asymptomatic women without prior cancer diagnosis, and women already diagnosed with or having had breast or ovarian cancer, both awaiting their first genetic counseling consultation. Inclusion criteria were being 18 years or above, having at least one first‐degree relative with breast and/or ovarian cancer, having family members who have not been previously tested for the BRCA1/2 mutation, and not having undergone any genetic counseling before. Exclusion criteria consisted of women under 18 years, belonging to families already tested for BRCA1/2 diagnosis, having previously undergone genetic counseling, or waiting for a cancer screening result.Prior to participation, potential participants were informed of the study objectives and were required to complete an informed consent form to take part in the study. Participation was completely voluntary and no compensation was offered. The study received formal ethical approval from the Ethical Committee of the “Regina Elena” National Cancer Institute (RS1721/22/2699).2.2The following data were collected: sociodemographic and clinical information, data from a self‐report questionnaire on emotional distress  and a self‐report questionnaire on cancer‐specific distress and personal and genetic risk perception.The sociodemographic and clinical data included age, educational level, information on previous cancer diagnosis, and the number of first‐degree relatives affected by breast, ovarian, and/or other types of cancer.2.3The Cognitive Behavioral Assessment‐Hospital Form CBA‐H19 is a 2.4The cancer worry scale was originally developed to evaluate the impact of receiving abnormal mammogram results on women's breast cancer worries, their breast self‐examination (BSE) frequency and intentions to obtain subsequent mammograms.The Italian version of the cancer worry scale–genetic counseling CWS‐GC21 was m2.5r coefficient) between the predictors, the mediator, and the dependent variables. Analysis of covariance (ANCOVA) was run to test for the effects of having had or not a previous diagnosis of cancer on the dependent variables , taking into consideration the number of first‐degree relatives with cancer as a covariate.Descriptive statistics was used to describe the sociodemographic characteristics of participants. Preliminary analyses were performed to calculate the correlations  and risk perception .Pearson's correlations were significant between all the psychological variables , after controlling for the effect of the number of relatives with cancer  . Marginal means of cancer worry were 43.24 and 34.20 for having or not a cancer diagnosis, respectively, with higher worries reported by patients having had a diagnosis of cancer. For risk perception, the effects of having had or not a diagnosis was nonsignificant  = 0.40, p = 0.53), after controlling for the effect of the number of relatives with cancer  = 14.86, p < 0.001) . Marginal means of risk perception were 49.08 and 48.95 for having had or not a cancer diagnosis, respectively, indicating similar perception of risk between patients previously diagnosed and asymptomatic women attending the genetic counseling.ANCOVA results regarding the effects of having or not a diagnosis of cancer on cancer worry and risk perception, considering the number of relatives with cancer as a covariate, were as follows. For cancer worry, the effect of having had or not a diagnosis of cancer was significant  of the variance in cancer worry and 16% (R2 = 0.16) of the variance in risk perception. Health care‐related fears partially mediated the effect of depressive reactions on cancer worry and fully mediated the effect of depressive reactions on risk perception  of the variance in cancer worry and 20% (R2 = 0.20) of the variance in risk perception. Health care‐related fears partially mediated the effect of state anxiety on cancer worry and did not mediate the effect of state anxiety on risk perception  of cancer worry, with the partial mediation of health care‐related fears, compared to depressive reactions (R2 = 0.41). In terms of risk perception, state anxiety also appeared to be a better predictor (R2 = 0.20) than depressive reactions (R2 = 0.16). However, while the relationship between depressive reactions and risk perception was fully mediated by health care‐related fears, the relationship between state anxiety and risk perception was only direct and not mediated by health care‐related fears.The comparison of the two mediation models suggests that state anxiety was a slightly superior predictor  to allow reliable analyses on the associations between the type of cancer and other psychological variables in the study. This study suggests that having had or not cancer influence cancer worry, so it would have been reasonable to conduct separate mediation models for the two subgroups of women (with or without a cancer diagnosis) in relation to cancer worry. However, mediation conclusions are dependent on sample size. Using a sample that is too small may pose a hindrance to adequately demonstrating the total effect. Consequently, it is advised to employ moderate sample sizes in mediation models.The present study is not without limitations, which should be acknowledged to ensure a realistic interpretation of the findings. First, the outcomes relied on self‐reported data, which are vulnerable to various biases and subjectivities. Second, the uncertainty around screening procedures may itself have induced anxiety and fear among participants, thus complicating the interpretation of results of the regression models. Additionally, patients' beliefs about the effectiveness of screening may have interacted with fear to affect their perception of risk. Third, given that the present study adopted a cross‐sectional design, it cannot infer causality, and longitudinal research in this area is warranted. Fourth, the generalizability of the findings is limited by the fact that the study's participants were highly educated women who were screened at a single institution. Therefore, caution should be exercised in generalizing the findings to other populations or screening contexts. Finally, the limited sample size of the study did not allow exploring the influence of the type of cancer previously diagnosed (breast or ovarian cancer) on the selected outcomes as well as running separate mediation models for women who had or not a diagnosis of cancer. Indeed, the number of patients who had ovarian cancer was too small ; data curation ; investigation ; methodology ; project administration ; resources ; supervision ; validation ; writing – original draft ; writing – review and editing . Gabriella Maggi: Conceptualization ; investigation ; writing – original draft ; writing – review and editing . Cristina Vigna: Data curation ; writing – review and editing . Antonella Savarese: Writing – original draft ; writing – review and editing . Laura Gallo‐: Writing – original draft ; writing – review and editing . Lara Guariglia: Conceptualization ; investigation ; methodology ; validation ; writing – original draft ; writing – review and editing . Giulia Casu: Data curation ; formal analysis ; investigation ; methodology ; supervision ; writing – original draft ; writing – review and editing . Paola Gremigni: Conceptualization ; data curation ; formal analysis (lead); investigation ; methodology ; software ; supervision ; writing – original draft ; writing – review and editing .This work was financially supported through funding from the institutional “Ricerca Corrente 2023.”The authors declare that they have no competing interests.


Lifestyle Modifications and Breast Cancer Risk. Although, overall, all articles highlight the beneficial effects of a healthy diet or enhanced physical activity, they also emphasize the importance of customizing these interventions in order to ensure the maximum benefit.Lifestyle modifications have been shown to be effective in reducing breast cancer ,2,3. AccIn a preclinical study utilizing two estrogen-receptor-negative transgenic mouse models, Brane et al.  demonstrThe concept of precision onco-nutrition, i.e., the use of specific nutrients and dietary factors to enhance antitumor activity, is explored by Thompson et al.  in a serThe protective effect of exercise against breast cancer may also not be uniform across the board but may differ depending upon the timing of physical activity in life or anthropometric characteristics. In a longitudinal study involving 15,983 women with a median follow-up of 23.2 years, Boraka et al. [Prescribing the minimum recommended amount of physical activity for general health and breast cancer survivors  is pCollectively, the manuscripts in this Special Issue highlight the multiplicity of the cellular mechanisms by which diet and exercise may influence breast cancer risk. They include: (a) alterations in body composition resulting in changes in adipokine profile  and possIn summary, all the articles in this Special Issue provide support in favor of promoting a healthy diet and exercise for reducing breast cancer risk. However, they also highlight critical gaps in our knowledge that need to be addressed in future research in order to optimally customize a specific intervention to the appropriate target population.


Breast cancer (BC) is the fifth most prevalent cause of cancer-related deaths in Iran. Given that the role of whole-diet on cancer risk is important, this study aimed to assess the association of MedDQI and breast cancer risk.This hospital-based case-control study was performed on 150 women with pathologically confirmed breast cancer within the period of less than 3 months. Controls were 150 apparently healthy that were matched by age. Dietary data was collected using a validated questionnaire. To examine participants’ adherence to MedDQI, the MedDQI was created according to foods and nutrients highlighted or minimized in the MedDQI construction.After adjusting for possible confounders, participants in the highest quartile of the MedDQI score had 55% lower odds of breast cancer than women in the bottom quartile . Stratified analysis by menopausal status showed such association in postmenopausal women  after controlling for age and energy intake.The results showed an inverse association between adherence to the MedDQI and risk of breast cancer among Iranian women. More prospective studies are needed to confirm our results. Breast cancer (BC), the second-high prevalent cancer, is spreading around the world, especially in developing countries. Based on GLOBOCAN statistics for 2018, about 11.6% of women were recognized with breast cancer that year, with 626,679 associated deaths , 4. The of breast cancer. They found a clear positive relationship and synergism between non-adherence to Mediterranean diet with current smoker, physical inactivity, and alcohol consumption . PreviouThe Mediterranean dietary quality index (MedDQI), a beneficial tool for assessing the quality of the diet, was developed by Gerber et al. . This in2), throughout a 45-min structured face‐to‐face interview by a standard questionnaire.This hospital-based case-control study was conducted between September 23, 2017 and June 21, 2018 among Iranian women (46.6 ± 10.7 years old) who referred to cancer research center, Imam Khomeini Hospital in Tehran. To calculate the sample size calculation, the type I error of 5% and the study power of 95% was used. We hypothesized 5% of the difference in mean and SD of dietary grains between cases and controls and reached almost 150 patients with breast cancer and 150 healthy controls . Cases   which inWe calculated the diet score based on the Mediterranean diet quality index (MedDQI) Table . This di2. A validated short from International Physical Activity Questionnaire [Weight was measured with light clothing and without shoes, by using a digital weighing scale  to the nearest 100 g and the height was assessed while standing and keeping the shoulders and hips against the wall without shoes, using a stadiometer  with an accuracy of 0.1 cm. Body mass index (BMI) was calculated as weight divided by squared height and presented as kg/mionnaire  was usedionnaire . Then, t2 tests for continuous and categorical variables, respectively. Data were shown as the mean ± SD for continuous variables and percent (%) for categorical ones. Odds ratio and 95% confidence intervals were obtained using logistic regression to determine the relationship of adherence to the MedDQI score with risk of breast cancer. The risk was reported in crude and 3 adjusted models including confounders such as age (year), energy intake , education ), urban-residency ), family history of breast cancer ), physical activity (Met/min/week), marital status ), smoking ), alcohol consumption  ), dietary supplement use ), length of breast-feeding (year), menopausal status ), history of hormone replacement therapy ) and BMI (kg/m2). In this analysis, the first quartile of exposure was considered as the reference category. All statistical analyses were done using the Statistical Package for the Social Sciences . We considered p < 0.05 as the significance level.All individuals were categorized according to the quartiles of MedDQI score. We analysed the study participants’ characteristics and dietary intakes according to MedDQI score quartiles, using one-way analysis of variance (ANOVA) and χ2 respectively. General characteristics of the study subjects with and without BC are indicated in Table The mean age of participants was 46.6 ± 10.7 year in both case and control groups. Moreover, the BMI of the participants in case and control groups were 28.1 ± 4.6 and 28.2 ± 5.2 kg/mDietary intakes of the patients across the case and control groups as well as across the quartiles of MedDQI are provided in Table fourth vs. first quartile: 0.47, 95% CI: 0.23, 0.92, P trend: 0.01). After controlling for confounders, participants in the top quartile of Med-DQI score had 55% less likely to have BC compared with those in the bottom quartile . These findings remained significant even after adjustment for BMI .Odds ratios and 95%CI of the BC across quartiles of the MedDQI are presented in Table fourth vs. first quartile: 0.24, 95% CI: 0.07, 0.8, P trend: 0.055). There was no significant association between MedDQI and odds of BC in premenopausal women in crude or adjusted models.Stratified analysis by menopausal status expressed that after adjusting for age and energy intake, postmenopausal women with the highest adherence to the MedDQI had 76% lower odds for having BC than those with the lowest adherence In this hospital-based case-control study, we found a significant inverse association between MedDQI scores and odds of BC among Iranian women. This inverse association was also seen in postmenopausal women after controlling for energy intake and age. No significant relation was found between MedDQI scores and BC in premenopausal women. This is the first study looking at the link between the MedDQI scores and the risk of BC in Iranian women. BC is the most common malignancy in women  StatistiSuitable sample size, careful assessment of confounding elements and their controlling in the analyses and being the first investigation in Middle East women could be considered as the strengths of the present study. However, some limitations should be considered. First, the case control design of the study does not permit us inferring causality. In addition, these kinds of studies are subject to selection and recall bias. In case-control studies, cases may report their past diet correctly due to their cancer diagnosis. This can attenuate this association. Another concern for case-control studies is that cases may have changed their diet before diagnosis due to early symptoms of the disease. To reduce this error, we recruited newly-diagnosed cases in the study. Furthermore, we used FFQ for assessing dietary intakes which can result in misclassification in our study participants. In addition, an energy adjusted MedDQI scores was applied which could reduce the possibility of subject misclassification. However, we used a qualified questionnaire to evaluate dietary intakes. Finally, we did not collect information about estrogen or progesterone receptor status of study patients.In conclusion, our findings showed an inverse association between diet with high MedDQI scores and odds of BC among Iranian women. More cohort studies are needed to approve our findings.


Ovarian cancer does not cause many symptoms in the early stages, which is why the majority of cases are of advanced disease. Increasing awareness of ovarian cancer symptoms may lead to earlier diagnosis and improved outcomes.n = 459).Participants in Britain completed the Ovarian Cancer Awareness Measure by online survey  ethnically diverse population . Individuals recalled 1.24 ± 1.30 symptoms, and recognised 5.96 ± 2.4 symptoms. We found higher levels of recall and recognition compared to previous research possibly due to using an online survey. Recognition was lowest for difficulty eating (39.4%) and persistently feeling full (38.7%). Males had slightly lower symptom recall and recognition than females. Participants incorrectly recalled an irregular menstrual cycle (22.4%) as an ovarian cancer symptom and 67% answered the age of incidence question incorrectly. Suggesting that participants incorrectly associate ovarian cancer as a disease of pre‐menopausal women.p = 0.018).Individuals recalled 1.47 ± 1.20 risk factors, and recognised 6.1 ± 2.4 risk factors. Family history of ovarian cancer was recalled by 59% of participants. Recognition was lowest for in vitro fertilisation treatment (23.0%) and talcum powder in the genital area (23.0%). The generic cancer risk factors of alcohol (9.3%) and poor diet (8.8%) were recalled as specific ovarian cancer risk factors. 57.9% of participants incorrectly answered that there is an ovarian cancer screening programme. Suggesting confusion between ovarian and cervical cancer as participants also recalled cervical cancer risk factors of sexually transmitted diseases (6.3%) and human papillomavirus (1.5%). 29.7% of female participants would seek help for an ovarian cancer symptom within 1–2 days. Help seeking was higher in the Black and Asian ethnicities (44.4% and 45.0%; Awareness of ovarian cancer symptoms is low. Ovarian cancer awareness campaigns should include common misconceptions identified in this research. Awareness of ovarian cancer symptoms is low. Participants incorrectly associate ovarian cancer as a disease of pre‐menopausal women as well as confusing it with cervical cancer. Ovarian cancer awareness campaigns should include common misconceptions identified in this research. Early detection of ovarian cancer through identification of early symptoms is therefore critical to patient outcome. In England, 5‐year survival for ovarian cancer is 93.3%The lifetime risk of ovarian cancer for a woman in the UK is 2%.In this study, participants in the UK completed the Ovarian Cancer Awareness Measure22.1Participants completed the Ovarian Cancer CAM2.2Participants were recruited through the social media networks of Biomedical Science dissertation students and staff at Middlesex University. Some Biomedical Science and Biology students completed the survey as an in‐class activity before a lecture on ovarian cancer. Participants were recruited between November 2015 and June 2022.The project received ethics approval from the Natural Science Research Ethics Committee at Middlesex University London. Students participating in the project were aware that it was for research and it was not a requirement for assessment or course credit. In the online survey, participants did not sign informed consent. However, the front page of the survey included a participant's information sheet, clicking into the survey acknowledged consent and participants were free to close the survey at any time and not participate. At the end of the survey, participants were given web links to the charity Target Ovarian Cancer if they wanted further information on ovarian cancer.2.3Participants had a free‐text response to recall their knowledge of ovarian cancer symptoms or risk factors. These free‐text responses were scored manually against the list of correct symptoms and risk factors on the Ovarian Cancer CAM.2.4Participants were given a list of known ovarian cancer symptoms or risk factors and asked if they thought they were associated with the disease. Participants were given a mark for each symptom or risk factor they recognised.2.5Knowledge of the age of ovarian cancer incidence was assessed with a multiple‐choice question of age ranges. This was a modification to the ovarian cancer CAM which uses a specific age2.6Participants were asked if they had been previously diagnosed with cancer in a multiple‐choice question. Participants were categorised has having a personal experience with cancer if they reported their partner, close family member or a friend having cancer.2.7Participants, who answered other or prefer not to say for a question, were excluded from the analysis of that individual question. The ethnicity question on the survey had 17 options for different ethnic groups as used in the UK census.2.8n = 355) were categorised as residing in areas of relatively high (Decile 1–5) or low (Decile 6–10) deprivation based on the English Indices of Deprivation 2019.Participants who provided their postcode data were mapped visually using Google Maps2.9p < 0.05 was considered significant. Graphs were made using Graphpad Prism.Statistical analysis was performed using Minitab.2.10It was calculated using UK female ovarian cancer incidence33.1In all, 449 participants responded to the survey. The gender balance was 75.1% female and 24.1% male. The mean age of participants was 27.89 years and the range was 18–75 years. The ethnic diversity of the participants was 40.3% White, 29.3% Asian and 18% Black  was 73.6% female and 25% male. Participants over 30 were significantly less ethnically diverse and were primarily female Table . The you3.2Participants recalled ovarian cancer symptoms unprompted by typing in a free‐text box, they recognised symptoms by choosing from a presented list. The most frequently recalled ovarian cancer symptoms were abdominal pain (36.7%) and bloating (24.8%) Figure . The leap = 0.003 and p = 0.003, Mann–Whitney Test). There was no difference in the recall or recognition of symptoms based on ethnicity, deprivation university education or experience with cancer in the young cohort. Participants over 30 recalled slightly more symptoms than younger participants   and weight loss (12.2%) Figure . 36.7% o) Figure . In the 3.3Participants recalled ovarian cancer risk factors unprompted by typing in a free‐text box, they recognised risk factors by choosing from a presented list. The most frequently recalled ovarian cancer risk factors were a family history of ovarian cancer (59.0%) and older age (23.8%) Figure . The leaThe most commonly recalled incorrect risk factors for ovarian cancer were alcohol use (9.3%) and poor diet (8.8%) Figure . 19.5% o3.4p = 0.20 and p = 0.028, chi‐squared test, Figure p = 0.004, chi‐squared test, Figure 57.9% of participants incorrectly answered that there was an NHS ovarian cancer screening program Figure . In the p = 0.019, chi‐squared test, Figure p = 0.048, chi‐squared test, Figure Only a third of participants answered the age of ovarian cancer incidence question correctly. In the young cohort, males were more likely to answer the age of incidence correctly .29.7% of female participants answered that they would seek help for an ovarian cancer symptom within 1–2 days Figure . In the p = 0.000, chi‐squared test, Figure p = 0.081, chi‐squared test). In the older cohort, help seeking was not associated with symptom or risk factor recall or recognition.Help seeking was lower in the older age group with only 9.6% of female responders over 30 answering that they would seek help quickly (3.6p = 0.063 chi‐squared test). No difference in confidence was found based on ethnicity, deprivation, university education or experience with cancer in the young cohort. In the young cohort, confidence (very or fairly confident) was associated with higher symptom and risk factor recall and recognition . There is a trend for the same pattern in the older cohort, but it is not significant due smaller sample size. There was no difference in confidence between the young and old cohorts.Confidence in recognising an ovarian cancer symptom was low with only 1.4% very confident and 22.6% fairly confident. In the young cohort, males tended to be less confident than females but the difference was not significant , as well as recall fewer ovarian cancer symptoms (1.05 ± 1.11). However, the in‐class group was more likely to be male (33.6%) and younger (22 ± 2.88) and this follows the same pattern we see in the previous analysis.Data were collected from November 2015 to June 2022. Some differences were seen based on year of recruitment. However, this does not reflect a change in ovarian cancer awareness over time but rather the demographics of participants based on different recruitment techniques. From 2015 to 2016, 160 participants were recruited via email/social media with an average age of 29.4 ± 11.4. From 2019 to 2020, 187 participants were recruited primarily through in‐class activities, with an average age of 21.9 ± 2.9. In 2022, 71 participants were recruited via email/social media deliberately targeting an older age group to balance the dataset with an average age of 40 ± 14.7.In all, 18 participants (3.9%) were determined to share an IP address with another respondent. Analysis of the demographic answers suggests that these are 18 unique participants. The answers did not improve on a subsequent submission from the same IP address. It is likely that family units were responding to the survey on the same device for dissertation students.44.1The UK charity Target Ovarian Cancer has been regularly campaigning about the symptoms of ovarian cancerIn our study, recall of ovarian cancer symptoms is in general low, but is higher in this study than previous studies in the UK.A similar pattern of symptom recall is seen in this study compared to the literature. Recall of abdominal or pelvic pain and bloating is the highest frequency, whereas feeling full persistently and difficulty eating the lowest.The ovarian cancer CAM was delivered as an online survey in this study, whereas the Low et al.'s study was conducted by telephone survey.4.2Recognition of ovarian cancer symptoms is similar in this study to previous studies in the UK.4.3p = 0.001; Mann–Whitney Test). Recall of the two highest risk factors, a family history of ovarian cancer (59.0%) and age (23.8%), were good, although less people linked older age to being post‐menopausal (8.35%)  as a risk factor for ovarian cancer. The use of talcum powder in the genital area has been associated with an increased ovarian cancer risk in retrospective case–control studies.A similar pattern of risk factor recognition is seen in this study with the literature. In our study, 93.0% of participants recognised family history of ovarian cancer, and 66.4% recognised a past history of breast cancer. This is a higher level of recognition than seen in the Fallowfield 2010 study, 5.9% more for family history of ovarian cancer and 46.8% more for past history of breast cancer.The Fallowfield 2010 study was conducted on 21,715 post‐menopausal women in the UK with an age range of 50–74 years, where 14.8% had a university education.4.4The correct symptoms and risk factors were taken from the original Ovarian Cancer Awareness Measure.22.4% of participants suggested that irregular periods were a symptom of ovarian cancer and 5.7% suggested infertility Figure . These iIrregular periods are not a symptom of epithelial ovarian cancer. However, irregular periods are associated with rarer non‐epithelial ovarian cancer subtypes such as granulosa cell tumours.Many of the incorrect risk factors recalled by participants show that they quite reasonably associate an unhealthy lifestyle with cancer risk. Excessive alcohol consumption is associated with the risk of many cancers57.9% of participants in our study thought that there was an NHS ovarian cancer screening programme indicating confusion between cervical and ovarian cancer. This is consistent with the results of other studies where 40.1%–67% of women thought that a smear test could detect ovarian cancer.The confusion between cervical and ovarian cancer could be used as a starting point for new education campaigns on gynaecological cancer. Rather than a campaign focusing on one cancer type, a campaign which explains that the HPV vaccine does not protect against all gynaecological cancers and alerting the public to key symptoms of cervical and ovarian cancer. A successful programme in the United States called Inside Knowledge: Get the Facts about Gynaecologic Cancer used a face‐to‐face information session approach increased women's knowledge that cervical screening does not screen for ovarian cancer and that genetic testing is available.4.54.5.1Our participants were more likely to have completed university education (62%) than the general London population (37.7%).p = 0.000; chi‐squared test). Some differences were seen in the high SES group, they were more likely to get the screening question correct (66.6%), as well as recall more ovarian cancer symptoms (1.70 ± 1.24) and recognise less risk factors (5.72 ± 2.34) . This follows the same pattern we see in the previous analysis on age of participants in It is unclear if our participants are more highly educated than the previous studies examining symptom recall.4.5.2Males recalled fewer ovarian cancer symptoms and risk factors than females Figure , 2C. The4.5.3p = 0.018). This effect has been observed previously in non‐White participants in the Low et al.'s UK ovarian cancer awareness study.Our participants were more ethnically diverse than the general London population which is 59.8% white.Participants from Black and Asian ethnicities were also more likely to incorrectly believe that there was a screening programme for ovarian cancer Figure . However4.6A limitation of this study is that it is not a population study designed to be representative of either the UK or London population. However, our opportunistic recruitment through the student population of Middlesex University was a strength of this study as it allowed us to examine a more ethnically diverse population. We show very little differences across demographic groups suggesting that there would be no benefit of a highly targeted campaign for a particular group. Another limitation is that the majority of our participants are not post‐menopausal women, who experience the highest incidence of ovarian cancer. Post‐menopausal women would be the primary group targeted by ovarian cancer awareness campaigns. However, the inclusion of men and a young population in general allows us to show that knowledge of ovarian cancer is low across this part of the population and that awareness campaigns would be of benefit to all.5Awareness of ovarian cancer symptoms is low and risk factors is good. This is the first UK study to include male participants and have high levels of ethnic diversity. Small differences in awareness are observed by gender and age. Our study demonstrates that delivering the ovarian cancer CAM by online survey is a viable research method. Ovarian cancer awareness campaigns should include common misconceptions such as a younger age of incidence and confusion with cervical cancer.This study was approved by the Department of Natural Sciences Research Ethics Committee at Middlesex University.Cristina‐Alexandra Radu: Formal analysis (supporting); project administration . Nadia Matos de Melo Fernandes: Project administration (supporting). Sumaira Khalfe: Project administration (supporting). Britta Stordal: Conceptualization (lead); formal analysis (lead); methodology (lead); supervision (lead); writing – original draft (lead).No funding to declare.The authors have no conflicts of interest to declare.Tables S1Table S2Table S3Click here for additional data file.


In conclusion, dietary Zn and Se intake were associated with breast cancer risk in Chinese women, and the optimal intake of Zn may be beneficial for breast cancer prevention.As major nonenzymatic antioxidant components in the body, dietary Zinc (Zn) and Selenium (Se) may have an impact on breast cancer development. This study aimed to investigate the relationship between dietary Zn, Se intake and breast cancer risk in Chinese women. The case-control study included 1591 cases and 1622 age-frequency matched controls. Dietary intake was collected using a validated food frequency questionnaire. Dietary Zn and Se were divided into four categories: Zn/Se from plants, Zn/Se from meat, Zn/Se from red meat, and Zn/Se from white meat. Unconditional logistic regression models and restricted cubic spline analyses were performed to identify potential associations. Zn from white meat intake was linearly and inversely associated with breast cancer risk, and Se from red meat intake was linearly and positively associated with breast cancer risk, with adjusted odds ratio and 95% confidence interval of 0.76 (0.61–0.95) and 1.36 (1.04–1.77), respectively. Non-linear relationships were found between total dietary Zn, Zn from meat, Zn from red meat intake and breast cancer risk ( Breast cancer is the most frequent malignancy in women worldwide and accounts for 30% of all newly diagnosed cancers . The canOxidative stress may be associated with the development of breast cancer ,5. As anIn the human body, Selenium (Se) protects against oxidative stress primarily via some selenoenzymes, such as glutathione peroxidases, possessing powerful effects of scavenging free radicals and preventing cancer ,18. SeleZn intake was found to be non-linearly associated with several other diseases ,36,37,38The detailed recruitment procedures and collection of data were described elsewhere ,40,41. TThe investigators conducted face-to-face interviews after obtaining informed consent from the participants. The Women’s Health Status Questionnaire and the Lifestyle and Dietary Habits Questionnaire were used, which asked about sociodemographic information , lifestyle habits, dietary habits, previous disease history and family history of cancer, fertility, and menstrual history.Investigators used the food frequency questionnaire (FFQ), which had been assessed for reliability and validity , to coll® version 25 , Stata 15.1 , and R version 4.2.1. Continuous variables were described by mean ± standard deviation (SD)  or median  , and a t-test or Wilcoxon rank-sum test was used to assess differences. The number of subjects (percentage) was used to describe the categorical variables and the χ2 test was used for the equilibrium test. The natural logarithm was used to turn the dietary data into a normal distribution, and the energy residual method was used to adjust the consumption of dietary nutrients [Two individuals extracted all the data separately and tested for consistency. All analyses were conducted with IBM SPSS Statisticsutrients . For theptrend was calculated by converting quartiles (Q1–Q4) to rank variables (1–4) in the logistic regression models with the minimum value as a reference. The interactions between different sources of Zn and Se were examined by including the multiplicative terms of Zn and Se (continuous variables) in the regression models. Additionally, stratified analyses were conducted according to menopausal status to investigate whether it modifies the potential association of dietary Zn/Se with breast cancer risk. The value of pinteraction was calculated by including multiplicative terms for menopausal status and dietary Zn/Se in multivariable logistic regression models.In unconditional logistic regression models, the odds ratios (ORs) and 95% confidence intervals (CIs) of the association between dietary Zn and Se intake and the risk of breast cancer were calculated for Q2–Q4, with the lowest intake group (Q1) as a reference. The following variables were considered as potential confounders based on prior research and the findings of the univariate analysis: age, education, household income, physical activity at work, ever smokers, second-hand smoke exposure, regular drinkers, BMI, family history of cancer, age at menarche, previous benign breast disease, ever use of oral contraceptives, and daily intakes of fat, fiber, vitamin A, vitamin C, and vitamin E. In regression analyses of Zn/Se from different sources, Zn/Se from plants and meat were adjusted for each other. Zn/Se from red meat and white meat were mutually adjusted, while Zn/Se from plants was adjusted concurrently. The value of pnon-linearity was calculated by the Wald test. The statistical significance level was set at p < 0.05 for all 2-sided tests.Based on logistic regression models, restricted cubic spline (RCS) curves were employed to explore the non-linear dose–response association between dietary consumption of Zn or Se and the risk of breast cancer . For difp < 0.05). Job, age at first childbirth, breastfeeding, menopausal status, and the number of births were similar for cases and controls (p > 0.05).The analysis included data from 1591 breast cancer cases and 1622 controls. p < 0.05); but the intakes of Zn from red meat, Se from red meat were significantly higher (p < 0.05).ptrend = 0.020). Total dietary Zn, Zn from plants, Zn from meat, and Zn from red meat were not statistically associated with the risk of breast cancer, with adjusted ORQ4vsQ1 (95%CI) of 1.06 (0.83–1.35), 0.86 (0.62–1.18), 1.11 (0.87–1.41), and 1.26 (0.99–1.60), respectively. Se from red meat intake was positively associated with the risk of breast cancer, with ORQ4vsQ1 (95%CI) of 1.36 . Total dietary Se, Se from plants, Se from meat, and Se from white meat were not statistically associated with the risk of breast cancer, with ORQ4vsQ1 (95%CI) of 0.86 (0.67–1.10), 0.88 (0.70–1.11), 0.93 (0.73–1.17), and 0.82 (0.66–1.02), respectively (pinteraction were not shown in the table).As shown in ectively . There wpnon-linearity < 0.0001). With increasing total dietary Zn intake, the risk of breast cancer decreased first, reaching a minimum at around 10.63 mg/d, and thereafter the risk gradually increased. The RCS curve showed an inverse L-shaped association between Zn from meat intake and breast cancer risk. The risk of breast cancer increased significantly as the intake of Zn from meat exceeded 6.18 mg/d (pnon-linearity = 0.0035) (pnon-linearity = 0.0326), and the risk of breast cancer significantly increased when the intake exceeded 4.37 mg/d. The non-linear associations of Zn from plants intake, Zn from white meat intake with breast cancer risk were not statistically significant (pnon-linearity > 0.05) (pnon-linearity > 0.05).As shown in  0.0035) C. Figure > 0.05) B,E. For  > 0.05) , no non-Q4vsQ1 (95%CI) of 0.74 , but the interaction was not significant (pinteraction = 0.113). No significant association was observed between other sources of Zn intake and the risk of breast cancer in either premenopausal or postmenopausal subjects (pinteraction > 0.05).There were 1021 (64.17%) and 1013 (62.45%) premenopausal women in cases and controls, respectively. As shown in Q4vsQ1 (95%CI) of 0.73 , and the interaction was statistically significant (pinteraction = 0.044). No significant association was found between other sources of Se intake and the risk of breast cancer in either premenopausal or postmenopausal subjects (pinteraction > 0.05).As shown in In this case-control study, we aimed to investigate the relationship between dietary Zn, Se, and breast cancer risk in Chinese women. The results demonstrated a linear and negative association between Zn from white meat and breast cancer risk, and a linear and positive association between Se from red meat and breast cancer risk. According to RCS analysis, there was a significant U-shaped non-linear relationship between total dietary Zn and breast cancer risk, and an inverse L-shaped association between Zn from meat, Zn from red meat and risk. No significant associations were found between Zn from plants, total dietary Se, Se from plants, Se from meat, Se from white meat intake and breast cancer risk.Total dietary Zn was not found to be linearly and significantly associated with breast cancer risk. Consistent with our result, some epidemiological studies did not find any evidence of the association between dietary Zn intake and breast cancer risk ,14,15,16To date, no study has reported on the relationship between Zn from different food sources and breast cancer risk. Some studies reported that the association of dietary Zn with cardiovascular disease (CVD), metabolic syndrome (MetS), and coronary artery calcium (CAC) varied depending on its source ,50. Zn fIn our study, Zn from white meat was observed to be linearly and inversely associated with breast cancer risk. It implied that the negative association of dietary Zn with breast cancer observed in previous studies may be due to the effect of Zn from white meat. The exact reasons for the inverse association are not clear due to limited literature. Further studies are warranted to verify our findings. Additionally, as the main source of dietary Zn intake in this studied population, Zn from plants was not associated with breast cancer risk.The results of this study suggested that food sources might influence the association between Zn intake and breast cancer risk. Consequently, the inconsistent results of previous studies on the association of dietary Zn with breast cancer risk can be partially attributed to the different food sources of Zn across different populations . For exaNeither linear nor non-linear analyses found a significant association between total dietary Se intake and breast cancer risk. Consistent with our results, four cohort studies ,26,27,28The observed linear and positive association between Se from red meat and breast cancer risk can be partially attributed to the presence of carcinogens in red meat . AdditioWe did not find an interaction between different sources of Zn and Se in relation to breast cancer risk. In contrast to the results of this study, a study found a significant interaction between Zn and Se intake on cognition in females . The intNo significant association was observed between Zn or Se intakes and breast cancer risk in either premenopausal or postmenopausal women in two previous studies ,16. HoweThis study has several strengths. First, this is the first study to assess the relationship between Zn, Se intake and breast cancer risk among Chinese women. Then, the sample size was large enough to provide sufficient statistical power to detect convincing associations. The large sample size also allowed us to conduct stratified analysis by menopausal status. Furthermore, our study examined the associations between different sources of Zn or Se intake and breast cancer risk, which provides new insights into the relationship between nutrients and cancer. Finally, the RCS regression models were used to analyze the shape of the dose–response relationship, which allowed us to observe how breast cancer risk varies at different levels of dietary Zn/Se intake ,70.This study also has several limitations. First of all, it can be challenging to avoid selection bias in case-control studies. However, for this study, patients with breast cancer were recruited from three large teaching hospitals within the Guangzhou area. To some extent, these cases might be representative of the patients in Guangdong province. The high response rate (89.99% for cases and 90.82% for controls) in this study also helped to reduce the impact of selection bias on the results. Second, in dietary surveys, study participants were asked to recall and report the kind and frequency of food intake in the previous year, which might be subject to recall bias. However, only new cases (diagnosed no more than 3 months before the interview) were included in this study, and an atlas of the illustrative food picture was provided to help subjects recall diet more accurately. Third, measurement errors and misclassification were also inevitable. This nondifferential misclassification might result in a dilution of the association between dietary Zn, Se intake and breast cancer risk in our study. Fourth, the subjects in this study may not be representative of women across the country. China Nutritional Transition Cohort Survey 2015  showed tTotal dietary Zn, Zn from meat, and Zn from red meat intake were non-linearly associated with breast cancer risk. An optimal intake of total dietary Zn, and Zn from white meat intake may be beneficial for breast cancer prevention, whereas Se from red meat intake may be associated with an increased risk of breast cancer. The findings reveal the potential effects of different dietary sources of Zn and Se on breast cancer risk and also provide a theoretical basis for dietary prevention of breast cancer in Chinese women.


As breast cancer incidence rises among younger women, there is a knowledge gap regarding the emotional, physical, and social effects of mastectomy, specifically in a crisis-affected country such as Syria. This study aimed to explore these effects on young women with breast cancer in Syria, taking into consideration the cultural significance of a woman’s breast as part of her feminine identity.A qualitative design, using semi-structured in-depth interviews with 10 young women with breast cancer who underwent mastectomy, was conducted between June to December 2022.Thematic analysis was used to analyze the data, and five main themes were identified: (1) psychological and emotional well-being ; (2) body image and breast reconstruction ; (3) social and interpersonal factors (lack of marriage choices and society’s view and stigma); (4) coping mechanisms with mastectomy effects  and (5) physical health and functioning .Mastectomy has significant physical, emotional, and social consequences on young women with breast cancer, particularly in crisis-affected Syria where access to breast reconstruction is limited. It is crucial for healthcare professionals to understand these impacts, to raise awareness, encourage early detection, and promote less aggressive treatments to improve women’s quality of life. Breast cancer is the most common cancer and a leading cause of death among women worldwide . HistoriThe woman’s breast is often considered a symbol of her identity in Syria and in other countries. It represents her femininity, sexuality, beauty, and motherhood , 8. TherThe cancer care in Syria has significantly deteriorated since the start of the crisis in 2011. Indeed, the Syrian crisis has resulted in many challenges affecting the quality of care and life of cancer patients. These challenges included the unavailability of a multidisciplinary team approach to cancer care, the high cost of different types of treatment, the insufficiency of health staff training for diagnosis, treatment, palliative care, and psychological care of cancer patients, as well as the lack of the educational programs designed for patients and oncology health professionals . All theUnfortunately, the current literature lacks information on the effects of mastectomy on young women with breast cancer in a crisis-affected country like Syria. Furthermore, breast cancer is a complex health issue, with repercussions that may extend beyond the immediate patient, but affecting her familial and spousal relationships as well . For exaThis study, which is part of a larger qualitative study undertaken to explore the psychosocial needs of young women with breast cancer in Syria, was conducted using a phenomenological approach to understand the mastectomy phenomenon through detailed explorations of the experiences of these participants.Prior to commencing the study, ethical approval was obtained from the institutional medical ethics committee of University Malaysia Sarawak (No: FME/22/42), and approval was also granted by the Department of Oncology of Tishreen University Hospital. Informed consent was also obtained from the participants that they agree to participate in the study.Purposive sampling method was used to recruit the participants from Tishreen University Hospital in Latakia, Syria, which is the second most comprehensive oncological center in Syria and receives oncological patients from many cities around Latakia. Purposive sampling means that researchers intentionally recruit participants who have experienced the central phenomenon, or the key concept being explored in the study . ParticiAfter recruitment, the participants were contacted by the first author to arrange for the time and place of the interview sessions. The in-depth, semi-structured interviews were conducted according to the participants’ time in a private room at home to allow the participants to freely answer the questions. The interviews were conducted using an interview guide consisting of these questions: (1) Can you please describe your experience with mastectomy? (2) How did you cope with the mastectomy? (3) How do you see the view of Syrian society towards women with breast cancer? (4) How did a mastectomy affect your sexual relationship with your husband? (5) Do you plan to go for breast reconstruction? These questions were developed by all the authors based on their experiences and the existing literature , 17–19. All the interviews were audio recorded, immediately transcribed verbatim by the first author, and translated into English by the first author to ensure accessibility and comprehension for all authors, as they are not Arabic speakers except for the first author. Thematic analysis was used to analyze the data, using the six-phases approach outlined by Braun and Clarke . ThematiAs shown in Table Six out of 10 participants expressed the feelings of losing the breast as equivalent to losing part of their femininity after the mastectomy, which in turn, affected their self-esteem and body image. They mentioned the importance of maintaining the appearance of their breasts through the use of fillings and bras. For example, the participants said:“A woman loses her femininity when she does such an operation (mastectomy), she loses her beauty from her perspective, and when she loses her beauty, she doubts her beauty in front of people”.—H“Look, the lady really misses a feminist part from her body, I think she feels there is something missing. She loses self- confidence, specifically if she is married. Life got more exhausting; you have to take care of the issue of the breast by putting pads. It becomes like a burden and you have to attend to it”.—RAThe participants expressed mixed feelings regarding the effects of mastectomy on their sexual relationships. Some avoided sexual contact because they felt shy, incomplete, and unattractive with only one breast, while others felt that their partners were supportive and understanding enough to help them cope with these challenges. When asked if mastectomy affected their relationships with their husbands, some participants answered:“For me, yes, but for him, no. I no longer want to have sexual intimacy, and I try to avoid it. I have always tried to hide the wound from him, but he says, ‘Let me see. I want to see how the wound has healed.’ He wants to tell me that he has no problem with it. He told me that as soon as I came out of surgery, while I was still under anesthesia. The first thing I asked was if he had seen me without a breast. Even when I was unconscious, I asked about this point. This shows how much this subject affects me, and I have no idea about that.” – RA.“I was distant from my husband sexually, especially in the beginning, and praise be to God, he accepted the situation and encouraged and supported me.” – Ri“No, not at all, thank God. My husband understands my situation, and he has never been affected by all these things. Especially when he sees me getting tired, he never forces me or tries to get close to me. Our relationship is usual, with foreplay, and our life is very normal.” – L.Most of the participants expressed that the mastectomy experience was very difficult and distressing. Some of them mentioned that it was very difficult to overcome this experience and its consequences, and others mentioned that they were unable to overcome it yet. In turn, this psychological impact affected their daily lives and interactions with others. For example, some participants said:“But the breast loss is more distressing than hair loss, it is very painful and till now it is still painful”- RA“It was very annoying, I can’t tell you what it can do with the female psyche, thank God”- GFour out of 10 participants mentioned the difficulty of viewing the mirror after the mastectomy. They mentioned that they avoided looking at themselves in front of the mirror or during the showers in order not to see such a valuable feminist organ missing from their bodies and feel upset. For example, the participants said:“It is very ugly. Till now I sometimes find it hard to accept this and I avoid looking at myself. Even in the bathroom.”- W“When you look at yourself in the mirror and see your feminist part is missing, you feel upset. I was crying and saying, Oh my Lord, why me”? L“When I was passing near the mirror, I was not looking at it at all.”- WThe majority of the participants expressed that they had not received adequate psychological care at the hospital, highlighting the need to have an in-house psychologist in the treatment plan of cancer patients specifically in addressing these distressing conditions where they live. They mentioned that the psychologist could play a positive role in supporting the patients psychologically and socially. For example, one of the participants said when she was asked, what are the needs you feel should be available at the hospital to feel that you had received adequate psychological care.“There should be a psychologist to support the patients both psychologically and socially”- LAnother participant said:“The psychologist is very helpful. For example, you can tell him things that you might not feel comfortable sharing with your doctor, husband, or anyone else in your family. He can be the keeper of your secrets. I am eagerly waiting to go to the hospital to meet the psychologist and tell him what I need. It is comforting to talk to him about the situations that have happened to you.” – A.Another participant also highlighted the need for psychologists by saying:“To have a psychologist is a very important thing, but unfortunately, this is not followed here due to a lack of psychologists, which could adversely affect us. The patient needs a companion, and the companion should never be from the relatives. He should be a psychologist, in my opinion.” H.Six of the participants expressed the desire to undergo breast reconstruction, noting that it could improve their psychological well-being and enable them to wear clothes they feel comfortable in. However, they mentioned that they are unable to restoring their pre-mastectomy body shape due to the high cost of reconstruction compared to their current financial status resulting from the ongoing crisis that has affected all the life aspects. For example, when asked on what they thought on reconstruction, some participants said:“Psychologically and physically, if I do the reconstruction, I may no longer feel ashamed, there are many t-shirts I can no longer wear them now because they are in open tops, I can no longer wear them if I don’t wear something higher under them, because it would look very bad. Even at the parties, I can’t wear what I want…. But the operation is very expensive, about $1000, it is impossible. It is a very big financial burden”- W“I want $1000 to reconstruct this breast and $1000 for the second breast because I want to do evacuation and filing, means I need $2000, and this is not easy at all”- A. For example, the following participant said:On the other hand, few participants expressed the decision that they have no desire to do reconstruction because they are scared from its side effects including the misconception that reconstruction would cause the cancer to recur“No, I don’t think of doing plastic surgery because I am afraid of the side effects later on. I am afraid that it will be a reason for the disease to return again. Scientifically, I do not know if it could be a reason, but I would say that I do not have to do it, maybe if I am younger, I can think about it, but at this age I want to complete my life with my children, this is my only concern”- R.Some participants also shared about their struggles with adjusting to their new body image and finding appropriate clothing post-mastectomy, as described by these two participants:“As for the clothes, I was feeling uncomfortable, I underwent the surgery in the winter and this helped me a lot really because I was wearing loose jackets that were hiding. I was unable to wear the bra, especially when the surgery had just been done. Once, I was gonging for a walk, I tried to wear a bra but I could not, then I put on a loose jacket. I was wondering, how would I wear the summer clothes? I think women suffer more in summer than winter. Now the wound is healing and I wear a normal bra and I put padding in it”- R.“I am one of those people who sometimes feel upset, because I like to wear a nice shirt, but because I am a patient with breast cancer, I find difficulty to fit the bra and the fillings, so I cancel the idea and say it would not be sweet on me to wear that shirt”- D.Half of the participants detailed the challenges they encountered in acquiring information and resources related to breast prosthetics, emphasizing the necessity for improved access to these services within their region. For instance, when asked if they were informed about the available services at the hospital to assist them in enhancing their appearance, one participant stated:“No, never. I have not heard about that at the hospital; we really need a lot of information. Recently, I have heard that there is a center in Latakia that provides free bras for women who have undergone mastectomy. I only heard about this one month ago, and I had no prior knowledge of this center, and I haven’t visited it yet”- R.Another participant recounted her experience in searching for a silicone breast as follows:“Do you know that I searched throughout Damascus to find a silicone breast, and when I finally found it, it was in a larger size and without a carrier? In Latakia, I could not find it anywhere. There should be a center in each governorate, or at least in three governorates in Syria, or in two – on the coast and in Damascus. There should be two comprehensive centers to provide services for both women and men in such circumstances”- H.Some unmarried participants lamented their concerns about the gloomy marital prospects post-mastectomy, worrying about how their future partners would perceive their physical appearance. For example,“It is possible that I or any other woman thinking of getting marriage, but now she may not think of that anymore. Why? Because who wants to marry a sick woman, who has undergone a mastectomy and she will be in a long- term treatment, and she has become deformed in her body? I will be ashamed of exposing myself to a man. He may not accept me, and he may be angry at me at once and stigmatize me for my illness, because in our culture, this is bad for men, friends, and family”- H.Another participant said:“I told my fiancé if they are going to do mastectomy, I will break up with you, I couldn’t let you see me distorted, if I cannot accept my appearance like this, how will he accept me?” W.All the participants talked about the negative society view and stigmatization of patients with breast cancer. They reported that society often focused on their chest area and showed curiosity about their condition. They also mentioned experiencing pity and unsolicited comments from others, which further contributed to their distress.“I sometimes get denounced by outsiders that I did the mastectomy. For example, I hear comments like, it is good that your husband is still willing to touch you, or it is good that he is not disgusted by your appearance”- A.“The only thing that made me sad was that I felt ashamed whenever I went outside of the house because anyone who knows what I have gone through would immediately focus on my chest and that makes me feel sad that my breast was removed and that I am a cancer patient. That was what I had to learn to cope with”- D.Despite the emotional distress from losing the breasts by mastectomy, some of the participants tried to accept and cope with their new situation by using different coping strategies, while others were unable to do so.Some participants highlighted the vital roles their partners and family members played in providing emotional support during their breast cancer journey. For example, the participant said:“At the first shower, the whole family was waiting for me at the door…this helped me really. There was my husband, my children and my mother, and I felt they are waiting for me outside, so I know I have to be strong and this helped me a lot, this helped me a lot really. My children keep asking, do you need anything mom? They just want to know my situation inside”-R.All the participants expressed that engaging in the spiritual practices such as offering the prayer and reading the Quran, and comparing themselves with those who were in worse situation helped them to accept their situation easier. They repeatedly expressed their strong faith in “God Almighty” taking the Quran and the religious as their shelter when they feel weak and stress. For example, a participant said:“The first shower was very difficult, but I didn’t care, I tried to help myself, I said it is something that had happened, I have to accept, and I wanted to live for my children. There are many people are suffering more and worse than this, there are people waiting to die, I mean, I kept helping myself with prayers and reading Al- Quran. This helped me a lot”- R.Some participants mentioned that comparing their situation to others who may be worse off helped them to accept as said by this participant:“Now I am suffering the discomfort in my hand and I can’t work that much because of it. But I say, praise be to God, it is the left hand, because I see someone else in suffering at her right hand, so I say, it should be easier for me to handle, praise be to God”-RO.In addition to that, the participants also tried to cope by using the pads and fillings to hide the shape of the missing breast. For example, when asked how you tried to cope with mastectomy, one of the participants said:“I don’t know, it was very difficult, but I encouraged myself that it could be compensated by implants, at least for a while, and hopefully it will pass. I made a hand making filling, I first got a silicone breast, and even this thing is not available”- H.. They mentioned that these effects were not only during the acute phase post-mastectomy, but they became long- lasting effects limiting of their activities as described by the participants below:Seven of the participants reported physical limitations due to the surgery, such as reduced hand mobility and the need for assistance in daily activities“I was more active, there are many things I can’t do because of my hand, is it right or not? This is what is bothering me that I can’t work like before”- RI“I need someone to help me at home. It is obligatory, I cannot do everything by myself. I find some difficult to do many things, I can do it but I feel uncomfortable”- ROSome participants also reported that they felt guilty over their shortcomings towards their children because, they were unable to cook for them after the mastectomy, and some of them depended on their children a lot to do the household chores after the surgery. For example, some participants said:“They (the children) were very upset, sad and got busy at home a lot, because before that, I did not have to rely on them a lot, may be like 20 or 30% of the chores only I asked them to do. But now I rely on them a lot in the household chores, especially because of my hand. The children really helped me a lot”- R“It was Ramadan. I couldn’t cook the foods they like while they were fasting. This affected me a lot psychologically, but then, thank God, now I am coming back a little by little, not fully functioning like before, but at least, a dish that they like, like sweet food something like that”- RiThe findings from this study suggest that mastectomy yields far-reaching consequences that can significantly impact various aspects of a woman’s life in a country experiencing a crisis; encompassing the physical, emotional, and social dimensions. For example, a substantial proportion of participants reported experiencing a diminished sense of femininity, an altered perception of their body image, and a decreased self-esteem as a consequence of undergoing mastectomy, which ultimately result in feeling of shame and perceived disfigurement. Moreover, the participants also shared a range of facilitative and obstructive factors that respectively promote and impede their capacity to manage the repercussions of mastectomy. We posit that these factors can be appropriately fit into the socio-ecological model of health . First pIn Syrian and other similar cultures, a woman’s breast represents her femininity , 8, hencVarious coping mechanisms were employed by the patients to handle stress, with social support and spiritual practices being the most common strategies used. Similar to other similar societies , Syrian Unfortunately, the results also showed that many women in this study experienced societal negativity towards breast cancer as this disease remains a stigma in many cultures, including the Arabic cultures , 13, 24.This study has several pertinent limitations that should be mentioned. First, purposive sampling was used in this study. While purposive sampling was intentional in qualitative research like this, it can also be a limitation because the sample might not be representative of the broader populations. Second, the interviews were conducted in Arabic and then translated into English by the first author for analysis. Translation can introduce potential biases or misinterpretations. Third, the interviews were conducted physically in a private room at the participant’s home. While physical sessions like these might make the participants feel comfortable, it might also introduce social desirability bias as participants might provide answers that they believed were socially acceptable in their home setting.Despite its limitations, this study has identified important points, that if addressed, can enhance the care given to young females with breast cancer in conflict-ridden countries. For example, pre-habilitation programs that cater to both the psychological and physical needs of these women should be introduced. These programs would help prepare them to cope with the physical, psychological, and social challenges associated with mastectomy. Sharing images and videos of post-mastectomy outcomes can also help these women in coming to terms with their changed body. Furthermore, setting up sexual health counseling units for these women and their partners can help them fostering healthier sexual relationships and avoid a lot of sexual issues in future. The implementation of educational programs on TV and other platforms can increase awareness of breast cancer and reducing societal stigma experienced by these women.Mastectomy is a traumatic experience for many young women with breast cancer, affecting them psychologically, physically, and socially. The ongoing Syrian war crisis has further exacerbated these issues, as these women are unable to access breast reconstruction due to high costs of treatment, leaving them more vulnerable to societal stigma. Nurses, health professionals, and organizations should understand these negative ramifications of mastectomy as well as the need to devise strategies for raising breast cancer awareness, encouraging early detection, and promoting less aggressive treatments like conservative surgery, which may improve women’s quality of life.