Women are concerned about reducing their breast cancer risk, particularly if they have daughters. Social media platforms, such as blogs written by mothers, are increasingly being recognized as a channel that women use to make personal and family health–related decisions. Government initiatives  and researchers have called for scientists and the community to partner and disseminate scientifically and community-informed environmental risk information.mommy bloggers to disseminate a message that we developed and tailored for mothers and daughters based on scientific evidence from the Breast Cancer and the Environment Research Program (BCERP). We posited that the intervention would influence women’s exposure to, acceptance of, and beliefs about environmental risks while promoting their intention to adopt risk-reducing behaviors.We developed and evaluated a blog intervention to disseminate breast cancer and environmental risk information to mothers. We teamed with Using a quasi-experimental design, we recruited 75 mommy bloggers to disseminate the breast cancer risk message on their respective blogs and examined the impact of the intervention on (1) readers exposed to the intervention (n=445) and (2) readers not exposed to the intervention .P<.001). Readers who recalled the intervention messages also had higher breast cancer risk and prevention information satisfaction scores compared with readers who did not see  the messages . Blog readers who recalled seeing the intervention messages were significantly more likely to share the breast cancer risk and prevention information they read, with their daughters specifically, than readers who did not recall seeing them . Those who recalled seeing the intervention messages reported significantly higher breast cancer risk and prevention information influence scores, indicative of behavioral intentions, than participants who did not recall seeing them . Most women ranked Facebook as their first choice for receiving breast cancer risk information.Following the intervention, blog reader scores indicating exposure to the breast cancer risk and prevention information were greater than scores of blog readers who were not exposed  the BCERP-adapted intervention messages from mommy bloggers had higher breast cancer risk and prevention information exposure scores and higher breast cancer risk and prevention information satisfaction and influence scores than those who did not see  them. Mommy bloggers may be important opinion leaders for some women and key to enhancing the messaging, delivery, and impact of environmental breast cancer risk information on mothers. Breast cancer is the second most common cancer diagnosed in women . Women, Breast Cancer and Environmental Research Act in 2008. This resulted in the initiation of the Interagency Breast Cancer and Environmental Research Coordinating Committee (IBCERCC), which was tasked with examining the state of this research. Their report identified 7 recommendations, 2 of which centered on the need for scientists to become engaged in dissemination, specifically prioritizing community stakeholder engagement and translating research for the public  1), the researchers used an online tracking program, Tracx , to captTracx. Out of 7897 total posts reported, 293 additional blog posts, social media posts, and engagements were added manually.The sample was collected between October 1 and December 31, 2017, by one of the authors, corresponding with the start of the intervention and 2 months following it. To ensure exhaustiveness, manual identification of posts and ensuing reactions across all platforms was performed in addition to using Tracx: A post was the initial piece of breast cancer content submitted to a blog post and/or other social media used by the participating bloggers to reach their reader audience. Engagement referred to any interaction with a post on a social network including Google+, Facebook, Twitter, and Instagram. An interaction included likes, retweets, replies, shares, favorites, and comments in relation to the original post. Comments were defined as any text or emoji response to a post on either the original blog post or a post on social media.The frequency of the following key variables was reported by Tracx was able to match up the engagement, comment, and reach with each mommy blogger original post. Reach was operationalized as the number of unique people who were potentially exposed to the original blog posts. The overall reach of bloggers was calculated by the number of readers who followed their blog. Multiple reactions from the same person across channels were counted as one reach. The blog reader survey included a variety of measures that are consistent with the diffusion of innovation theory , includiDid you notice breast cancer risk and prevention information from the BCERP  organization in any of the blog posts you read recently? Respondents were also asked to list up to 5 different blogs they followed in the past year to help the researchers detect exposure to the intervention message on other blogs the readers follow. In this way, the researchers could also determine whether reader comparison group participants had been exposed to the intervention message.Recall of the intervention messages was assessed by the following question: The blog(s) I follow has/have increased my exposure to information about breast cancer risk and prevention, ranging from Strongly Disagree to Strongly Agree.Exposure to information about breast cancer risk and prevention was measured with a 5-point Likert-type scale item: Please indicate how satisfied you are with the way the blog(s) you follow present breast cancer risk and prevention information, ranging from Not Satisfied at All to Very Satisfied.Satisfaction with the breast cancer risk and prevention information that blog readers were exposed to was measured using a 5-point Likert-type scale item: How much did reading the recent breast cancer risk and prevention blog posts influence your acceptance of the message regarding breast cancer risk?; How much did reading the recent breast cancer risk and prevention blog posts influence your beliefs about breast cancer risk?; and How much did reading the recent breast cancer risk and prevention blog posts influence your behaviors to reduce your risk of breast cancer? Each response ranged from Not at All to Very Much. These measures were added together to create a composite score .Breast cancer risk and prevention message acceptance or influence was measured with 3 5-point Likert-type scale items, including: In the future, how likely are you to share with others any information about breast cancer risk and prevention from the breast cancer risk blog post(s) you read in the past year?, ranging from Not Likely at All to Very Likely.Participant likelihood of sharing breast cancer risk and prevention information from blogs was measured with a 5-point Likert-type scale item: With whom did you share the information from the breast cancer risk and prevention blog post(s) you read? Participants could make their selection from a drop-down menu that included various family members, friends, coworkers, and others within their social networks.All participants were asked, How important to you is breast cancer risk and prevention as a topic?, ranging from Unimportant to Very Important.Participant perceptions of the importance of breast cancer risk and prevention as a blog topic was measured with a 5-point Likert-type scale item: t tests were performed in an initial assessment of differences between blog reader intervention and comparison groups. Analysis of covariance (ANCOVA) was conducted to test H1 and H2. Finally, a chi-square analysis was performed to analyze between-group differences in sharing breast cancer risk and prevention information with others, specifically daughters. Values were considered statistically significant at P<.05.Statistical analyses were conducted using IBM SPSS. Independent sample t794=−1.004; P=.31. As expected, participants in the reader intervention group were significantly more likely to recall seeing one or more of the intervention messages (n=165), χ21=42.9; P<.001. However, 32 individuals in the comparison group also recalled seeing the intervention messages on 1 of 5 other blogs they follow. These individuals were treated as members of the intervention or exposed condition in analyses, bringing the total number of participants who recalled seeing one or more of the intervention messages to 197 (n=197) versus the comparison group (n=321).In terms of the perceived importance of breast cancer risk and prevention as a topic, there was no significant difference between members of the intervention and comparison groups, F1,409=25.78; P<.001; partial eta2=0.06). In addition, those readers who recalled the intervention messages had higher breast cancer risk and prevention information satisfaction scores  than participants who did not recall seeing the intervention messages  supporting H1.H1 posited that the use of a targeted online blog intervention would increase blog reader’s exposure to and satisfaction with the breast cancer risk and prevention information they received compared with blog readers who were not exposed to  the intervention messages. An ANCOVA test comparing breast cancer risk and prevention information exposure scores between participants who recalled seeing the BCERP intervention messages versus those who did not, while controlling for level of education, revealed that participants who recalled seeing the intervention messages had higher breast cancer risk and prevention information exposure scores  than those who did not  and age , showed significantly higher breast cancer risk and prevention information influence scores  for those who recalled seeing the intervention message when compared with those who did not .H2 predicted that a targeted online blog intervention will influence breast cancer risk and prevention message acceptance, beliefs, and intentions to act on the information provided to reduce breast cancer risk. An ANCOVA test comparing breast cancer risk information influence scores of intervention and comparison groups, while controlling for level of education  who ranked blogs as their first choice, and 0.01% (4/445) who ranked email as their first choice.The second research question (RQ2) asked about mommy blog readers’ media or channel preferences for receiving future information about breast cancer risk and prevention. For the intervention group, 14.4% (64/445) of participants ranked Facebook as their first choice for receiving future information about breast cancer risk, followed by 0.07% (31/445) who ranked Twitter as their first choice, 0.05% (22/445) who ranked other social media as their first choice, 0.01% (5/353) ranked blogs as their first choice, 0.008% (3/353) ranked email as their first choice, and 0.003% (1/353) ranked mail  as their first choice. In terms of other preferred social media, the most frequently mentioned channels were Instagram (n=27) and Pinterest (n=9). Other suggested channels for disseminating breast cancer risk and prevention messages were YouTube (n=3), text messages (n=3), medical websites, such as WebMD or PubMed (n=2), Google (n=2), and Tumblr (n=1).In the comparison group, 0.09% (35/353) of participants ranked Facebook as their first choice for receiving future information about breast cancer risk and prevention, 0.06% (21/353) ranked Twitter as their first choice, 0.01% (6/353) ranked The aim of this study was to examine whether a targeted intervention in which mommy bloggers disseminate evidence-based information could increase mothers’ exposure to and dissemination of breast cancer environmental risk and prevention information and, ultimately, be a potential means of persuading mothers to engage in behavioral changes that could reduce their disease risk. To better determine the potential for women to engage in risk-reducing lifestyle behaviors advocated for in the messages, we investigated several antecedents to behavior change . Additionally, to ascertain the potential reach of this intervention approach, we explored women’s dissemination of and preferences for information via other social media platforms, allowing us to explore the potential for rapid diffusion via this intervention approach.Results indicated that mommy blog readers who were exposed to  the seeded intervention message adapted from BCERP guidance had higher breast cancer risk information exposure scores and higher breast cancer risk and prevention information satisfaction and influence scores than those who did not see  them. These findings are consistent with previous theory and research on the influence of social networks and opinion leaders within them on health perceptions ,19,32,45Our intervention involved both evidence-based and user-generated message development. As such, our targeted intervention demonstrated that future designers of breast cancer communication interventions can provide online opinion leaders such as mommy bloggers with health information adapted from evidence-based research from authoritative groups . This may be especially important in better ensuring that information posted on blogs is accurate and credible given a recent study that showed that blogs are often less accurate than other online sources . Our finTracx analysis indicated that initial mommy blog message posts were shared on a variety of social networking sites, including Facebook, Twitter, Instagram, and other blogs, with Instagram being the most widely used. However, data from the blog reader survey (RQ2) indicated that participants varied widely in terms of self-reported preferences for how they would like to receive environmental breast cancer risk information in the future. Overall, these findings suggest that disseminating health information through blogs may have an extensive reach. Information may be encountered by individuals in one social media platform and then shared with others across other (perhaps more preferred) social media. Our Tracx data on message reach showed that some form of the initial seeded intervention messages from the participating bloggers was shared well beyond their initial blog reader audience.In addition, findings revealed that disseminating health messages through opinion leaders may influence the further dissemination and amplification of those messages, meaning that there is potential for rapid diffusion of information via social media interventions. Findings of the Moreover, this study found that reach, or rapid diffusion of information, extended beyond online communities and platforms to individuals’ personal networks. Our data showed that mommy bloggers’ posts spurred interaction about breast cancer risk among women and their daughters, specifically. This finding is an important reminder that health information encountered via social media is often shared in close relationships, which may reinforce the impact of the information on health behaviors. This finding is consistent with Rogers’ diffusion of innovation theory  and assoThe findings also prompt questions about how to best prepare women who use blogs and other social media for conversations with their daughters about environmental breast cancer risk. Communication competence is particularly of concern when mothers talk to their daughters about risk-related topics since these conversations can increase psychological and physiological distress for daughters ,50. OtheTracx, it is often difficult to assess (outside of self-reports) where people encountered specific intervention messages within the social media landscape or how these transfer to interpersonal conversations. In addition, since 42% of women in the comparison group had a family history of breast cancer, it is likely that these individuals had a keen interest in breast cancer prevention and could have been prone to seek this information on blogs (increasing the chance for contamination between the treatment and comparison groups).Moreover, the findings indicated that the intervention message had a modest impact on key study measures of exposure, satisfaction with the message, intentions to act on the information, and likelihood of sharing the information with others. One intervening variable was participant’s recall of the message. Although we know that individuals who recalled the message were more exposed and satisfied with them, and they had stronger intentions to act on the information than the comparison group, it is unknown whether they were recalled from the original blogger post, comments from online or face-to-face social network members, or another social networking site . Future researchers should take this into account when attempting similar types of seeded messaging strategies. Although researchers can track where information has been reposted or replied to using programs such as other social media platform for blog readers. This is likely because of Instagram’s ability to conveniently share or obtain breast cancer information on a variety of other social media channels (such as Facebook and Twitter). Future research should examine how Instagram (and similar platforms) may enhance the reach and impact of future interventions that attempt to seed similar online opinion leaders with evidence-based breast cancer and environmental risk and prevention messages.The findings also suggest that Instagram was the most popular There are a number of limitations in this study. First, the study relied on a convenience sample of participants using a quasi-experimental design as opposed to a randomized treatment or control group study. One of the reasons for this was the desire to work with naturally occurring bloggers and their established online social networks of readers. However, the lack of randomized groups limits the generalizability of claims regarding the efficacy of the seeded mommy blogger intervention used in this study.Additionally, the bloggers and blog readers tended to be highly educated overall. Less than 10% of the intervention group or comparison group members had a high school education or less. The researchers are in the process of analyzing qualitative interview data from a subset of ethnic minority and lower socioeconomic status respondents who participated in this study to assess how intervention messages could be tailored in more culturally sensitive and educationally appropriate ways in future research.Yet, the findings provide insights into the value of this approach while highlighting consideration for future research. One future direction would be to systematically assess what factors are associated with greater likelihood of recall among participants in this type of intervention. The education level was controlled in this study, but other factors associated with education, such as health  literacy, could influence message recall. To explore the impact of such factors on participant recall, studies might employ interviews and/or other qualitative methods to see how user-centered design can be integrated with scientifically accurate information to develop more memorable messages.In terms of other limitations, blog readers typically follow more than one blog, and this might have led to contamination between the intervention and comparison groups. However, we attempted to correct this by asking readers to report up to 5 blogs they visited most frequently in the past year. This allowed us to discover individuals in the comparison group who saw the intervention message. Furthermore, we were limited by the number of survey items we could reasonably include, which contributed to not being able to use larger multidimensional measures of the key variables of interest. In future research, we hope to capture more nuanced aspects of complex variables, such as behavioral intentions to act on environmental breast cancer guidance, as well as finding ways to better distinguish between people who actively disseminate intervention messages and those who are more passive recipients of these messages .Finally, the use of longitudinal research designs is important when assessing health knowledge and behavior change that may result from a social media intervention such as the one reported here. Given that the reader survey was administered over a 2-month period following the start of the mommy blogger intervention, it is difficult to know about the long-term effects of exposure to these types of messages. Future studies need to find creative ways to measure variables longitudinally in an environment that is dynamic in terms of online network membership and the stability of specific social media channels . This presents numerous challenges in terms of deciding the best channel(s) for health intervention messages, including those regarding environmental breast cancer risk. Moreover, future researchers should consider assessing mommy bloggers’ satisfaction regarding their participation in terms of serving as opinion leaders in similar interventions.The study results showed promise for the utilization of online opinion leaders such as mommy bloggers as influential channels for the dissemination of both evidence-based and user-generated environmental breast cancer risk messages. Moreover, this study shed light on how blog readers share environmental breast cancer risk and prevention messages across different social media platforms and the preferred channels for receiving this type of information. Results also revealed the potential reach of disseminating health risk information via bloggers. Mommy bloggers may be especially primed to disseminate health risk information geared toward mothers, and this channel may effectively serve as a catalyst for mother-daughter communication about breast cancer risk reduction. Mommy bloggers may also aid interventionists in enhancing the messaging, delivery, and impact of environmental breast cancer risk information.


The microbiome is undoubtedly the second genome of the human body and has diverse roles in health and disease. However, translational progress is limited due to the vastness of the microbiome, which accounts for over 3.3 million genes, whose functions are still unclear. Numerous studies in the past decade have demonstrated how microbiome impacts various organ-specific cancers by altering the energy balance of the body, increasing adiposity, synthesizing genotoxins and small signaling molecules, and priming and regulating immune response and metabolism of indigestible dietary components, xenobiotics, and pharmaceuticals. In relation to breast cancer, one of the most prominent roles of the human microbiome is the regulation of steroid hormone metabolism since endogenous estrogens are the most important risk factor in breast cancer development especially in postmenopausal women. Intestinal microbes encode enzymes capable of deconjugating conjugated estrogen metabolites marked for excretion, pushing them back into the enterohepatic circulation in a biologically active form. In addition, the intestinal microbes also break down otherwise indigestible dietary polyphenols to synthesize estrogen-like compounds or estrogen mimics that exhibit varied estrogenic potency. The present account discusses the potential role of gastrointestinal microbiome in breast cancer development by mediating metabolism of steroid hormones and synthesis of biologically active estrogen mimics. Humans are not merely individuals but a complex ecosystem harboring trillions of microbial cells. Although microbes inhabit multiple body sites, most of the microbial biomass resides in the gastrointestinal tract. The 100 trillion microbes residing in the GI tract carry a collective genome called the metagenome that is 150 times larger than human genome  whose fuClostridia, Enterobacterium, Lactobacilli, Bacteroides, and Escherichia coli were enriched in breast cancer patients . F. F15]. F≤ 0.003) C. MultivClostridiales   [p = 0.11 [Another study in 2014 by Fuhrman et al. investigated the association of fecal microbiome with estrogen and its metabolites in urine of postmenopausal women . In a gr = 0.02) B. Simila = 0.03)   . Total ep = 0.11 . Contrarp = 0.009) but not in cancer cases  [p = 0.006) as well as lower α-diversity, p = 0.004. All mean estrogens were 2-fold higher in cancer cases as compared to controls, but remained statistically insignificant, p ≥ 0.1 [p = 0.08) but not in cancer cases . Cancer cases exhibited lower alpha diversity in fecal microbiota (p ≤ 0.004) except Shannon index, p = 0.09 [Clostridiales, cancer cases carried higher levels of Ruminococcaceae, Clostridiacae and Faecalibacterium but lower levels of Dorea and Lachnospiraceae [ptrend = 0.28). The ratio of 2-pathway metabolites to parent estrogens as well as total estrogens inversely correlated with breast cancer risk. Comparing the levels of urinary estrogens and estrogen metabolites, it was three-fold higher in Asian American women compared to women from Shanghai. Concentrations of 2-pathway and 16-pathway metabolites were found to be similar to the parent estrogens (31% and 36% against 29%) [Further in 2015, Goedert et al. investigated the differences in gut microbial population of 48 postmenopausal women with breast cancer and same number of age matched healthy women  Figure D. Surpri = 0.77) . Cancer  p ≥ 0.1 . In contp = 0.09 . Microbipiraceae . In 2016piraceae   . The 2 anst 29%) . Breast nst 29%) . Breast nst 29%) . These dnst 29%) ,47. We tEubacterium limosum, demethylate the hydroxyl group activating the estrogenic compounds [Adlercreutzia equolifaciens, Eggerthella spp., and Slackia isoflavoniconvertens [In addition to metabolizing estrogens, enteric microbes perform a very important role in synthesis of estrogen-like compounds or estrogen mimics from dietary sources ,50,51,52ompounds . Biotrannvertens .Eggerthella [Plant-based lignans are present in high concentrations in soy, flax seeds, and sesame, and to some extent in fruits, vegetables, and berries . These lerthella . The deberthella . It is aerthella . Multiplerthella ,32,51,52erthella . Antibioerthella .p < 0.01) [Proteobacteria species such as E. coli, Klebsiella, Enterobacter, and Citrobacter [Multiple studies have been conducted to examine the role of enterolignans in cancer incidence and progression . While s < 0.01) . Interes < 0.01) . As such < 0.01) . In post < 0.01) , suggestrobacter . All therobacter .In addition to estrogen, at least two other steroid pathways have been implicated in breast cancer and are currently being investigated as therapeutic targets. In ER positive breast cancers, androgen receptor (AR) and androgenic enzymes are known to antagonize ERα, suppressing carcinoma progression. AR may also play an important role in luminal androgen receptor (LAR) subtype of triple negative breast cancer. These steroids are thought to aid in stroma activation necessary for breast cancer progression . NeitherStructural similarities between phytoestrogens and estrogens were discovered in 1980s  and compIn an effort to understand the microbiome–estrogen connection and its effect on breast cancer risk, we decided to investigate the functional impact of enterolignans on estrogen receptor positive breast cancer cells. Current knowledge regarding the role of enterolignans and other phytoestrogens in breast cancer is discordant but we have to appreciate that the impact of enterolignans may be context specific and not uniform. We hypothesize that enterolignans are potent estrogenic compounds, however their circulating levels can vary dramatically depending on dietary habits, age, menstrual status, and most importantly the gut microbiome composition. Moreover, the levels of enterolignans are variable throughout life and only long-term exposure to high levels of these compounds can cumulate to a significant biological outcome. Tissue specific effects can again vary depending on total estrogen bioavailability and metabolic efficiency. We utilized in silico approaches to predict potential targets of enterodiol (END) and enterolactone (ENL) and their binding efficiency to estrogen receptor (ER) followed by in vitro functional assays to evaluate their effects on ER positive breast cancer cells.In silico target prediction using SwissDock target scan suggested that the enterolignans can act as ligands to multiple targets including kinases and their receptors in addition to estrogen receptors (ERs) .Molecular docking using AutoDock Vina and UCSF Chimera showed that both END and ENL can bind to ERα and ERβ similar to estrogen (E2) . Next, wBreast cancer cells treated with END and ENL exhibited nuclear translocation of estrogen receptor within 15 min post-treatment that was diminished by 6 h post treatment A,B. ExprTo test the effect of END and ENL on the migration potential of breast cancer cells, we performed wound healing and spheroid migration assays A–C. MigrMost epidemiological studies have shown a protective effect of phytoestrogens and enterolignans against breast cancer especially in premenopausal women while a few studies have shown no effect or even negative effects. However, most of the studies estimate the levels of these active compounds based on the dietary consumption of plant-based foods but plant-based diets are rich source of multiple other active phytochemicals and health outcomes associated with plant-based diets cannot be attributed to enterolignans alone. For example, one study has shown that a flax seed rich diet in pregnant or lactating rats increases the risk of breast carcinogenesis in the progeny  and incr


Evidence from basic research links exposure to endocrine disrupting chemicals (EDCs) with a higher risk for breast cancer. However, there is less evidence from observational epidemiological research and the results are equivocal. Therefore, we examined the association between occupational exposure to substances where exposure to EDCs is likely and the risk of breast cancer.N = 988) were determined by linkage with the Singapore Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for exposure to substances, job titles, and industries.A prospective study consisting of a population-based cohort of 33,458 Singaporean Chinese women aged 45–74 years enrolled in the Singapore Chinese Health Study (SCHS) from 1993 to 98 and followed through 2014. Subjects’ self-reported occupational exposure and duration to industries, job titles, and substance types were garnered at baseline, and cases of incident breast cancer , medium (HR 1.03 95% CI: 0.77–1.38) and low  combined substance exposure groups when compared with those who were not exposed via occupation. Similar null associations were observed when examining job titles and industry categories.There was no association between EDC related occupational exposures and breast cancer risk in working women of the Singaporean Chinese Health Study. Future studies that employ rigorous methods with regard to exposure assessment of EDCs are needed.The online version of this article (10.1186/s12889-018-5862-2) contains supplementary material, which is available to authorized users. Endocrine disrupting chemicals (EDCs) refer to exogenous substances that can interact with an organism’s endocrine system or general hormonal action –3. TheseIt has been hypothesized that part of the increase in the incidence of hormone related cancers, such as breast cancer, could be the result of the increased presence of EDCs in the environment due to westernization and industrialization –17. Yet Our primary aim was to examine the association of EDC related occupational exposures with the risk of breast cancer in women. We hypothesized that a proxy for higher composite exposure to EDC via occupational exposures was associated with higher breast cancer risk.N = 34,028), with complete data , after excluding participants with incomplete data regarding diet pattern (n = 570). Written, informed consent was obtained from all study participants. Institutional review boards at the National University of Singapore, University of Pittsburgh, and the University of California, Irvine approved this study.The design of the SCHS has been previously described . BrieflyAt the baseline interview participants self-reported lifetime exposure through their occupations. The job titles included, “Welder, Textile Machine Mechanic, Other Mechanic, Cotton Spinner or Weaver, Painter, Textile Dyer, Machinist, Printer, Tailor or Seamstress, Janitor or Cleaner, Vocational Driver, Food Hawker, Cook or Kitchen Worker” . The indA priori group classification of EDC related occupational exposures was identified from the literature and this included: Chlorophenol, heavy metals, polycyclic aromatic hydrocarbons (PAH), pesticides, organic solvents, dyes, bisphenol A, phthalates, synthetic resins, alkylphenols. PCBs, phenylphenol, and brominated flame retardants. To test the study hypothesis, substances from the above list were assigned to the EDC group list as probable exposure to EDCs based upon literature evidence; the analysis was repeated for the industry categories, as well as the job title categories. The details of these groupings as well as the references for the selections are presented in Additional file 2), contraception history, hormone therapy use, reproductive factors, physical activity and a vegetable-fruit-soy rich dietary pattern score [Covariate information was ascertained from the baseline interview. This included age, dialect, educational attainment, smoking habits, alcohol use, body mass index (kg/mrn score .n = 52 participants (0.08%) were lost to follow-up due to migration out of Singapore. This suggests that emigration within this study population is negligible and vital statistics at follow-up was essentially complete.Incident primary invasive breast cancer cases as well as deaths were ascertained through record linkage with the population-based Singapore Cancer Registry and the Singapore Registry of Births and Deaths through 2014. A unique national identification number given to all Singaporeans was used for linkage. Thus far, only To test whether greater exposure to occupational related EDCs is associated with higher risk for breast cancer we created an index from the occupational exposure assessment as described in Additional file N = 18,138). Lastly, women who reported working in an industry, job title, or reported occupational exposure to a specific substance that did not fit the a priori definition for likely EDC exposure were defined as a category as well.Participants with a non-zero exposure index score were ranked into tertiles. Women who reported no occupational exposure to any of the substances, jobs or industries were another category . For each study subject, person-years were counted from the date of the baseline interview to the date of incident breast cancer diagnosis, death, date of last contact (for the few subjects who migrated out of Singapore), or 31 December 2014, whichever occurred first. There was no evidence that proportional hazards assumptions were violated as indicated by the lack of a interaction between indices and a function of the survival time in models, and by viewing log ) plots.Cox regression models were used to estimate the Hazard Ratios and corresponding 95% confidence intervals for the association between the occupational exposure groups and incident breast cancer. The referent group was women who reported no occupational exposure to any industry, job, or substance (2), contraception history (never/former/current), hormone therapy use (never/former/current), physical activity (time in strenuous sports and/or vigorous work) and a vegetable-fruit-soy rich dietary pattern score; [2 versus ≥23.0 kg/m2), smoking (ever/former/current), alcohol use (never/ever), menopausal status (pre-menopause/menopause), and age group . We also carried out a sensitivity analysis to inform the interpretation of our a priori groupings by examining specific substance types, job titles, and industry of potential occupational EDC exposure. All analyses were performed with SAS version 9.3 .Two models were constructed to examine the association between likely occupational exposure to EDCs and risk of breast cancer during follow up. Model 1 included age at baseline, dialect (Cantonese or Hokkiens), year enrolled (between 1993 and 1995 vs 1996–1998), educational attainment , smoking habits (never/former/current), alcohol use (never/ever), body mass index . Descriptive participant characteristics at baseline for the different exposure categories are presented in Table As of December 31, 2014, 2.95% of the study population developed a primary invasive breast cancer


Background: Ultrasound is an important modality for breast cancer screening. However, the evidence on the effectiveness of ultrasound screening in population-based cancer screening program in lacking. We aimed to evaluate the diagnostic yield of ultrasound screening in a population-based breast cancer screening in China.Methods: The analyses were conducted in the context of the Cancer Screening Program in Urban China, which recruited 1,938,996 eligible participants aged 40–69 years from 16 provinces in China from 2012 to 2016. We included 72,250 women assessed to be high-risk for breast cancer who undertook ultrasound screening per study protocol. Diagnostic yield according to the Breast Imaging Reporting and Data System (BI-RADS) was evaluated. Risk factors associated with the positive findings of ultrasound were also explored by univariate and multivariable logistic regression analyses.Results: Overall, there were 9,765 (13.51%) women had positive findings of ultrasound screening, including 8,487 (11.75%), 1,210 (1.67%), and 68 (0.09%) of BI-RADS categories of III, IV, and V, respectively. Younger ages, late age of 1st live birth and short-term breast feeding were found to be positively associated with positive findings under ultrasound in multivariate analyses stratified by menopause status and family history of breast cancer. Multivariable prediction models were constructed and yielded only modest prediction accuracy, with AUCs around 0.55.Conclusions: We found the diagnostic yield of ultrasound screening for breast cancer in high-risk population was satisfactory. Prediction models based on environmental risk factors had limited prediction accuracy and need to be improved in the future. With an estimate of 2,088,849 newly diagnosed cases in 2018 worldwide, breast cancer is the most frequently diagnosed cancer for women and is also the leading cause of cancer-related deaths –5.In most cancer screening programs, mammography was regarded as main screening method. However, the diagnostic accuracy of mammography for breast cancer was not equal in all women. The overall sensitivity of mammography for detecting breast cancer was around 85%, but it dropped dramatically to 47.8–64.4% for women with dense breast tissue . The curSince October 2012, the China government initiated a population-based Cancer Screening Program in Urban China (CanSPUC), in which breast cancer screening is a major component. For the present study, we reported the results of breast cancer screening using ultrasound conducted between October 2012 and October 2016. We aimed to evaluate the diagnostic yield of ultrasound screening in high-risk Chinese populations and to identify risk factors associated with the clinical findings of ultrasound screening.We performed a cross-sectional study under the framework of Cancer Screening Program in Urban China (CanSPUC). CanSPUC is an ongoing national cancer screening program which was initiated in October 2012. Briefly, residents aged 40–69 years old living in the selected communities of the participating cities were approached by trained staffs by means of phone-calls and personal encounter. After obtaining signed written informed consent, all the eligible participants were interviewed by trained staffs to collect information about their exposure to risk factors and to evaluate their cancer risk using an established risk score system. For the present screening program, to optimize use of the limited healthcare resources and to enhance the detection rate of positive findings, only participants who were assessed to be at high-risk of breast cancer were recommended to undergo subsequent ultrasound and/or mammography intervention at tertiary-level hospital designated by the program at free of charge. The study was approved by the Ethics Committee of National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College and all participants provided written informed consent.The overall screening strategy for breast cancer in this program was tailored according the age. For participant aged 40–44 years old, ultrasound was provided firstly and only those with suspicious findings under ultrasound  were recommended to take subsequent mammography examination. For participants aged 45–69 years old, both ultrasound and mammography were provided to the participants. For patients with positive findings, further treatment were suggested according the up-to-date clinical guidelines.N = 903,936), participants with invalid risk assessment results , and those not at high-risk for breast cancer , 200,462 participants were evaluated to be high-risk for breast cancer. We further excluded 126,426 participants who did not attend ultrasound screening and 1,786 participants with invalid ultrasound results, yielding an overall of 72,250 participants included in the final analyses. A flow-diagram showing the recruitment of study population is shown in the For the present analyses, we only used the data of the ultrasound screening conducted in the first 4 years between October 2012 and October 2016, which covered a total of 22 cities in 16 provinces. Overall, there were 1,938,996 eligible participants recruited. After excluding participants of male sex , age of menarche, total years of menstruation, age of first marriage, total months of breastfeeding, history of breast benign diseases, History of female reproductive system surgery, and family history of breast cancer. Each risk factor was allocated a score by the expert panel based on the magnitude of its association with breast cancer. The cumulative risk scores were calculated and were then divided by the average risk score in general population to get the final individual relative risks. Individuals with relative risks over 1.50 were defined as high-risk for breast cancer.Screening ultrasound was performed by color Doppler and high-resolution transducers scanning for transverse and sagittal planes by experienced radiologists (attending physician or above having experiences of endoscopy for at least 5 years). Any findings during ultrasound examination were required to be photo documented. Clinical information such as morphology, thickness, and structure of gland, features of breast space occupying solid lesions  and clinical diagnosis were collected and documented in the data system. In this study, the Breast Imaging Reporting and Data System (BI-RADS) was used to interpret the ultrasound screening results and derive diagnosis reports, with the following categories: I, negative; II, benign; III, probably benign; IV, suspicious malignancy; and V, highly suggestive of malignancy.For quality and consistency among all study sites, central capacity training programs were conducted annually to ensure that uniform standard of BI-RADS was implemented by radiologists from all participating hospitals. In addition, the images of all positive findings  and 1% of randomly selected negative findings (BI-RADS categories of I and II) were centrally reviewed by an expert panel from National Cancer Center. Any discrepancy with the original diagnosis were discussed until consensus were reached.Paper-based standardized documentation forms  were filled by trained study staffs and physicians. Validity of forms were checked and entered into the data management system by trained study staffs. Consistency check was conducted, and mistakes were corrected by retrieving the original records if inconsistencies were identified. Each participant had a unique identification code using to track all the individual's relevant documentation forms. All data were transmitted to the Central Data Management Team, who were responsible data monitoring and subsequent data analyses.p-values of 0.05 or less were considered to be statistically significant.Descriptive statistically analyses regarding the characteristics of the study population were firstly performed. The distribution of risk factors by different BI-RADS categories  were presented. Chi-square tests were used to compare the distribution of risk factors between participants with or without positive findings (BI-RADS category of III-V) under ultrasound screening. Multivariable logistic regression models stratified by the menopause status (pre-menopause or post-menopause) were employed to explore the associations between the risk factors and positive findings of screening ultrasound, and odds ratios (ORs) and their 95% confidence intervals (95% CIs) were also calculated and reported. Receiver operating characteristics (ROC) curves were constructed to estimate the diagnostic accuracy of multivariate logistic model using the selected risk factors for predicting the abnormal findings (BI-RADS II-IV) under screening ultrasound. Area under the curves (AUCs) along with the 95% CIs were also calculated and reported. All statistical analyses were performed with the statistical software R version 3.5.1. All tests were two-sided and Overall, 72,575 participants having valid ultrasound screening results were included in our analyses. N = 40,458) had negative findings (BI-RADS I). For the participants with abnormal findings, the proportions of BI-RDAS categories of II (benign), III (probably benign), IV , and V  were 30.49% , 11.75% , 1.67% , and 0.09% (N = 68), respectively For the nodule findings, the mean sizes for patients with BI-RADS categories of II, III, IV, and V were 5.00, 6.57, 8.58, and 16.31 mm, respectively.Regarding the clinical diagnosis of ultrasound screening, 56.00% of the participants  and 1.92 (1.32–2.90), respectively. For pre-menopause women with family history of breast cancer, age, BMI and total years of menstruation were also found to be associated factors. Similarly, for post-menopause women without or with family history of breast cancer within 2-degree relatives, age were also identified to be a potential risk factor associated with the abnormal findings of ultrasound screening.By using the above-mentioned risk factors, we further constructed multivariable logistic regression models to predict abnormal findings under ultrasound screening for the four subgroups, and the diagnostic accuracy was evaluated by constructing ROC curves. The results of ROC curves are shown in We reported here the preliminary results of 72,575 high-risk women who undertook ultrasound screening in a population-based cancer screening program in China. The analyses showed that positivity rate for abnormal findings (BI-RADS III-V) of ultrasound screening in this high-risk population was 13.51%, with BI-RADS categories III, IV, and V of 11.75, 1.67, and 0.09%, respectively. Additionally, we identified several factors including age, BMI, age of first live birth and duration of breast feeding were potentially associated with the positive findings of ultrasound. However, multivariable prediction models using these factors only conferred modest diagnostic performance. To our limited knowledge, this is the first large-scale study reporting the diagnostic findings of ultrasound screening in a population-based cancer screening program in China. The finding of our study provided timely estimate of screening yield of ultrasound in breast cancer screening programs and will be helpful for designing effective breast cancer screening strategies in future.Ultrasound was suggested to serve as an adjunctive screening method for women having dense breasts . RegardiIn our study, the detection rate for suspicious malignancy (BI-RADS IV and V) was 0.17%. Our results were in line with previous researches conducted in China , 16. As Previous studies have identified a series of risk factors of breast cancer and risk prediction models based on such risk factors such as the Gail breast cancer risk model have been developed to identified women at high risk for breast cancer for preventive interventions or more intensive surveillance –21. In oIt deserves to be noted that the overall positivity rate of ultrasound screening was high in a high-risk population in urban China, with around 44% participants having benign or potential malignancies. Therefore, the potential harms of ultrasound screening including the consequences of false-positive and false-negative tests, and the occurrence of over-diagnosis cannot be neglected. Further studies addressing the estimates of the positive and negative effects of ultrasound screening in women based on the latest evidence are required to help policy makers in their decision-making about implementation of the breast cancer screening programs. Although ultrasound had several advantages over mammography such as lower cost and easier accessibility especially in resource poor regions, it had barriers in screening programs, such as operator dependence procedure, limited ability to detect calcifications, lack of trained technologist, and limited reproducibility. Further large-scale trials and rigorous health-economic evaluations should be conducted to illustrate whether ultrasound screening is cost-effective in breast cancer screening programs.Specific strengths and limitations deserve careful attention when interpreting our results. A major strength of our study is the fact that our analyses were the first to illustrate diagnostic yield of ultrasound screening in a large-scale population-based cancer screening program in China. Furthermore, detailed patient information including epidemiological questionnaire and clinical examination data were collected in a standardized manner by trained study staffs to ensure the quality of data. Capacity training and central review of ultrasound reports by an expert panel were also conducted yearly to enhance the consistency and accuracy of clinical diagnoses. Limitations include that the study population was a pre-selected high-risk population using the predefined risk model which was not representative of entire general population of China and therefore selection bias cannot be ruled out. In addition, follow-ups tracing the outcomes of all the participants are undergoing, so evaluation of detection rate of breast cancer or occurrent of interval cancer cannot be evaluate at the current stage.In summary, in this large-scale cancer screening program in China, we found the diagnostic yield of ultrasound screening for breast cancer in high-risk population was satisfactory. Using environmental risk factors associated with positive findings of ultrasound identified in this study only carried limited prediction accuracy and further improvement by incorporating other effective factors could contribute to the development of a useful risk prediction model for identifying high-risk populations of breast cancer in the future.The study was approved by the Ethics Committee of National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College and all participants provided written informed consent.JH and MD: conception and design. YW and HC: statistical analyses and drafting of the article. YW, HC, NL, JR, and KZ: data acquisition and data interpretation. All authors revised the manuscript and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Breast cancer risks were particularly increased at ages <50 . Mortality was borderline significantly raised for breast cancer  but not significantly raised for other cancers or causes. Individuals diagnosed with t appear to be at several‐fold increased breast cancer risk, with the greatest risks at premenopausal ages. Further research is required to understand the genetic mechanism involving 11q23 and 22q11 and there may be a need for enhanced breast cancer surveillance among female carriers.The constitutional t translocation is the only recurrent non‐Robertsonian translocation known in humans. Carriers are phenotypically normal and are usually referred for cytogenetic testing because of multiple miscarriages, infertility, or having aneuploidy in offspring. A breast cancer predisposition has been suggested, but previous studies have been small and had methodological shortcomings. We therefore conducted a long‐term prospective study of cancer and mortality risk in carriers. We followed 65 male and 101 female carriers of t diagnosed in cytogenetic laboratories in Britain during 1976–2005 for cancer and deaths for an average of 21.4 years per subject. Standardised mortality (SMR) and incidence (SIR) ratios were calculated comparing the numbers of observed events with those expected from national age‐, sex‐, country‐ and calendar‐period‐specific population rates. Cancer incidence was borderline significantly raised for cancer overall , and significantly raised for invasive breast cancer  and  What's new?The constitutional translocation between chromosome bands 11q23 and 22q11 is recurrent in human populations, with highly consistent breakpoints. A breast cancer predisposition among carriers has been suggested, but previous studies have been small and had methodological shortcomings. In this first long‐term follow‐up study of site‐specific cancer and mortality risks among carriers, an increased risk of breast cancer was observed compared to the general population, with greatest risks in younger women. The results suggest that carriers of t may require enhanced surveillance for breast cancer and point to the importance of the chromosomal regions 11q23 and 22q11 in breast cancer development. AERabsolute excess rateCIconfidence intervalICDInternational Statistical Classification of DiseasesSIRStandardised incidence ratioSMRStandardised mortality ratioThe constitutional t11;22) translocation is the only recurrent non‐Robertsonian translocation known in humans, with highly consistent breakpoints.1;22 carriers is important for counselling of carriers and can additionally provide insights into our understanding of cancer aetiology. A predisposition to breast cancer among female carriers has been suggested based on the presence of subjects with a history of breast cancer among relatively small clinical series of carriers,A prospective investigation, in which subjects diagnosed with the translocation are followed up over time for subsequent cancer risk would avoid these potential biases. However, there are no such prospective studies except for one very small investigation including 16 carriers.We collected information on carriers diagnosed postnatally with t from all but one cytogenetic centres in Britain between 1976 and 2005 (exact years varied by centre). Carriers whose records indicated they had been ascertained because of cancer were excluded. Information on subjects was matched to the National Health Service Central Registers (NHSCRs) for England and Wales and Scotland, which provided information on deaths, emigrations and other exits from the NHS, and are effectively population registers for these countries. Permission for our study was obtained from appropriate ethics committees in the UK and the national personal information advisory group.in situ breast cancer and that analyses of nervous system tumours included non‐malignant registrations. Analyses were conducted for all subjects combined and, for breast cancer outcomes, by attained age <50, ≥50 years as a proxy for menopausal status in females. In order to investigate the possibility that mortality or cancer incidence might have been biased because some subjects were cytogenetically tested as a consequence of a prior illness, analyses were repeated after excluding from follow‐up the first 36 months after cytogenetic diagnosis.Follow‐up for cancer and mortality risk started at cytogenetic diagnosis and ended on the latest date event notifications were thought to be complete , the patient's 85th birthday, date of death or date of other loss to follow‐up, whichever was earliest. The observed numbers of deaths and cancers since cytogenetic diagnosis were compared against the expected number of cases based on age‐, sex‐, country‐ and calendar‐year specific mortality and incidence rates from the general population. We computed standardised mortality (SMR) and incidence (SIR) ratios and their 95% confidence intervals (CIs) using exact methods.We ascertained 217 subjects diagnosed with t at the study centres, 170 of whom could be matched on the NHSCRs because sufficient details were available. After excluding 4 subjects referred for testing because of cancer, the cohort study consisted of 166 individuals   and in situ  breast cancer, with all cases occurring in females. Risk of breast cancer was more greatly raised at younger ages. For invasive breast cancer, the SIR was 4.37 (95% CI: 1.42–10.2) at ages <50 and 1.69 (95% CI: 0.35–4.93) at ages ≥50 years  and risk was also significantly raised at older ages .During follow‐up, 20 subjects died, 134 were followed‐up to the end of the study or age 85, and 12 emigrated or exited in other ways. There were 22 incident malignancies recorded during follow‐up, a borderline significantly greater number than expected from national rates  . SIRs for other sites were not significantly raised or reduced, but the numbers of cases were small , and was borderline significantly raised for invasive breast cancer , but not for other cancer‐sites. The SMR for all malignancies except breast cancer was 1.07 (95% CI: 0.39–2.33). Two of the deaths from breast cancer were among women aged <50 . After excluding the first 3 years after cytogenetic diagnosis from the analysis, the SMR for breast cancer at all ages was 5.34 (95% CI: 1.10–15.6). Mortality from other causes than cancer was not raised (q23:q11), one of the two subjects who developed cancer during follow‐up had breast cancer, but this did not reach statistical significance .in situ than invasive breast cancer. A greater proportion of in situ than invasive tumours are first detected by mammographic screening, and in situ cancers represent a greater proportion of screen‐detected cancers among women screened at ages <50 years than older ages.in situ breast cancer are somewhat inflated because carriers are invited for enhanced breast cancer screening due to their family history.It is unclear why the relative risk increases were greater for et al observed four cases of breast cancer among 16 female carriers identified from eight pedigree families, which they estimated constituted a 10‐fold increased risk.et al, did not observe an excess of breast cancer cases among 103 female carriers from 80 pedigrees ascertained for reproductive‐related reasons.Previous reports of a breast cancer predisposition in t carriers have been based on identification of individuals with a history of breast cancer in pedigree studies or case series of carriers.The observed raised risks of breast cancer, in particular among younger women, point to importance of the 11q23 and 22q11 regions in breast cancer development. Two common regions of loss of heterozygosity have been identified in the region 11q23 in breast cancer.The number of calendar years for which we extracted records varied by centre depending on the years the centre was operational, availability of historical records and the calendar period of extraction. The availability of records for operational reasons is unlikely to have caused bias in the results. However, most carriers are not detected unless they get referred for cytogenetic testing for experiencing reproductive problems or abnormalities in offspring. Our study is therefore of patients with t who are eventually diagnosed, but from a clinical and counselling perspective this is the group of carriers of relevance. It is possible that the raised risks of breast cancer are related to the selective forces that lead to cytogenetic diagnosis of carriers: for instance if women who get referred for cytogenetic testing are of higher socioeconomic status than those who are not referred (breast cancer rates being greater in higher socioeconomic strata).et alThe translocation t11;22) represents 1.2% of all diagnosed reciprocal translocations,In conclusion, individuals diagnosed with t showed increased rates of breast cancer compared with the general population, in particular in women aged under 50 years. The mechanistic involvement of the breakpoints on 11q23 and 22q11 in breast cancer development needs to be investigated and increased breast cancer surveillance in female carriers may be warranted.AJS was the principal investigator of the study. AJS and MJS organised the collection of the national data and AFW contributed to this collection. MJS, CDH and MEJ analysed the data. MJS drafted the manuscript and all authors contributed to the interpretation of the findings. All authors contributed to the final draft.Authors and affiliations from the UK Clinical Cytogenetics Group are as follows: Paul J Batstone ; Nick Bown ; Catherine Delmege ; Carolyn Campbell ; Angela Douglas ; David Duckett ; Sandra Edwards ; Lorraine Gaunt ; Michael Griffiths ; Richard Hall ; Christine Maliszewska ; Katherine Martin ; Karen Marks ; Lucy Platts ; Andrew Pearce ; Paul Roberts ; Kath Smith ; David Stevenson ; Peter Thompson ; Christine Waterman ; Catherine Waters . We additionally thank the following centres for providing data: West of Scotland Regional Genetics Service, Yorkhill NHS Trust, Glasgow, UK; East Anglia Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK.


In families with high risk of hereditary breast/ovarian cancer (HBOC), women before age 30 do not yet undergo clinical screening, but they are exposed to contradictory information from diverse sources. They may be presented with surgical prevention options at a key moment of their identity construction, the start of a marital relationship and/or at the onset of procreation projects. We tested an original psychoeducational intervention to help these women better cope with these difficult issues.Seven young female counselees (26.4 ± 2.9 years [23–30]) from the Oncogenetics Department at Jean Perrin Comprehensive Cancer Center were enrolled. A weekend group workshop composed of short conferences, group sharing and role playing activities was supervised by a psychotherapist. A longitudinal analysis of questionnaires over one year of follow-up was performed. The Herth Hope Inventory was evaluated, as well as self-esteem, anxiety, perceived control, coping, and quality of life. Participants’ comments were collected by a genetic counselor throughout the workshop.p = 0.0003). Coping by focus on the problem increased in the first 6 months (p = 0.011) and returned to baseline values at one year, while coping by focus on emotions decreased steadily (p = 0.021). Debriefing from the workshop highlighted the new medical opportunities proposed and the challenges these young women face, such as whether to have prophylactic surgery, and if so before or after having children, and how surgery might affect their relationship with their partner.All participants were BRCA mutation carriers and six had lived with a close relative affected by breast/ovarian cancer. Hope, self-esteem and quality of life increased during the year after the workshop  contains supplementary material, which is available to authorized users. Young adults carrying mutations favoring the development of cancer encounter various life difficulties, notably questions concerning the future and how to build long-term projects. In western countries, regular screening for the early detection of cancer is the standard of care, but psychosocial consequences remain unaddressed. This is particularly true in hereditary breast ovarian cancer (HBOC) for family members 18–25 years old: women who are not yet screened by mammography or proposed preventive measures such as annexectomy, but who have often already been witness to their mother’s disease and sometimes her death. During this early life period, women are often vulnerable as they face identity issues, the onset of romantic relationships, and questions about future procreation .These young women are subject to a plethora of conflicting information and advice spread by the media, websites, internet forums, and family members. The rapid evolution of medicine adds to the confusion, proposing prophylactic surgery, assisted procreation and embryo selection, or promising the advent of gene therapy. Moreover, specialists’ opinions are sometimes discordant. Unfortunately for these young women, such medical measures directly address issues such as self-image, sexuality, and relationships, while these are still in development. A woman’s familial and cultural environment may also influence the complexity of this situation.We developed a psychoeducational intervention tailored for these young women . A two-dClinicalTrials.gov, no NCT02705924.A prospective, mono-center, psychoeducational cohort study was performed. Ethical approval was obtained from the “Comité de Protection des Personnes” in March 2016 (CPP SUD-EST-6: n° IRB00008526) and was registered in Childless participants 18 to 30 years old belonging to hereditary breast/ovarian cancer (HBOC) families and tested for BRCA mutations (positive or negative), but without personal history of cancer, were recruited. Families negative for BRCA mutations were included if their risk scores were ≥ 6 on the Eisinger scale or ≥ 16 on the Manchester scale –7. To liPregnant women were excluded as well as individuals unable to answer questionnaires either for language difficulties or because they could not connect to our website. Psychiatric troubles and/or ongoing related treatments or any treatment incompatible with a 2-day stay in a hydrothermal spa center also prevented entry in the study.Our primary objective was to observe the evolution of the subjects’ expectations and methods of coping with their cancer risk.Subjects’ improved understanding of genetic and cancer risk informationSubjects’ improved self-imageUnderstanding how these young women respond to issues like marital relationships and family planning, including their emotional and sexual fulfillmentHigher participation in medical screening programs later in lifeSecondary objectives included :SubjectsSeveral self-questionnaires were used to evaluate psychological parameters and their evolution. Responses were collected at four points: at inclusion, at the conclusion of the workshop, then 6 and 12 months after the workshop. A hierarchical model .Among the reasons explaining the high refusal rate  was the feeling that cancer did not concern the candidate at such a young age, and that they had time before acting on it. Others thought that cancer predisposition was not worth spending a weekend listening to experts, or the workshop dates were not compatible with their agenda. Others had children or were pregnant and did not meet the inclusion criteria after all. The age of participants and refusers did not differ Breast health and screening: methods of breast cancer detection . Patient’s pathway when a cancer is suspected or diagnosed. Justification of the screening frequency. Special practical session to learn self-palpation of the breast.Assisted procreation: possibility of ovarian preservation in case of cancer treated by chemotherapy. Description of how an ovarian sample is obtained after stimulation and how it is re-implanted. France does not allow oocyte donation for BRCA mutation carriers.Nutrition: nutritional measures to prevent cancer and also to limit the risk of relapse. Recall of guidelines for better nutrition to control weight and abdominal adiposity. Description of nutrients increasing disease risk and those recommended for better health.Physical activity (PA): presentation of the level recommended with proven benefits for prevention and in limiting the risk of relapse. Sedentarity is also a risk factor for many diseases, independently of the level of PA.Transportation, meals and lodging at the workshop hotel were paid for by the foundation that funded our project. A documentary about a family with a BRCA mutation was shown . There was a 2-h session for Moreno psychodrama with topics chosen by participants, and a group sharing session. Ten conferences lasting 15 to 30 min were given by experts in the following domains:Throughout the different phases of the workshop, a genetic counselor noted participants’ comments so that a debriefing could be performed retrospectively. Notes were taken during the role playing session, and particularly once the role-play was over, when the group shared their opinions and feelings about what was played, especially regarding echoes in their personal lives. We performed a qualitative analysis of participants’ comments to extract main issues raised.Quantitative analysis was used for scores obtained by questionnaire.p-value < 0.05 was used as significance threshold.Categorical variables are described using counts per category and quantitative variables using means ± standard-deviation [range]. Longitudinal analyses of questionnaire scores were tested using one-way ANOVA or Kruskal-Wallis H-test depending on normality and/or homoscedasticity of distributions. Pearson’s correlation test was performed in complement to check the significance of trends over time, when ANOVA or H-test was close to significance. Differences between sub-dimensions of questionnaires were tested using two-way ANOVA. All tests were two-sided and standard Data gathered via the internet website was managed using Ennov Clinical software, version 7.3.1., and statistical calculations were performed with SEM software .N = 6) or ovarian (N = 2). Participants reported other cancer locations in family members, including lung and esophagus. Six participants had at some time shared her daily life with a relative with cancer. The age at cancer diagnosis of the closest relative was 42.0 ± 11.9 [29–65] while participants’ age at the time of these diagnoses was 11.9 ± 7.4 [2–24]. All participants considered their personal cancer risk as either average (N = 3) or high (N = 4). As a matter of concern, this was rated occasional by four participants, frequent by two others, and permanent for one.All seven participants were BRCA mutation carriers. Mean age was 26.4 ± 2.9 years, range 23 to 30. Five had a university educational, including two students. Four studied or worked in a medical domain. All had close relatives with a history of cancer, including the mother for five participants, the grandmother for five and an aunt for three. For six participants, more than one close relative had cancer: mainly breast ; all dimensions increased similarly and no curve-effect was observed (p = 0.42). The strongest increase concerned the “positive readiness” component . Connectedness and temporality/future increased respectively by 20 and 24% (p = 0.01).All three dimensions of Herth’s hope index (HHI) increased over time Fig.  a, confip-value using one-way ANOVA was 0.07 and Pearson’s correlation was 0.02  and quality of life  followed the same trend. A decrease in state-anxiety by 43% was close to significance (p = 0.19 with ANOVA and 0.05 with Pearson’s correlation), and trait-anxiety decreased non-significantly . Altogether, the improvement over 1 year of hope, self-esteem and quality of life was very significant (p = 0.00032).Global scores for HHI increased by 24% over the 12-month follow-up period. The associated p < 10− 7) and did not evolve over time (p = 0.74).Locus of control was measured by the IPC scale Fig.  c. Interp = 0.011) then returned to baseline values at 1 year; “search for support” exhibited a similar but milder trend. “Focus on emotions” exhibited a steady slope (0.021).Coping changed slightly over time Fig.  b. The “p = 0.54, curves not shown), although the “environment” and “psyche” dimensions exhibited a slight increase over the year. Anxiety levels at inclusion evaluated with the trait-STAI questionnaire were low: five participants had very low or low anxiety, while two had medium anxiety levels.WHOQOL sub-dimensions did not significantly change over time  unavailable to their mothers.○ No one spoke of the utility of prenatal or preimplantation diagnosis. Although a significant burden, BRCA mutations were not considered stigmatizing or as an injustice.Childbearing:Participants’ comments concerned several topics summarized below:Considering our recruitment difficulties, young women in HBOC families may not be ready to spend time “bothering” about their cancer risk at this period of their lives,. At their young age, their low cancer risk was likely not a priority issue. This contrasted to the proactive attitude of our participants, many of whom worked in a medical field and/or were highly educated. This attitude was not associated with an anxious background: only two participants had a medium trait-anxiety level, while the five others had either low or very low trait-anxiety levels. In a study by Listøl et al.  that tesAnother characteristic of the participants made the group unrepresentative of young women at risk: although the study was open to women in families without BRCA mutations, only women positive for a mutation participated. This selection bias is not surprising and we showed in another survey that members belonging to HBOC families where no mutation was found tend to seek less information about their cancer risk than mutation carriers . It is lOur participants were in search for a “solution” to their issue. Gathering all possible information was one way of managing their cancer risk. However, with more information they then faced further difficult choices: whether to have a prophylactic intervention, and if so, before or after childbearing. Moreover, the evolution of surgical practices has brought new controversies, such as skin or nipple areolar plate preservation (SNAPP). Certainly, the role of the surgeon is essential in making this decision, and the free discussion with the young female surgeon during the session was very important from the participants’ point of view. Two participants decided on surgery without SNAPP a few months after the session: For them, there should be no compromise with cancer risk, and the fact that one of the other participants was diagnosed with breast cancer soon after the session seemed to credit their choice.In deciding on prophylactic mastectomy, the participants considered issues beyond the obvious benefit to themselves in reducing their cancer risk versus the medical risks of the intervention. The inability to breast-feed future babies seemed to be of secondary importance, while the attitude of the partner had both positive and negative aspects. Prophylactic mastectomy with reconstruction alters a woman’s body image and femininity, both for herself and for her partner. On the other hand, it reduces the perspective for the partner to see their wife die prematurely. It also prevents the participants’ mother, if alive, to experience a second cancer via her daughter. Aside from these considerations, other doubts surround the consequences of the surgery, which may induce changes that cannot be anticipated and that threaten the relationship: in all cases, this constitutes a real test for reciprocal feelings and confidence. All the participants downplayed any anticipated negative effects for themselves, focusing instead on their partner.The session dedicated to role playing and group sharing enabled participants to express their feelings about the consultation providing genetic testing. All the participants reported receiving their molecular diagnosis as BRCA mutation carriers as traumatic, even “brutally” so. Although geneticists are aware of such issues, participants’ declarations tended to show that the distress is generally much deeper than expected. The duration of this trauma has been discussed, some authors considering it to be transient , 22 whilThe results drawn from the questionnaires were unexpected considering the small sample size. Overall, the psychoeducational session proved to be efficient for hopefulness (HHI), coping (WCC) and overall quality of life (WHOQOL). In particular, participants seemed to be more positive regarding their future, and exhibited a better capacity to face their cancer risk (decrease of the focus on emotions).The overall result of the week-end session was positive and confirmed our goal: bringing to these young women a wide spectrum of information and helping them to express their distress seemed to change their attitudes in a significant and positive manner. This suggests that we should not change the content of our intervention but perhaps recruit slightly older women (up to 40 years) who have new childbearing projects and/or question the cancer risk they transmit to their children.Aside from the small sample size and thus the limited confidence that can be given to results, the main weakness of our study seems to be the lack of representativeness of our young BRCA carriers. The results might have been different for young BRCA mutation carriers declining participation. Our participants were already invested in the resolution of their genetic problem. Their high educational level was corroborated by their locus of control which was mainly internal and their coping style not very emotional. In concordance with Listøl et al. , our stuYoung females exposed to HBOC, partly due to lethal familial events that disrupted their childhood, see their psyche strongly modulated. Our results suggest that a weekend workshop dedicated to high quality information and favoring individual expression can significantly improve what they know about their cancer susceptibility, they feel and how they live it, and likely it can help them figure out the most adapted solution enabling them to handle their cancer risk. An extension of this study is planned, targeting HBOC women up to age 40 who already have children and/or with a new child project, and who have questions on heredity issues and/or possible present or future prevention measures for themselves and their children.Additional file 1:Table S1. Detail of scores by questionnaire and by completion time. (DOCX 21 kb)


Cyclic hormonal stimulation of the breast tissue plays a significant role in breast carcinogenesis. Current risk factor models do not include direct measures of cycle characteristics although the effects of possible surrogates of cycle activity such as age at menarche and menopause, parity, and nursing time have been investigated. Future risk models should also include menstrual cycle length, regularity, number of cycles before first full-term pregnancy, and life-time number of cycles. New risk factor models for pre- and postmenopausal breast cancer are proposed here. Furthermore, there is a need for more long-term, prospective studies investigating menstrual cycle characteristics as data currently available are primarily retrospective and collected at one time-point only. In the 1990s, our research group pioneered studies on menstrual cycle length, menstrual regularity, and the number of menstrual cycles as risk factors for breast cancer . Women wFurthermore, several studies regarding the risk of exogenous hormones and breast cancer revealed that the combination of progestins and estrogen increased the risk of breast cancer compared with the effects of estrogen alone –13. We aA list of studies concerning the menstrual cycle is presented in LMA is calculated for natural cycles using the following variables: age at menopause and menarche, average cycle length, number of pregnancies, and duration of nursing excluding periods of exogenous hormone use. There are however a number of relevant caveats: first, cycle length may vary during reproductive life and studies thus consider the average cycle length. In retrospective studies, there may be a recall bias for cycle length. Furthermore, there are discrepancies regarding the number of cycles counted during exogenous hormonal treatment , 28. In Benign breast disease is characterized by irregular menstrual cycles and is more common at the end of reproductive life . IrregulWe have postulated that women whose breast size is maintained or increased after hormonal exposure may have a higher risk of cancer than those whose breast size decreases upon such exposure . HoweverFinally, the effects of oral contraceptive (OC) use should be investigated. For example, it is unclear whether lengthening menstrual cycles artificially via administration of OCs in women with naturally short cycles decreases cancer risk. Conversely, it is also unclear whether cancer risk increases in women whose naturally long cycles are artificially shortened by the use of OCs.A number of risk factors have been identified for breast cancer such as age at menarche, age at first full term pregnancy, parity, age at menopause, obesity , number of menstrual cycles, weight gain, hormone replacement therapy, early oral contraceptive use, breast size, preecclampsia, birth weight, nursing, height, breast density, physical activity, night shift work, radiation exposure, tobacco use, alcohol use, family history, mutation carrier of a predisposing gene. Some of the above factors are still under investigation with partly diverging findings such as for tobacco use, breast size and night shift work and others like preecclampsia and high physical activity are protective. Some factors like radiation exposure, reproductive and genetic factors are more important premenopausally, while obesity is more important for older women.Development of better methods to describe the menstrual cycle more exact is needed. One method is of course to use a calendar recording the start of each menstruation, another way is to record basal body temperature daily, women in the luteal phase have a higher body temperature, or study the cervical mucus. However, it can be difficult to pinpoint ovulation using these methods, especially if your menstrual cycles are irregular. Research in fertility medicine especially in women with irregular menstruations is mainly driven to better time ovulation through ovulation prediction kits either using urine (measuring LH) or saliva (studying ferning patterns in relation to estrogen increase). Again these latter methods are too cumbersome and expensive to be used in large epidemiological risk factor studies and explain their absence in literature.The characteristics and number of menstrual cycles before the first full-term pregnancy, LMA, and menstrual regularity require further investigation as part of epidemiological studies of breast cancer, as other risk factors such as age at menarche and menopause, parity, and nursing are only surrogates for cyclic hormonal exposure. Menstrual cycle characteristics should be included in risk factor models of breast cancer. Current models such as Gail, Tyrer-Cusick, Rosner Colditz BCRAT, BCPRO, and BOADICEA only include family history, germline mutation status, breast density, polygenic risk scores, and surrogates of cycle activity such as age at menarche, age at first full-term pregnancy (AFFP), parity, nursing, and age at menopause –39. The All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.