Sexual dysfunction is a prevalent, long-term complication of breast cancer and its treatment and can be treated effectively with face-to-face sexual counselling. However, relatively few women actually opt for face-to-face sex therapy, with many women indicating that it is too confronting. Internet-based interventions might be a less threatening and more acceptable approach, because of the convenience, accessibility and privacy it provides. Recent studies have demonstrated the efficacy of internet-based programs for improving sexual functioning in the general population. The objective of the current study is to investigate the efficacy of an internet-based cognitive behavioral therapy (CBT) program in alleviating problems with sexuality and intimacy in women who have been treated for breast cancer.In a multicenter, randomized controlled trial we are evaluating the efficacy of an internet-based CBT program in reducing problems with sexuality and intimacy in breast cancer survivors. Secondary outcomes include body image, marital functioning, psychological distress, menopausal symptoms, and health-related quality of life. We will recruit 160 breast cancer survivors (aged 18-65 years) with a formal DSM-IV diagnosis of sexual dysfunction from general and academic hospitals in the Netherlands. Women are randomized to either an intervention or waiting-list control group. Self-report questionnaires are completed by the intervention group at baseline (T0), ten weeks after start of therapy (T1), post-treatment (T2), 3 months post-treatment (T3), and 9 months post-treatment (T4). The control group completes questionnaires at T0, T1 and T2.There is a need for accessible and effective interventions for the treatment of sexual dysfunctions in breast cancer survivors. This study will provide evidence about the efficacy of an internet-based approach to delivering a CBT intervention targeted specifically at these sexual health issues. If proven to be effective, internet-based CBT for problems with sexuality and intimacy will be a welcome addition to the care offered to breast cancer survivors. Hopefully this therapy will lower the barrier to seeking help for these problems, resulting in improved quality of life after breast cancer.NCT02091765).The study is registered at ClinicalTrials.gov ( Breast cancer is the most common type of cancer among women in the Netherlands . ImproveThe prevalence rates for sexual dysfunctions as a result of breast cancer treatment vary between 30% and 100% . Breast The different components of breast cancer treatment can all directly or indirectly affect sexual functioning . PreviouSexual dysfunctions can be treated effectively with face-to-face forms of sex therapy -41. Sex The efficacy of different types of face-to-face therapy for female sexual dysfunction (FSD) has been demonstrated, including sexual desire and sexual arousal disorder ,46,47, oDespite the availability of effective treatments for sexual dysfunctions, there is a significant discrepancy between the self-reported need for professional sexual health care in cancer survivors and the actual uptake of care ,55. KeddAlthough sexual functioning is an important issue, health care professionals may be reluctant to query breast cancer patients about sexual problems during medical consultations, due to time constraints, embarrassment, lack of knowledge and experience in this area, and/or lack of resources to provide support if needed ,57. It mThere is growing evidence that internet-based CBT is an effective method to treat a range of psychosocial problems -73. MoreIn this article, we describe the design of a randomized, controlled, multicenter trial that evaluates the efficacy of an internet-based CBT program for sexual dysfunctions in women who have been treated for breast cancer. We hypothesize that women in the internet-based CBT group will report a significantly greater improvement in sexual functioning and intimacy than women in a waiting-list control group. Secondarily, we hypothesize that women who undergo the internet-based CBT will report significantly less psychological distress and fewer menopausal symptoms, and a significantly greater improvement in body image, marital functioning and HRQL than women in the control group.In this study, patients are randomized to either an intervention group or a waiting-list control group. Women in the intervention group will undergo an internet-based CBT aimed at alleviating problems with sexuality and intimacy. The design of the trial and the anticipated flow of participants are displayed in Figure The study sample will be composed of 160 women fulfilling the following inclusion criteria: (1) age 18-65 years ; (2) a history of histologically confirmed breast cancer ; (3) a diagnosis of breast cancer six months to five years prior to study entry; (4) completion of breast cancer treatment (with the exception of endocrine therapy and immunotherapy); (5) disease-free at time of study entry; (6) a basic fluency in the Dutch language (for assessment and therapy purposes); and (7) a formal diagnosis of sexual dysfunction according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV  (to be eExclusion criteria are: (1) no access to internet; (2) serious cognitive or psychiatric problems  as determined on the basis of the Mini International Neuropsychiatric Interview ; (3) trePatients are recruited from 10 community and university hospitals in the Netherlands and are identified through the hospital registries by their physician, or by means of the database of the Netherlands Cancer Registry. Selected patients are sent an invitation letter describing the study and internet-based therapy, and are asked to return a response card to indicate if they are interested in participation. In case of no interest, women are asked to specify their reason(s) for this on the card. In the absence of a response, a reminder is sent three weeks after the first mailing. Women who are not interested in participation or who do not respond to the reminder are not contacted again.Interested women are screened for eligibility twice: first by a member of the study staff and subsequently by a sexologist. In these interviews, more information about the study procedures and therapy is given and eligibility criteria are checked. The sexologist carries out a diagnostic interview to determine final eligibility of the woman, and the Mini International Neuropsychiatric Interview  is complEligible women are sent a baseline questionnaire (T0) and an informed consent form. Study questionnaires can be completed online or in a paper-and-pencil format. The baseline questionnaire assesses sociodemographic and medical background variables, and the study outcomes. If the score of the marital adjustment subscale of the Maudsley Marital Questionnaire  see ‘St’ sectionConsenting women are randomized to either an intervention group (n = 80) or a waiting-list control group (n = 80) using the minimization technique, with type of surgery , current endocrine treatment for breast cancer , time since breast cancer diagnosis , and menopausal status  as stratification variables.Each woman is assigned a sexologist who guides her through the internet-based CBT program. Contact with the therapist is web-based, via a secured, password-protected website. From a total of 10 modules, the sexologist selects four to five modules that best fit the sexual problems of the client. The internet-based CBT program was originally developed for use in the general population at Virenze, a mental health center located in Utrecht, the Netherlands. The program was adapted for use specifically for breast cancer survivors. This involved editing and adding text related to the physical and psychosexual problems often experienced by women who have had breast cancer. The therapists are licensed psychologists and sexologists who have undergone additional training in issues relating to breast cancer, and in the use of the internet program.A description of the content of the different program modules is provided in Table Participants in the control group are asked to refrain from undergoing any psychological or medical interventions for sexual problems during their participation in the study. To increase the likelihood that women will remain in the study until they are offered the CBT program, they are provided with a booklet addressing questions about sexuality and cancer. Additionally, six weeks after randomization and upon completion of the second questionnaire, women in the control group are contacted by telephone to address any questions or comments that they may have about their participation in the study, and to reconfirm that they will be eligible for the internet-based CBT program upon their completion of the study.Patients in both study arms complete a battery of self-report questionnaires at equivalent moments in time for the first three assessments  or 13 weeks after randomization (control group); and T2: post-treatment (intervention group) or 23 weeks after randomization (control group), see Figure Only partners of the women in the intervention group are asked to complete questionnaires regarding problems with sexuality and intimacy , medication use and comorbidity.Detailed descriptions of the outcome measures are provided in Table The level of compliance is established via a question that is posed to the sexologist at the completion of therapy: ‘How many of the total number of therapy sessions that you considered to be optimal for this client has the client actually completed?’. This question is answered on a five-point scale, ranging from ‘the client has done all of the sessions I deemed necessary (100%)’ to ‘the client has not/barely done the sessions I deemed necessary (less than 25%)’. Additionally, the actual number of completed modules and interventions are extracted from the client’s records at the mental health center where the internet program is housed. Additionally, at completion of therapy, both the client and the sexologist are asked to indicate the frequency with which homework assignments were completed on a five-point scale , and to indicate the reasons for not completing all homework assignments, if applicable. Women who do not complete the internet-based CBT program are asked to indicate their reason(s) for discontinuation . Every effort will be made to obtain all questionnaires of all participants, regardless of whether they do or do not complete their therapy.Upon completion of the CBT, women in the intervention group are asked to complete an evaluation questionnaire about the program. Questions are posed about their satisfaction with the program, the perceived efficacy of the program in alleviating sexual problems, their satisfaction with the choice of modules and exercises, the usability of the program, if they would recommend the treatment to other women experiencing similar problems, and if they would suggest any changes to the program. Women who discontinue the CBT program are asked the same questions.A subset of women (approximately 15 from the intervention group) will be asked to participate in an evaluation interview by telephone. This semi-structured interview covers the same topic areas as addressed by the self-report evaluation questionnaire, allowing women to provide feedback in a more narrative form. Where applicable, women will also be asked if their partner would be willing to share his or her experience with the program.The SAQ, FSFI, FSDS-R and PAIR Inventory are the primary outcome measures on which sample size calculations are based. With a total sample of 130 women (65 per group), and under the assumption of no interaction, the study will have a 80% power to detect a 0.5 standard deviation difference (Cohen’s effect size ) for theWe will recruit 160 women into the study, to allow for an attrition rate of approximately 20% . Those women who discontinue the therapy but complete the follow-up assessments will be included in the intention-to-treat analysis.First, student’s t-tests or appropriate non-parametric statistics will be used to evaluate the comparability of the intervention and control group at baseline in terms of sociodemographic and clinical characteristics. If, despite the stratified randomization procedure, the groups are not comparable on one or more background variables, those variables will be employed routinely as covariates in subsequent analyses.Questionnaire scores will be calculated according to published scoring algorithms. Between-group differences over time in mean scores will be tested using multilevel analysis. Effect sizes will be calculated using standard statistical procedures. All analyses will, to as great an extent as possible, be conducted on an intention-to-treat basis. Per protocol analyses will also be carried out , comparing women who meet minimal compliance levels with the program with the control group. We will use correlation analyses to examine the relationship between degree of program adherence, partner involvement, and program effect. For the analysis of the secondary outcome measures, appropriate statistical  adjustments will be made for multiple testing. The semi-structured interview data will be transcribed and content analyzed to extract narrative, qualitative information about the women’s experience with the intervention.A relatively large percentage of breast cancer survivors experience sexual problems as a consequence of their disease and its treatment. Studies show that CBT is an effective treatment method for alleviating sexual dysfunctions in the general population, when provided in a face-to-face setting. Recently, more attention has been paid to developing internet-based interventions targeting sexual functioning. However, research into internet-based interventions for FSDs is scarce, and even less is known about the efficacy of internet-based CBT specifically targeted at breast cancer survivors. In the current trial, we are investigating the efficacy of an internet-based CBT in reducing problems with sexuality and intimacy, psychological distress and menopausal symptoms, and in improving body image, marital functioning and health-related quality of life of breast cancer survivors.This trial has several notable strengths, including: (1) the randomized trial design, (2) the multicenter nature of the trial, (3) the comparison of the intervention group with a waiting-list control group, (4) the use of intention-to-treat analyses, and (5) the long-term follow-up assessments of outcomes in women in the intervention group.This trial also has several limitations. First, it would be valuable to compare the internet-based CBT group not only with a control group, but also with a face-to-face CBT group. However, our previous experience in offering breast cancer survivors the opportunity to participate in face-to-face sexual therapy proved problematic [de Blok G. Thesis on the outpatient clinic for sexuality and breast cancer of The Netherlands Cancer Institute. Unpublished manuscript]. Very few women were willing to take that step, indicating that they found the face-to-face setting too confronting. Thus, we anticipated that including a face-to-face therapy arm in the trial would result in substantial recruitment problems. Also, we consider it important to first establish the efficacy of the internet-based CBT program. If the program proves to be efficacious, a subsequent step could be a comparative effectiveness study with face-to-face treatment . Second,In conclusion, given the high rates of sexual dysfunction in breast cancer survivors, there is a need for effective and accessible treatments for these problems. If proven to be effective, internet-based CBT can be a valuable addition to the standard care offered to breast cancer survivors. Hopefully, this treatment will lower the barrier to seeking help, resulting in an improved quality of life after treatment of breast cancer.


Known prediction models for breast cancer can potentially by improved by the addition of mammographic density and common genetic variants identified in genome-wide associations studies known to be associated with risk of the disease. We evaluated the benefit of including mammographic density and the cumulative effect of genetic variants in breast cancer risk prediction among women in a Singapore population.We estimated the risk of breast cancer using a prospective cohort of 24,161 women aged 50 to 64 from Singapore with available mammograms and known risk factors for breast cancer who were recruited between 1994 and 1997. We measured mammographic density using the medio-lateral oblique views of both breasts. Each woman’s genotype for 75 SNPs was simulated based on the genotype frequency obtained from the Breast Cancer Association Consortium data and the cumulative effect was summarized by a genetic risk score (GRS). Any improvement in the performance of our proposed prediction model versus one containing only variables from the Gail model was assessed by changes in receiver-operating characteristic and predictive values.2, 21-30cm2, 31-40cm2, 41-50cm2, 51-60cm2, and 1.10 (1.03–1.16) for GRS. At the predicted absolute 10-year risk thresholds of 2.5% and 3.0%, a model with mammographic density and GRS could correctly identify 0.9% and 0.5% more women who would develop the disease compared to a model using only the Gail variables, respectively.During 17 years of follow-up, 680 breast cancer cases were diagnosed. The multivariate-adjusted hazard ratios  were 1.60 (1.22–2.10), 2.20 (1.65–2.92), 2.33 (1.71–3.20), 2.12 (1.43–3.14), and 3.27 (2.24–4.76) for the corresponding mammographic density categories: 11-20cmMammographic density and common genetic variants can improve the discriminatory power of an established breast cancer risk prediction model among females in Singapore. The primary goal of breast cancer screening is to enable early detection of disease so that prognosis can be improved by more timely intervention. Although screening offers the benefit of reduced mortality for potential patients, the level of over-diagnosis and subsequent treatment of healthy individuals is worthy of concern: for every breast cancer death prevented, three women would be unnecessarily treated for the disease . More imTo facilitate the decision-making process, a woman’s risk is often assessed using her demographic and reproductive information, as well as the presence of a positive family history . One of et al evaluated the applicability of the Gail model in Singapore. They found that the Gail model over-estimated the population’s 10-year breast cancer risk by 85% overall, with women aged 60–64 having a predicted incidence that was thrice as high as observed . Since each subject’s 10-year absolute risk is the desired score, an individual’s 10-year risk (with covariate X) of being diagnosed within ten years is 1- S (10|x).Cox proportional hazards (PH) models were used to build the predictive models including breast density and common genetic variants and compute (approximately) 10-year risk for each individual. The validity of proportional hazards assumption was assessed by Schoenfeld residuals and all variables were not subject to time-varying effects across all the models. Three models  were constructed and compared in terms of their ability to accurately assess each woman’s 10-year absolute risk. We note that Cox PH models leave the baseline hazard un-estimated and therefore we approximated 10-year cumulative baseline hazard to compute the absolute risk (explained below). The first model consisted of variables from the Gail model, ethnicity and BMI; the second included breast density; the third had breast density and GRS. In Cox PH models, the probability that a woman will survive beyond a certain time point given a set of covariates x is calculated as Improvement in the prediction performance was assessed by the changes in the AUC of the ROC for each model, as well as positive and negative predictive values at fixed 10-year absolute risk thresholds. We also computed the concordance probabilities using the Cox proportional hazard model fits as additional performance metric . To accoAll statistical analyses were performed using R version 2.13.0. Statistical tests were two-sided and P<0.05 was considered statistically significant.in-situ (n = 106) or invasive (n = 574) breast cancer. As of 31 December 2011, 680 women were diagnosed with either We evaluated the associations of the Gail model predictors, ethnicity, BMI, mammographic density and GRS with breast cancer risk. From Performance in the three risk prediction models was examined by plotting ROC curves and comparing their areas under the curve. As genotypes were simulated, the average of 1,000 ROC curves for the model with GRS is reported in a priori) become more stringent from 1% to 3%, the difference in the proportion of patients that are correctly identified between the modified models and the Gail model, increases in general  tool, unlike the others who focused on percent density instead. Such errors in qualitative measurement tend to attenuate the association between mammographic density and risk of disease [The Gail model has previously been shown to be poorly calibrated to the Singapore population, over-estimating an individual’s 10-year absolute risk by close to two-fold . A recen disease . Althoug disease ,42–45, t disease , such thBreast cancer patients and healthy individuals were significantly different in all variables except ethnicity . Due to et al have carried out a similar study recently, investigating the impact of BMI, percent mammographic density and 18 common genetic variants on Swedish post-menopausal women [To our knowledge, we are the first to consider the cumulative effect of the largest number of SNPs in breast cancer risk prediction for an Asian setting, using data from the only prospective trial conducted outside Europe and North America. Darabi al women . Their rMost groups have initially used estimation and subsequently computer-assisted methods to measure breast density. We have applied a fully-automated, high-throughput method of measuring mammographic density, which can minimize any visual irreproducibility related to more subjective assessments. Also, this measure has been shown to be highly correlated with Cumulus, an established semi-automated tool .et.al. had recommended the integration of both methods for enhanced accuracy [We have made a few assumptions in our study. Firstly, since cancer notification is mandatory in Singapore and all Singaporeans have a unique identification number, we expect the completeness of reporting to be close to 100% . Secondlaccuracy , unnecesAlthough we had intended to compare our modified model with the Gail model, some of our study’s categories differed from the original model. Previous breast biopsy was recorded as “Yes/No” instead of the number and presence of atypical hyperplasia; family history was coded as “None/At least 1” instead of the actual number of affected first-degree relatives. However, we believe these minor coding differences will not affect our conclusion drastically .The use of SNPs is dependent on the cost of genotyping, ease of collection of genetic material through blood samples or buccal swabs, as well as the identification of additional SNPs in future. As the women from the SBCSP were recruited in the 1990s, the results from this study may not be very relevant to a cohort of individuals two decades later where lifestyle patterns are more westernized. Further studies are required to gauge the applicability of the modified models on women younger than 50 years. The modified model we propose will also not be very feasible in developing nations where resources for large-scale implementation of mammography screening and genotyping are scarce , or the In conclusion, we have demonstrated the potential benefit of mammographic density and common genetic variants in improving the performance of an established risk prediction model in a developed Asian context. The better discriminatory power observed here may encourage future efforts to identify a large panel of novel polymorphisms and thus improve the cost-effectiveness of the current nation-wide screening program in Singapore.S1 FigFor the model with GRS, the average of 1000 ROC curves is drawn. Areas under the curves (AUCs) are 0.63, 0.65 and 0.67 respectively. The straight dashed line represents the ROC curve expected by chance only.(TIF)Click here for additional data file.S2 FigAs mean percent breast density and GRS are added to the model, the discrimination between cases and non-cases increases. Y-axis is the density which reflects the number of subjects.(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 TableMean percent breast density is used in the prediction models.(DOCX)Click here for additional data file.


Breast cancer is the most common cancer in the UK. Lifestyle factors including excess weight contribute to risk of developing the disease. Whilst the exact links between weight and breast cancer are still emerging, it is imperative to explore how women understand these links and if these beliefs impact on successful behaviour change.Overweight/obese premenopausal women (aged 35–45) with a family history of breast cancer (lifetime risk 17–40%) were invited to a semi-structured interview following their participation in a 12 month weight loss intervention aimed at reducing their risk of breast cancer. Interviews were carried out with 9 women who successfully achieved ≥5% weight loss and 11 who were unsuccessful. Data were transcribed verbatim and analysed using thematic analysis.how women construct and understand links between weight and breast cancer risk is composed of two subthemes, the construction of weight and breast cancer risk and making sense of weight and breast cancer risk. This theme explores women’s understanding of what contributes to breast cancer risk and whether they believe that weight loss could reduce their breast cancer risk. The second theme motivation and adherence to weight loss interventions explains that breast cancer risk can be a motivating factor for adherence to a weight loss intervention. The final theme, acceptance of personal responsibility for health is composed of two subthemes responsibility for one’s own health and responsibility for family health through making sensible lifestyle choices.Three themes were developed from the analysis. The first theme Beliefs about weight and breast cancer risk were informed by social networks, media reports and personal experiences of significant others diagnosed with breast cancer. Our study has highlighted common doubts, anxieties and questions and the importance of providing a credible rationale for weight control and weight loss which addresses individual concerns. Counselling and health education material should be tailored to facilitate understanding of both genetic and modifiable risk factors and should do more help individuals to visualise the weight and breast cancer link. Breast cancer is the most common cancer in the UK with 49,564 women newly diagnosed in 2010 ,4. ExperBRCA1/2) (60-80% lifetime risk)  would be better able to generate healthy cells and fight invading cells and again if you go back to evolution people must have been pretty fit, you know, they must have been pretty fit .Participants spoke of exactly how they considered weight and breast cancer to be linked. Cathy speculated that body fat “fuelled” cancer growth and that a fit body or that healthy weight would be better able to “defend” itself from disease.If you said chocolate, cheese and chips increase my risk of breast cancer then I would never eat them again… but it’s because it isn’t specific I think it’s really easier to ignore it and think oh I’ll do it tomorrow, I’ll do it another day. I need someone to say yes it is definite then I’m fairly sure I would lose some weight .The lack of a clearly defined mechanism of how weight causes breast cancer made it difficult for many women to conceptualise the link between weight loss and their breast cancer risk. All held the view that weight loss was difficult. For women, like Amanda, this appeared to be potential disincentive to their weight loss efforts and one of the ways they justified their delay in tackling their weight.If I hadn’t wanted to lose weight for other reasons as well I might not have been 100% convinced that it was worth it at that stage, but the more I've looked into it now having been involved in this study I think it’s quite a big part. It’s not my only motivating factor in what I'm going to eat, but it’s there and that’s good, it keeps reminding us .Over the course of the study, participants developed a greater understanding of the research linking weight, hormone levels and breast cancer, through both study information and outside resources helping them to maintain motivation to achieve weight loss target over the year-long intervention.It’s quite helpful really, [its] another motivation. Fat people like me need a lot of motivation. I didn’t find it a negative….you cannot remove your body make-up unfortunately but you know I don’t think you should be devoid of all responsibility; it’s up to you to do something about it .Women who successfully lost weight primarily did so to improve confidence and appearance, and also for their general health. Believing that they could exert some control over their breast cancer risk was a secondary motivation for weight reduction. Some of our participants viewed their breast cancer risk as unchangeable because of their family history, yet still valued general disease risk management information including weight loss advice and support.additional motivation to be healthier weight. Diane had recently suffered a family bereavement from breast cancer; losing weight was imperative for her as it gave her a sense that she had some control over her risk and increased her sense of well-being.If gaining extra weight could increase my risk of having breast cancer by 50% there was no choice. I didn’t want to live with that so there was absolutely no choice so I’m going to feel better anyway on a day to day basis and hopefully lower my risk. Well I’ve got a win-win situation .For women who achieved their target weight loss, the possible link between weight and breast cancer provided She’s got 3 young children [friend diagnosed with breast cancer] and said ‘have I done this to myself because I’m fat and she said am I depriving my children of a mother because I like my food and I’m overweight?’ And I said ‘[friend’s name] don’t be stupid’, but part of me thought I could be doing that to my family and that frightens me to death .Not all women could easily translate information about weight and risk into action. Being informed that weight is an influential and contributory factor in breast cancer risk, did not motivate some women who instead experienced feelings of guilt and self-blame that they were not doing what they could to reduce risk. This would be a particular problem if these women were to develop breast cancer.I’d rather someone help me and tell me now than help me when I'm on the operation table having an operation. It’s the real world. It’s no good someone telling me later when it’s too late. .Despite feelings of guilt, most women in this group still valued the information that weight is a modifiable risk factor, believing that this would attenuate further weight gain or motivate a future weight loss attempt. Joan projected how she would feel if they were diagnosed with breast cancer and had not known this.She’s [her sister] tried to cut down her weight a bit as well and exercise… and the alcohol, cutting down on alcohol …. I think has been particularly proven recently and I've been passing some of that on to her as well .Women reflected on how they would disseminate advice on maintaining a healthy weight to sisters and daughters who may also have an increased risk of breast cancer because of the family’s history. Nicola reported that sharing knowledge about the link between breast cancer and weight appears to have an impacted on her sister’s lifestyle behaviours.Well because I know that I’ve found it so hard at my age to make these changes. I think the longer you get into these bad eating habits the harder it is. So I don’t want her to have the same struggle that I’ve had when she’s older .Women were very aware of the key role they have in determining their daughter’s dietary choices. Participants did not feel it is appropriate to discuss the links with diet and cancer with younger children. Hannah has two daughters less than 10 years of age and reflected on her own battle with weight and its implications for her cancer risk. She was determined to improve her family’s diet which was largely based around high fat convenience foods in order to ensure her daughters did not develop eating habits which were difficult to alter later in life.My daughter’s quite interested in health issues anyway. I think some of the message is getting across but then you don’t want to make teenage girls become too obsessive, which she doesn’t show any signs of, but you have got to be careful I think .So it’s knowing how to manage that transition, to manage to get her [teenage daughter] to eat healthily but not make a big deal about it and I spoke to [dietitian’s name] about it and she was quite helpful really in giving me some guidance on that .Women with teenage daughters stated that they would be more likely to discuss the importance of a healthy lifestyle and avoiding excessive weight gain in preventing disease. As Nicola and Nina explain, there was evident concern to avoid making their daughters worry about weight gain and mothers were anxious to avoid precipitating an eating disorder.We have explored how women with a family history understood advice that weight loss may reduce their breast cancer risk in women following risk counselling and a 12-month weight loss intervention. Participants received intensive one to one counselling on the links between weight and risk from doctors and a research dietitian in a specialist FHC. Despite this advice their understanding of factors they consider to be influential to their cancer risk were largely informed by social networks, media reports and personal experiences of significant others diagnosed with breast cancer, indicating that for many women specialist counselling does not override these deeply held beliefs. Beliefs are an important construct in behaviour change theories. The theory of planned behaviour argues  that belKeogh et al. suggest that some women with a family history see little value in making lifestyle changes when they remain well  and ReesBRCA1 carriers and 50% of cases amongst BRCA2 carriers [BRCA carriers [Excess weight in the pre and post-menopausal years is consistently linked to the development of postmenopausal breast cancer -9, whilscarriers . Tacklincarriers  and diffcarriers . Recent carriers  and to Bcarriers . Our finWe found that some participants, particularly those who struggled to control their own weight, had strong feelings about trying to ensure their daughters did not encounter similar problems in the future. Women attending FHCs could influence siblings and future generations, as mothers with a family history have a significant role in influencing the preventive health behaviours in their daughters ,37. FromThis study presents data from a population of women participating in a weight loss intervention aimed at reducing their risk of breast cancer. Weight gain is a sensitive issue and by utilising a one-to-one interview approach, largely conducted in participant’s homes (23 out of 24 interviews), with a female researcher of a similar age to the participants enabled us to obtain detailed, reflective accounts where women were able to explain and contextualise their beliefs about weight and breast cancer in a non-judgemental environment . Our stuWomen with a more positive experience of the weight loss study could have been more willing to be interviewed; however, we were able to recruit similar numbers of successful and unsuccessful women and several who dropped out of the weight loss study. We feel that this range of women reflects both positive and negative experiences of weight loss intervention. Qualitative research does not aim to be statistically generalisable but gives insight into individual experiences. Our findings may be transferable to other family history populations at risk of weight-related cancers . Our quaCurrently, weight management is not part of clinical practice in breast cancer family history clinics, despite NICE guidelines advising health care professionals to inform women of the probable increased post-menopausal breast cancer risk from being overweight . Our datWeight control is one of the few risk factors for breast cancer which is modifiable and our study has shown that advising high risk women on weight loss can give some a sense of control over their risk. It should be made clear that it is only one of the many factors associated with cancer development, avoiding any misconception that being a healthy weight could provide absolute control over cancer risk . Around Professionals who provide genetic counselling and develop health education material should be mindful that beliefs about weight and breast cancer risk are informed by social networks, media reports and personal experiences of significant others diagnosed with breast cancer. These factors limit the effectiveness of risk counselling concerning the link between weight loss and breast cancer risk. Our study highlights the importance of providing a credible rationale for weight loss which addresses common doubts, anxieties and questions. Counselling and health education material should be tailored to facilitate understanding of both genetic and modifiable risk factors and should do more help individuals to visualise the weight and breast cancer link.Ethical approval was obtained from the South Manchester Ethics Committee (reference 03/SM/159).


Many women at increased risk for breast cancer could benefit from preventive therapy. Preventive therapy options for breast cancer risk reduction have expanded in the last few years to include both selective receptor modulators  and aromatase inhibitors (anastrozole and exemestane).Risk factors that place women at high risk for breast cancer, as well as risk calculation models appropriate for the selection of candidates for preventive therapy, are presented, followed by a review of current guidelines for chemoprevention and results of chemoprevention trials.The modified Gail model or Breast Cancer Risk Assessment Tool is the most widely utilized risk assessment calculator to determine eligibility for chemoprevention. Women most likely to benefit from preventive therapy include those at high risk under the age of 50 years and those with atypical hyperplasia. Physician and patient barriers limit widespread acceptance and adherence to preventive therapy.Published guidelines on chemoprevention for breast cancer have been updated to increase awareness and encourage discussion between patients and their physicians regarding evidence-based studies evaluating the benefits of preventive options for women at increased risk for breast cancer. However, even with increasing awareness and established benefits of preventive therapy, the uptake of chemoprevention has been low, with both physician and patient barriers identified. It is prudent that these barriers be overcome to enable high-risk women with a favorable risk-to-benefit ratio to be offered chemoprevention to reduce their likelihood of developing hormone receptor-positive breast cancer. Defining breast cancer risk incorporates knowledge of individual risk factors known to be associated with increased risk. These risk factors are included in various available risk-calculation models to provide a numeric risk that can be used to help quantify the level of individual risk.1Breast cancer risk factors have historically been described as modifiable versus nonmodifiable factors. Modifiable risk factors in general are associated with lifestyle behaviors and exogenous hormone exposure. These include physical inactivity, increased alcohol consumption, obesity, and use of estrogen and progestin therapies, all of which are associated with increasing breast cancer risk.Breast cancer risk can be categorized as average, high, and very high risk.Women presenting with a strong hereditary predisposition, or known BRCA1 or 2 mutation carriers, are, by definition, considered at very high risk for developing breast cancer. A family history that entails multiple affected relatives with early-onset breast or ovarian cancer over several generations would be an indication to refer to a genetic counselor to discuss the options of genetic testing. The lifetime risk of developing invasive breast cancer for a BRCA mutation carrier is estimated at 40–85 %.17Several complementary risk assessment and calculation tools are available to assist physicians with making decisions regarding preventive therapy, and individualizing risks. These tools incorporate most of the breast cancer risk factors described above and are easily available to the physician at the point of care. When counseling women about preventive therapy, it is recommended that physicians use a shared decision-making approach with women at high or very high risk as they are most likely to benefit from risk-reduction options.The American Society of Clinical Oncology, the NCCN, the Canadian Task Force on Preventive Health Care, and the US Preventive Services Task Force (USPSTF) advise counseling women ≥35 years of age who are at increased risk for breast cancer regarding available medications to reduce their risk and to offer medication to women at low risk of medication-related side effects (USPSTF B recommendation).27This model does not include the age of onset of breast cancer in family members, paternal family history, or any family history of ovarian cancer. It is suitable for women ≥35 years of age with no history of ductal carcinoma in situ (DCIS) or LCIS, no prior history of thoracic radiation, and without a strong family history of breast cancer or ovarian cancer suggestive of a genetic predisposition. The model was updated in 2008 to provide adjusted estimates for African American women derived from the Women’s Contraceptive and Reproductive Experiences (CARE) Study and from Surveillance, Epidemiology and End Results (SEER) data, and in 2011 to include Asian and Pacific Islander women using data from the Asian American Breast Cancer Study (AABCS) combined with the SEER database.28Any woman with a 5-year risk of ≥1.7 % determined by using the Gail model can be considered for preventive therapy. This is the risk estimate utilized for the major breast cancer prevention trials and supported by NCCN guidelines.23In general, women with a history of AH, or women under the age of 50 years, are more likely to benefit from preventive therapy. This is based on the Breast Cancer Prevention Trial (BCPT) data subgroup analysis that demonstrated a significant 86 % risk reduction for women with AH. Furthermore, the evidence supports that women under the age of 50 years are far less likely to incur the harms of therapy seen in women 50 years of age or older.The NCCN Breast Cancer Risk Reduction Panel has adopted the 1.7 % or greater 5-year actuarial breast cancer risk defined by the modified Gail model as the risk threshold for discussion of chemoprevention. This is consistent with eligibility criteria utilized in the NSABP BCPT and the Study of Tamoxifen and Raloxifene (STAR).The recently updated American Society of Clinical Oncology guideline on the use of pharmacological interventions for breast cancer risk reduction states that the risk for breast cancer may be determined by the aforementioned BCRAT tool “or other validated models including Tyrer–Cuzick”.20In a head-to-head comparison of the BCRAT and the IBIS model looking at the absolute 10-year risk of breast cancer, the IBIS model showed better discrimination .34There is no validated model that accounts for breast density, yet it is hoped that one might be developed in the future that will include breast density and be capable of effectively identifying women suitable for both enhanced screening and chemoprevention.35Tamoxifen and raloxifene, both SERMs, as well as two aromatase inhibitors (AIs), exemestane and anastrozole, have been shown in randomized controlled trials to significantly reduce breast cancer incidence in women at increased risk of the disease.38In the landmark BCPT, tamoxifen reduced the risk of breast cancer in both pre- and postmenopausal women at increased risk of the disease by approximately one-half . Women with AH had a highly significant 86 % breast cancer risk reduction , whereas women with LCIS, due to the small sample size, had a nonstatistically significant reduction of 56 % .14Tamoxifen is associated with an increased risk of endometrial cancer , venous thromboembolic events, including stroke , pulmonary embolus , deep vein thrombosis , cataract development , and the need for cataract surgeries .The STAR demonstrated that raloxifene was equivalent to tamoxifen in reducing breast cancer risk for postmenopausal women at increased risk of the disease while on therapy.In the National Cancer Institute of Canada (NCIC) Mammary Prevention 3 (MAP.3) trial, after 35 months of follow-up, exemestane reduced breast cancer risk by 65 %  in high-risk postmenopausal women.Neither exemestane nor anastrozole were associated with an increased risk of thromboembolic or cardiovascular events, or other cancers. In the MAP.3 trial, although short-term use of exemestane was shown to worsen age-related bone loss in spite of calcium and vitamin D supplementation, long-term follow-up will be needed to assess the effect on fracture risk in a prevention population.37Although it is important that high-risk women be considered for chemoprevention, several barriers have been identified that impact uptake, compliance, and adherence. These include fear of possible side effects of the anti-estrogen therapies, specifically thromboembolic events and an endometrial cancer risk, which may be perceived as outweighing the potential benefits of the pharmacologic therapy on reducing the incidence of breast cancer.46Physicians are strongly encouraged to assess breast cancer risk and appropriately identify high-risk women with a positive risk–benefit ratio eligible for chemoprevention. Communication of the risks and benefits of SERMs and AIs as preventive therapies and shared decision-making approaches are critical to patient uptake and adherence. More widespread utilization of these agents can reduce the incidence of estrogen receptor (ER)-positive breast cancer but will have no impact on ER-negative breast cancer. Future opportunities for breast cancer risk reduction should target hormone-negative, especially triple-negative, breast cancer.


Many epidemiological studies point to an increased risk of breast cancer among female airline cabin crew. Possible causes include occupational factors , as well as lifestyle and reproductive factors.To investigate the frequency of various risk factors in German flight attendants which are recognised to be associated with breast cancer.2708 current and former female cabin crew were randomly selected by a flight attendants’ union and mailed a questionnaire; 1311 responded (48% response). Descriptive statistics were used to compare the distribution of breast cancer risk factors with general German population data.2 (95% CI 2.4-2.6) lower. We found less use of hormone replacement therapy, but longer average use of oral contraceptives. Nulliparity among respondents aged 45+ was 57% (95% CI 54%-60%) compared to 16%. Average age at first birth was 32.1 years (95% CI 31.7-32.4) vs. 25.5 years. The birth rate was 0.62 (95% CI 0.58-0.67), less than half the population average of 1.34. Alcohol consumption was considerably higher, whereas cabin crew tended to smoke less and performed more physical exercise.On average, cabin crew were 3.0 cm (95% CI 2.7-3.3) taller than the comparison group, while their body mass index was 2.5 kg/mWe found important differences in terms of anthropometric, gynaecological, reproductive and lifestyle factors. Some of these differences  could contribute to a higher breast cancer risk, whereas others could lead to a reduction . Breast cancer is currently the most frequently diagnosed form of cancer in women in Germany, accounting for 31% of incident cancer cases in 2010 . A smallThe causes of increased breast cancer incidence in this group have not been clearly established: few studies on this topic exist, showing inconsistent results. In particular, it is unclear to what extent occupational factors  play a role versus other factors, e.g. lifestyle or reproductive factors. Tokumaru et al. claim that 29% of breast cancer in flight attendants may be attributable to their occupation . No assoWe conducted a cross-sectional study of current and retired cabin crew in Germany. The aim was to investigate the distribution of several known and suspected breast cancer risk factors among this group and perform comparisons to reported prevalences in the general female German population of similar age.The source population consisted of current and retired female cabin crew who were resident in Germany, had served at least one year of active duty and were member of the German Cabin Crew Union “Unabhängige Flugbegleiter Organisation” (UFO) between 2000 und 2004. A total of 7616 eligible women were identified from the membership database. A questionnaire was sent to 3000 randomly selected members. 292 letters were returned undeliverable, which yielded 2708 successfully mailed questionnaires. A reminder postcard was sent after one month to all 2708 adresses. All responses were anonymous, and thus only fully anonymous data was available for the analysis.Information was collected on: a.) demographic factors including age, marital status, education; b.) anthropometric factors including height and weight; c.) occupational factors including service history, disturbances related to disruption of circadian rhythm, exposure to pesticides; d.) lifestyle factors including alcohol consumption, smoking and physical exercise; e.) gynaecological factors including menstruation, use of hormone replacement therapy and contraceptives; f.) reproductive factors including pregnancies, child birth, miscarriages and abortions, breast feeding; g.) family history of breast cancer, participation in screening programmes; h.) general health status. This paper focuses on a subset of the information collected: specifically anthropometric, lifestyle, gynaecological and reproductive factors, for which we found clear differences between cabin crew and the general population.All questionnaires were captured electronically and responses were coded into a database. The participant’s age was calculated as 2009 – year of birth (the study period was Nov 2008 through March 2009). We calculated the body mass index (BMI) based on the formula weight (in kg) divided by height (in metres) squared. Alcohol consumption was measured in grams per week, based on reported consumption in multiples of 0.33 litres of beer, 0.25 litres of wine, 2 cl of spirits, and average alcohol content.Data from our study was then compared to general population data, which was taken from two main sources: Firstly, data on birth statistics, abortions and miscarriages, anthropometrics, marital status and education was supplied directly by the German Federal Statistical Office; secondly, the Robert Koch-Institute (RKI) provided data on lifestyle factors , hormonal and gynaecological factors, general health status .Since the age composition of our study group was very different from the general population, it was necessary to control for age. To this end, we stratified the sample into 5-year age groups from 25–29 up to 65–69 years. For each risk factor, we calculated relative frequencies  or averages (for metric variables) and 95% confidence intervals, by age group and for the total study population. This was compared to general population data, both by comparing each individual 5-year age group and by calculating age-adjusted averages, where we weighted each age group in the general population with the frequency of our study population.Ethical approval for the study was obtained from the ethical review board of the medical chamber Rhineland-Palatinate, Mainz, Germany.A total of 1311 flight attendants returned the questionnaire , yielding a response rate of 48%. Participants were between 25 and 69 years old  with a mean age of 41.6 years.2 (95% CI 21.7-21.9), significantly lower than the corresponding population average of 24.3 kg/m2.Women in our study were on average 169.3 cm tall (95% CI 169.0-169.6), that is 3.0 cm taller compared to the general population. This applied consistently across age strata. The average BMI was 21.8 kg/mUse of oral contraceptives (OC) was widespread among cabin crew; 96% of respondents indicated that they had ever used OC, for an average duration of 11.1 years (95% CI 10.7-11.5), which is 2.0 years longer than the population average. We also investigated the use of hormone replacement therapy (HRT). 23% (95% CI 15%-31%) of 50–54 year old flight attendants have “ever used” such treatment. Unfortunately, suitable data for comparison were lacking. A study by the Robert Koch-Institute, however, indicated that 33% of 50–54 year old and 18% of 45–49 year old women “currently” use HRT. This suggests that the use of HRT among cabin crew could be lower than for the general female public in the respective age group.68% (95% CI: 65%–70%) of flight attendants had performed regular physical activity in the last three months, only slightly more than the population average of 63.7; however, at 3.9 hours/week (95% CI 3.7-4.0), they exercised 48% longer. Alcohol consumption was significantly increased: 42% vs. 15% of respondents consume more than 10 g of alcohol daily. Average consumption was 73.9 g per week (95% CI 69.3-78.5), i.e. 10.6 g daily. This compares to a typical daily consumption rate of 6.0 g in industrialised countries . ReporteCabin crew reported differences in reproductive history compared to the general population. 57% (95% CI 54%-60%) of cabin crew aged 45 years and older were nulliparous, compared to only 16%. Those with offspring tended to have their first birth with 32.1 years (95% CI 31.7-32.4), 6.6 years older than the population average. Overall, the birth rate among the study group was only 0.62 (95% CI 0.58-0.67), 54% lower than the corresponding population average of 1.34.Earlier studies showed a significant increase in breast cancer incidence among female flight attendants in several countries -6,9,10. In terms of anthropometric differences, we found that flight attendants were on average taller than the general female population, while their BMI was lower. This difference could be explained by entry selection criteria for the occupational group. Height is a well-established risk factor for breast cancer: both pre- and postmenopausal risk increase with height. A pooled analysis found a relative risk (RR) of 1.02 (95% CI: 0.96-1.10) for pre- and 1.07 (95% CI 1.03-1.12) for post-menopausal breast cancer per 5 cm difference in height . A higheIn addition, we found higher than average usage levels of oral contraceptives by flight attendants. This finding is consistent with the result that cabin crew are more likely to remain nulliparous or have their first birth at a higher age than the average population. The impact of oral contraceptives on breast cancer risk is not clearly established; some studies suggest that there may be a small increase of risk ,20. HormWe also discovered significant differences between female cabin crew and the general population for three lifestyle factors: alcohol consumption, smoking and physical exercise. Increased alcohol consumption, as we found among our study group, has been recognised as an important independent driver of breast cancer risk  . ContrarNulliparity and age of the mother at first birth are strong, well-recognised breast cancer risk factors. According to a meta-analysis, nulliparous women have a 30% higher risk compared to those with offspring . SimilarChronodisruption, although not specifically assessed in this analysis, has been discussed as a potential contributor to breast cancer risk in populations such as aircrew exposed to shift work and/or repeated time zone changes . Shift wAlthough we found rather clear differences between female cabin crew and the general population, we are aware that we compared data from different sources  and the methods of measurement may have been different. The above results also need to be viewed in light of the limitations of our study. Firstly, our study design as a cross-sectional study does not give insight into causal relationships between breast cancer incidence and risk factors. All conclusions therefore need to be viewed with caution, and further research is needed to validate these findings. Secondly, due to our choice of study population (mostly women of working age) there is a bias towards younger women: only n = 35 are 60 years or older, the maximum age is 72. Therefore, our study includes only a small sample of older retired cabin crew, for whom breast cancer risk and prevalence is likely to be particularly high. Thirdly, we need to consider non-response bias, which is likely to exist in our study because women, who are affected by breast cancer  might have a higher probability to respond. This could on the one hand lead to individuals with higher than average breast cancer risk to be over-represented in the sample. On the other hand, the study does of course not include cases who suffered from breast cancer and subsequently died. Finally, it should be noted that survey participants were all union members. This may introduce some selection bias in principle, but we believe that union membership is not likely to be strongly associated with health aspects, and union membership is common in this occupational group.At the same time, there are clear strengths to our study. Firstly, the study is the first of its kind in Germany, making use of the database of a large union of flight attendants. Secondly, at 48% the response rate was rather high and exceeded our expectations during study design. Nevertheless, more than half of all contacted flight attendants chose not to reply, inducing a non-negligible potential for selection bias.In summary, we found several factors among the study group that might help explain an increased incidence of breast cancer among the occupational group: higher nulliparity, later first birth, higher levels of alcohol consumption, a taller physique, (possibly) oral contraceptive use, and  a lower BMI. In contrast, we also found factors which would lead to a reduction of risk: Lower use of hormone replacement therapy, higher levels of physical exercise, (possibly) lower levels of smoking and  a lower BMI. Within the scope of this study it is not possible to assess the combined effect of these factors, and to clarify to what degree risk increases are outweighed by risk reductions. We did, however, see marked differences in some reproductive and lifestyle factors, and the role of these factors in breast cancer has been recognized in many studies.The authors declare that they have no competing interests.MW, MB and HZ jointly designed the study. MW wrote the study protocol and conducted the data acquisition together with HZ. MW did the statistical analysis and wrote the first draft of the paper. MB supervised the data analysis. All authors contributed the interpretation of data, revised the manuscript, read and approved the final version.


Breast and ovarian cancers are predominant female cancers with increasing prevalence. The purpose of this study was to estimate the population attributable risks (PARs) of breast and ovarian cancer occurrence based on the relative risks (RRs) of modifiable reproductive factors and population-specific exposure prevalence.The PAR was calculated by using the 1990 standardized prevalence rates, the 2010 national cancer incidence with a 20 year lag period, the meta-analyzed RRs from studies conducted in the Korean population for breast cancer, and the meta-analyzed RRs from a Korean epithelial ovarian cancer study and a prior meta-analysis, and ovarian cancer cohort results up to 2012. For oral contraceptive and hormone replacement therapy use, we did not consider lag period.The summary PARs for modifiable reproductive factors were 16.7 % (95 % CI 15.8–17.6) for breast cancer (2404 cases) and 81.9 % (95 % CI 55.0–100.0) for ovarian cancer (1579 cases). The modifiable reproductive factors included pregnancy/age at first birth (8.0 %), total period of breastfeeding (3.1 %), oral contraceptive use (5.3 %), and hormone replacement therapy use (0.3 %) for breast cancer and included breastfeeding experience (2.9 %), pregnancy (1.2 %), tubal ligation (24.5 %), and oral contraceptive use (53.3 %) for ovarian cancer.Despite inherent uncertainties in the risk factors for breast and ovarian cancers, we suggest that appropriate long-term control of modifiable reproductive factors could reduce breast and ovarian cancer incidences and their related burdens by 16.7 % and 81.9 %, respectively.The online version of this article (doi:10.1186/s12885-015-2040-0) contains supplementary material, which is available to authorized users. Worldwide, breast cancer is the most common cancer among females, and its incidence is increasing continuously. Ovarian cancer is the third most common gynecological cancer worldwide, next to cervix uteri and corpus uteri cancers, and has the second highest mortality rate among gynecological cancers, following that for cervix uteri cancer. Globally in 2008, breast and ovarian cancers accounted for 26.6 % of all cancers among females . The maith most common among females [In Korea, breast and ovarian cancers account for 14.3 % and 2.0 %, respectively, of all female cancers. In Korea, breast cancer is the second most common cancer following thyroid cancer, while ovarian cancer is ranked as 10 females . Breast  females , and the females . Increas females –10. PartThe epidemiological patterns of breast and ovarian cancers and their risk factors in Korean women may require the development of population-specific strategies for cancer prevention. The determination of population attributable risks (PARs), defined as the quantified contribution of each risk factor to a disease, can help policymakers establish appropriate public health interventions .The purpose of this study was to estimate the burden of reproductive risk factors on the prevalence of breast and ovarian cancer in Korea using Korean-specific risk estimates. Since breast and ovarian cancers are major female cancers in the Korean population, such population-specific prevalence and risk estimates should help in the development of cancer control plans in Korea.Prior studies focused on breast cancer risk factors in Korea were based on a subset of data from the Seoul Breast Cancer Study (SeBCS) –17, the In our previous studies using subset of data from the SeBCS, we have identified various risk factors of breast cancer in Korea including early menarche, late menopause, nulliparity, later first full-term pregnancy, family history, postmenopausal obesity, breastfeeding, and OC use –17. For For ovarian cancer, Holschneider et al. reviewed the literature and proposed family history, genetic mutations, nulliparity, late menopause, and early menarche as risk factors for ovarian cancer. In addition, they suggested that multiparity, oral contraceptive use, and hysterectomy or tubal ligation were protective factors . We seleConsidering the effect of the population control policies through national birth control programs on the rapid decline of the fertility rate in Korea , we inclWe applied the number of cancer incidents in the female population aged 20 years and older in the year 2010 from the Korea Central Cancer, a nationwide cancer registry in Korea . AlthougTo obtain the pooled relative risks (RRs) for the selected risk factors, we conducted a meta-analysis of the results of large-scale, case–control studies in Korea (SeBCS for breast cancer and Ko-Eve for ovarian cancer) and the results from other previous studies. For breast cancer analysis, because the SeBCS included large numbers of cases and matched controls, we restricted the data selection to studies conducted in Korea and did not restrict the study design to reflect Korean risk estimates. For ovarian cancer analysis, given that the Ko-Eve is the only study conducted in Korea, and includes a limited number of cases, we included data from international studies to perform a meta-analysis with Ko-EVE results to obtain stable risk estimates. The priority for inclusion of international data was meta-analysis or pooled analysis data. In cases where studies were not available, we included cohort study results. In cases where we could not obtain RR or the raw data necessary for calculating a RR estimate, the data were excluded from the meta-analysis.http://www.ncbi.nlm.nih.gov/pubmed/), Embase (http://www.embase.com/home), and KoreaMed (http://www.koreamed.org/SearchBasic.php). The search keywords were cancer  and each of the risk factors. For each article, we checked whether data resources overlapped. When more than one study from the same study population was available, the study with the most complete data was used.Studies published in English or Korean before December 2012 were identified through PubMed  and the RRs for each particular risk factor, the PAR for each risk can be calculated. The PAR was calculated by using the modified Levin’s formula for multiple categories, as proposed by Hanley [From the estimated prevalence of exposure in the population . PARs of HRT use for breast cancer was estimated using the prevalence of menopause (32 %) in women aged 20 years or over in 2010.By using the obtained PARs, we calculated the proportions and numbers of cases and deaths of breast and ovarian cancer due to modifiable reproductive factors in females 20 years of age and older.The RRs and prevalences for breast and ovarian cancer applied in the current study along with the data sources are summarized in Table The PARs and numbers of breast and ovarian cancer incidences due to modifiable reproductive factors among females aged 20 years and older for the year 2010 in Korea are presented in Table For ovarian cancer, OC use and tubal ligation were the most important modifiable reproductive factors , whereas breast feeding and pregnancy were attributed to 2.9 % and 1.2 %, respectively. The PAR for the selected modifiable reproductive factors was 81.9 % (95 % CI 55.0–100.0) of ovarian cancer cases and they were responsible for 1579 (95 % CI 1059–1927) ovarian cancer incidences in the year of 2010 in Korea.In Korea in the year 2010, 16.7 % of breast cancer and 81.9 % of ovarian cancer cases in women were attributable to modifiable reproductive factors. The modifiable reproductive factors included pregnancy/age at first birth (8.0 %), total period of breastfeeding (3.1 %), OC use (5.3 %), and HRT use (0.3 %) for breast cancer and included pregnancy (1.2 %), breastfeeding (2.9 %), tubal ligation (24.5 %), and OC never use (53.3 %) for ovarian cancer.Several recent studies have reported PARs of reproductive factors for breast cancer. In one study, a combination of parity number and age at first birth explained 17.9 % of breast cancers , a perceAmong the assessed modifiable reproductive factors, large differences in PARs between studies were observed in HRT use. In French women, HRT use was associated with 12.7 % of breast cancer cases and 10.2 % of breast cancer deaths , whereasRegarding the classification of risk factors, parity was considered a non-modifiable factor in the work of Barnes et al., but was assessed as a modifiable factor in this study. Barnes et al. restricted their PAR calculation to post-menopausal women, and parity-related factors could thus be considered as non-modifiable . In contWith regard to the PAR in ovarian cancer, Granstrom et al. reported that the PARs for family history, parity/age at first birth, and residential area were 2.6 %, 22.3 %, and 7.2 %, respectively . ParazziThere are several study limitations to be considered. Although the standardized population used in this study was from 1990, prevalence of most reproductive factors in 2005 was used because of the lack of representative data for 1990. Considering the increased age at first birth and the decreased fertility rate between 1990 and 2005, our results might underestimate the PAR for reproductive factors in Korea. In addition, the prevalence of tubal ligation showed limited representativeness because it was estimated by using control subjects from a hospital-based case–control study (Ko-Eve). Thus, we compared our estimates of the prevalence of tubal ligation with results from the National Survey on Fertility, Family Health & Welfare in Korea, a nationwide representative survey for females of childbearing age (15–44 years) , and theDespite these limitations, this study has several strengths. First, we used nationwide cancer incidence data that are representative of nearly the entire population. Thus, we had access to precise numbers of cancer cases for inclusion in our PAR estimation. Second, the estimated prevalence of exposure to each risk factor in 1990 was used in the consideration of a 20-year lag period between exposure to a risk factor and subsequent cancer development. Although we did not measure the quality of each study, the studies included in the meta-analysis for breast cancer were conducted within the Korean population, thus providing Korean-specific results.In summary, the results of this study represent a systematic assessment of breast and ovarian cancer risks and the proportion of the risk associated with modifiable reproductive factors. A total of 16.7 % of breast cancer cases (2404 cases) and 81.9 % of ovarian cancer cases (1579 cases) in Korea among female individuals 20 years of age in 2010 were attributable to modifiable reproductive factors. Since breast and ovarian cancers are the most prevalent female cancers, and are showing a trend to higher prevalence, appropriate control of preventable or modifiable risk factors is an important strategy for reduction of the female cancer burden in Korea. Combining the current Korean family planning policy of childbirth encouragement with cancer control strategies that affect modifiable reproductive factors may help achieve reductions in breast and ovarian cancer incidences.


Evidence suggests that premenopausal obesity decreases and postmenopausal obesity increases breast cancer risk. It is unclear why this dual relationship is observed. We here study whether body mass index (BMI) affects (a) age at breast cancer diagnosis and (b) the probability of being diagnosed with a specific breast cancer phenotype, taking menopausal status into account.All patients with non-metastatic operable breast cancer from UZ Leuven diagnosed between January 1, 2000 and December 31, 2013 were included (n=7020). For statistical analysis, linear models and logistic regression were used to study respectively the association between BMI and age at diagnosis and BMI and breast cancer phenotype by menopausal status. Where necessary, a correction for the relation between BMI and age will be applied, based on publicly available data from the Belgian Health Interview Surveys.There was a quadratic relationship between BMI and age at breast cancer diagnosis studying the overall population (p<0.0001). A 5kg/m2 increase in BMI was associated with the following increases in age at diagnosis: +1.8y (95% CI 1.4-2.3y) at BMI=18, +1.2y (95% CI 0.95-1.5y) at BMI=23 and +0.6y (95% CI 0.4-0.9y) at BMI=28 (corrected for menopause). Correction for the relation BMI with age are ongoing and not yet available in this abstract.The relationship between BMI and the probability of being diagnosed with specific breast cancer phenotypes will be presented during the congress.The relation between BMI and age at diagnosis and between BMI and the chance of being diagnosed with specific breast cancers is complex. New analyses taking into account the relation between BMI and age are ongoing. We look forward to present the final results on the congress.


EIG121) has been associated with breast and endometrial cancers, but its mechanism of action remains unknown. In a genome-wide search for tandem repeats, we found that EIG121 contains a short tandem repeat (STR) in its upstream regulatory region which has the potential to alter gene expression. The presence of this STR has not previously been analysed in relation to breast or endometrial cancer risk.The estrogen-induced gene 121  contains supplementary material, which is available to authorized users. The recent emphasis on high-throughput assays in the search to find genetic variants responsible for familial cancer risk has failed to account for a significant proportion of cases. Instead, the use of genome-wide association studies and next-generation sequencing has revealed variants that account for a small portion of heritability and has now resulted in the phrase “missing heritability” to explain that which remains unaccounted for , 2. AnotEIG121 . In endometrial cancer cases, EIG121 is highly induced by estrogen in the endometrium and differentially expressed in endometrial cancer types [http://www.oncomine.com), shows EIG121 to be over-expressed in breast cancer compared to other cancer types  in the upstream regulatory region of genes that are candidates for conferring cancer risk . One sucer types , 6. Studer types . Our anaEIG121 has already been associated with estrogen levels and cancer, we analysed the variability of this newly identified STR in a series of breast and endometrial cancer cases and in a healthy control population to determine if there was any association between its length and the risk of developing these estrogen-driven cancers.Breast and endometrial cancers are estrogen-driven malignancies, and in both diseases, higher expression of estrogen-induced genes is associated with tumours that tend to be low-grade and less aggressive , 11 suggThis study included 223 breast cancer cases, 204 endometrial cancer cases and 220 healthy controls from whom blood-derived genomic DNA had been collected for previous studies in Newcastle, New South Wales (NSW), Australia –14. StudEIG121 was genotyped by polymerase chain reaction (PCR) and fragment analysis using forward (5′-aggctaatccaggagaatctcttg-3′) and reverse (5′-aggctaatccaggagaatctcttg-3′) primers designed to amplify a 232 bp length fragment. PCR was performed with Platinum Taq DNA Polymerase High Fidelity (Invitrogen), an annealing temperature of 61 °C and 1.5 mM MgSO4. Fragment analysis was conducted on the ABI3730 DNA Analyzer (Applied Biosystems (AB)) after denaturation in the presence of HiDi Formamide (AB) and GeneScan 600 LIZ Size Standard (AB). The resulting electropherograms were analysed using Peak Scanner v1.0 software (AB). Sanger sequencing [The STR (a dinucleotide AG repeat) situated 518 bp upstream of the transcription start site for quencing .p value < 0.05 (two-sided) and corrected for multiple comparisons using the Bonferroni method.Statistical analyses were performed using the Stata 11.1 software package  and involved non-parametric Mann–Whitney U tests, Cox proportional hazard regression, Pearson’s Chi squared and Fisher’s exact tests. The significance levels of all tests were set at EIG121 was highly variable, and showed a bimodal distribution of lengths with sizes ranging from 27 to 72 copies across all three cohorts (Fig. Based on genotyping results, the AG repeat in the upstream regulatory region of p values for the allelic and genotypic analyses (p = 0.185 and p = 0.102, respectively; Table A non-parametric Mann–Whitney U test was used to test for any association between STR lengths, using both allele lengths for each individual, and cancer types. This demonstrated a lack of association between STR length and breast and endometrial cancers when compared to healthy controls Table . To testEIG121 is a highly polymorphic STR, making it a variable genetic element with the potential to influence the expression of EIG121 and subsequently impact disease risk and/or severity. No statistically significant association was identified between the length of this dinucleotide repeat and the age at diagnosis or risk of developing breast or endometrial cancer in the cohorts analysed. Hence, while this STR in the regulatory region of EIG121 is highly polymorphic, it is unlikely to be associated with the risk of developing breast or endometrial cancer. We cannot exclude its involvement in recurrence or overall survival as this information was not available for this study.In conclusion, the AG dinucleotide repeat in the upstream regulatory region of


To assess the importance of heredity in the etiology of inflammatory breast cancer (IBC), we compared IBC patients to several carefully chosen comparison groups with respect to the prevalence of first-degree family history of breast cancer.n = 141) were compared to non-inflammatory breast cancer cases (n = 178) ascertained through George Washington University (GWU) with respect to the prevalence of first-degree family history of breast cancer and selected environmental/lifestyle risk factors for breast cancer. Similar comparisons were conducted with subjects from three case–control studies: breast cancer cases (n = 1145) and unaffected controls (n = 1142) from the Cancer Genetic Markers of Susceptibility (CGEMS) study, breast cancer cases (n = 465) and controls (n = 9317) from the Women’s Health Initiative (WHI) study, and ovarian cancer cases (n = 260) and controls (n = 331) from a study by University of Toronto (UT).IBC cases  and controls . Oral contraceptive use was significantly higher among IBC cases compared to WHI breast cancer cases  and controls . IBC cases had a significantly higher frequency of regular alcohol consumption (≥1 drink per day) compared to WHI controls  and UT controls  and higher  prevalence (21.3 %) compared to breast cancer cases from GWU (18.2 %) and WHI (15.2 %).The prevalence of first-degree breast cancer family history among IBC cases was lower compared to breast and ovarian cancer cases but higher than unaffected individuals. Our multiple-case inflammatory and non-inflammatory breast cancer families may reflect aggregation of common genetic and/or environmental factors predisposing to both types of breast cancer. Our findings that oral contraceptive use and regular alcohol consumption may be associated with IBC warrant further investigations. Inflammatory breast cancer (IBC) is a rare form of breast cancer characterized by an early average age of diagnosis (52 years versus 57 years for non-inflammatory breast cancer), aggressive histopathologic features (at least stage IIB at diagnosis), and poor survival . ClinicaBRCA mutations  nested within the Nurses’ Health Study (NHS) cohort   susceptibility genes in the affected families . Ovariant cancer  and ovart cancer . In addit cancer . TherefoBRCA mutation status [BRCA carrier status) in our study but a slightly higher prevalence than general breast and ovarian cancer cases in some studies reported in the literature. A recent nested case–control study in the Breast Cancer Surveillance Consortium (BCSC) investigated the association between IBC risk and number of factors, including family history of breast cancer. This study also found a higher risk of IBC in association with first-degree family history of breast cancer [The prevalence of breast cancer among first-degree relatives of both breast and ovarian cancer cases in our study was between 16.9 % and 24.4 %, which is within the range reported in the literature .t cancer . An earlt cancer .The prevalence of first-degree breast cancer family history among UT controls (11.2 %) and WHI controls (12.6 %) was slightly higher than the range (4.8–7.3 %) of estimates reported in the literature for healthy women with no personal history of breast or ovarian cancer , 45. TheBRCA2 mutation responsible for the disease in that family [BRCA mutation frequency among IBC cases from systematic studies remain to be reported. Our results indicate that a proportion of IBC cases occur in the context of familial breast cancer which may be explained by aggregation of common hereditary factors and/or shared environmental risk factors predisposing to both inflammatory and non-inflammatory breast cancer in these families. Our findings and the previous case report of hereditary IBC highlight the importance of obtaining pedigrees on IBC cases and noting all diagnoses of cancer and benign disease among the relatives.We identified several IBC cases with non-inflammatory breast cancer and other cancers among first- and second-degree relatives, as discussed in the previous section. Three families with multiple cases of IBC were also identified in our study; one index case had a daughter with IBC, one had a sister with IBC and the third had a cousin with IBC. A case report of hereditary IBC in a mother and a daughter had identified a deleterious t family . AccuratAs part of this study, we also conducted comparisons between IBC and other groups with respect to the prevalence of selected environmental/life style risk factors for breast cancer, such as parity, BMI, oral contraceptive use, and consumption of alcoholic beverages. These comparisons were secondary to the main study objective and the secondary nature of some of the comparison groups was a limitation with respect to the ability to conduct a comprehensive analysis of all relevant environmental/lifestyle factors. Therefore, our findings with respect to the selected environmental/life style factors need to be interpreted with caution. Our comparisons revealed a higher prevalence of nulliparity, oral contraceptive use and regular alcohol consumption (≥1 drink on daily basis) among IBC cases.The prevalence of ever use of oral contraceptives was significantly higher among IBC cases (80.1 %) compared to all other comparison groups including breast cancer and ovarian cancer cases in our study. The differences between groups with respect to oral contraceptive use may be due to differences in age or other confounding factors between groups. Therefore, the association between oral contraceptive use and IBC risk needs further investigation in future studies accounting for all potential confounding variables. We had previously reported associations between aggressive (high-grade) breast cancer with long-term oral contraceptive use .Our findings with respect to the association between alcohol consumption and IBC are also novel. The prevalence of regular alcohol use (≥1 drink per day) was higher among IBC cases compared to all other comparison groups in our study. These findings are particularly noteworthy given that excess alcohol consumption (>35 g per day) is an established risk factor for non-inflammatory breast cancer –37. EthaAs mentioned earlier, the secondary nature of some of the comparison groups is a limitation of our study, particularly with respect to analysis of environmental/life style factors. Strengths of our study include systematic data collection through the use of epidemiologic questionnaires on all case and control groups; the exact same questionnaire was used on the IBC and non-inflammatory breast cancer cases from GWU. Other strengths include validation of the family history-related questions through collection of detailed pedigrees on a subset of IBC cases and access to raw (secondary) data from several case–control studies, which could be used as additional comparison groups. The case–control comparison groups in our study were sufficiently large to allow statistically meaningful comparisons and the unaffected individuals used as controls in these studies were appropriately matched to the breast and ovarian cancer cases on important criteria such as age and ethnicity.In summary, our study found the prevalence of first-degree family history of breast cancer among IBC cases to be slightly lower or similar compared to breast and ovarian cancer cases but higher than unaffected individuals. Therefore, similar contribution of hereditary components to IBC risk as that to non-inflammatory breast cancer risk cannot be ruled out. Our findings of multiple-case inflammatory and non-inflammatory breast cancer families may further reflect aggregation of genetic factors and gene-environment interactions predisposing to both types of breast cancer. Our findings that oral contraceptive use and regular alcohol consumption may increase the risk of IBC are noteworthy due to modifiable nature of these potential risk factors. Collection of multi-generation pedigrees and detailed epidemiologic information noting the factors associated with an increased risk of IBC in studies by us and others will help decipher the etiologic role of hereditary and environmental factors in susceptibility to IBC in future studies. Because of the rarity of IBC and multiplex IBC families, the importance of developing consortia to enable epidemiologic investigations including gene-environment interaction studies should be emphasized.AJCC, American Joint Committee on Cancer; BC, Breast Cancer; BMI, Body Mass Index; CGEMS, Cancer Genetic Markers of Susceptibility; GWU, George Washington University; IBC, Inflammatory Breast Cancer; NHS, Nurses’ Health Study; OC, Ovarian Cancer; UT, University of Toronto; WHI: Women’s Health Initiative.


These associations were limited to those with stage II or III cancer. Diet may be an important factor in relation to quality of life among Korean breast cancer survivors, however our findings warrant further prospective studies to evaluate whether healthy diet improves survivors’ quality of life.There is limited evidence on the association between adherence to guidelines for cancer survivors and health-related quality of life (HRQoL). In a cross-sectional study of Korean breast cancer survivors, we examined whether adherence to the guidelines of the American Cancer Society (ACS) and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) for cancer survivors was related to levels of HRQoL, assessed by the Korean version of Core 30 (C30) and Breast cancer module 23 (BR23) of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ). We included a total of 160 women aged 21 to 79 years who had been diagnosed with breast cancer according to American Joint Committee on Cancer (AJCC) stages I to III and had breast cancer surgery at least six months before the interview. Increasing adherence to ACS guidelines was associated with higher scores of social functioning ( Breast cancer is the most frequent cancer among women worldwide ; nonetheEvidence regarding how breast cancer survivors try to improve their prognosis is limited to date. In 2007, the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) advised that cancer survivors should follow recommendations for cancer prevention . For breA recent review of epidemiological studies on breast cancer survivorship reported that high body fat and most likely low physical activity increase the risk of breast cancer mortality; however, the association of dietary factors with cancer survivorship was unclear . SeveralAlthough healthy lifestyle may benefit Korean breast cancer survivors, evidence is limited. Therefore, we examined whether adherence to lifestyle behavior recommendations was associated with HRQoL levels among Korean breast cancer survivors.n = 9), women who had been diagnosed with stage 0 breast cancer (n = 6), women who had metastasis (n = 14), women who had been diagnosed with other cancers before the interview of our study (n = 16), of whom medical records were missing (n = 17) or women who did not appropriately complete dietary records (n = 5). As a result, a total of 160 women were eligible for this study. The institutional review board at Seoul National University Hospital, Seoul, Korea, approved this study.Study participants who had been diagnosed with breast cancer according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual were enrolled at University Hospital in Seoul between September 2012 and July 2014. Two-hundred and nineteen women aged 21 to 79 years signed an informed consent form. We included participants who had been diagnosed with invasive primary breast cancer at AJCC stages I to III and had breast cancer surgery at least 6 months before the interview. We excluded the following respondents: women who had breast cancer surgery less than 6 months before the interview (2). We obtained information about the duration and frequency of post-diagnosis physical activity and calculated the scores for metabolic equivalent task (MET) hours per week by multiplying the hours per week engaged in that activity by the activity’s corresponding MET value [.Participants were surveyed by well-trained nurses using a structured questionnaire. Data on height and weight, socio-demographic status, smoking status, alcohol intake, physical activity, HRQoL, reproductive history, and use of dietary supplements were collected. Clinical features including T stage (tumor), N stage (node), M stage (metastasis), and hormone receptor status were obtained from hospital medical records. The participants recorded their food intake for 2 weekdays and 1 weekend day. Body mass index was calculated as weight (kg) divided by the square of height , fruit and vegetable intake (g/day), proportion of whole grain to total grain intake (%), and red and processed meat intake (g/day). The highest adherence levels were given a score of 2, middle levels were given a score of 1, and the lowest levels were given a score of 0. Because the third guideline includes three sub-guidelines, in order to treat the three guidelines the same, we regrouped the participants into three categories of 0, 1, and 2 based on tertiles of the sum of the three adherence scores of the sub-guidelines. We calculated the overall adherence scores by summing the three scores of adherence to the ACS guidelines (range 0–6).The ACS guidelines for cancer survivors are as follows: (1) achieving and maintaining a healthy body weight; (2) adopting regular physical activity; and (3) achieving a dietary pattern that is high in vegetables, fruits, and whole grains . The scoThe WCRF/AICR has released 10 recommendations including 2 special recommendations for cancer prevention . We cons2 of BMI, respectively. We grouped the participants into three groups based on tertiles of adherence levels for physical activity (MET-hour/week), energy-dense food intake , non-starchy vegetable and fruit intake (g/day), refined grain intake (g/day), red and processed meat intake (g/day), and sodium intake (mg/day). The highest adherence levels were given a score of 2, middle levels were given a score of 1, and the lowest levels were given a score of 0. We assigned 0, 1 and 2 to >50, 0–50, and 0 g/day of sugary drinks, respectively. Because the third and fourth guidelines include two sub-guidelines, to treat the scoring the same, we regrouped the participants into three categories of 0, 1, and 2 based on tertiles of the sum of two adherence scores of the sub-guidelines of the third or fourth guidelines. We calculated the overall adherence scores by summing the six scores of adherence to the WCRF/AICR guidelines (range 0–12).The scoring criteria of the WCRF/AICR recommendations are presented in We assessed HRQoL in breast cancer survivors using a validated Korean version of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3.0 and Quality of Life Questionnaire Breast Cancer Module 23 (QLQ-BR23) . The QLQSocio-demographic, lifestyle and clinical characteristics of the study participants are presented as the mean or frequency according to quartiles of adherence scores to ACS or WCRF/AICR guidelines. To examine the association between adherence scores to ACS or WCRF/AICR guidelines and HRQoL levels, we calculated the least square means (LS means) and 95% confidence intervals (95% CIs) using generalized linear models (GLMs).n = 17) with stage III. The statistical tests were two-sided, and p < 0.05 was considered statistically significant. All analyses were conducted using the SAS software 9.3.We log-transformed variables and exponentiated them if they did not meet normality. To test for trends, we assigned the median values of the quartiles of adherence scores and treated the variable as a continuous variable. In the multivariate-adjusted models, we adjusted for age (year), energy intake , dietary supplement use , marital status , education level , stage at diagnosis , and time since surgery . We also conducted subgroup analyses to examine the associations by breast cancer stage at diagnosis  or time since surgery . We grouped stage II and III because of the small number of breast cancer survivors , and never smokers (86.88%). The prevalences of breast cancer stages I, II, and III were 45.63%, 43.75%, and 10.63%, respectively  age of the study participants was 50.96 (8.72) years . Of the study participants, 83.75% had undergone breast cancer surgery less than five years before the interview. The mean (SD) of physical activity level was 37.88 (37.78) METs-hour/week, and the mean (SD) of BMI was 22.58 (2.84) kg/mectively . Breast ectively .p for trend = 0.05) compared to those with lower adherence to ACS guidelines (p for trend = 0.05), and sexual functioning scores significantly increased with increasing scores of adherence to ACS guidelines (p for trend = 0.01) among those with stages II or III (p for trend = 0.01)  .p for trend = 0.01) and tended to have higher scores of insomnia (p for trend = 0.05) compared to those with lower adherence to WCRF/AICR recommendations (p for trend = 0.01) and higher scores for upset by hair loss (p for trend = 0.03) compared to those with lower adherence to WCRF/AICR recommendations (Breast cancer survivors who had higher adherence to WCRF/AICR recommendations had significantly higher scores of arm symptoms (ndations . When wendations . Breast ndations .p for trend = 0.05) or increasing scores of adherence to WCRF/AICR recommendations (p for trend = 0.04) among those who had 1.9 or more years since surgery. Among breast cancer survivors who had less than 1.9 years since surgery, those who had higher adherence to WCRF/AICR recommendations tended to have higher arm symptoms scores (p for trend = 0.05) compared to those who had lower adherence to WCRF/AICR recommendations (Data not shown).When we examined the association between adherence to ACS or WCRF/AIR guidelines and HRQoL levels according to the time since surgery , social functioning scores tended to increase with increasing scores of adherence to ACS guidelines  study . That stOur study found that those who had higher adherence to WCRF/AICR recommendations had higher scores of arm symptoms compared to those with lower adherence, however, four cross-sectional studies aforementioned did not find positive association between pain and adherence to guidelines. Differences between our study and previous studies may be partly because time since diagnosis was relatively shorter in our population than other study populations. We found that this association existed among only breast cancer survivors with a short time since surgery, but not among those with a relatively longer time since surgery. It is possible that emotional anxiety, which could be stimulated by pain or symptoms, promoted adherence to healthy diet among those who had a relatively short time since diagnosis. There is a report that breast cancer survivors who initiated dietary changes after diagnosis were more likely to have psychological distress than those who did not . FurtherFor body mass index and physical activity, there is evidence that maintaining healthy weight and being physically active improved quality of life. A recent meta-analysis of 25 physical exercise intervention trials on quality of life of breast cancer survivors reported increased overall quality of life in the intervention group compared to control group . Short-tThis is the first study to examine the association between the AICR guideline or WCRF/AICR recommendation adherence and HRQoL among Korean breast cancer survivors. Other strengths of our study include dietary assessment by three-day dietary records, which is regarded as the gold standard, and good medical information related to breast cancer diagnosis and treatment. However, we do not have information on the comorbidity status at diagnosis, which has been suggested as a predictor of impaired overall quality of life as well as functional status ,43, and In conclusion, we identified that adherence to ACS guidelines was associated with better social functioning scales, and this association was more pronounced among survivors with stage II or III cancer. We found that adherence to WCRF/AIRCR recommendations was associated with worse arm symptoms scales. Our results suggest that although ACS and WCRF/AICR guideline adherence by cancer survivors is associated with the status of health-related quality of life among breast cancer survivors, it may differ according to the breast cancer stage or the time since surgery. Although our study does not directly infer a causal relationship, significant association between lifestyle factors and quality of life observed in our study emphasizes the need of Korean breast cancer survivorship studies that examine the role of diet, physical activity, and other lifestyle factors in the progression of breast cancer.