To examine the body image and hopelessness status of early‐stage breast cancer survivors who received a one‐time dressing change after surgery and were ready to be discharged from a hospital in China.A cross‐sectional study.Participants were 211 women with breast cancer who had received a one‐time dressing change postsurgery. Spearman's correlation and structural equation modelling were used for data analysis.Participants in the 35–45 age group and those who underwent bilateral mastectomy presented higher scores for hopelessness. Married participants showed lower scores for the feelings about the future subscale compared to other subscales. Body image was significantly and positively associated with and had a positive effect on hopelessness. Women with a more positive appraisal of their body image tended to report lower levels of hopelessness. Healthcare providers should evaluate patients’ distress levels after a mastectomy to identify women who may require early psychosocial intervention. The last inclusion criterion was a very specific one for this study; immediate post‐op period was defined as the period of time during women's surgical recovery in which they had already experienced a one‐time dressing change and had the chance to see the surgical scars over their chest wall. The exclusion criteria were (a) women who underwent breast reconstruction and breast‐conserving therapy; (b) having a severe mental health disorder; (c) not being able to read, understand or speak Chinese; (d) or having any other severe complications.In total, 230 questionnaires were distributed. Ten questionnaires had more than 50% of missing data, and nine survivors refused to participate. Thence, 211 survivors completed all questionnaires and had their data analysed. The participation rate was 91.7%.3.23.2.1The socio‐demographic information we collected included patients’ age, occupation, marital status, educational level, illness duration (months) and type of surgery .3.2.2The Beck Hopelessness Scale (BHS) was designed by Beck et al., . It meas3.2.3The BIBCQ was designed by Baxter . It is aIn our study, owing to the inclusion and exclusion criteria (i.e. only patients who underwent a mastectomy were included), we deleted some items about having a lumpectomy, a mastectomy with breast reconstruction and no breast surgical treatment . Thus, the total score of the modified questionnaire ranged from 48 to 240 (48 items). We used its Chinese version, which showed appropriate levels of reliability and validity in a Chinese sample  was used to test the effect of body image on hopelessness while controlling for participants’ socio‐demographic variables. The fit indices for the model were evaluated using the following criteria: χ2/df < 3, root‐mean‐square error of approximation (RMSEA) < 0.08 and the goodness‐of‐fit index (GFI), adjusted goodness‐of‐fit index (AGFI), comparative fit index (CFI) and Tucker–Lewis index (TLI) > 0.90.All statistical analyses were performed using SPSS 22.0 (IBM Corp.). Mean and standard deviations were used to report continuous data, and percentages were used to report categorical data. Kruskal–Wallis and Mann–Whitney tests were used to compare differences in hopelessness by participants’ socio‐demographic characteristics. Spearman's correlation analysis was used to explore the linear correlation between participants’ body image and hopelessness. Structural equation modelling , ranging from 29 to 77 years; the age group with the highest proportion was the 44–55 years group ; most completed primary (34.1%) and secondary school (37.9%); approximately a third (29.9%) were employed and most were married (87.7%).Participants’ socio‐demographic characteristics are presented in Table SD = 25.06), and the mean hopelessness score was 3.81 (SD = 3.48). Most participants reported minimal (0–3 scores) hopeless scores, accounting for 61.1% of the total sample.Moreover, participants who had been diagnosed with breast cancer for less than 6 months accounted for 84.4% of the total sample, and 89.6% had a unilateral mastectomy. Their mean body image score was 126.95 , higher scores for the loss of motivation  and higher scores for the expectations subscale ; participants who underwent bilateral mastectomy presented higher scores for hopelessness , higher scores for the feelings about the future  and higher scores for the expectations subscale ; married participants showed lower scores for the feelings about the future subscale compared to other subscales . There were no other significant differences in participants’ socio‐demographic factors.Participants’ scores in the BHS scale according to the three subscales and their socio‐demographic characteristics are presented in Table 4.2r = 0.423, p < .01) and its subscales .Table 4.3SEM to test the effect of body image on hopelessness. Owing to consideration of the covariance parameters problem, these were included in the model. The fit indices for the model were χ2 = 61.385, df = 38, χ2/df = 1.615 < 3, RMSEA = 0.054 < 0.08, GFI = 0.952, AGFI = 0.916, CFI = 0.968 and TLI = 0.954. The results suggested that body image had a positive effect on hopelessness .Figure 55.1Our results showed that participants had a mean hopelessness score of 3.81 ± 3.48; it was lower than that of Iranian breast cancer patients in a previous study (4.06 ± 2.67) , our sample experienced a relatively low sense of hopelessness. Thus, future longitudinal studies are warranted to explore the variance in breast cancer survivors’ hopelessness levels after surgery.Our results also showed that participants’ mean body image score was 126.95 ± 25.06; these scores were lower than those of a previous study conducted among breast cancer survivors on body image (137 ± 16.75) . Such negative outcomes, in turn, might disrupt Chinese women's common daily routine in the near future (e.g. daily work) causing them to experience more negative feelings about their future and lower expectations compared to unilateral breast cancer survivors, justifying these high scores.Additionally, single/divorced/widowed participants showed higher scores for the feelings about the future subscale (i.e. lower expectancies about the future) compared to married participants. This may be because of differences in access to social support for each of these socio‐demographic groups; women in such circumstances need to cope with the emotional effects of the illness and of the procedures undertaken, and being married denotes that they have better access to social support during this difficult time (e.g. from their husbands). Conversely, single/divorced/widowed women may have more difficulties in accessing such support. However, most studies do not find statistical differences about this subscale when comparing it by marital status ; this was corroborated by Öztunç et al.,  and hopelessness. This is corroborated by Avci et al.,  who foun6First, we did not include more detailed socio‐demographic variables to be compared with breast cancer survivors’ body image and hopelessness (e.g. caregivers’ attitude and behaviour); hence, future studies are warranted to compare these interest variables with a greater number of socio‐demographic characteristics.Second, the current study only investigated participants’ body image and hopelessness during a very specific period of time, and it used a cross‐sectional design; thus, generalizations should be made with caution, and our results do not denote any type of causality. Future longitudinal studies are warranted to clarify the fluctuations in body image and hopelessness scores of the studied sample over time.Third, our sample size was relatively small and a power calculation was not initially conducted; thus, future research with larger samples and power calculations before sample recruitment are warranted.Fourth, although the current study excluded patients with clinically diagnosed mental health problems, we did not use any type of measurement for depressive symptoms and anxiety levels, and these were not used as possible covariates; thus, future studies are warranted to analyse these covariates and assess for these psychological problems upon sample recruitment.7Our most meaningful result was that, although we did not have baseline information on our sample's body images prior to the surgery, breast cancer survivors’ bodily changes related to the surgical procedure may be associated with an increase in their body image scores—denoting higher body image problems. Moreover, such an increase was associated with increased hopelessness. These findings indicated that healthcare providers should pay attention when evaluating patients’ distress levels after a mastectomy procedure, as this may allow for identifying the most important issues they face after surgery. For example, rehabilitation exercises could improve breast cancer survivors’ upper limb function (Hong & Hui‐ling, 8Body image was significantly and positively associated with and had a positive effect on hopelessness among early‐stage breast cancer survivors in China. These findings suggest that breast cancer survivors’ positive reappraisal of body image may be associated with reduced hopelessness levels. However, the underlying mechanism of these associations is still poorly understood and warrants further study.The authors have declared no conflicts of interest.Qiong W. and Y.Y. contributed to conceptualization; Qiong W. and Y.Y. contributed to methodology; Qiong W. contributed to software; Qiong W. and Y.Y. contributed to validation; Qiong W. contributed to formal analysis; Qing W. and X.J. contributed to investigation; Qing W. and X.J. contributed to resources; Qiong W. contributed to data curation; Qiong W., Y.Y. and S.W. contributed to writing—original draft preparation; Y.Y. and Qing W. contributed to writing—review and editing; Qiong W. and S.W. contributed to visualization; Y.Y. and S.W. contributed to supervision; Y.Y. contributed to project administration; and Y.Y. contributed to funding acquisition.


The debate continues among medical professionals regarding the frequency, starting age, and stopping age for mammography screening. Some experts suggest tailoring recommendations based on individuals’ personal breast cancer risk. Previous studies have not compared the impact of annual versus biennial mammography stratified by age group and risk category. The purpose of this study was to examine the relationship between mammography frequency and mortality by age group and risk category in the California Teachers Study.Using data from study questionnaires from 93,438 women between the ages of 40 and 85 and linkages to the California Cancer Registry and other indices, overall and breast cancer-specific mortality by mammography frequency were estimated using multivariable Cox proportional hazards models, stratified by age group and risk category at baseline as determined by the Gail breast cancer risk model.During the follow-up period of 20 years, overall mortality risk was lower in women who had annual or biennial mammography compared to less frequent or no mammography in all age groups. Annual mammography was associated with lower overall mortality risk compared to biennial mammography among women age 50–85. This difference was especially apparent in women age 60–74, regardless of estimated Gail risk category at baseline. Breast cancer-specific mortality was lower among women who had annual mammography compared to biennial or less frequent mammography among women age 60–74, regardless of their baseline risk.Our findings suggest that at least biennial mammography is beneficial to most women age 40–85 and that annual mammography is more beneficial than biennial mammography to most women age 50–85 in terms of overall mortality.The online version contains supplementary material available at 10.1186/s12885-021-09071-1. Different professional and scientific organizations have different recommendations regarding the frequency, starting age, and stopping age for mammography screening in women. For example, currently the U.S. Preventive Services Task Force (USPSTF) recommends biennial mammography for most women age 50–74 , whereasSystematic reviews of randomized clinical trials have generally reported that screening in women age ≥ 40 is associated with decreased breast cancer mortality, with a larger magnitude of benefits observed in women age 50–69 compared to 40–49 –13. The While there have been studies examining the impact of getting mammography compared to not getting mammography on mortality in women with different risk statuses , 18, to https://www.calteachersstudy.org/past-questionnaires).The California Teachers Study (CTS) is a prospective cohort of current or retired female public school teachers and administrators who were members of the California State Teachers Retirement System at the time of study inception in 1995–1996. As previously described [n = 8851), had a history of breast cancer at baseline (n = 6216), were age < 40  or > 85 years (n = 1833) at baseline, whose follow-up were < 6 months (n = 407), those who had missing information regarding mammography use (n = 2407), and those whose baseline questionnaires were invalid or who withdrew from the study (n = 6). 93,438 women comprised our analytic cohort  were identified through annual linkage with the California Cancer Registry (CCR), a population-based, statewide cancer registration system that was legally mandated in California since 1988 and shown to be > 95% complete .Deaths were identified via linkage with the State of California mortality files, the Social Security Administration Death Master File and the National Death Index. For overall mortality analyses, follow-up for this analysis was from baseline questionnaire completion until the earliest of the following: date of death due to any cause, move outside of California, or December 31st, 2015. For breast cancer-specific mortality, follow-up was from baseline until the earliest of the following: date of death due to invasive breast cancer, move outside of California, death due to other causes, or December 31st, 2015.The main independent variable was derived from questions in the baseline questionnaire which asked if the participant had ever had a mammogram (yes/no) and how long it had been since her last mammogram . These questions served to estimate a woman’s approximate mammography frequency , 22. Forhttp://www.cancer.gov/bcrisktool/), which includes age, race/ethnicity, history of breast biopsies, age at menarche, age when the woman gave birth to her first child, and first-degree family history of breast cancer, based on the Gail model [Age at baseline was categorized into four groups: 40–49, 50–59, 60–74, and 75–85. Other covariates included race/ethnicity, alcohol consumption, body mass index, lifetime strenuous and moderate physical activity, smoking status, menopause status, comorbidities and hormone therapy use. Participants’ comorbid conditions  were collected from the baseline questionnaire and Office of Statewide Health Planning and Development (OSHPD) hospital discharge records from 1991 to 2015 . In addiil model , for eacChi-square tests were used in bivariate analyses to test for differences in demographic, behavioral characteristics and family history between mammography frequency groups. Overall and breast cancer-specific mortality rates were calculated for each age group. For each age group, time-to-event analysis was performed for the time from baseline to death or death due to breast cancer using Cox proportional hazards models. Participants who were alive at the end of follow-up were censored for overall mortality analysis. Participants who were alive or died from other causes were censored for breast cancer-specific mortality. Hazard ratios with 95% CI by mammography frequency were estimated adjusting for baseline age, race/ethnicity, alcohol intake, BMI, lifetime physical activity, smoking status, menopause and hormone therapy status, history of heart attack, history of stroke, history of diabetes, or history of any cancer. Time-to-event analysis was also performed stratified by high or low/average Gail risk groups.p-values were two-tailed. Statistical significance was defined as p ≤ 0.05. Data were analyzed using SAS and SAS/STAT Version 9.4 .All p-values ≤0.05), most notably by race/ethnicity, menopause/hormone therapy status, breast cancer family history, and Gail risk score. While differences were observed in all age groups, differences for some variables were most evident in women age 40–49. For example, among women age 40–49, 62.7% of women with at least one first-degree family member with breast cancer had annual mammography compared to 44.0% of women with no family history. Similarly, 69.5% of women in the highest quintile of Gail 5-year risk had annual mammography compared to 39.8% in the lowest quintile  . Univariate and multivariable analyses showed that overall mortality risk was statistically significantly higher in women in the never/less frequent group compared to the biennial and annual groups among all age groups (Table p < 0.05) in the high risk category.Stratified analysis revealed that the increased overall mortality risk in women in the never/less frequent group compared to the biennial group was observed among women in both risk categories among all age groups but statistically significantly in the low/average Gail risk score category  as well as in women age 75–85  and in women 60–85 in the high risk category . Among women age 40–49, there was no difference in overall mortality risk between women who had annual versus biennial mammography in either risk category.The decreased overall mortality risk in women age 50 years and older who had annual versus biennial mammograms remained statistically significant among women age 50–74 in the low/average risk category   are consistent with previous studies , 8 and m5 are conOur results that, among women age 60–74, annual mammography was associated with decreased mortality risk compared to biennial mammography, regardless of risk category, are also consistent with current ACR  and NCCNThe USPSTF stated that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women aged 75 years or older . HoweverWhile we elected to use the modified Gail model  because its ease of use and validation in multiple large population databases in the U.S. , it woul. Further, we performed a sensitivity analysis using this subset of Q1/Q5 participants who had not been diagnosed with breast cancer before Q5, which showed estimates from multivariable models for overall mortality using mammography frequency reported in Q5 were similar to those using mammography frequency reported in Q1 but were not statistically significant due to the smaller number of events (and shorter follow-up time) in this subset (unpublished data).Strengths of this study include the large, well-characterized prospective cohort, long follow-up time, high number of incident invasive breast cancer cases and deaths, and inclusion of major breast cancer risk factors including alcohol intake and physical activity in the multivariable analyses. The mortality outcomes were validated by linkage to the CCR and death indices as outlined in the Methods section. Limitations include that the participants were mostly non-Hispanic white, educated, and had health insurance. 87.7% of women age ≥ 40 in our cohort reported having had a mammogram within the past two years (of 1995–1996), compared to the national statistic of 60.9% in 1994 . Thus, tLastly, our study did not address potential harms of more frequent mammography, for example, false positive results, over-diagnosis, and decreased quality-adjusted life expectancy. However, these issues were not within the scope of this study, nor were other issues related to policy making. With that said, simulation modeling has shown that women who had higher breast cancer risk had lower rates of false positives and higher gains from screening than lower risk groups .Our findings suggest that most women age 40–85 would benefit from biennial mammography compared to never/less frequent mammography in terms of overall mortality risk. Further, most women age 50–85 would likely benefit from annual mammography compared to biennial mammography. Among women age 60–74, decreased mortality risk with annual mammography was seen among women in both high and low/average Gail risk categories. Further studies are needed to examine these associations stratified by risk categorizations based on different breast cancer risk models.Additional file 1: S1 Table. Baseline characteristics of 93,438 participants from California Teacher Study by age group.


Breast cancer is the most common tumor in women worldwide, and an increasing public health concern. Knowledge of both protective and negative risk factors is essential for a better understanding of this heterogenous disease. We undertook a review of the recent literature and evaluated the relationship between obesity mediators and breast cancer development depending on menopausal status. Excess weight is now pandemic and has replaced tobacco as the main lifestyle-related risk factor for premature death. Although the prevalence of obesity/overweight has increased globally over the last 50 years, the potential harm attributable to excess fat has generally been underestimated. The relationship between overweight/obesity, breast cancer and overall risk appears to be highly dependent on menopausal status. Thus, obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women. We evaluate the role of different clinical factors potentially involved in this seemingly contradictory relationship, including estrogen, mammogram density, adipokines, insulin-signaling pathway activation, and inflammatory status. A key focus of this review is to better understand the impact of body mass index and menopausal status on these clinical factors and, hence, provide some clarity into the inter-relationships involved in this controversial issue. The incidence of obesity has nearly tripled since 1975 and it is now considered one of the worst pandemics of the 21th century. In 2016, more than 1.9 billion people aged over 18 years were considered to be overweight, and >650 million were obese; representing 39% and 13% of the adult global population, respectively  of the global adult population failed to get enough physical activity with the highest prevalence 43%) in women, particularly in high-income countries  and/or progesterone-receptor (PR) positive breast cancer was associated with BMI in all age groups, whereas hormone-receptor negative breast cancer was associated with BMI only in women aged 18-24 years. In this younger age group, the strength of the association between ER- and/or PR-receptor positive breast cancer and BMI  was much stronger than that for ER- and PR-receptor negative breast cancer . The lack of association of triple-negative breast cancer with BMI in women above 25 years-of-age was contrary to previous reports   aged 50-64 years for a mean period of 5.4 years. The study identified an approximate 30% higher risk of breast cancer in postmenopausal women with obesity compared to women who were not obese  . These f<0.0001) , 16.Why obesity is a risk factor for breast cancer in postmenopausal women, but appears to be protective during premenopause is clearly an important question. A better understanding of the mechanisms involved could provide significant clues to the underlying pathophysiology and have clinical implications for breast cancer prevention and treatment. Mapping the precise cellular and molecular landscape of breast tissue in the context of an evolving physiology has shed light into potential driving factors responsible for breast cancer risk and progression; including the role of serum estrogens, leptin and adiponectin imbalances, mammogram density, insulin deregulation pathways and chronic inflammation.Physiologically, estrogen production decreases during aging, with the natural consequence that postmenopausal women have lower blood levels of estrogenic hormones, such as estradiol, relative to premenopausal women. Estrogen synthesis in premenopausal women mainly localizes to the ovary, whereas in postmenopausal women estrogen production shifts to peripheral tissues. In postmenopausal women with obesity the main source of estrogen biosynthesis is adipose tissue.The primary mediator of postmenopausal estrogen biosynthesis is aromatase , an enzymatic complex found both in breast adipose and tumor tissues . AromataSeveral meta-analyses of prospective studies have confirmed a relationship between increased serum estrogen levels and postmenopausal breast cancer –24. Alth® Atlas, Breast Imaging Reporting and Data System) which describes 4 categories for breast density: a). almost entirely fatty; b). scattered fibroglandular tissue; c). heterogeneously dense fibroglandular tissue; and d). extremely dense fibroglandular tissue (Mammographic breast density (MBD) is defined by the proportion of glandular to fatty tissue and is usually classified using a scoring classification proposed by the American College of Radiology , stromal fibrosis and/or epithelial hyperplasia; all of which represent potential breast cancer risk factors . AnotherIn general, MBD correlates negatively with BMI; i.e., women who are obese or overweight have lower breast density than leaner women. The seemingly paradoxical relationship between obesity, breast density, and breast cancer risk lies in the fact that although adiposity has a positive correlation with absolute non-dense area and is a recognized risk factor for breast cancer, some reports indicate that absolute non-dense area correlates negatively with breast cancer risk . In thisThere is a tendency for MBD to decrease with age, while breast cancer incidence generally increases. This apparent contradiction fundamentally reflects that “true” breast tissue-age possibly results from the cumulative exposure to changing patterns of hormone and growth factor secretion and levels over time, rather than absolute age.Breast tissue is primarily composed of adipose and fibrous tissue, and mammary glands. Adipose tissue acts as an energy reservoir, but it is also responsible for the secretion of a variety of metabolites, hormones, and cytokines, collectively known as adipokines, and in this regard it can be considered as a complex endocrine organ . In humavia two adiponectin receptors, AdipoR1 and AdipoR2 , which circulates in the plasma as low- and high-molecular weight multimers . Plasma  AdipoR2 . Activat AdipoR2 . AMPK-me AdipoR2 . In brea AdipoR2 .Current data in support of a direct involvement of adiponectin in breast cancer is controversial. A meta-analysis by Gu et al. showed that serum adiponectin levels were lower in breast cancer patients irrespective of menopausal status; however, no information on BMI was collected . In contAnother adipokine, leptin, also represents a key molecular mediator in the relationship between obesity and breast cancer. Leptin is a hormone predominantly produced by adipocytes in healthy and malignant tissue and is overexpressed in individuals who are obese/overweight. Serum levels in humans usually range between 5–50 ng/ml, but in individuals with obesity, concentrations can exceed 100 ng/mL .Leptin displays pleiotropic effects and regulates adipose and breast tissue cell proliferation. Upon binding to its receptor ObR, leptin activates JAK2/STAT3, MAPK, and PI3K/Akt signaling pathways to promote cell proliferation, hence acting as a growth-factor in cancer and involved in regulating tumor development, growth, and metastasis , 49. LepSeveral studies strongly support the hypothesis that serum leptin levels correlate with breast cancer occurrence and tumor behavior , 53. To Insulin is a peptide hormone synthesised by islet β-cells in the pancreas in response to elevations of glucose. Insulin regulates glucose uptake by muscle and adipose tissue and inhibits gluconeogenesis and glucose secretion by the liver. High insulin levels lead to an overload of glucose stores in liver and muscle. In addition to glucose homeostasis, insulin facilitates fatty acid transport, promotes lipogenesis, and inhibits lipolysis, thus contributing to the build-up of energy stores ready for mobilisation when insulin levels are low  .Under certain physiological and pathological conditions, cells may become less responsive to insulin and they eventually develop insulin resistance, causing both insulin and serum glucose levels to increase . Such ouWhen assessing type 2 diabetes as a risk factor for breast cancer the results appear to vary according to menopausal status. For example, a meta-analysis of 20 studies from nine different countries showed a 20% increase in breast cancer risk, independent of BMI, in postmenopausal women with diabetes compared with individuals who were not diabetic; significance was lost in premenopausal women . LikewisInsulin receptors are usually 6- to 10-fold overexpressed in breast cancer epithelial cells compared to healthy cells . AlthougWhite adipocyte tissue (WAT) comprises the largest energy storage and the major endo- and paracrine organ in the human body. WAT consists of a variety of cell types  and these support tissue homeostasis and insulin sensitivity. In healthy-weight individuals, adipose tissue is well vascularized and the microenvironment is rich in anti-inflammatory cytokines such as IL-4, IL-10 and IL-13. WAT contains a variety of type 2 immune cells, including alternatively activated (M2-like) macrophages, group 2 innate lymphoid cells, type 2 T helper (TH2) cells and IL-4-producing eosinophils. Thus, in healthy individuals the adipose tissue molecular milieu is largely comprised of anti-inflammatory immune cells and cytokines . Weight 2) individuals (p<0.001). The results remained statistically significant in a multivariate model after adjusting for age, menopausal status, and use of non-steroidal anti-inflammatory drugs (NSAIDs) or statins (p<0.001). The authors noted that WAT inflammation and the presence of CLS-B is associated with elevated tissue levels of proinflammatory mediators and aromatase (the rate-limiting enzyme for estrogen biosynthesis), and this provides a plausible explanation for the paradoxical observation that hormone-dependent tumors are more common during the age-related menopausal transition when circulating estrogen levels have declined  or to reduce the risk of (n=26) breast cancer, and evaluated WAT inflammation as manifested by CLS-B (crown-like structures in the breast) . Overalldeclined .Both adipocytes and macrophages release pro-inflammatory mediators associated with WAT inflammation such as TNF-α, IL-1β, IL-6 and COX-2–derived prostaglandin E2, which can upregulate aromatase expression . AromataThe precise mechanisms whereby obesity plays a protective role against breast cancer in premenopausal women, but represents a risk factor after the menopause remain elusive . ChronicIt seems clear that the combination of oestrogens and obesity are able to protect against breast cancer, however the mechanism by which this interaction occurs is yet unknown. Zhao et al. conducted a study to address the impact of obesity in the breast according to menopausal status . Random via mTOR (Regarding adipokines, there exists a distinct relationship between leptin/adiponectin and breast cancer in postmenopausal women and such an association is far from clear in premenopausal women . Accordivia mTOR . AdiponeIn contrast to this hypothesis is the case-control study by Tworoger et al. showing a positive although non-significant association between adiponectin levels and breast cancer in premenopausal women; this suggests a differential role for the adipokine in breast tissue according to menopausal status .Obesity can have a marked impact in women since it is associated with an increased risk for many chronic conditions such as diabetes and heart disease, as well as it increases the risk of malignancies such as breast cancer. Whilst most evidence suggests an inverse relationship between obesity and breast cancer risk during premenopause, no clinical strategy could contemplate weight-gain as a therapeutic approach taking into consideration the complications associated with excess fat and the risk of perpetuating a state of overweight through menopausal transition and into the menopause itself. The metabolic and cardiovascular risks associated with excessive weight would undoubtedly exceed any benefits achieved for breast cancer. Of greater importance is to research and fully understand the complex interplay between the various metabolic and hormonal factors involved, since this could potentially help define possible alternative treatment strategies. In an obese environment, the relationship between estrogens and adipokines and the activation of specific signaling pathways clearly differs between menopausal stages, and this is an area where future research can help determine the molecular/biochemical processes involved. Ultimately, a better knowledge of how obesity and adipose tissue inflammation interact with female sex hormones, and how these changes affect the pathogenesis of breast cancer, should enable us to develop new therapeutic strategies to reduce breast cancer risk and improve patient outcomes in individuals who are obese.LG-E and GM-B designed and wrote the manuscript. All authors provided editorial support and read the manuscript. All authors contributed to the article and approved the submitted version.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


RealRisks is a patient-centered, web-based decision aid (DA) designed to promote the understanding of breast cancer risk and to engage diverse women in planning a preference-sensitive course of decision making about taking chemoprevention.Chemopreventive agents such as selective estrogen receptor modulators and aromatase inhibitors have proven efficacy in reducing breast cancer risk by 41% to 79% in high-risk women. Women at high risk of developing breast cancer face the complex decision of whether to take selective estrogen receptor modulators or aromatase inhibitors for breast cancer chemoprevention. RealRisks—a DA designed to promote the uptake of breast cancer chemoprevention—and to understand their information needs.This study aims to understand the perceptions of women at high risk of developing breast cancer regarding their experience with using RealRisks. We conducted semistructured interviews with a subset of 21 high-risk women enrolled in the intervention arm of the randomized controlled trial who initially accessed the tool  to understand how they interacted with the tool. All interviews were audio recorded, transcribed verbatim, and compared with digital audio recordings to ensure the accuracy of the content. We used content analysis to generate themes.We completed enrollment to a randomized controlled trial among 300 racially and ethnically diverse women at high risk of breast cancer who were assigned to standard educational materials alone or such materials in combination with RealRisks after being granted access to the DA. In total, 4 overarching themes emerged from the qualitative analyses: the acceptability of the intervention, specifically endorsed elements of the DA, recommendations for improvements, and information needs. All women found RealRisks to be acceptable and considered it to be helpful . Most women  reported that RealRisks was easy to navigate, user-friendly, and easily accessible on the web. The majority of women  felt that RealRisks improved their knowledge about breast cancer risk and chemoprevention options and that RealRisks informed their  decision about whether or not to take chemoprevention. Some women  shared recommendations for improvements, as they wanted more tailoring based on user characteristics, felt that the DA was targeting a narrow population of Hispanic or Latina by using graphic novel–style narratives, wanted more understandable terminology, and felt that the tool placed a strong emphasis on chemoprevention drugs.The mean age of the 21 participants was 58.5 (SD 10.1) years. The participants were 5% (1/21) Asian, 24% (5/21) Black or African American, and 71% (15/21) White; 10% (2/21) of participants were Hispanic or Latina. All participants reported using RealRisks web-based DA among a diverse group of high-risk women, who provided some recommendations for improvement.This qualitative study demonstrated the acceptability of the  Breast cancer is the most commonly diagnosed cancer among women in the United States and the second leading cause of cancer-related deaths; therefore, prevention of the disease would significantly improve public health . An estiPatient-level barriers to chemoprevention uptake include inadequate knowledge and negative attitudes, the fear of potential side effects, and inaccurate perceptions of breast cancer risk ,12. Prev, RealRisks, which is currently being tested in 3 clinical trials . And I do feel that I got information that I would not have gotten otherwise. I mean, I felt a little bit more informed. So, I’m happy about that.Participant #18RealRisks was easy to navigate. For instance, women shared the following:Most women  felt that It was pretty simple and easy to do, and I didn’t feel like there were a lot of issues with using the tool and taking the surveys at all...I didn’t find it to be off putting. I didn’t find it to be hard to do. I didn’t find it to suck up a lot of my time.Participant #27It was easy to access. The instructions were pretty good...Simple and basic and not overwhelming and I like the fact that if you didn’t know something you could just hover over a term and you could get a definition.Participant #26I liked the fact that it was quick. I was able to just go through it.Participant #21I thought it was easy to use. It answered the questions that I would have. Like it was very thorough in the questions, so I didn’t have to wonder what it meant. It wasn’t up for interpretation. I thought it was pretty clear.Participant #25None of the women who used the DA reported encountering any technological issues. One woman stated:No. I was able to get in. I was able to answer all the questions. I don’t remember any glitches at all.Participant #15Other women felt that the DA was user-friendly, straightforward, simple to follow, and easy to understand. They shared the following:It was pretty easy to understand. I have no medical background and it gave, I thought, very clear, information about how different drugs could help. And then I could answer the questions that came next.Participant #23Pretty easy. Sort of user-friendly in terms of just accessing all the steps.Participant #18It was simple to follow-simple to use. It didn’t take up too much time. I mean, it’s been a while. It’s been over a year, right? But I remember just being able to just quickly go on my tablet and answer the questions.Participant #7I thought it was easy to understand and to complete. I thought it was pretty user-friendly for someone like myself.Participant #5RealRisks. The exceptions were 2 Spanish-speaking participants who reported having no access to a computer at home and came to the hospital to receive in-person support to access the tool from one of our research team members. The women who had access to technology liked that the DA was web-based, which allowed them to access it on the web at their own convenience. For example, women shared the following:Most women  reported having access to technological devices such as cell phones, tablets, laptops, and desktop computers to access It was easy because I could do it online. You know, I could like start it at work. I could finish it at home. I did not have to go back and re-answer questions. I thought it was user-friendly.Participant #1I could do it online, could start it at work and finish it at home.Participant #2It was good that it was online and it was easy to navigate.Participant #14I didn’t really have any trouble following through. But, you know, I guess, with everything that’s done online, you’re doing it on your own time.Participant #18RealRisks. A total of 11 women described learning new information about breast cancer prevention drugs. The participants described learning new information such as which chemoprevention drug was appropriate for them, for example, tamoxifen and other available drugs. Other women described learning which drug was appropriate for premenopausal and postmenopausal women. The women described the following:Most women  described gaining new knowledge after using New information was the information around the drugs to take. I can’t remember what they were called, but the preventive, I guess that’s what they are, drugs.Participant #5I knew about the existence of the drug, tamoxifen. I know it opposes estrogen. An anti-estrogen-type drug. I did not know about other drugs. So that was new information.Participant #24RealRisks reinforced some of the information that they had already heard from their health care providers, which contributed to an improvement in their overall knowledge:In total, 2 of these women explained that Being diagnosed with the BRCA2 gene mutation, I was getting so much information at that time and doing so much research and meeting with so many different doctors because of trying to be very, very proactive about being diagnosed with the BRCA2 gene that it actually turned out to have been helpful in terms of reinforcing some ideas that I didn’t necessarily—that hadn’t quite sunk in yet.Participant #8risk of breast cancer. These women stated that they now understood the factors contributing to risk, such as genetics, personal history, family history, and lifestyle factors. One woman appreciated the way RealRisks presented risk information in a story format. Another woman who had a pathogenic variant in the BRCA2 gene felt that RealRisks was thought provoking. The women learned actions that they could take to reduce their risk and shared the following:A total of 8 women described learning about their Oh, it made me think about what the risks are, specifically having to do with my situation and being in a high-risk category...Well, I guess I surmised that I was high risk, given my family history. But it solidified that, and it also taught me about options that were available to me should I choose them to reduce my risk.Participant #15I like the way that it was set up, as a possibility of being at risk, and that was for me, a sensitive issue...I remember there was a story—the way that it was presented by story. So it became more real rather than just the data, medical data, and to try to identify through the just numbers. It was like real.Participant #17RealRisks reported that the DA played a role in informing their decision making about chemoprevention. The women reviewed the modules in RealRisks and became familiar with the options that exist to reduce their breast cancer risk, including developing an understanding of the benefits and risks of taking a chemoprevention pill. The women explained:Most women  who used Yes, because the information that was provided was thorough. I mean, there was plenty of it. And I feel comfortable that—I’ve seen both sides of it. I could see why a person would take it. I believe I have made an informed decision.Participant #6I think it is because I did not know about it [chemoprevention] until I saw RealRisks. But definitely it played into it [my decision-making]. And I didn’t really look into it because I thought I wasn’t really the best person to be eligible for it. And now I know I do have an elevated risk.Participant #20healthy and decided not to take chemoprevention, their experience with using RealRisks informed an autonomous decision about whether chemoprevention was the right choice for them:Although 95% (20/21) of the women in the study viewed themselves as I made a decision for who I am and what I want right now. So I didn’t ask my doctor. I didn’t ask anyone. I just made the decision by myself. I just took my decision because I don’t want to put anything in my body. That’s it.Participant #9I remember when they talked about the differing types of procedures you could go through to help prevent breast cancer. It was in-depth and I read it all but I was not in agreement with taking any kind of medicine...It was very informative, and I think if I was in poorer health, I would probably be willing to try anything. But my health is relatively good.Participant #22RealRisks, some women  pointed out aspects of the DA that they did not like and shared recommendations for improvement.In addition to positive perceptions about RealRisks appeared to be tailored for Hispanic or Latina women. The women recognized that it was difficult to design a tool for diverse target audiences, especially those with varying health literacy and numeracy. One woman felt that RealRisks was designed for people who were not native English speakers. Another woman who was not of Hispanic descent was confused as to why Hispanic characters were used in the illustrations. In addition, 3 women shared that the comics were not appealing to them:Some women  who were not of Hispanic or Latina descent were concerned that It was trying so hard to be ethnically diverse. It felt like it might have been for people where English was not their original language.Participant #8Found it interesting that if you’re going to draw pictures of—I actually discussed this with my doctor. If you’re going to draw pictures of people, it’s hard not to racially profile. Even though it was a line drawing, it clearly looked like a person of color. So I mean, not that it meant any good or bad to me.Participant #24A few women  felt that the DA made assumptions about where they were in the care continuum and did not give them the opportunity to input their own risk factors. For instance, women shared the following:There was not an opportunity to discuss why I didn’t think I was at risk. I felt that there were assumptions made about me without even simply asking. For example, cigarette smoking causes a great deal of cancers and I do not smoke.Participant #6Some of it did not apply to me because I was already under care. I was already diagnosed with a BRCA2 gene mutation and already had surgery and already in the middle of this. But it wasn’t quite flexible enough...I sort of stepped into the RealRisks halfway through if you know—I didn’t need to assess my risk.Participant #8RealRisks included difficult terminology, and the content was not written in layman’s terms. Of these 3 women, 2 (66%) stated that if they were not intelligent, it would have been difficult to understand the information in RealRisks. The participants explained the following:In total, 33% (3/9) of women felt that I did find some of the terminology a little difficult, because I wasn’t familiar with some things. I do remember like, having to look some things up, particularly when it came to the treatment options.Participant #7The language used in RealRisks was not layman’s language. If I wasn’t intelligent, I wouldn’t have understood it all. Maybe it was like reading The Times paper.Participant #22For me, being a white, middle-class, Jewish college-educated woman, I had no trouble with it. But I wouldn’t want to speak for other cultures. I am married to a Puerto Rican man and like I could see where his mother, if she were reading this, would’ve really—she might’ve struggled...I think it tried to be very clear and very easy to understand, but I don’t know, I think it can be hard for people—sometimes the way people have a block on math, sometimes when they read about medical things they get a bit of a block.Participant #23RealRisks DA placed a strong emphasis on chemoprevention drugs. Despite the importance of these drugs, these 2 women felt that they would have preferred more emphasis on the lifestyle and environmental factors affecting breast cancer risk:Overall, 22% (2/9) of women felt that the I have two graduate degrees. I’m not saying this to brag. I taught college for many years. So I thought the graphics and the cartoons and all of that, were useful in general, not necessarily for myself. I felt a little bit that the chemoprevention was being pushed.Participant #5I felt, throughout the whole process that it was very much pushing some type of drug on me, that I felt I wasn’t really ready to consider that.Participant #24Participants were asked “what additional information do you need to make decisions about reducing your breast cancer risk?” With respect to women’s information needs, 33% (7/21) of women described at least one unmet need. One woman wanted to learn more about mammography screening:I was having this conversation with my sister recently. Because so much of the information around mammography and the frequency of mammography is changing. And so I was just having this conversation with her, that, you know, should I still be getting a yearly mammogram, I know that, age-wise, I think someone my age, and probably, with our risk, we should be getting it. But I feel like, because a lot of the information is changing, there is some confusion in terms of trying to make a decision about certain things.Participant #5Other women were interested in learning more about breast cancer risk factors, including modifiable lifestyle factors. Some women still desired to understand their individual breast cancer risk and what puts a woman at high risk of developing breast cancer. For example, women shared the following:Well, I think the only information I would need or want would be during the course of my visits with my doctor is to go over my lifestyle, and just to find out if there’s any additional information that’s become available. And if there’s any additional thoughts on the benefits or risks of taking the medications. I would always consider it as I get older.Participant #26It’s a good question. I guess, printed materials probably, maybe like how to avoid putting myself in harm’s way, stuff that you can prevent. You know, I mean, of course there’s a lot of stuff that you can’t prevent. But I mean, if it proves that, if there was a reason for them to say, “Oh, yeah, you’re at really high risk,” I, you know, I would do whatever and apply what was suggested.Participant #4Probably just you know, a one-page outline of all the risks, you know, maybe just outlining everything in a concise way so that I could look at it and just know what the risks are and just have it—just be more conscious of what the risks are on a day-to-day basis and without having to go through a lot of reading and stuff.Participant #18RealRisks. The high-risk women who participated in the intervention arm of the chemoprevention trial and were granted access to the DA reported that they generally liked the DA and considered it to be helpful. This result confirms the need for decision support for women at a high risk of developing breast cancer. In line with our objective to understand the perceptions of women at high risk of developing breast cancer regarding their experience with using RealRisks, our analysis generated 4 themes:In our racially and ethnically diverse sample of women at high risk of developing breast cancer, all participants reported that they used the web-based DA The acceptability of the intervention: women found the tool to be acceptable, easy to navigate, user-friendly, and easily accessible on the web.Specifically endorsed elements of the DA: the DA was favored for its ability to improve knowledge and inform decision making.Recommendations for improvement: participants wanted more tailoring based on user characteristics.Information needs: participants reported wanting to learn more about mammography screening and breast cancer risk factors, including modifiable lifestyle factors.RealRisks to be an acceptable intervention and had positive attitudes overall. The web-based nature of the intervention was very appealing to participants who appreciated being able to access the tool at their own convenience. In addition, the tool was acceptable to women in a variety of age groups, as the average age of our participants was 58.6 years (SD 10.1). Regarding theme 2, the women reported that RealRisks increased their knowledge about chemoprevention. This finding is aligned with the results of our pilot study, which found an increase in chemoprevention knowledge after exposure to RealRisks [RealRisks DA is aligned with the SDT, the underlining premise of the DA [Regarding theme 1, participants found ealRisks . The obsf the DA . SDT, a f the DA . TherefoRealRisks may consider incorporating tailoring with a broader focus on breast cancer risk reduction and should incorporate guidance on other breast cancer risk factors.Regarding theme 3, despite the general acceptability of the DA, high-risk women wanted a more holistic approach to reducing their breast cancer risk based on tailoring that incorporates user characteristics . The womOur study has several important strengths and limitations. A strength of this study is that we had about 40%  racial and ethnic minorities, which is representative of the US population. However, we only included participants from the intervention arm of the chemoprevention trial who had accessed the tool, on average, 1 year earlier and, therefore, may have experienced recall bias. In addition, this study was conducted at a large urban academic medical center, which may not be generalizable to other geographic and practice settings.RealRisks, which will provide evidence-based information on mammography screening and other methods of breast imaging.Future studies should focus on developing interventions that target the knowledge gaps identified in this study and meet the needs of high-risk women to empower them to make informed decisions about reducing their breast cancer risk. Our research group is currently developing a breast cancer screening module to be added to RealRisks web-based DA among a diverse group of high-risk women, with a few caveats and recommendations for improvement. Women’s perceptions about RealRisks were influenced by the tool’s ability to increase their knowledge about breast cancer risk and the pros and cons of taking chemoprevention drugs; they indicated that this information facilitated their informed decision making about taking chemoprevention. We found that after using the DA, women wanted a more tailored and holistic approach to reducing breast cancer risk. The findings will inform the future development of the web-based DA. Next steps include translating the results from this study into further development of the DA and optimizing the tool’s module architecture to add a breast cancer screening module.This study has demonstrated the acceptability of the


Leptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk.In the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (BMI), waist–hip rate (WHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant-associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database.2 or WHR ≥ 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data.There were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101  and rs4655555  significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI ≤ 24 kg/mOur study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer. According to Global Cancer Statistics 2021, breast cancer is the most commonly diagnosed cancer worldwide, which accounts for 30% of all new cancers in women. Furthermore, breast cancer is the second leading cause of cancer death among women . Based oLeptin (LEP), the circulating product of the obesity gene, is a 16-kDa glycoprotein expressed and secreted primarily by the adipocyte. LEP plays an important role in body weight homeostasis by influencing food intake and energy expenditure and maintaining constant energy stores . In addiThe expressions of LEP and LEPR were associated with enhanced cell proliferation and angiogenesis in both benign and malignant breast epithelial cells –17. HighStudies have identified genetic variants of LEP and LEPR correlated with susceptibility of various malignant tumors, including breast cancer , 23. SevCharacteristics of the study participants have been reported previously . BrieflyPersonal information and samples from each participant were obtained after signing the informed consent. The demographic information and lifestyle habits of the participants, clinical data including age, body mass index (BMI), waist–hip rate (WHR), personal medical history, family backgrounds, the clinical examination results of visual examination, palpation, and related diagnostic tests such as breast ultrasound and mammography were documented. The statuses of the estrogen receptor (ER) and progesterone receptor (PR) were determined by immunohistochemical staining and obtained from the patients’ medical records. According to the American Society of Clinical Oncology/College of American Pathologists (2020) guideline recommendations, samples with 1% to 100% of tumor nuclei positive for ER or PR are interpreted as positive . For eachttps://www.ncbi.nlm.nih.gov/snp/), which were selected for further analysis. All participants were genotyped using the Sequenom MassARRAY SNP system , as previously described . According to previous studies, 7 SNPs were reported in relation with obesity, weight, or cancer risk including rs10244329 , rs21672escribed .2 tests were used to compare the differences in demographic and lifestyle data between the case and control groups. A population representative was detected using Hardy–Weinberg equilibrium (HWE) in the control group. Unconditional logistics regression was used to assess the co-dominant (heterozygous or mutant homozygous vs. wild-type homozygous), dominant (heterozygous and mutant homozygous vs. wild-type homozygous), and recessive (mutant homozygous vs. wild-type homozygous and heterozygous) models of genetic variants and breast cancer risk. Odds ratios (OR) with 95% confidence interval (95% CI) were estimated after adjustment for menstrual status and family history of breast cancer. Subjects were further stratified into subgroups according to BMI, WHR, ER, and PR statuses. Bonferroni correction was used to adjust for multiple testing, and the level of significance was set at α < 0.01 (0.05/5) for testing the five loci of LEP and α < 0.025 (0.05/2) for testing the two loci of LEPR.SPSS 26.0 statistical software  was used to analyze the data. Among them, χhttps://portal.gdc.cancer.gov/) were further analyzed by using the two-tailed paired Wilcoxon rank-sum test. The association between related genes and the survival rate of breast cancer patients were analyzed by the Kaplan–Meier survival analysis based on TCGA Breast Invasive Carcinoma (TCGA-BRCA) data. The curves were generated with an optimum cutoff value for LEPR or LEPROT expression. A p-value < 0.05 was considered as statistically significant unless otherwise specified.The eQTLGen database was used to identify affected genes related to the risk SNPs . The expIn this study, we enrolled 963 controls and 953 cases. The general demographic characteristics of the participants are presented in The association of LEP and LEPR SNP genotypes with breast cancer risk after adjustments for risk factors, including menstrual status and family history of breast cancer, is shown in Among the 953 cases, 848 (89.0%) patients had explicit joint ER and PR statuses. Overall, 572 (60.0%) cases were ER+/PR+, 189 (19.8%) cases were ER-/PR-, 72 (7.6%) cases were ER+/PR−, and 15 (1.6%) cases were ER-/PR+. Due to the limited sample size, we excluded ER+/PR- and ER-/PR+ cases for further analysis. The association between the genotypes of LEP/LEPR and the risk of ER+/PR+ or ER-/PR- cases is shown in We further performed stratified analysis to determine the association between LEP/LEPR polymorphisms and breast cancer risk according to obesity indicators including BMI and WHR  were associated with rs4655555 based on the eQTLGen database   of 1.68 (95% CI: 1.01–2.80) , a missense SNP, has been analyzed for the correlation with cancer risk and development; however, the previous results were not consistent. In the current study, we found that the GA and GA+AA genotypes of rs1137101 were associated with decreased breast cancer risk. Some previous case–control studies reported that the A allele of rs1137101 is a protective factor against cancer occurrence , 40, 41,2 and WHR ≥ 0.85, adjusted OR = 0.446, 95% CI: 0.264–0.754, p = 0.003), which was the indicator of central obesity. Our previous study indicated that central obesity was positive with ER-/PR- breast cancer risk , XM, and SH wrote the first draft of the manuscript. LY, FZ, and CZ contributed to the manuscript revision and statistical analyses. YX, WZZ, CY, GY, and ZM contributed to the DNA extraction. SC, FT, ZF, CG, XC, ZLY, XW, HL, SW, HJ, XD, HW, GL, QW, JZ, FJ, JT, LL (27th author), SZ, and WSZ contributed to the collection of the data and biological samples. All authors contributed to the manuscript revision and read and approved the submitted version.This study was funded by the National Natural Science Foundation of China (82072914), Natural Science Foundation of Shandong Province (ZR2019PH016), and National Key Research and Development Program of China (2016YFC0901300).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Carriers of pathogenic variants causing hereditary breast and ovarian cancer (HBOC) are confronted with a high risk to develop malignancies early in life. The present study aimed to determine the type of psychological distress and coping ability in women with a suspicion of HBOC. In particular, we were interested if the self-assessed genetic risk had an influence on health concerns and coping ability. Using a questionnaire established by the German HBOC Consortium, we investigated 255 women with breast cancer and 161 healthy women before they were seen for genetic counseling. The group of healthy women was divided into groups of high and low self-assessed risk. In our study, healthy women with a high self-assessed risk stated the highest stress level and worries about their health and future. A quarter of the women requested psychological support. Overall, only few women (4–11%) stated that they did not feel able to cope with the genetic test result. More women  worried about the coping ability of relatives. The results of our exploratory study demonstrate that the women, who presented at the Department of Human Genetics, Hanover Medical School, Germany were aware of their genetic risk and had severe concerns about their future health, but still felt able to cope with the genetic test result. BRCA1 and BRCA2 and up to 15% by other HBOC risk genes  [BRCA1-pathogenic variant range from 65% to 79% for breast cancer and from 36% to 53% for ovarian cancer [BRCA1 and BRCA2 are referred to an intensified surveillance, including clinical examination, ultrasound, mammography and MRI scan in order to detect breast cancer at an early stage. Furthermore, prophylactic surgery, i.e., salpingo-oophorectomy, is recommended to them [BRCA1- or BRCA2-pathogenic variant can be severely distressing as it means living with a lifelong risk of developing cancer [Breast and ovarian cancers are among the most common cancers in women in the developed world . Approxin cancer . These ig cancer . There hg cancer .Psychological distress is a broad term that commonly includes anxiety, stress, worry, panic, and fears . In thisInitial inclusion criteria covered women between the age of 18 and 80 years with suspected HBOC, who presented at the Department of Human Genetics, Hanover Medical School for genetic counseling and genetic testing. Exclusion criteria were insufficient German language skills. Between 2012 and 2017, 416 women were included in the study. The suspicion of HBOC was defined according to the criteria of the German Consortium of HBOC (2012–2017):⁃three women with breast cancer or⁃two women with breast cancer, one of them under the age of 51 years or⁃one woman with breast cancer and one woman with ovarian cancer or⁃two women with ovarian cancer or⁃one woman with breast cancer and one man with breast cancer or⁃one woman with ovarian cancer and one man with breast cancer or⁃one woman with breast cancer under the age of 36 years or⁃one woman with bilateral breast cancer and first diagnosis with 50 years or before or⁃one woman with breast and ovarian cancer.(1) For Index patients, the family had to fulfill the following criteria:(2) Women, in whose family no Index patients were alive or present and risk calculation of heterozygote risk (HZR) and breast cancer lifetime risk (LZR) using pedigree risk calculation program CYRILLIC 2.1 was HZR >= 20% and/or LZR => 30%(3) Women, in whose family a pathogenic variant had been detected before.BRCA1, BRCA2, CHEK2, in case of additional ovarian cancer; additionally, RAD51C. In 2016 and the following years, the gene panel was continually expanded for several more genes including PALB2, ATM, CDH1, NBN, RAD51D, and TP53. All women provided written consent, approved by the Ethics Committee of Hannover Medical School . Sociodemographic variables, such as age, parenthood, and family history of cancer, were pseudonymized.For women, in whose family a pathogenic variant had been diagnosed before (3) a predictive test was offered. For index patients (1) and healthy women (2) fulfilling the criteria given above a diagnostic test was offered. The following genes were analyzed in 2012–2016: The questionnaire was developed and validated by psychologists and other members of the German HBOC Consortium . The queM) and standard deviations (SD) for numeric data, differences between the three groups and between respondents with and without children were assessed using Pearson’s chi-square tests. In the case of expected cell frequencies below 5, a Fisher’s exact test was performed. The data is characterized by several non-responses . Thus, all reported results are based on those respondents who answered the respective question and are therefore presented as valid percentages. In the tables, the percentage of valid answers for each question is indicated and total percentages as well as valid percentages are reported. In chi-square tests, cases with missing values were removed. All data were analyzed using IBM SPSS Statistics for Windows .The sample was divided into three groups by first separating healthy women and women suffering from breast cancer. Healthy women were asked to estimate their subjective numeric genetic risks. Healthy women were then divided into two groups based on their self-assessed genetic risk. A median split (median = 50) was performed to divide healthy women into two groups of low (50 or lower) vs. high (higher than 50) self-assessed risk. Besides descriptive analyses of the sample using absolute and relative frequencies for categorical data and means , (2) healthy women with low self-assessed genetic risk , and (3) healthy women with high self-assessed genetic risk . Breast cancer was diagnosed previously in 255 women (61%), the remaining 161 women are referred to as healthy women (39%). None of the investigated women was suffering from ovarian cancer. The healthy respondents were further divided based on their self-assessed genetic risk, which resulted in three groups in total: (1) women suffering from breast cancer (Sixty-nine (17%) of the women belonged to the second group, healthy women with high self-assessed risk. The mean age was 37 years, which was comparable to healthy women with low self-assessed risk. Two thirds of the women had children (67%): On average, women in this group had one child at the age of 9. The family history was comparable to the first group. In 64% of the cases the mother was diagnosed with breast cancer, on average at the age of 47, and 55%  of the respondents who answered the question stated that their mother had died from breast cancer, and 34%  of respondents who answered this question indicated that at least one of their sisters was diagnosed with breast cancer, on average at the age of 40. Moreover, 21%  of the respondents who answered this question stated that at least one of their sisters died from breast cancer. In this group, most other relatives were diagnosed with cancer. On average, 1.63 of the respondents’ other relatives were diagnosed with breast cancer, 0.46 were diagnosed with ovarian cancer, and 2.41 were diagnosed with other cancer types.The third group included 255 women who were previously diagnosed with breast cancer (61%). In this group, the mean age was with 51 years higher compared to the mean age in healthy women (39 and 37 years old). Likewise, the current age of the youngest child, was higher (22 years compared to 14 and nine years). Most women (80%) had two children. Compared to the healthy women, fewer women had a mother who had been diagnosed with breast cancer (29%) and the age of the mother at the time of diagnosis had been higher (58 years). Fewer mothers  had died from breast cancer than compared to the healthy women, while 25%  of respondents with breast cancer who answered this question indicated that at least one of their sisters was diagnosed with breast cancer, on average at the age of 53, and 23%  of the respondents who answered this question stated that at least one of their sisters died from breast cancer. In the third group, on average, 1.12 of the respondents’ other relatives were diagnosed with breast cancer, 0.30 were diagnosed with ovarian cancer, and 2.51 were diagnosed with other cancer types. Thus, on average, fewer other relatives were diagnosed with breast or ovarian cancer than in the other two groups.In order to analyze the differences of psychological distress depending on cancer status and risk perception in women with suspected HBOC, we asked the participating women to estimate their subjective numeric genetic risks .M = 60.34 . Almost half of the women reported their perceived risk with exactly 50 (47%), 9% with 11–40 and 38% with 51–99. Two percent estimated that they have no genetic risk (self-assessed risk: 0) and four percent thought they will definitely develop HBOC (self-assessed risk: 100).Across all healthy women under investigation, the self-assessed risk perception was n = 391) = 17.28; Cramer-V = 0.21; p ≤ 0.001; insomnia: χ²  = 9.25; Cramer-V = 0.15; p ≤ 0.01). Significantly more women with breast cancer were suffering from these disorders. Women who considered their own risk to be low were the least affected by concentration, memory, and sleep disorders.In this study, we asked for specific fears, worries and stressors to analyze psychological distress that may arise before women at high risk of hereditary breast and ovarian cancer come to the Department of Human Genetics for genetic counseling. First, we asked if the women were suffering from mental illnesses. Between 38% and 54% affirmed this question . There wn = 401) = 7.10; Cramer-V = 0.13; p ≤ 0.05), which played a great role for all women (35–53%), whereas stress exposure by financial problems was the least frequently mentioned cause of stress (12–16%). Particularly, women with a high self-assessed genetic risk were more likely to rate themselves as anxious and pessimistic than women with a low self-assessed risk or women suffering from breast cancer, although this difference was not statistically significant. There were also no significant differences between the three groups regarding different problems with genetic testing and requests for psychological counseling. Nevertheless, descriptively, our results showed that women with a high self-assessed genetic risk worried about the future more frequently compared to the other groups (48% versus 28% and 29%). Health concerns were the most prominent among all participants (85–97%). Healthy women were only rarely concerned about a possible lack of coping ability after genetic testing (11–12%). Women suffering from breast cancer were even less concerned about a possible lack of coping ability (3%) or due to their relative’s lack of coping abilities (11%). Healthy women with a high self-assessed risk worried less about a possible lack of coping ability of relatives than women with a low self-assessed risk (13% vs. 23%). Psychological counseling for decision support was requested by healthy women the most (19% and 20% versus 12%). Some women (16–26%) wished to receive psychological counseling in order to cope with the test result.In this study, women with a high self-assessed genetic risk tended to be more exposed to stress caused by problems within family or their partnership and also by job-related problems compared to women with low self-assessed genetic risk and women suffering from breast cancer. The three groups differed significantly regarding stress exposure by problems within the family  = 11.02; φ = 0.26; p ≤ 0.001). While 51%  of respondents without children who answered this question reported problems with genetic testing because of worries about the future, only 25%  of women with children who answered this question indicated such worries.In order to examine the problems with genetic testing in more detail, we analyzed differences between women with and without children . ResultsIn this study, we analyzed the psychological distress of women with suspected HBOC before they presented for genetic counseling and testing. Besides analyzing the difference in psychological distress of women with or without breast cancer, we were interested if psychological distress was associated with self-assessed genetic risk. Most women considered their genetic risk to be high. In a study of Rutherford et al. , 84% of Focusing on different types of psychological distress and stress exposure, we observed that a large proportion of women reported suffering from depression. It has been shown that especially women with breast cancer who undergo the process of genetic testing are confronted with breast cancer-related fear and have an elevated level of vulnerability compared to healthy individuals at increased risk for breast cancer . The diaWomen in our study showed a high level of stress exposure especially due to problems within their family. Women suffering from breast cancer have been reported to develop stress disorders or even posttraumatic events as a result of the breast cancer diagnosis . HoweverFurthermore, we observed that women with a high self-assessed risk rated themselves as rather anxious and pessimistic and had concerns about their future. Women with an increased risk of developing breast cancer have displayed traumatic responses related to the genetic testing process similar to cancer patients . We suppWomen in all analyzed groups reported worries about their health as a result from genetic testing. Notably, only a few women stated a lack of coping ability. Coping has been described as a mediator of the relationship between illness perception and distress in the Self-Regulatory Model of Illness Behavior . AlthougAlthough this study provides valuable insights into psychological distress of women with suspected HBOC, who presented for genetic counseling and testing at the Department of Human Genetics at the Hanover Medical School, the limitations of the study need to be considered. Our study is based on a small sample size and is not representative. Moreover, the data is characterized by several non-responses to some of the questions, which needs to be considered when interpreting the results. Since the results are mostly descriptive, missing values were not substituted to avoid distortion of the results. A median split always poses the problem of assigning respondents with medium values to one of the two groups (low vs. high) and, thus, making it impossible to reveal differences between this moderate group and the low and high groups. Therefore, our study only gives first insights into differences between women with relatively low- and high-risk perceptions regarding psychological distress. We agree that distinguishing between women with a low perceived risk vs. medium perceived risk vs. high perceived risk could yield further information and should be explored in future studies with larger sample sizes. Our findings hint to certain conclusions, but studies based on larger sample sizes are needed to further examine these first insights. In addition, the close-ended questions allowing only yes- or no-answers do not allow for in-depth conclusions on the subjects under investigation. Future research should collect more in-depth data to explore women’s rationale regarding different aspects in the context of genetic testing and counseling.In conclusion, this study demonstrates that women undergoing genetic counseling to seek advice regarding hereditary breast and ovarian cancer, whether diseased from breast cancer or not, present with a variety of worries, particularly about their health and future. This should be taken into account and lead genetic counselors and doctors to actively addressing these personal concerns. For example, the counseling session could start with a short query to get an overview about the individual psychological distress of the counselees. Although most of the women stated that they felt able to cope with the test results, a quarter of the women requested psychological support. Therefore, psychologists familiar with psycho-oncology and genetic risk assessment should be integrated into multi-disciplinary teams of HBOC centers.


Trials of risk estimation in breast cancer screening programmes, in order to identify women at higher risk and offer extra screening/preventive measures, are ongoing. It may also be feasible to introduce less frequent screening for women at low-risk of breast cancer. This study aimed to establish views of women at low-risk of breast cancer regarding the acceptability of extending breast screening intervals for low-risk women beyond 3 y.Semi-structured interviews were used to explore views of low-risk women, where “low-risk” was defined as less than 2% estimated 10-year risk of breast cancer aged > 46 years. Low-risk women were identified via the BC-Predict study, where following routine screening, women were given their 10-year risk of breast cancer by letter, along with additional information explaining breast cancer risk factors. To gain diversity of views, purposive sampling by ethnicity and socioeconomic background was used to recruit women. Data were analysed using thematic analysis.A good opportunity to receive risk estimation, where women found it worthwhile to receive a low-risk result although some were surprised if expecting a higher risk result; (2) Multi-faceted acceptability of extended screening intervals, with reactions to less frequent screening dependent on whether women were confident in being low-risk status and current safety evidence, (3) Passive approval versus informed choice, highlighting that women found it difficult to consider choosing less frequent screening without professionals’ recommendations, as they generally viewed attending breast screening as positive.Twenty-three women participated in individual interviews. Three themes are reported: (1) Risk assessment and receiving a low-risk of breast cancer is acceptable although, further research is required with more diverse samples of women. Any recommendation of less frequent screening in this risk group should be evidence-based in order to be acceptable. Communication needs to be carefully developed, with a focus on ensuring informed choice, prior to trialling any extended screening recommendations in future studies.The online version contains supplementary material available at 10.1186/s12885-021-08347-w. The UK NHS Breast Screening Programme (NHSBSP) invites women 3-yearly from age 50–70 years . This haThere are specific UK national guidelines to offer additional screening to women at higher risk of breast cancer . HoweverAlthough much of the impetus for risk-stratified screening comes from the potential to identify high risk women and offer them prevention and early detection options, discussion about the implementation of a risk-stratified breast cancer screening programme (BCSP) has led to consideration of whether it is safe to reduce screening for women at low-risk. Not only are such women by definition less likely to develop cancer, they are also less likely to develop faster growing, high-grade tumours . EnsurinAlthough previous surveys indicate women think risk-stratified breast screening is a good idea, the samples were more accepting of additional screening if high-risk than less frequent screening if low-risk , 19. HowA cross-sectional, qualitative design using semi-structured interviews was employed. Women were identified from an on-going study investigating breast screening risk stratification, BC-Predict , and hadWomen were invited by post to participate in an interview between 23 and 246 days after having received their BC-Predict risk feedback. Only women with a 10-year risk estimate of < 2% were invited to participate i.e., low-risk. To recruit a diverse sample, up to two additional reminder letters were posted to women who self-reported Black and Minority Ethnic Refugee ethnicity or had an Index of Multiple Deprivation (IMD)  HRT because of the prediction said low [...] going on HRT may not be that bad because although it may be only an increase of one in a 100 people, women, who get breast cancer from being on HRT, I’m already at a low level. Shelagh;45-54Overall, women explained that their results provided a sense of relief and for many, ‘…perhaps you don’t take it in so much because it’s not a direct immediate threat to your own health . Despite this, many recognised that receiving low-risk breast cancer estimates does not mean that they will never be diagnosed and although helpful information to receive, expressed realistic views that they could still be diagnosed with breast cancer. Subsequently, most voiced intentions to maintain healthy lifestyles, attend future screening and remain breast aware.It means that, sort of, lifestyle, things that have…you know, things that have happened in the past genetically, I’m probably at a lower risk of getting breast cancer, but anyone can get it still. It could happen at any time so it’s not that I’m never going to get it, it’s just that I’m at, sort of, the low risk end of the scale of likely to get it. Annie;45-54Due mainly to receiving validation of how they already felt, some women were somewhat dismissive re-counting the experience as not having much impact Actually, the truth of the matter is I think I’d rather feel a bit miffed about it […] my immediate reaction would be ‘it’s a money saving’ […] Maybe I’m being cynical, but I take it as being a money saving device. Violet;65-74Initial reactions to the idea of less frequent screening were positive, or neutral, across most of the sample. Women who did not expect to receive a low-risk estimate, and who wanted to know more about the stability of their risk, were more apprehensive when discussing longer screening intervals. Several questioned whether longer intervals are being considered for cost cutting reasons, rather than safety. This concern led to some expecting a backlash from women feeling entitled to remain on 3-yearly intervals.…it’s just me using my brain isn’t it? They’re at greater risk; give them the chance to have it caught early and then if somebody doesn’t have to go through full blown chemotherapy and maybe can just potentially have radio [therapy]. Enriquetta;45-54In contrast, assuming that longer screening intervals would allow those at higher risk of breast cancer to be offered more screening, others viewed the proposal altruistically, as a better use of national funding. Regardless of viewpoints, women wanted to know more about why less frequent screening for low-risk should be introduced.Women considered what breast screening could look like if low-risk women were offered less frequent screening and, thoughts were generally based on their opinions about current breast screening. This was challenging for women to discuss without having previously thought much about how screening programmes are generally organised.…at my age now I’d feel a duty towards my family, my children, that I should go through treatment and that’s how I feel […] really catching any cancer early would be important to me, as most people, I guess, but especially the younger you are. Maxine;45-54Despite being largely accepting of the possibility of less frequent breast screening, women viewed the current 3-yearly programme favourably overall. Some women acknowledged that interval cancers and false positives already exist within 3-yearly screening however, concerns about having fewer mammograms related to a loss of safety that breast cancer will be detected quickly. Women often cited present life circumstances, or knowing individuals who have experienced cancer, as reasons to continue with 3-yearly screening invites.‘I am low risk, there’s no history in the family, but it doesn’t mean to say I’ll never get it’  approach, was expected to minimise interpreting the change as license to ignore breast health. On two occasions, women highlighted the need for a clear rationale from experts to minimise contradicting the early detection agenda initiatives aimed at improving screening uptake.…you are very much encouraged to go for any screening that’s available and I think knowing what kind of breast cancer can involve in treatment and things like that. Lydia;45-54Therefore, in spite of being given information that those at low-risk could be less likely to be diagnosed with ‘aggressive’ breast cancer, women were worried that longer intervals would result in later stage cancer diagnoses. Communication about longer screening intervals, emphasising the importance of self-examination with a …people are living longer and it used to be that people died between 50 and 70…shift everybody along a bit. Eleanor;65-74Improvements in life expectancy led some to state that the upper age limit (70 or 73 years) is no longer fit for purpose and, introducing low-risk screening provides opportunity for reviewing the entire programme.some screening once low-risk has been established. However, many were unsure what the current interval or invite age range is and how these were decided. It was quite difficult for women to elicit a specific interval although expected it to be underpinned by evidence.I would kind of assume that lots and lots of research and thinking had gone on behind all of that, it wouldn’t just be a magic figure plucked from thin air. Ellen;45-54All women discussed what screening interval length could be offered, with quite varied opinions. Everyone felt there should be I suppose it seems like a big gap to me, six years seems quite a lot […] I’m currently going through the menopause, and the amount of physical change that has happened over the last year is quite staggering. Marie;45-54When prompted by the interviewer, an interval of 5 years was viewed most positively although, many were unable to articulate why; 10 years seemed too long for most. Some women referenced age-adapted cervical screening intervals to explain their views and often highlighted they have not questioned the lengths in this programme. Others felt a change should not be too drastic as women are already experiencing health changes.…instead of waiting until 50 you’re almost selling it as a, ‘we’re actually going to screen you early’ […]at 45 and then every five years after that, unless the risk changes Victoria;45-54A number of women wondered whether low-risk screening frequencies would be different depending on age and whether risk could change over time. Reasoning conflicted relating to perceptions that older women are at greater risk but, breast cancer diagnoses would have a greater negative impact on younger women. Given that risk assessments would identify higher risk women (to offer more frequent screening), two women suggested risk-stratified screening should start earlier than age 50-years.When asked how they would decide whether to opt for longer screening intervals, women identified the limits of ensuring informed choice within screening as felt unaccustomed to deliberate about how much they interact with such programmes. This led women to expect that guidance from healthcare professionals in the field would be provided.I mean I wasn’t aware that there was any deleterious effect from the actual screening process. So under those circumstances I think I’d probably prefer to carry on being screened. Emmeline;65-74Deciding whether to accept longer screening intervals was often difficult for women to consider. Many women could not remember the harms  and benefits of breast screening provided with their invite and, most viewed false positives as good in order to rule out cancer.…if I was to feel something that I’m not used to within my body, just because my screening is in five years, I don’t have to wait for five years, I can go to the GP and say, 'look, this is not comfortable', the GP will refer […] It’s not, like, 'this is it, we’ve set it in stone' and it cannot be changed. Clara;45-54Whether it is possible to implement a ‘strict’ longer screening interval, where women are not offered choice, influenced many women’s thoughts about longer intervals. Knowing they could easily re-access screening with suspected symptoms, and be taken seriously, were assumed by many:‘quite happy to have it every three years’  for reassurance. In one account, a woman viewed it as unfair to not be allowed to make her own decision despite acknowledging that the cervical screening interval changes depending on age. However, others wanted to be told how frequently they should attend mammograms as would feel unable to decide on their own:I’m a natural born worrier, so I then think back to the research that says, 'well it might be more harmful to have them more frequently'. Then I’d be torn as to, 'oh what do I do, it could be more harmful to have them every three years?' […] Or, what if I’m the one that’s low risk and does get cancer? I’m the one that’s low risk and gets a false positive because I’ve been going every three years? Lucy;45-54Regardless, when asked what decision they would make if it were a choice, several women initially ‘on the fence’ when first discussing longer intervals, reported that they would be …if the NHS feel confident in giving that advice then I would feel confident in taking because you are a trusted supplier of messages. Joanne;55-64Given the complexities women highlighted when considering how they would opt for extended screening intervals, provided a clear, evidence-based explanation was given, the majority described feeling accepting of the idea that less frequent screening for low-risk might be introduced.So if they automatically said every five years I’d probably be a bit annoyed, just because there is going to be a percentage of people who do get it. Not annoyed, but I’d be a bit worried. If I was given the choice and made my own decision based on more accurate details and facts and then that would be my decision, rather than every three years, then I’d be happier with that than just being told ‘you’re in that category, we’re going for every five years’. Caroline;45-54Without having been able to review evidence demonstrating the safety of less frequent screening, one woman explicitly disagreed with this.maybe that for a period of transition might be the solution rather than having a big outcry of women being deprived mammograms . However several wondered if this would be possible financially.Is it a good use of resources? I mean if it turns out that a larger number of women want to stay on the three-year cycle and yet professionally it’s not considered necessary, it’s a tricky one. […] If it were very low numbers, it wouldn't matter too much. But it doesn't seem right to be offering some expensive procedures or whatever when they are not medically necessary. Ethel;65-74Women viewed the proposal as placing greater responsibility on women for their breast health therefore, a number identified a default longer interval with the ability to opt back in to 3-yearly intervals could improve acceptability; one woman suggested this could be temporary ‘…Overall, women felt generally positive about breast cancer risk being assessed as part of routine breast screening and receiving a low-risk estimate. Less frequent screening for women at low-risk appeared acceptable, as long as safety evidence is available and is not only due to saving money. Women did not believe screening should stop altogether for this group and indicated an interval length not too dissimilar to the current 3-yearly programme could be appropriate. It was difficult for most women to think about deciding to choose a longer interval; most wanted guidance from expert health professionals. Women appeared to base their views about the acceptability of less frequent screening on their experience of others having breast cancer, their understanding of the BCSP and how they currently interact with screening.Women appreciated the chance to receive their 10-year risk of breast cancer and the majority were pleased with receiving a low-risk estimate. This is in line with findings of a previous quantitative study that found that women told they were at lower risk felt less cancer worry and general anxiety than other women . HoweverAlthough balanced information is likely to be included in invites to breast screening, women with positive attitudes towards cervical screening downplay the harms , so it iThe study explored views about risk-stratified breast screening from women who with a low 10-year breast cancer risk estimate; other research has focussed on women with average or above risk. Recruitment methods aimed to ensure a diverse sample from an ethnicity and socioeconomic perspective but, were limited by those eligible from the BC-Predict study. Over 80% of the eligible sample were of White British background, reflecting the current study sample however, the recruitment approaches used may not have been the optimal method of engaging with non-White groups of women. The median IMD decile (five) for the sample interviewed matched that of BC-Predict women invited to the study and, recruitment rates were slightly higher (29%) for women living in areas with an IMD ranging from 1 to 5 than those living in less deprived areas (24% for IMD range 6–10). Women who took part were, on the whole, highly educated and were willing to have their breast cancer risk assessed. It could be that this sample are particularly interested in breast cancer risk and could be more accepting of extended screening intervals however, the interview topic guide was open allowing positive and negative views to be expressed. Due to the lack of ethnic diversity within both the recruited sample and BC-Predict, it may be that non-White women have particular views about the acceptability of breast cancer risk assessment as well as less frequent screening for women at low-risk.Any risk-stratified screening approach where screening is reduced for low-risk women should clearly explain the rationale and supporting evidence given that having adequate knowledge partly underpins informed choice . Some woFurther research is required to assess how women might respond to a recommendation of extending BCSP screening intervals in receipt of a low 10-year breast cancer risk estimate. Views from women who do not currently adhere to screening recommendations i.e., invited to the BCSP but do not attend for a mammogram, should be obtained to determine whether risk-stratified screening may be more or less acceptable if a low-risk pathway is introduced. This is particularly important given the high educational attainment of the present sample as evidence suggests lower uptake and poorer understanding of risk is associated with socioeconomic status, such as qualifications . Future The findings have demonstrated that it is acceptable to receive a low-risk breast cancer estimate as part of breast screening, from the perspective of a generally well educated, mainly White British sample. Several challenges were highlighted in ensuring informed choice should risk-stratified screening approaches to breast cancer screening introduce less frequent screening for women identified at low-risk of breast cancer.Additional file 1. Interview topic guide