Identifying women aged 30–39 years at increased risk of developing breastcancer could allow them to consider screening and preventive strategies.Research is underway to determine the feasibility of offering breast cancerrisk assessment to this age group. However, it is unclear how best todeliver and communicate risk estimates to these women, in order to avoidpotential harms such as undue anxiety and increase benefits such as informeddecision-making.This study aimed to investigate women’s views on, and requirements for, thisproposed novel approach to risk assessment.A cross-sectional qualitative design was used.Thirty-seven women aged 30–39 years with no family history or personalhistory of breast cancer participated in seven focus groups (n = 29) andeight individual interviews. Data were analysed thematically using aframework approach.Acceptability of risk assessmentservice concerns the positive views women have towards theprospect of participating in breast cancer risk assessment.Promoting engagement with the service describes thedifficulties women in this age group experience in relation to healthcareaccess, including mental load and a lack of cultural awareness, and theimplications of this for service design and delivery. Impact ofreceiving risk results focuses on the anticipated impacts ofreceiving different risk outcomes, namely, complacency towards breastawareness behaviours following low-risk results, an absence of reassurancefollowing average-risk results and anxiety for high-risk results.Women’s information requirements highlights women’sdesire to be fully informed at invite including understanding why theservice is needed. In addition, women wanted risk feedback to focus on plansfor management.Four themes were developed. The idea of breast cancer risk assessment was received favourably among thisage group, providing that a risk management plan and support from healthcareprofessionals is available. Determinants of acceptability of a new serviceincluded minimising effort required to engage with service, co-developmentof invitation and risk feedback materials and the importance of educationalcampaigning about the potential benefits of participation in riskassessment. In recent years, risk prediction models haveincorporated polygenic risk scores and mammographic breast density, which haveimproved their discriminatory accuracy.1518 The merits of personalisedrisk assessment for breast cancer has predominantly been explored within the contextof implementing risk stratification into breast cancer screening programmes, thatis, tailoring of screening practices based on individual variation inrisk.19 This approach has the potential to improve the benefit to harmratio of screening.20 Recruitment is ongoing for several international trials todetermine the potential effectiveness of a risk-based screening regimen incomparison to standard screening practice.22One proposed approach to identify women at increased risk of breast cancer involvesthe use of personalised breast cancer risk estimates.23 it isimportant to consider acceptability to potential recipients of a new service as amajor determinant of feasibility. To date, the views and attitudes of women who aretoo young to attend breast screening and who are not at known increased risk ofbreast cancer have rarely been investigated. Previous research with screening agewomen has demonstrated that concerns about inducing unnecessary worry and perceivedability to cope emotionally with risk feedback influence decisions to participate inbreast cancer risk assessment.25 In addition, a recentmulticriteria decision analysis identified service access as the most valuedcriteria influencing decisions to participate.26 However, it remains unclearhow best to implement breast cancer risk assessment and communicate risk informationoutside of an organised screening programme to younger women.Given the increasing burden of breast cancer in pre-menopausal women, the feasibilityof offering breast cancer risk assessment to women aged 30–39 years is currentlybeing investigated (NCT05305963). In line with the Medical Research Council (MRC)Framework for Developing and Evaluating Complex Interventions,This study aimed to investigate prospective service users’ attitudes towards aproposed new breast cancer risk assessment service to inform the delivery modeladopted in the feasibility study.Specific objectives were to:Understand women’s views on, feelings about and attitudes towards introducingbreast cancer risk assessment.Understand women’s preferences for access to and delivery of a breast cancerrisk assessment service.Identify women’s information and support needs with respect to breast cancerrisk assessment and risk communication.27 Focusgroups also allow participants to consider their views in relation to others,which might result in opinions shifting during the course ofdiscussion.28 Therefore, this interaction between participants allowsinsight into the degree of group consensus on the topic.29One-to-one interviews were carried out when participants were unable to attendscheduled focus groups.A cross-sectional qualitative design was used. Given the novel and hypotheticalnature of the discussion topic, focus groups were chosen as the primary methodof data collection. Participants were unlikely to have considered breast cancerrisk assessment previously, and therefore, the debate within the group wouldencourage participants to reflect on and clarify their own perspectives,resulting in a depth of dialogue not often found in interviews.Participants were recruited through responding to study advertisements outliningthe inclusion criteria and topic. Inclusion criteria were chosen to ensure thatthe resulting sample matched the intended recipients of the planned studyassessing feasibility of offering breast cancer risk assessment to women aged30–39 years (NCT05305963). Participants met study inclusion criteria if theywere (1) born female, (2) aged 30–39 years, (3) residing in Greater Manchester,(4) able to provide informed consent and (5) able to understand and communicatein the English language. Women could not take part if they had received a breastcancer diagnosis or had a first-degree female relative (mother or sister)affected by breast cancer.Poster advertisements were shared on social media platforms (Facebook andTwitter) and displayed on noticeboards in public buildings (e.g. libraries andcommunity centres). The co-founder of a community organisation made directcontact with the research team after seeing an advertisement on Twitter andfacilitated the recruitment of four members of the community group who were fromethnic minority backgrounds. Prospective participants were screened againstinclusion criteria via email/telephone and sent information sheets.Supplementary Material 1).Topic guide development was informed by the aims of the study and a review of theliterature. An initial draft was developed by the lead author, a doctoralstudent in health psychology with qualitative health services researchexperience. Feedback on this draft was obtained from public contributors and therest of the research team who have extensive clinical and research expertise inbreast cancer and screening services, medical oncology, health servicesresearch, health psychology and qualitative methods. Modifications to thecontent and structure of the topic guide were made in response to the feedbackreceived. Questions focused on the acceptability of breast cancer riskassessment in relation to the process being used in the planned feasibilitystudy. There were three proposed components of the study process, and each ofthese were discussed in turn: (1) a questionnaire for self-reported assessmentof breast cancer risk factors, (2) a saliva sample for assessment of polygenicrisk and mutations in high-risk genes and (3) a low-dose mammogram forassessment of breast density. In addition, views on methods of access,information and support needs, risk communication and anticipated barriers toengagement were captured  or later via telephone and Zoom conferencing due to COVID-19 restrictions.Following consent, participants gave demographic information. Participants werecompensated for their time with a £20 cash payment. Focus groups and allinterviews were audio-recorded and transcribed verbatim. A recording malfunctionoccurred during one online focus group meaning that only the first half ofdiscussion was recorded. Field notes were taken to capture insights from theremaining discussion. Personally identifiable information was anonymised, andparticipants were assigned pseudonyms. Data collection was primarily conductedby the lead author (S.H.) with another member of the research teamco-facilitating the focus groups (R.E.H.). Both facilitators are femaleresearchers and have postgraduate qualitative health services researchexperience. Interviews were conducted by the lead author (S.H.). No one waspresent during the focus groups and interviews besides the participants andresearchers. Data collection continued until the research team were satisfiedthat sufficient data had been collected to answer the researchquestion.Community and patient stakeholders were involved in the design of this study. Aresearch advisory group – consisting of Black, Asian and minority ethniccommunity leaders – was consulted regarding the research idea and intendedrecruitment procedures. Wording and terminology used in the recruitment posterand participant information sheet were revised following feedback from nineBlack African women aged 30–39 years with no personal history of breast cancer.The topic guide was piloted with four White women aged 30–39 years with nopersonal history of breast cancer, and they advised on wording and relevance ofquestions, prompts and flow.3133 Primary data analysis wasconducted by the lead author with input from L.G. and D.P.F. The analysisinvolved five main stages. (1) The lead author read transcripts, noting initialthoughts and impressions of the data. (2) The lead author conducted line-by-linecoding on a selection of transcripts. Initial coding was deductive based on thestructured questions in the topic guide to inform the design of the plannedfeasibility study in terms of the delivery model adopted, the information andsupport provided and communication of risk feedback. Inductive methods were thenused to capture additional codes and context to ensure important aspects of thedata were not missed. Codes were then grouped according to similarities anddifferences, producing categories. This resulted in a working thematic frameworkof codes contained within categories, which was refined in collaboration withL.G. as more transcripts were coded. (3) This thematic framework was thensystematically applied to all remaining transcripts. (4) Each category wasplotted onto a separate thematic matrix using the ‘framework’ feature inNVivo12, with codes presented in separate columns, and participants (cases) onseparate rows. To reduce the data set into a more manageable form, data in eachcell were summarised and illustrative quotations were noted . (5) The resulting data in theframework matrices were compared across and within cases to highlightsimilarities and differences. This facilitated the development of the finalthemes. Regular meetings were held between members of the research team  throughout analysis and interpretation to discuss explanationsfor findings, deviant cases and agreement on themes. The final thematicstructure was agreed by the entire research team as representing participants’views.Data were analysed in NVivo12 using thematic analysis with a framework approachto data management from a critical realist perspective.34Sixty-one women contacted the research team expressing an interest in the study.Prospective participants were asked to confirm that they met the inclusion criteria.Twenty-four women did not respond to the research team following three contactattempts. This drop-off is likely to be attributable to the primary recruitmentperiod coinciding with the beginning of the COVID-19 pandemic (February to March2020). Thirty-seven women participated; seven focus groups (participant rangen = 3–5) and eight interviews were conducted. Focus groups lasted between 71 and90 min (median = 85 min) and interviews ranged from 40 to 81 min (median = 55 min).The majority of participants were White British see . Based oData are presented as four overarching themes with seven sub-themes . Quotes my first thought is, do you know what, I don’t think I want to knowbecause then that would just give me anxiety. . . I think the anxietywould probably kill me before the cancer does. The majority of women stated they would welcome the opportunity to find out theirbreast cancer risk. However, some women expressed reservations, citing concernsabout the potential for acute emotional distress while awaiting results andsignificant impacts on mental health thereafter:Participants contextualised the risk assessment process by reflecting on previousencounters with healthcare, for example, cervical screening, pregnancy andchildbirth. Consequently, participants were accepting of the questionnaire,saliva sample and mammogram as they were not regarded as invasive procedures.The content of the risk factors questionnaire was considered reasonable due tothe factual, medical nature of questions. However, reliance on self-report wasflagged as a potential concern in relation to how incorrect recall ofinformation may affect accuracy. Providing a saliva sample for genetic testingwas considered commonplace and therefore acceptable due to availability ofdirect-to-consumer genetic testing from companies such as 23andMe. The mostfrequently reported concern about the risk assessment process was anticipateddiscomfort during the mammogram. This was influenced by older relatives’anecdotal experiences of mammograms being uncomfortable and painful.if you know what you’re facing you can deal with it, can’t you? You cansay, ‘Oh well, that’s fine, we’ll do this, this and this, and we canhave a plan of action’. The main benefit of participating in breast cancer risk assessment was perceivedto be the ability to plan and prepare for the future in terms of accessingbreast cancer risk management strategies to maintain good health:the most common thing you take medication for is if there’s somethingwrong with you right now. So it would almost make you feel like therewas I guess. Participants were generally aware of the importance of early detection of cancerfor increased chances of survival and as such, viewed the service favourably asan opportunity to detect breast cancer earlier and thus reduce breast cancermortality. Willingness to undergo risk assessment was contingent on there beingoptions to reduce or manage the risk, preferably with the support of healthcareprofessionals. There was limited awareness of preventive measures amongparticipants. However, when prompted, many women were uncomfortable with theprospect of taking medication for reduction of risk in the absence of disease:In contrast, one woman stated she would find medication a reassuring andpreferable option to lifestyle advice, owing to the strong motivation requiredto change health-related behaviours.This theme describes the difficulties women experience accessing existinghealthcare services and the implications of this for service design anddelivery.it’s not unusual for people at my age to have one, two or threechildren of a certain age. So your time’s already spread a bit thin,it would be spread even thinner especially if you’ve got multiplechildren, a job, a house, things like that. Women perceived the proposed timing of invitation to the breast cancer riskassessment service to coincide with a defining decade in terms of managingthe often competing demands of professional and family life:As a group of women in their 30s, often it can be other people’shealth, other things going on and we’re often at the bottom of thepile. As a result, women reported being time-poor and experiencing difficultiesaccessing healthcare services at a time that suited them. In addition tophysical access requirements, women described a high mental load in the formof invisible labour involved in managing a household and family, which oftenresults in putting the needs of others before their own:Get it all done in one go, yeah, and then you don’t have to use brainspace for it twice. Therefore, women desired a ‘one-stop shop’ delivery model whereby all threecomponents of breast cancer risk assessment would be completed at one appointment:Participants stated they would be more likely to engage with the service ifit was available in their local area. Poor public transport routes tohospitals and the resources needed to travel were identified as potentialbarriers to engagement. To overcome these issues, some women expressed apreference for a mobile service in community settings such as workplace andsupermarket car parks.if they can book it themselves online or over phone or whateveroption is available to them something that they can select the dateand the time [. . .] that would be really helpful if they were ableto do it themselves rather than getting told you need to be here onthis date and this time. Availability of appointments outside of normal working hours was consideredan essential requirement of the service. Furthermore, the ability to book aconvenient appointment online or via phone was desired to reduce thecognitive burden of re-arranging a pre-specified appointment:if you’ve got community groups or community leaders involved theyknow how to talk, how to communicate the information to the peopleof their community [. . .] they know there’s this misconception orthere’s fear [. . .] and they are able to address thosesensitivities that the healthcare industry might not actually beaware of. Involvement of community leaders in service delivery was considered vital.Participants described how community leaders often share the culture andlanguage of the community they support and this shared background helps tobuild rapport. In addition, community leaders were perceived to possesscultural awareness of beliefs and perceptions women may have whenconsidering engagement with healthcare services. For example, oneparticipant described how young women in her community worry about attendingcervical cancer screening for fear of bringing dishonour to their familiesbecause of the intimate nature of the test. Participants explained howservices could work with community leaders to tailor health messaging in amore meaningful and sensitive way, which women felt would increase thelikelihood of engagement, particularly for women from ethnic minority backgrounds:This theme captures participants’ perceptions of anticipated impacts followingreceipt of low, average and high-risk results. The labelling of risk resultsreflects the terminology the women used when asked for their thoughts about theuse of risk categories.scrap the language so you don’t use the word low risk because thatwould lead to complacency in behaviours. Participants expressed reservations about provision of a low-risk result. Itwas thought that women labelled as low-risk may no longer perceive breastcancer as a pertinent concern, which could result in complacency towardsbreast awareness behaviours. One woman perceived complacency as aninevitable consequence of labelling a woman as low-risk and as such felt theword ‘low’ should not be used:people need to be made aware that just because it’s low doesn’t meanit’s not impossible. Examples of possible complacency reported by women included losing vigilancearound breast awareness and reluctance to seek help for breast symptoms. Toavoid these potential negative impacts, women thought it would be necessaryto make sure those labelled as low-risk understood that the result did notguarantee they would never develop breast cancer:So if you are gonna tell somebody they’re of average risk is therestill options to prevent it [. . .] or is average not good enough toprevent. Participants discussed the possibility of a risk category between low andhigh indicating average risk for the population. Some women questioned thevalue of receiving such a result with one woman describing it as the ‘worstcategory to fall into’ . For these women, it was unclear whatmanagement strategies would result from this level of risk:I feel like I’d be in the same boat now, you, kind of, don’t knoweither way do you? You don’t know, there’s a chance you could butthere’s a chance you might not whereas that would be our positionnow. Furthermore, women felt they would not have gained any new knowledge fromparticipating in the risk assessment service if they received anaverage-risk result:if the average risk if it was just like oh well there’s not much youcan do just keep checking your breasts I might be a bit I don’tknow. I don’t know if I’d get panicked about that or not. Consequently, an average-risk result was considered to hold no meaning and inturn, women were not reassured by this result. One woman suggested it mightmake her feel panicked:can you imagine being invited back to a breast centre . . . you’d bethinking ‘right I’m a cancer patient’. In anticipation of significant anxiety following a high-risk result,participants welcomed the prospect of attending a clinic appointment todiscuss their risk result further. However, feelings of vulnerability andapprehension were expected in anticipation of attending this appointment.Women thought attending a hospital, particularly one specialising inoncology, would imply current illness, which would lie in tension with theintended purpose of the appointment being to reduce the risk of developingbreast cancer in the future. Furthermore, women felt the name of the clinicneeded careful consideration as inclusion of the word ‘risk’ implied threat.These aspects of the appointment are important to consider, as they mayincrease women’s perceived threat to a level that results in disengagementwith risk management:if you found out you were super high-risk and you were a very logicalperson, you might just go, okay, well, I’m not going to do that[have children] because if there’s a chance that within the next tenyears my life’s going to be on the line, I don’t want to bring kidsinto the world only to then leave them. During the clinic appointment, women wanted to discuss the implications oftheir risk result for their children’s lives, particularly daughters. Onewoman thought a high-risk result could be ‘life-changing information’ as itcould potentially influence reproductive decision-making:In addition to a clinic appointment, a few women desired a peer supportgroup. For these women, an interaction with a healthcare professional wasconsidered inadequate in fulfilling emotional support needs. Peer supportwas valued as an opportunity for women with shared experience to connect andlearn from each other.This theme describes the information participants expected to be included ininvitation and risk feedback material.I think the fact that they don’t even offer mammograms to anyoneunder 50, kind of, it automatically makes you think that thereforeit’s not a risk to you, you know, it’s like oh the authorities havedecided that that’s the age that you’re likely to get it thereforeif you’re younger than that like don’t worry about it almost.Women expected to be informed about evidence supporting the introduction ofthe service and the benefits of participation. This need was rooted inwomen’s beliefs and assumptions of breast cancer and screening. Participantsassumed that screening is offered to women when breast cancer poses thegreatest risk. Consequently, women perceived breast cancer as a diseasepredominantly affecting women older than 50 years:The ‘helping you decide’ leaflet accompanying cervical cancer screeninginvitations was considered a good exemplar of information giving. Some womendesired a simple diagrammatic representation of the different pathwayspossible from engaging with the service.maybe putting more information with people that look like thecommunities that you’re trying to reach [. . .] it becomes morepersonal to them like ‘oh wow, if someone who looks like me has beenaffected by it, maybe I need to take this seriously’. Participants with professional experience of designing and producinghealthcare information thought that information should be made available indifferent languages and formats such as easy read and braille to increaseaccessibility and equity of access. One woman from an ethnic minoritybackground felt that more ethnically diverse images should be used ininformation materials to convey the importance of engaging with the serviceirrespective of cultural or racial background:usually if it’s to do with the actual procedure I prefer looking atit and sort of seeing it visually happen so I can imagine myselfgoing through that. Whereas if you’re just telling me over thephone, ‘Oh, well, you just go into a room, then you get your bra offand stand at a machine’, I can visualise it but I don’t know how Iwould react in that situation. Participants wanted access to a video resource showing a woman having themammogram procedure. Perceived benefits of this approach included womenfeeling more reassured and prepared for what to expect and making theprocedure easier to imagine:women that come from maybe religiously conservative backgrounds, theymight want to be absolutely reassured that they’re going to be seenlike in a women only environment. Women expected to be informed about timescales of activity within theservice. For example, the duration between completing the risk assessmentprocess and receiving results. A few women said they would feel morecomfortable attending the clinic appointment if it was made clear in theinvitation material that the radiographer performing the mammogram was a woman:Women wanted to be informed about the intended scope of genetic testing. Thisincluded information on how DNA would be stored and shared as a means ofreassurance that personal information was safe.I think you would assume that a mammogram would pick up on cancer ifit was there [. . .] I guess that’s a really important message toget out there if you do this isn’t it, this isn’t a replacement fora cancer screening. Participants were familiar with the use of mammograms in breast cancerscreening to detect breast cancers. Therefore, participants presumed therisk assessment mammogram would have diagnostic capability and found itdifficult to understand why the presence or absence of a breast cancer couldnot be confirmed at the same time as assessment of breast density. For thisreason, explicit communication of the purpose of the mammogram in theinvitation materials was considered essential to avoid any misunderstandings:Do I want to be ambushed on the phone with someone telling me that Ishould go and discuss my breast cancer risk? Women described not wanting to be caught off guard when receiving their riskresult. For example, receiving advanced notice of a phone call. This can beseen to function as a means of retaining some control in an uncontrollable situation:For high-risk results, women preferred a telephone call or face-to-faceconsultation with a healthcare professional as this would allow theopportunity to ask questions immediately, mitigating the anticipatedemotional distress to receiving a high-risk result. It was acknowledged bysome women that being in this heightened emotional state may interfere withcognitive processing of information and as such, written information torefer back to was desired. In contrast, receiving a low-risk result vialetter or text message was considered acceptable.Irrespective of risk result, all participants expected to be given the optionof accessing a healthcare professional with appropriate expertise. Generalpractitioners were perceived as lacking the required expertise needed.Overall, there was a lack of consensus regarding the optimal method ofdisplaying risk information. Women thought multiple formats of riskpresentation should be offered to accommodate different learning styles andlow levels of literacy and numeracy.It [national average] kind of creates a bit of understanding doesn’tit in your mind [. . .] what that actually means in terms of yourincreased risk. Women assumed that each risk category would span a broad range ofpercentages. Consequently, women perceived knowing where they were in thecategory as a more informative result. In contrast, one woman felt thatprovision of the risk category was sufficient and easier to process from anemotional point of view. Providing comparative risk information in the formof the national average was considered beneficial to contextualise theseverity of the risk result:Participants expressed reservations about using colour to differentiatebetween risk levels. In particular, strong emotional reactions were observedin response to the suggestion of using red to denote high risk:Jasmine:If I was a high risk and I saw red, I’d be like, ‘Oh, I’m going to dienow’. [Laughter] And it would probably be a bit off-putting.Carrie:Yeah, ‘High alert. Death round the corner’. [Laughs].Nancy:Yeah, ‘Your boobs are going to fall off’. (FG2)I would want it to be focussed on what I do next and not on what theresult is. Because if the result’s scary, then I just want to knowand then I want to move on and know what to do next. In terms of risk feedback, information about the factors contributing to riskwas perceived as interesting but generally unhelpful due to the perceptionof many breast cancer risk factors as non-modifiable. Instead, informationabout what would happen next in terms of proactive risk management was ofutmost importance to all participants:Participants expected risk feedback to contain information on lifestylerecommendations because receiving risk was considered an opportune time forwomen to review and modify unhealthy lifestyle behaviours such as smokingand excessive alcohol consumption. Furthermore, guidance on how to performbreast checks and recommended frequency of doing so was desired.To our knowledge, this is the first study to investigate views of young women, notknown to be at increased risk of breast cancer, regarding a proposed novel approachto risk assessment outside of an organised breast screening programme. Overall,women responded positively to the prospect of a breast cancer risk assessmentservice. However, the findings illustrate certain conditions of acceptability thatwill be key considerations in implementation. Participants desired a ‘one-stop shop’delivery model whereby all components of a breast cancer risk assessment would becompleted at a single appointment. Various concerns were apparent when anticipatingreceiving all risk results, not just results indicating high risk. Women expressedlow perceived susceptibility to developing breast cancer and reported limitedawareness of breast cancer as a potentially preventable disease. Consequently, womenwanted to be fully informed ahead of engaging with breast cancer risk assessment.Verbal communication methods (telephone and in person) were preferred for high-riskresults to mitigate any induced emotional distress. In comparison, a letter or textmessage was deemed acceptable for low risk. In terms of risk presentation, womenadvocated the use of multiple formats that combine quantitative and qualitativefeatures. Overall, presentation of risk was considered less important thanimplications of the result for risk management. Irrespective of risk result, womenexpected to be given the option of support from a healthcare professional withappropriate expertise.36 Theinclusion of Black women is considered a strength of this study as their voicesare typically under-represented in cancer prevention and early detectionresearch.37 However, we recommend that future research focuses onexamining Black women’s views in greater detail.The sample matched the intended recipients of the feasibility study. Adoptingthis approach allowed the needs of the communities who are eligible toparticipate to be identified, increasing the likelihood of successfulimplementation in the feasibility study and subsequent wider implementation. Inaddition, we were interested in including the voices of Black British women asthey are at greater risk of developing breast cancers with less favourablecharacteristics, at younger ages, resulting in reduced survival.Limitations include that many participants were motivated to participate in thestudy having witnessed the negative impacts of a peer or second-degreerelative’s breast cancer diagnosis. These experiences might have resulted inmore positive views of breast cancer risk assessment, leading to overestimationsof acceptability. However, participants were given the opportunity to expresspositive and negative views, and particular attention was given to dissentingvoices during data analysis.Second, women were responding to the idea of a hypothetical breast cancer riskassessment service meaning their responses reflect anticipated thoughts andfeelings. Nevertheless, although women may respond differently if the service isimplemented in clinical practice, the approach taken is the most appropriate,given that the present research is designed to inform a new service that doesnot currently exist.Finally, we did not assess educational attainment or health literacy of theparticipants, which is likely to have influenced the findings particularly inrelation to information requirements. Women with low health literacy may havedifferent views and preferences with respect to the information required, andthis should be taken into account when developing invitation and risk feedbackmaterials.39 Women also described ahigh mental load, defined as the cognitive and emotional labour involved inmanaging a household and family life.40 In addition, womenrecommended involving community leaders in service delivery to increaseengagement of women from ethnic backgrounds which has been found to be aneffective approach among ethnic minority groups for improving uptake to cancerscreening programmes.41The ease of accessing a breast cancer risk assessment service was identified as acritical determinant of engagement, leading to women desiring a ‘one-stop shop’delivery model. Women reported being unable to attend healthcare appointmentsdue to a lack of time and service availability constraints. This finding is inline with previous research exploring non-attendance at other healthcareservices such as cervical cancer screening.43 women expressed concernabout provision of a low-risk result for fear it could result in complacencytowards breast awareness behaviours such as performing breast checks. One studyfound that receipt of risk information did not significantly change low-riskwomen’s intentions to attend subsequent mammograms.44 However, it remainsunknown how receipt of a low-risk result at a younger age may affect breastawareness behaviours and subsequent engagement with breast screening.Consistent with previous research,46 However, women in this study were unable to identify atangible benefit of receiving an average-risk result.This study offers novel insight into anticipated appraisal of average-riskfeedback, which has received little attention in previous research. The findingssuggest women would not feel reassured by an average-risk result. The purportedbenefits of receiving low- and high-risk results have been reported by women inprevious studies.Given the high mental load women report experiencing which negatively affectshealthcare access, a ‘one-stop shop’ delivery model that minimises the physicaland cognitive energy required to engage with breast cancer risk assessment wouldbe an attractive approach to implementation.47The findings suggest that women may not understand the value in engaging withbreast cancer risk assessment because of their beliefs and assumptions of breastcancer and screening. Therefore, it is imperative that information is providedin the invitation materials to assure women of the need for the service.Furthermore, a mass media education campaign should be delivered prior to andduring implementation to help women understand why it is important for them toconsider engaging with the service. Invitation and risk feedback materials needto be co-developed and piloted with women to ensure information requirementsidentified in this study are addressed and informed choices can be made aboutparticipation. Future qualitative research should examine the views and needs ofdiverse communities in terms of protected characteristics, socioeconomicvariability, health literacy and other geographical areas to inform localisedapproaches to implementation. This research would benefit from adopting anintersectional approach to reduce health disparities among marginalisedpopulations in subsequent implementation research.This study also highlighted the possibility of harmful effects from communicatinglow-risk estimates. Implementation studies should consider assessing thelong-term impact of communicating risk estimates on breast awareness behaviourssuch as performing breast checks. In addition, appraisals of average-riskfeedback warrant further attention to determine the purpose and utility ofproviding such information if not perceived as reassuring.This research has demonstrated that a breast cancer risk assessment service isacceptable for women aged 30–39 years providing that a risk management plan andsupport from healthcare professionals with appropriate expertise is available.Minimising the effort required to engage with the service has been identified as akey determinant of acceptability. There is a need for co-development of invitationand risk feedback materials and educational campaigning about the potential benefitsof risk assessment to facilitate informed decision-making about participation.Click here for additional data file.Supplemental material, sj-docx-1-whe-10.1177_17455057231160348 for Optimising thedelivery of breast cancer risk assessment for women aged 30–39 years: Aqualitative study of women’s views by Sarah Hindmarch, Louise Gorman, Rhiannon EHawkes, Sacha J Howell and David P French in Women’s Health


It has also been linked to finger dermatoglyphics where certain patterns have been associated with breast cancer. This study suggests a possible relationship between finger dermatoglyphic patterns and single nucleotide polymorphism of BRCA1 gene.in a quantitative cross-sectional approach, finger dermatoglyphic patterns were obtained using the ink method from 70 female breast cancer patients and 70 age-matched apparently healthy females. Approximately 5 ml of venous blood was obtained from each participant from which DNA was extracted from the white blood cells collected after centrifugation. DNA was amplified and sequenced and the data aligned with the wildtype template of BRCA1 gene. Fingerprint patterns were analyzed with Chi-square. Mean frequency of fingerprint patterns was analyzed with independent student’s t-test. Differences in data set with p<0.05 were statistically significant.luminal B was the predominant breast cancer molecular subtype among the patients. The predominant fingerprint pattern among breast cancer participants was the loop. Six or more loops had higher frequency among breast cancer females. The predominant BRCA1 gene variant locations were c.34311, c.34320, and c.34321 with c.34311A>C being the predominant variant. Higher percentage frequency of six or more loops in relation to c.34311A>C was observed in apparently healthy females compared to breast cancer females.the study reports for the very first time in Ghana, BRCA1 gene variants and finger dermatoglyphics among breast cancer patients. Although the results are preliminary and inconclusive it creates an avenue for extended studies. Cancer of the breast is a malignant disease that results from abnormal proliferation of cells within the breast tissue, which in advanced cases metastasize to other organs including bony skeleton, brain, lung and the liver ,2. GlobaIt has been established that breast cancer development has genetic undertones with breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) as the most famous . Breast et al. . Five hundred (500) microliters of genomic lysis buffer  was added to 150 μl of thawed buffy coat. The mixture was vortexed for 5 seconds and then let to stand for 10 minutes at room temperature. The mixture was transferred to a zymo-spin column placed in a collection tube and centrifuged at 10,000 xg for 1 minute. The collection tube together with the flow-through was discarded. The zymo-spin column was transferred to a new collection tube. Subsequently, 200 μl of DNA pre-wash buffer was added to the spin column and centrifuged at 10,000 xg for one minute. Five hundred (500) microliters of gDNA wash buffer were then added to the spin column and centrifuged at 10,000 xg for 1 minute. The spin column was then transferred to a clean microcentrifuge tube. 40 μl of DNA elution buffer was added to the spin column and incubated for 5 minutes and then centrifuged at 10,000 xg for 30 seconds to elute the DNA. The purity and concentration of the eluted DNA were determined using a NanoDrop Spectrophotometer. The purity of 1.8-2.0 (A260/A280) and concentration of ≥20 ng/μl were required to qualify the eluted DNA as good. The extracted DNA served as a template DNA for the polymerase chain reaction.Polymerase chain reaction (PCR) procedure and conditions: polymerase chain reaction (PCR) was used for amplifying the DNA extracted using appropriate primers. A total reaction mixture of 25 μl was constituted for cycling in each reaction tube. It was composed of master mix (12.5 μl), nuclease-free water (10.5 μl), template DNA (1 μl), BRCA1 forward primer (0.5 μl) and BRCA1 reverse primer (0.5 μl). The reaction mixture was placed in a thermocycler  and ran for 29 cycles with the following reaction conditions: initial denaturation at 94°C for 5 minutes; denaturation at 94°C for 1 minute, annealing at 62.5°C for 3 minutes, an extension of DNA strand at 72°C for 3 minutes and final extension at 72°C for 3 minutes. The PCR products were subsequently subjected to agarose gel electrophoresis to visualize and confirm correct amplification.Agarose gel electrophoresis: agarose gel (1.5%) was prepared by weighing 1.5 g of agarose powder  and mixed with 100 ml of Tris-acetate-EDTA (TAE) buffer. The 1.5% Agarose mixture was heated till boiling on a hot plate. The beaker was covered with aluminum foil to prevent evaporation of the mixture during heating. The mixture was then removed from the hot plate and allowed to cool after which 2 μl of ethidium bromide  was added and then poured into a casting tray (with a comb fitted) and allowed to solidify. The electrophoresis tank was disinfected with 70% ethanol before the running buffer (1XTAE) was introduced. The solid gel which was within the casting tray was placed in the electrophoresis tank. Approximately 8 μl of PCR product from each sample was loaded into separate wells in the gel. A 100bp DNA ladder  was used as a molecular marker. Gel electrophoresis was run for 45 minutes at 100V. After gel electrophoresis, the gel with the amplicons was visualized using an Amersham imager .Breast cancer type 1 gene sequencing: having confirmed the successful amplification of the target gene, the aliquots of PCR products of samples were shipped to Inqaba Biotechnical Industries (PTY) Limited, South Africa for BRCA1 gene sequencing. The forward strands of the amplified DNA (BRCA1 gene) of samples specifically exon 11, with upstream and downstream introns were sequenced by Sanger Sequencing. The BRCA1 forward and reverse primers were, respectively, 5’CACACAGCTAGGACGTCATC-3’ and 5’TCCATCAAGGTGCTTACAGTC-3’.Single nucleotide polymorphisms determination: when the sequencing results were received, Molecular Evolutionary Genetics Analysis software (MEGA X) was used to retrieve forward sequences of BRCA1 gene exon 11 and surrounding introns. Benchling® software was used to align the forward sequence of the BRCA1 gene (template or wild type) and the forward sequences of the amplified BRCA1 gene from study participants. After alignment of the forward sequences, nucleotides present on the amplified BRCA1 gene which mismatched the template sequence at specific locations were noted as SNPs.Statistical analysis: data was entered and cleaned using IBM SPSS Statistics 20. Data on molecular subtypes among breast cancer and fingerprint patterns were summarized using tables and analyzed with Chi-square. The mean frequency of fingerprint patterns among study participants was analyzed with independent samples student t-test using Graph pad prism version 8 software. Six or more whorls and six or more loops were analyzed with Chi-square. The normality test confirms the normal distribution of data (p > 0.05) before conducting the independent samples t-test. Differences in data sets with p < 0.05 were considered statistically significant.Ethical considerations: ethical approval for the study was obtained from the Ethics and Protocol Review Committee of the College of Health Sciences, the University of Ghana with Protocol Identification Number CHS-Et/M2-5.6/2019-2020. Participation in the study was voluntary and informed consent was sought before recruitment. Participants were given the liberty to withdraw from the study at any time with no consequences.Funding: the Department of Anatomy of the University of Ghana Medical School, partly funded the research through its postgraduate research support fund.Age distribution among study participants: breast cancer females were age-matched with apparently healthy females; therefore, the age distribution was similar for both groups. More than 50% of the participants were pre-menopausal. The age groups of 20-30, 31-40, 41-50, 51-60, 61-70, 71-80 and 81-90 years recorded, respectively, 1, 18, 19, 19, 8, 4 and 1. The minimum and maximum ages of study participants  were 29 and 85 years, respectively. The modal age was 47 years. Generally, individuals 40 years and below were classified as “younger women” while those 41 years and above were classified as “older women”. Of the 70 breast cancer patients, 19 (27%) were younger and 51 (73%) older.Clinico-pathological characteristics of breast cancer participants: in 50% of the breast cancer participants, the pathology affected the left breast, while in 47% of the cases, it was the right breast. In about 3% of the cases, the pathology was bilateral. In 11 of the 19 “younger” cancer patients, the left breast was affected while in 8 it was the right breast. The “older” group of 51, 24 and 25 individuals, respectively, had the left and right breasts affected and bilateral in 2 cases. Of the 70 breast cancer participants, 49 (70%) had been diagnosed with invasive carcinoma of no special type, 18.6% with invasive ductal carcinoma, and 4.3% with mixed carcinoma . Other less frequent histopathological subtypes are shown in Of the breast cancer participants, 48.6% were diagnosed with Grade II, 35.7% with Grade III and 12.9% with Grade I . Stage IFingerprint patterns among study participants: generally, the loop was the predominant fingerprint pattern on all right fingers of breast cancer participants. In apparently healthy participants, the loop fingerprint pattern had the highest frequency on the right index finger, right middle finger, right ring finger and right little finger. However, there were more whorls than loops on the right thumb (Annex 1). The right ring fingers of breast cancer participants did not have an arch fingerprint pattern. On the left hand, the loop was the predominant fingerprint pattern among breast cancer participants. In apparently healthy participants, the loop fingerprint pattern had the highest frequency of occurrence on the left index fingers, left middle fingers, left ring fingers and the left little fingers, however, there were more whorls than loops on the left thumb (Annex 1). Among breast cancer participants, the mean frequencies of fingerprint patterns for loop, whorl and arch were 48.6, 14.9 and 6.5, respectively; and for the control participants, 42.2, 19.6 and 8.2 in the same order. There was, however, no significant difference between the two groups.Six or more loops and six or more whorls among study participants: comparing the presence of six or more loops or whorls among breast cancer participants and controls, no difference was observed. Although six or more loops were more common among breast cancer participants, compared to apparently healthy participants, but the difference was not statistically significant (p = 0.61). Also, six or more whorls had higher frequency among apparently healthy participants compared with breast cancer participants, but the difference was not statistically significant, (p = 0.30). Single nucleotide polymorphism of BRCA1 gene:Annex 2). Variant location c.34320 was the second predominant location of nucleotide mismatch having two heterozygous alleles c.34320A>C (major) and c.34320A>T (minor) among study participants. The third predominant variant location was c.34321 and the resulting variant was c.34321A>T (Annex 2). These variants c.34311A>C, c.34320A>C (major) and c.34320A>T (minor), c.34321A>T are introns located upstream of exon 11.Molecular subtypes of breast cancer and variant location of BRCA1 gene: out of the seventy (70) samples from breast cancer participants, 21 amplified DNA samples from breast cancer participants were selected through simple random sampling and sequenced. Out of the 21 breast cancer participants, 5 were diagnosed with luminal B breast cancer, 5 had triple-negative breast cancer, 5 had HER2 enriched breast cancer, 5 had normal-like breast cancer and one was diagnosed with luminal A breast cancer. From Annex 3, all 5 participants with HER2-enriched breast cancer had c.34311 as the predominant variant location, 4 participants with triple-negative breast cancer had c.34311 as the predominant variant location, 3 participants with normal-like breast cancer had c.34311 as the predominant variant location and 2 participants with luminal B breast cancer had c.34311 as the predominant variant location. Of the seventy (70) breast cancer participants only one was diagnosed with Luminal A and had the variant locations c.34311, c.34320 and c.34321.Fingerprint patterns (six or more loops) and predominant BRCA1 gene variants: forty-eight per cent (48%) of breast cancer participants had six or more loops and c.34311A>C  as such protein folding would not be adversely affected since lysine and arginine have similar qualities ,27. ExonAnnex 3) followed by triple-negative. A subtype of HER2-enriched and luminal B breast cancers are noted for their fast growth and poorer prognosis  and c.34321 (c.34321A>T). The loop pattern was the commonest fingerprint pattern in both right and left hands in cancer patients similar to that exhibited by the controls. The study could not establish any tumour characteristic(s) that relate(s) to fingerprint patterns. The frequency of occurrence of six or more loops was common in c.34311A>C SNPs in both cases and controls. Besides the BRCA1 variants reported, the results are very preliminary and inconclusive and create an avenue for extended studies.Breast cancer development is linked to mutant single nucleotide polymorphism of BRCA1 gene usually harboured within exon 11;Breast cancer has been linked to finger dermatoglyphics where certain patterns have been associated with breast cancer.c.34311, c.34320 and c.34321 are the predominant BRCA1 gene variant locations in the study population with c.34311A>C being the predominant variant;Six or more loops had higher frequency among females with breast cancer compared to apparently healthy females.


We investigated whether dietary patterns of insulinemia, inflammation and overall dietary quality are associated with the risk of total cancer, site-specific cancers, and pathological subtypes among postmenopausal women. We followed 112,468 women, 50–79 years of age, in the Women’s Health Initiative for a median of 17.8 years, documenting 18,768 incident invasive cancers. A higher overall dietary quality was associated with lower risk of total cancer and colorectal cancer. The potential of the dietary pattern to contribute to higher insulinemia and inflammation was associated with greater risk of total cancer, colorectal cancer and more strongly associated with risk of endometrial cancer and breast cancer (including triple negative breast cancer) than overall dietary quality. Additionally, a higher score of metabolites reflecting higher dietary quality was associated with lower lung cancer risk. Dietary patterns associated with cancer risk, therefore, warrant testing in clinical trials for cancer prevention among postmenopausal women.Q5vsQ1(95% CI): EDIH, 1.10 (1.04–1.15); EDIP, 1.08 (1.02–1.15); HEI-2015, 0.93 (0.89–0.98). The multivariable-adjusted incidence rate difference(Q5vsQ1) for total cancer was: +52 (EDIH), +41 (EDIP) and −49 (HEI-2015) per 100,000 person years. All three indices were associated with colorectal cancer, and EDIH and EDIP with endometrial and breast cancer risk. EDIH was further associated with luminal-B, ER-negative and triple negative breast cancer subtypes. Dietary patterns contributing to hyperinsulinemia and inflammation were associated with greater cancer risk, and higher overall dietary quality, with lower risk. The findings warrant the testing of these dietary patterns in clinical trials for cancer prevention among postmenopausal women.We evaluated associations of the Empirical Dietary Index for Hyperinsulinemia (EDIH), Empirical Dietary Inflammatory Pattern (EDIP) and Healthy Eating Index (HEI2015) and their metabolomics profiles with the risk of total and site-specific cancers. We used baseline food frequency questionnaires to calculate dietary scores among 112,468 postmenopausal women in the Women’s Health Initiative. We used multivariable-adjusted Cox regression to estimate hazard ratios (HR) and 95% confidence intervals for cancer risk estimation. Metabolomic profile scores were derived using elastic-net regression with leave-one-out cross validation. In over 17.8 years, 18,768 incident invasive cancers were adjudicated. Higher EDIH and EDIP scores were associated with greater total cancer risk, and higher HEI-2015 with lower risk: HR Hyperinsulinemia and sustained inflammation are two proposed mechanisms driving cancer risk ,2,3. DieEDIH and EDIP scores have shown stronger associations with cancer risk ,9,10,11 Nutritional metabolomics may inform on more specific mechanistic pathways linking diet and cancer. Our metabolomics studies in the Women’s Health Initiative (WHI) suggested that patterns of cholesteryl esters(CEs), phospholipids, acylglycerols and acylcarnitines, may reflect the metabolic impact of insulinemic dietary patterns , while mclinicaltrials.gov as NCT00000611.The WHI enrolled 161,808 postmenopausal women aged 50–79 years between 1993 and 1998 in the United States. The study design has been described . BrieflyDietary data from baseline—self-administered food frequency questionnaire (FFQ) representing intake in the preceding three months—were used to calculate the dietary indices . The FFQStudy outcomes included total cancer, invasive breast cancer , colorectal cancer , non-cancerous intestinal polyps, endometrial cancer , ovarian cancer  and lung cancer . Primarily, CT and OS participants were contacted semi-annually and annually, respectively, to identify cancer diagnoses. Information on cancer incidence was initially verified by medical records and pathology reports and then underwent local and central adjudications by trained physicians . IntestiTime-to-cancer-development was defined as days from enrollment to the return of the follow-up questionnaire in which the event was reported. Participants were followed from enrollment to death, lost to follow-up or to the most recent follow-up (through 1 March 2019), whichever was first.The metabolomics profiling method used has previously been described . BrieflyEach dietary index was adjusted for total energy intake using the residual method . We usedIn addition to the relative risk estimates, we calculated multivariable-adjusted absolute risk (incidence rate) of cancer in quintiles of each dietary index. Using the residual method , each diMetabolomics profile scores were categorized into tertiles because of the lower sample size and examined in relation to cancer risk  using Cox regression and adjusting for the same covariates as in the diet analyses. Furthermore, we used Spearman correlation coefficients to assess correlations between metabolomics classes and dietary index food group components for each dietary pattern, adjusting for BMI, physical activity, and pack years of smoking.p < 0.05 was considered statistically significant, and we further adjusted the nominal p-values for potential false discovery rate (FDR) using the Benjamini–Hochberg procedure.Analyses were conducted using SAS version 9.4 , and R Studio (2021.09.0) was used for data visualization. Two-sided Over a median of 17.8 years of follow-up, 18,768 incident invasive cancers were diagnosed. Participants who consumed the most hyperinsulinemic or most pro-inflammatory dietary pattern (EDIH/EDIP quintiles 5) or the lowest overall dietary quality per DGA (HEI-2015 quintile 1) were more likely to be Black or Hispanic or Latino, have a higher BMI and report lower physical activity and education levels.There are 27 food groups comprising the EDIH and EDIP and nine are common to both indices, including red meat, processed meat, non-dark (non-fatty) fish, sugar-sweetened beverages (regular sodas), artificially sweetened beverages (diet sodas) and refined grains, contributing higher scores; leafy-green vegetables, wine and coffee contributed lower scores . Unique Participants consuming a more hyperinsulinemic dietary pattern consumed fewer calories from total carbohydrates and more calories from total fat, saturated fat, added sugar and animal protein. The macronutrient distribution  for EDIPOf the 464 metabolites retained, elastic-net regression selected 93 for EDIH, 88 for EDIP and 67 for HEI-2015. Correlations among the metabolomics profile scores (m---) were mEDIH-mEDIP (0.73), mEDIH-mHEI-2015 (−0.61) and mEDIP-mHEI-2015 (−0.29). In addition, correlations between the metabolomics profile scores and their corresponding dietary scores were: mEDIH-EDIH (0.45), mEDIP-EDIP (0.33), and mHEI-2015-HEI-2015 (0.50). Higher EDIH was associated with higher amino acids and glycerophosphocholines (glyceroPC), and with lower mono/di-carboxylic acids , CEs, phosphosphingolipids (phosphoSL), alkaloids, purines, pyridines and pyrimidines . The metWomen classified in the highest quintile of EDIH had greater risk of total cancer compared to those in the lowest quintile, with a multivariable-adjusted incidence rate difference of 52 per 100,000 person years and corresponding HR (95% CI) of 1.10 (1.04–1.15). Findings from the categorical analyses were aligned with EDIH modelled as a continuous variable . A 1 sd Women in the highest EDIP quintile were at greater risk of total cancer compared to those in the lowest quintile, with a multivariable-adjusted incidence rate difference of 41 per 100,000 person years and corresponding HR (95% CI) of 1.08 (1.02–1.15) . A 1 sd Women classified in the highest HEI-2015 quintile were at lower risk of total cancer compared to those in the lowest quintile, with a multivariable-adjusted incidence rate difference of −49 per 100,000 person years and corresponding HR (95% CI) of 0.93 (0.89–0.98) . Higher p values for the interactions of the dietary patterns and the potential effect modifiers were generally not significant. The results for total cancer, breast cancer and endometrial cancer remained robust for EDIH after mutually adjusting for EDIP and HEI-2015  or chronic systemic inflammation (EDIP) and risk of developing total cancer and site-specific cancers among postmenopausal women, while also examining these associations with an established index of overall dietary quality (HEI-2015). While all three dietary indices were significantly associated with risk of total cancer, colorectal cancer and intestinal polyps, EDIH and EDIP were further associated with risk of breast cancer and endometrial cancer. In addition, EDIH was associated with multiple breast cancer subtypes including the more aggressive triple negative breast cancer.Although a previous study found that higher EDIH was associated with higher total cancer mortality in both men and women , most pr2 increment in BMI was associated with a nearly 3-fold increase in endometrial cancer risk [Although EDIH and EDIP were associated with higher risk of overall breast cancer and ER-negative subtype, only EDIH was associated with risk of multiple other breast cancer subtypes, while HEI-2015 showed no association. Only one study has examined EDIH in relation to breast cancer risk, and found higher risk for overall breast cancer with stronger associations for ER- and HER2+ tumors . Two stucer risk . While Ecer risk .The metabolomic profile of HEI-2015 had 23 metabolites that overlapped with the EDIH, and had 17 metabolites overlapped with the EDIP, which may partly explain the higher correlation between the HEI-2015 related metabolomics score is and EDIH-related metabolomics score, compared with the EDIP-related metabolomics score. We observed no associations between the metabolomics profile scores of the three dietary patterns and cancer risk, except for the associations between HEI-2015 score and overall lung cancer. We had 441 cancer cases in the metabolomics sample compared to 18,768 in the overall sample. It is therefore possible that the lack of associations in contrast to the dietary analysis is indicative of the low statistical power in our metabolomics sample. The association observed had wide 95% CIs, reflecting potentially unstable point estimates. Nevertheless, we characterized the correlations of metabolomics classes with the food group components of the dietary scores, which yielded novel and confirmatory findings. In the two previous metabomomics studies ,17, highp-values to minimize the potential for false discovery. Potential limitations include using self-reported dietary intake though the FFQ was evaluated for bias and precision [Our study has several strengths. We investigated EDIH, EDIP and HEI-2015 in relation to multiple cancers, and dietary pattern-related metabolomics profiles and their association with cancer risk. We estimated multivariable-adjusted incidence rates in addition to the usual relative risk estimates, providing better clinical and public health context for interpreting the relative risk estimates, e.g., incidence rate among the non-exposed (reference—quintile 1). We adjusted recision . Althougrecision ,47. Thourecision ,49.In summary, our findings suggest that hyperinsulinemic and pro-inflammatory dietary patterns, as well as overall dietary quality, are associated with risk for several cancers among postmenopausal women, supporting further investigation of these dietary patterns in relation to cancer risk in dietary intervention studies to modify cancer risk.


Alcohol consumption is internationally recognized as one of the compelling risk factors for breast cancer, but it does not necessarily correlate with the prognosis of breast cancer patients. Alcohol consumption in breast cancer patients was addressed in the 2022 Breast Cancer Clinical Practice Guidelines. A systematic review and meta-analysis of epidemiological studies on alcohol consumption and breast cancer recurrence, breast cancer-related mortality, all-cause mortality, and cardiovascular disease mortality in breast cancer patients was performed. The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant publications reporting cohort or case–control studies published until March 2021. A total of 33 studies (32 cohort studies and 1 case–control study) met the eligibility criteria; 4638 cases of recurrence, 12,209 cases of breast cancer-specific mortality, and 21,945 cases of all-cause mortality were observed. With regard to breast cancer recurrence, 7 studies assessed pre-diagnosis alcohol consumption (relative risk (RR) 1.02, 95% confidence interval (95% CI) 0.77–1.37, p = 0.88) and 3 studies assessed post-diagnosis alcohol consumption , and no significant increase or decrease in risk was observed. With regard to breast cancer-related mortality, 19 studies assessed pre-diagnosis alcohol consumption , 9 studies assessed post-diagnosis alcohol consumption , and no significant increase or decrease in risk was observed. With regard to all-cause mortality, 18 studies assessed pre-diagnosis alcohol consumption , 8 studies assessed post-diagnosis alcohol consumption , and pre-diagnosis alcohol consumption was associated with a significantly decreased risk. With regard to cardiovascular disease mortality and alcohol consumption, 2 studies assessed it, and the RRwas 0.47 , showing that alcohol consumption was associated with a significantly decreased risk. The limitations of this study are that drinking status was mainly based on a questionnaire survey, which is somewhat inaccurate and has many confounding factors, and the cut-off value for the maximum alcohol intake in many studies was low, and it is possible that the actual intake was only an appropriate amount. In many countries, a standard drinking amount is set, and wise decisions are required. Alcohol consumption is internationally recognized as one of the compelling risk factors for breast cancer. Ethanol contained in alcoholic beverages and its metabolite acetaldehyde have been experimentally shown to be carcinogenic . HoweverIn June 2022, the Japanese Breast Cancer Society practice guidelines, the 2022 edition, was published by the Japanese Breast Cancer Society. In the guidelines, we addressed the clinical question, “Is alcohol consumption associated with prognosis in breast cancer patients?” To make recommendations for this clinical question, we assessed the benefits and harms of alcohol consumption after patients were diagnosed with breast cancer by performing a systematic review and meta-analysis of the relevant literature. The results of this systematic review and meta-analysis are reported.A quantitative and qualitative systematic review was performed according to the Minds Handbook for Clinical Practice Guideline Development Ver. 3.0, 2020 [The PubMed, Cochrane Library, and Ichushi-Web databases were searched using the terms “breast neoplasms”, “breast cancer”, “alcohol drinking”, “alcohol consumption”, “prognosis”, “recurrence”, “survival”, and “mortality”. The search was limited to articles published up to March 2021.According to these criteria, two authors (TN and YK) independently reviewed all titles and abstracts of the retrieved articles. The full articles were evaluated for relevance. Systematic reviews were eligible when they were judged to be of moderate quality according to AMSTAR  and inclThe qualities of the trials selected through the process described above were evaluated according to the Minds Handbook for Clinical Practice Guideline Development Ver. 3.0, 2020 [https://review-manager.software.informer.com/5.4/) was used for statistical analysis. The summary of relative risk (RR) (hazard ratio or risk ratio) and 95% confidence intervals (95% CI) for the highest and lowest categories of alcohol intake were estimated using the inverse variance method.Review Manager software 5.4 , and no significant risk was observed. The RR for the post-diagnosis alcohol intake was 0.96 , showing no heterogeneity in the effect (I2 = 0%), and no significant risk was observed , showing high heterogeneity in the effect , but not significant. In nine studies, the RR for post-diagnosis alcohol intake was 0.96 , showing slight heterogeneity in the effect (I2 = 38%), but not significant , showing high heterogeneity in the effect , and the risk was slightly reduced , but not significant  expression status were reported in relation to breast cancer-related death , 19, 27,ced Fig. C. The RRFig. 2 = 9%, but nThere were 18 pre-diagnosis studies , 33, 34 2 = 37%), and the risk was significantly reduced , and the risk was not significantly reduced , showing slight heterogeneity in the effect , and the risk was significantly reduced , and the risk was significantly reduced , showing slight heterogeneity , and the risk was significantly reduced  .The Ministry of Health, Labour and Welfare of Japan recommends consuming not more than 20 g of alcohol per day. However, this evidence is based on Tsugane’s study  and is tRegarding ER status, we examined it in 5 studies , 19, 27.There are several limitations of this systematic review. First, study selection involved filtering for English and Japanese language articles, potentially resulting in the exclusion of relevant, non-English publications. Second, in some studies, analyses were either performed without adjusting for any confounding factors, or analyses did not account for the factors considered most important in regard to the outcome of interest, such as age, BMI, and stage of the initial breast cancer.Third, since alcohol consumption status is mainly based on questionnaire surveys, the exact amount and frequency of alcohol consumption are not known. In addition, there is the possibility of underreporting.The present findings led us to create the recommendation for the clinical question in the Japanese Breast Cancer Society Clinical Practice Guideline Committee, 2022 edition, as follows: Whether pre-diagnosis or post-diagnosis, alcohol consumption has a substantial effect on risk and is unlikely to increase the risk of breast cancer recurrence and death from breast cancer.However, excessive alcohol consumption increases the relative risk of all-cause mortality, and alcohol consumption should be limited to a moderate level as defined by each country.


Among controls, the reported use of mosquito control products were mosquito coils (65%), followed by insecticide-treated nets (56%), repellent room sprays (53%), and repellent skin creams (15%). Compared to a referent group of participants unexposed to mosquito control products, there was no significant association between breast cancer risk and mosquito coils. There was an association in breast cancer risk with reported use of insecticide-treated nets; however, that association was weak and not statistically significant. Participants who reported using repellent sprays were at elevated risks compared to women who did not use any mosquito control products, even after adjustment for all other mosquito control products . We had limited power to detect an association with repellent skin creams. Although only a few participants reported using repellent room sprays weekly/daily or < month-monthly, no trends were evident with increased frequency of use of repellent sprays, and there was no statistical evidence of heterogeneity by estrogen receptor (ER) status (p-het > 0.25). Our analysis was limited when determining if an association existed with repellent skin creams; therefore, we cannot conclude an association. We found limited evidence of risk associations with widely used mosquito coils and insecticide-treated nets, which are reassuring given their importance for malaria prevention. Our findings regarding specific breast cancer risk associations, specifically those observed between repellent sprays, require further study.Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (ORThe online version contains supplementary material available at 10.1186/s13058-023-01737-x. Breast cancer incidence is increasing in many countries in sub-Saharan Africa (SSA), with about half of the cases diagnosed among women less than 50 years of age –3. The GThe most commonly used measures for mosquito control include indoor residual spraying, insecticide-treated nets, or a combination thereof . There hAs malaria coexists with breast cancer in Ghana, we aimed to determine if the reported use of different types of mosquito control products with possible insecticide exposures was associated with breast cancer risk in the Ghana Breast Health Study .We used data from the Ghana Breast Health Study (GBHS), a multi-disciplinary population-based case–control study conducted from 2013 to 2015 in two major cities of Ghana: Accra and Kumasi. Participant characteristics and methods of screening and recruitment have been described in detail previously , 15. In Controls were frequency-matched to cases based on the area of residence and were cancer-free at the time of recruitment. Hospital data from 2010 to 2012 were used to identify enumeration areas with the highest concentration of breast cancer patients to frequency match controls to cases according to location . The arePrevious studies have evaluated the questionnaire data and reported on associations of breast cancer risk with education, reproductive factors, body size, and family history of breast cancer , 2, 16. p-value of 0.05 was considered to denote statistical significance.Data analysis was conducted using Stata MP14.2 . Chi-squared tests were used to estimate associations with anti-mosquito control products by case–control status and determine associations among controls only. We calculated Spearman correlations between different mosquito control products. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression to determine associations between breast cancer risk and malaria-related insecticide exposures . Minimally adjusted models adjusting for matching factors (age and site) were first performed. Fully adjusted variables included age, site, education, age at menarche, body size, number of pregnancies, age at first birth, the median duration of breastfeeding months, menopause, and age at menopause, as previously described , mosquito coils , or other mosquito control products . In the partially adjusted model, we observed increases in breast cancer risk with the use of both repellent room sprays and skin creams . In the multivariable model , the ORs for repellent room sprays and skin creams were attenuated but remained statistically significant for repellent room sprays [ORadj = 1.56 (95% CI=1.32–1.84)] and for repellent skin creams [ORadj = 1.35 (95% CI=1.08–1.67)].Table We also assessed reported daily, weekly, monthly, and more than monthly use , p = 0.002], although the use of insecticide-treated nets alone was also elevated [ORadj = 1.39 (95% CI 0.96–2.01)]; it was not statistically significant. Due to the limited number of cases, we could not evaluate the single use of repellent skin creams alone and their association with breast cancer risk. Mutually adjusting for the use of the different mosquito control products attenuated the associations for all products, with only repellent spray remaining statistically significant compared to those not reporting any mosquito control products [ORmadj = 1.42 (95% CI=1.15–1.75), Table Many participants used multiple products in combination . There was also a marginal suggestion of differences by age for mosquito coil with an inverse association among the older age groups  compared to ER-negative (N = 35) tumors, although the test for heterogeneity was not significant . The association of any reported repellent room sprays and mosquito coils compared to no mosquito control products showed no evidence of heterogeneity (p-het > 0.19).To determine if there might be differences in associations by ER status, potentially pointing to a hormonal effect, we estimated breast cancer risk by ER status of tumors  or commercially available products on the market . To clarify whether these easily accessible over-the-counter commercial products may represent a risk for breast cancer, additional research is required to investigate insecticide exposures from these products. Another drawback is the lack of precise assessments of each participant’s insecticide exposure and scant data on other possible exposures and confounding factors that could present alternative explanations for our findings. Of particular concern was the possibility of residual confounding by education since mosquito control products were more frequently reported among those with higher education. Recall bias is another potential limitation of all case–control studies; however, we suspect this to be minimal since we only observed associations for specific types of products. In this study, only 32 controls (2%) reported using other mosquito control products, suggesting that we captured the common ways Ghanaian women are exposed to anti-mosquito-related insecticides.In conclusion, the lack of association between insecticide-treated nets and mosquito coils with breast cancer in our study findings is encouraging, given their wide use globally for malaria control programs. Further research on specific products and active chemical formulations is needed, especially for repellent sprays, to determine if the risks observed in our study are plausible.Additional file 1. Table S1. Frequency of combinations of mosquito control product use among 2096 controls.Additional file 2. Table S2. Rho (in bold) and p-values from Spearman correlation for mosquito control product use among 2096 controls.Additional file 3. Table S3. Mosquito vector control products among controls by identified study breast cancer risk factors.Additional file 4. Table S4. Association results of mosquito control methods and frequency of use and breast cancer risk in the Ghana Breast Health Study.Additional file 5. Table S5. Association of insecticide exposures and breast cancer risk stratified by age at diagnosis/recruitment.


Women at lower socioeconomic status (SES) had lower awareness than those at higher SES . Women reported several anticipated help-seeking barriers . Waiting to see if a symptom will pass was the most commonly reported barrier to help-seeking (71.5%). Most women  reported that they would seek medical help within 2 weeks of discovering a breast cancer symptom. Interventions to increase awareness of non-lump breast cancer symptoms and reduce help-seeking barriers are needed, with considerations of appropriate reading levels and modalities for women with lower education and SES.Women with a family history of breast cancer have an increased lifetime risk of the disease. Delay in symptom presentation can lead to poorer outcomes. Low awareness of breast cancer symptoms and help-seeking barriers have been associated with delay in presentation in the general population. Symptom awareness and help-seeking barriers among women at increased risk of breast cancer are unknown. We conducted analysis of survey data which included women with moderate and high risk of breast cancer from 20 secondary and tertiary care clinics in England (n = 408). Women completed a validated survey assessing breast cancer symptom awareness, barriers to help-seeking and anticipated delay in help-seeking. Women recognised an average of 9.1/11 breast cancer symptoms (SD = 2.1). Nipple rash was the least recognised symptom (51.0%). Women educated to at least degree level had higher awareness than those with lower education (β = 0.14, 95% CI 0.13, 0.99,  More adAccording to the Model of Pathways to Treatment , there aIncreased time taken to present a potential breast cancer symptom to primary care  may increase the risk of later stage diagnosis . LimitedWomen with a family history of breast cancer are at increased risk of developing the disease . HealthcKnowledge of cancer symptoms is likely to be one of several factors that affect help-seeking. During the help-seeking interval in the Model of Pathways to Treatment, several barriers to help-seeking may occur . In the Symptom awareness and barriers to help-seeking for cancer symptoms can vary between socio-demographic groups . In UK sWe aimed to explore breast cancer symptom awareness, anticipated barriers and delays in help-seeking among women at increased risk of breast cancer. Our objectives were to (1) assess levels of symptom awareness, anticipated barriers to help-seeking, and anticipated delay in help-seeking among women at higher breast cancer risk and (2) investigate the sociodemographic and clinical factors associated with these outcomes.2This analysis is part of the ENGAGE study. The ENGAGE study was a large UK multicentre prospective project, investigating cancer prevention decision-making in women with a family history of breast cancer . The ENG2.1Participants were recruited across 20 secondary and tertiary clinics. These included family history clinics (n = 12), breast clinics (n = 4), clinical genetic centres (n = 3) and a family history clinic with genetics support (n = 1). Most clinics were in major cities across England, and recruitment was open between September 2015 and December 2016. Following an appointment at the clinic, women were approached by a research nurse or healthcare professional to discuss the study. Women who verbally consented were given an ENGAGE study pack, which contained the survey and a freepost envelope. Participants who did not return the survey after 2 weeks were sent a reminder postcard, and after 4 weeks were resent the survey. The study team were sent the personal data of women who verbally consented to participate in the study team via a secure online portal. The patient’s data supplied was their email address, home address, age, and their risk classification (‘moderately high’ or ‘high’).The ENGAGE study was granted ethical approval by the National Research Ethics Service Committee North West – Preston (14/NW/1408). Women were eligible to participate if they were classified as having moderately high or high risk of developing breast cancer according to NICE guidance CG164  Full in. Women p2.2The following measures from the ENGAGE baseline survey were used for the current analysis.2.2.1https://osf.io/mqz9y/.We recorded self-reported education level (‘≥degree level’ vs. ‘<degree level’), ethnicity (‘white ethnic groups’ vs. ‘ethnic minority groups’) and perceived health status . We assessed numeracy with a single item (“Which of the following numbers do you think represents the biggest risk of getting a disease?”), with three response options (e.g. 1 in 100). Numeracy was dichotomised as “poor” if the answer was incorrect, and “good” if the answer was correct. Participants’ breast cancer risk category was provided by staff at the clinic . Partic2.2.2Eleven items were used to measure recognition of breast cancer symptoms, which were adapted from the validated Breast Cancer Awareness Measure (Breast-CAM) . All ite2.2.3We measured barriers to help-seeking that were included in the Breast-CAM scale . Partici2.2.4Participants were asked ‘If you found a change in your breasts, how soon would you contact your doctor?’, from the Breast-CAM scale . Options2.3p < 0.05.We reported levels of breast cancer symptom awareness, number of help-seeking barriers endorsed, and anticipated delay in help-seeking in proportions, frequencies, and means. Univariable and multivariable linear regression models were conducted to investigate the relationship between participants’ socio-demographic and clinical factors on the outcomes of number of breast cancer symptoms identified and help-seeking barriers endorsed. We intended to use univariable and multivariable logistic regression models to examine whether awareness of breast cancer symptoms and number of help-seeking barriers endorsed were associated with an anticipated delay in help-seeking (‘≤2 weeks’ and ‘>2 weeks’). However, we did not complete these analyses due to insufficient numbers in the ‘delay to help-seeking’ group. All analyses were conducted in SPSS version 26, with statistical significance set at a 2-sided 33.1p = 0.086), clinical risk (p = 0.62), or SES (p = 0.054) between survey responders (408 women) and non-responders (324 women). Participant characteristics are displayed in In total, 732 women were invited to complete the survey, and 408 (55.7%) completed the survey. There were no significant differences in age  . Lump orp = 0.011; p = 0.027) and those classified as having an unclear level of risk  were aware of fewer breast cancer symptoms. In univariable models, those with good numeracy were aware of fewer symptoms of breast cancer , but this did not retain significance in the multivariable model.A multivariable linear regression model examined the relationship between the number of symptoms women are aware of and their socio-demographic and clinical variables. In the multivariable model (n = 384), those educated at degree level or above (vs. less than degree level) were aware of a higher number of breast cancer symptoms , out of a possible 11 barriers. Waiting to see if a symptom will pass on its own was the most frequently reported barrier , followed by difficulty making an appointment with the doctor  . Difficup = 0.040), fair  and good health status  were all associated with an increased number of barriers to help-seeking compared to those reporting excellent health  . Of the 4In this UK study involving women at higher risk of breast cancer, there was good recognition of most breast cancer symptoms, but poorer recognition for non-lump symptoms such as nipple rash and skin redness. Despite participants being at increased risk of breast cancer, several anticipated barriers to seeking medical help for a cancer symptom were highly endorsed, such as waiting for a potential symptom to pass before contacting their doctor. However, most women reported they would seek medical help after identifying a potential breast cancer symptom within 2 weeks.Recognition of lump-based breast cancer symptoms in our sample of women at higher risk of breast cancer was similar to the general population. In our sample, 96.3% and 94% of women recognised a lump in their breast and armpit respectively as a symptom of breast cancer, similar to findings in two UK based population studies exploring cancer awareness in the general population . In our Our study found evidence for existing health inequalities affecting symptom awareness among women at higher cancer risk, with those at lower SES and lower levels of education presenting with poorer symptom recognition. These sociodemographic associations reflect findings in general population samples . Women wIn our sample, practical and service barriers were endorsed more than emotional barriers to help-seeking. Practical and service barriers most commonly endorsed in previous UK based population studies include difficulty making an appointment with the doctor, and not wanting to waste the doctor’s time. These barriers were similarly frequently endorsed within our sample , in whic4.1There is a need for targeted support to increase awareness of several non-lump based breast cancer symptoms and reduce help-seeking barriers among women at higher risk of the disease. Previous interventions have successfully improved cancer symptom recognition among the general population. For example, the Promoting Early Presentation intervention involved a scripted interaction between a radiographer covering breast cancer symptoms and how to check for breast changes, supplemented by an educational booklet. The intervention increased breast cancer symptom awareness in older women, but had limited effects on help-seeking barriers . An educ4.2The study had limitations. We collected data on recognition of a list of presented symptoms, however previous evidence has found symptom recall is significantly lower when using an unprompted recall format . Therefo4.3In this UK study involving women at higher risk of breast cancer, there was poorer recognition of non-lump symptoms, and several help-seeking barriers were endorsed. Lower education and SES were associated with reduced symptom awareness, indicating a need for interventions to support this group. Increasing symptom awareness, particularly of non-lump based symptoms of breast cancer, and reducing help-seeking barriers could reduce time from symptom identification to presentation, and consequently improve outcomes among women at higher risk of breast cancer.Sophie M.C. Green: Formal analysis, Conceptualization, Data curation, Writing – original draft, Writing – review & editing. Kelly E. Lloyd: Formal analysis, Conceptualization, Data curation, Writing – original draft, Writing – review & editing. Samuel G. Smith: Funding acquisition, Conceptualization, Methodology, Data curation, Writing – review & editing, Supervision, Project administration.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.