P < 0.001; pre-treatment versus 3-month follow-up, 0.83 , P = 0.08; pre-treatment versus 6-month follow-up, 0.92 , P = 0.006; and pre-treatment versus 12-month follow-up, 0.21 , P = 0.40. For the anxiety score, the pooled results of the random effects model were as follows: pre-treatment versus post-treatment, 0.97 , P < 0.001; pre-treatment versus 3-month follow-up, 1.45 , P = 0.21; and pre-treatment versus 6-month follow-up, 1.00 , P = 0.02). The pooled result of the fixed effects model for the comparison between pre-treatment and the 12-month follow-up was 0.10 . The subgroup analysis revealed that the geographical location, treatment time and treatment form were not sources of significant heterogeneity. CBT significantly improved the depression and anxiety scores of the cancer survivors; such improvement was maintained until the 6-month follow-up. These findings support recommendations for the use of CBT in survivors of cancer.This study aimed to investigate the effects of cognitive behavioral therapy (CBT) on anxiety and depression in cancer survivors. The PubMed, Embase, PsycINFO, and Cochrane Library databases were searched. Randomized controlled trials that evaluated the effects of CBT in cancer survivors were included. The standardized mean difference (SMD) was used as an effect size indicator. Fifteen studies were included. For the depression score, the pooled results of the random effects model were as follows: pre-treatment versus post-treatment, SMD  = 0.88 ,  According to the National Coalition for Cancer Survivorship, “an individual is considered to be a cancer survivor from the time of diagnosis through the balance of his or her life.” This definition includes family members, caregivers, and friends because survivorship experience also affects them2. With the promotion of cancer screening and improvements in treatment, the survival rate of patients with cancer continues to improve. This leads to a dramatic increase in the number of survivors over the past few decades4. As reported by the National Cancer Center based on data from 17 cancer registries in China, the 5-year survival rates for 26 types of cancer increased from 30.9 to 40.5% between 2003 and 20155. In the United States, the number of cancer survivors increased from approximately 3 million in 1971 to nearly 15.5 million in 20168. This number is expected to reach more than 26 million by 20407. Owing to the prolonged survival period after treatment, efforts need to be made to improve the quality of life and survival status of cancer survivors.The concept of cancer survivors was first proposed by Fitzhugh Mullan, a physician diagnosed with cancer10. It has been reported that they are prone to experiencing fatigue, sleep disorders, chronic pain, fear of recurrence, anxiety, and depression, which not only disrupt the quality of life and return to usual activities but can also be barriers to engaging in survivorship care13. Among these psychosocial challenges, psychological problems, such as depression and anxiety require early identification, because they are often under-diagnosed and under-treated14. Some cohort studies have shown that cancer survivors report higher rates of anxiety and depression than individuals without a history of cancer16. Depression is reported in approximately 8–33% of patients with cancer and anxiety in approximately 17–23%18. Depression is associated with poor adherence to cancer treatment and poor survival20. Additionally, it is detrimental to quality of life and is correlated with a two-fold increase in the risk of all-cause death among cancer survivors21. Psychological anxiety makes patients irritable, unable to concentrate, negative, and very pessimistic, all of which can decrease their quality of life22. For cancer survivors, these psychological disorders not only interfere with quality of life but can also become barriers to engaging in survivorship care. This is especially for women, adolescents, and young individuals, because they are particularly at risk for mood disturbances23. Seriously, these disorders are difficult to alleviate with drugs, leaving the needs of cancer survivors for improved quality of life, especially their psychosocial needs, far unmet. Health-related quality of life is a multidimensional construct that encompasses physical functioning as well as psychosocial aspects of emotional and social functioning. There has been a paradigm shift in health service delivery to a more holistic approach, which considers quality of life and overall functioning24.Cancer survivors often face physical, psychological, and psychosocial challenges that extend into long-term survivorship25. The term CBT describes a group of psychotherapeutic techniques that treat psychological distress and maladaptive behaviors by changing cognitions and behaviors26. CBT describes a hybrid of strategies to facilitate cognitive, behavioral, emotional and social change. The interventions include the teaching of social skills through role playing, problem solving techniques, coping skills, examining alternative ways of perception, and engagement in verbally mediated self-control27. According to CBT, the emotions and behaviors of individuals are determinants of their cognitive processes. Once cognitive defects are corrected, negative emotions and behaviors improve. As a result, CBT aims to modify cancer survivors’ wrong cognition into a more rational manner of thinking, helping them gain a sense of control over the disease and increasing their confidence in fighting it28. Furthermore, CBT has been traditionally used for patients with mental health disorders, such as depression and anxiety29. Many randomized controlled trials (RCTs) have examined the effects of CBT on anxiety and depression among cancer survivors. However, the results are inconsistent and not comprehensive because of the wide variations in sample sizes, ethnicities, and outcome assessment methods used.Several studies have reported that psychosocial interventions can effectively treat these distressing emotions, with cognitive behavioral therapy (CBT) being the most frequently used approachIn this study, a meta-analysis of RCTs was conducted to comprehensively evaluate the effect of CBT on anxiety and depression in cancer survivors through a dynamic follow-up from 3 to 12 months.30. As this study analyzed data from previously published studies, ethical ratification was not required. Considering that this study is a meta-analysis study using the existing peer-reviewed literature,and no human/animal patients were directly involved in the study, receiving their con-sent to participate or consent to publish was not considered as necessary.The meta-analysis procedure was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelinesAccording to the predefined search strategy, we identified appropriate literature using the following electronic databases: PubMed, PsycINFO, Embase, and Cochrane Library. The search keywords included “cognitive behavioral therapy,” “cognitive behavior therapy,” “neoplasms,” “cancer,” “anxiety,” and “depression.” Keywords in the same category were combined with “OR” and those in different categories with “AND.” Subject terms and free words were searched in combination, and the retrieval method was adjusted according to database characteristics. The retrieval steps for the PubMed database are presented in Supplementary table The inclusion criteria for the studies were as follows: (1) participant: cancer survivors ; (2) variable compared: differences in the effects of CBT and treatment as usual (TAU) on depression and anxiety in patients with cancer; and (3) study type: RCT.The exclusion criteria were as follows: (1) non-literary research, such as review and meeting abstracts; (2) third-generation CBT, such as mindfulness-based cognitive therapy and acceptance and commitment therapy; (3) patients receiving or preparing to receive standard treatments, such as surgery, radiation, chemotherapy, or immunotherapy; and (4) repeated publications or multiple articles with the same data (only the article with the most complete research information was retained).31.Two reviewers independently completed literature screening. After obtainment of the included literature, information on the first author, publication year, country, basic participant characteristics , cancer type and stage, follow-up time, intervention period, and study outcome was independently extracted according to the pre-designed table. After the data extraction, the two reviewers exchanged the tables, and disagreements were resolved via discussion. The quality of the RCTs was assessed using the Cochrane Collaboration’s tool2 test were used for heterogeneity testing32. P < 0.05 or I2 > 50% indicated significant heterogeneity, and the random effects model was used for the data analysis. Random-effects model attempted to generalize findings beyond the included studies by assuming that the selected studies are random samples from a larger population33. P ≥ 0.05 or I2 ≤ 50% indicated non-significant heterogeneity, and the fixed effects model was applied for the meta-analysis. Fixed-effect models assume that the population effect sizes are the same for all studies33. Subgroup analysis was performed according to the geographical location and treatment time. The effect of a single study on the meta-analysis was evaluated using a one-by-one exclusion method34. Publication bias was evaluated using the Egger test35. When significant publication bias existed, the stability of the combined results was assessed using the trim-and-fill method36. All statistical analyses were performed using the Stata 12.0 and RevMan 5.3 software.The standardized mean difference (SMD) and 95% confidence interval (CI) were used as the effect size indicators to evaluate the differences in the anxiety and depression scores between post-treatment and the 3/6/12-month follow-up. Cochran’s Q test and I49 and 2 qualitative analyses.The literature retrieval results and screening processes are presented in Fig. 51, one on patients with melanoma47, five on patients with mixed cancers53, one on patients with laryngeal squamous cell carcinoma49 and one on patients with head and neck cancer54. The average age of the participants ranged from 37.45 to 59.7 years. The CBT intervention period was 2–12 weeks, and the follow-up period was within 12 months after the intervention. The rating scales used for anxiety and depression are listed in Table The publication dates of the 15 articles ranged from 2003 to 2022. These studies were conducted in China, the United Kingdom, South Korea, Iran, the United States, and Canada. The sample size ranged from 29 to 294, with 1979 cases. Of the included articles, seven reported on patients with breast cancerThe methodological quality assessment results of the included articles are shown in Supplementary Fig. 2 > 50%, P < 0.05). The pooled results of the random effects model were as follows: pre-treatment versus post-treatment, SMD (95% CI) 0.88 , P < 0.001  showed significant heterogeneity among the included articles . The pooled results of the random effect models were as follows: pre-treatment versus post-treatment, SMD (95% CI) = 0.97 , P < 0.0001 , whereas the combined effect values of the other subgroups were significant  , while the combined effect values of the more than 6 weeks subgroup were significant  , while those of the other subgroups had a significant difference   and more than 6 weeks subgroup  were significantly different . However, the results of the trim-and-fill method suggested that the program did not fill in the fictitious negative results to enhance the symmetry of the funnel plot; further, the meta-analysis results did not change, indicating that the original pooled results were stable. The included studies that investigated the other outcome indicators did not have a significant publication bias (P > 0.05).The Egger test was used to evaluate the publication bias between the studies Table . The inc54 reported differences in the depression rates between patients with cancer who underwent CBT and TAU at the 6-month follow-up, with the rate in the CBT group decreasing from 68 to 21% and that in the TAU group from 70 to 24%, showing no significant difference between the two groups (P > 0.05). Savard et al.51 suggested that CBT significantly influenced the depression and anxiety scores at the end of the intervention (P < 0.05).Duffy et al.This study analyzed the efficacy of CBT for anxiety and depression across 15 RCTs that included 1979 cancer survivors. The analysis showed that CBT can significantly reduce depression and anxiety in cancer survivors during the intervention period and until 6 months of follow-up, as measured by the depression and anxiety scores, when compared with TAU. The observed effects persisted until the 6-month follow-up, suggesting that CBT provided significant, lasting improvements in depression and anxiety. However, more high-quality RCTs are required to confirm these findings. Additionally, there was no finding that the geographical location, treatment time and treatment form of the included studies affected the heterogeneity.16. Although antidepressants are effective for the treatment of anxiety and depression, they yield poor tolerance, rebound insomnia, and adverse side effects after discontinuation55. Given the effects of depression and anxiety on symptom burden and quality of life, evidence supporting effective interventions with minimal side effects and long-term benefits is needed for cancer survivors with anxiety and depression. Evidence from RCTs has indicated that several behavioral approaches, such as mindfulness-based approaches, hypnosis, and self-management strategies, are effective in improving anxiety and depression in cancer survivors58. However, most studies have been conducted in breast cancer survivors; thus, these interventions need to be further tested in different groups of survivors.In a previous meta-analysis and systematic review, with pooled samples of approximately 50,000 long-term cancer survivors, the prevalence of depression and anxiety was 12% and 18%, respectively59. Currently, CBT is recommended as the first-line treatment for depression and anxiety by the National Institute for Health and Care Excellence in the United Kingdom. However, among cancer survivors, the majority of CBT-related studies have focused on those with insomnia61, with less attention paid to those with depression and anxiety. A recent meta-analysis examined the effect of CBT on the quality of life and psychological health  of patients and survivors of breast cancer. It revealed that CBT is effective in improving the psychological symptoms of both patients and survivors, with meaningful clinical effect sizes62. In our study, the beneficial effects of CBT on depression and anxiety in the cancer survivors were maintained until the 6-month follow-up, which suggests the durability of this treatment. Our results are consistent with a previous finding that “individual CBT has short-term effects (< 8 months)” on both depression and anxiety among cancer survivors63. Therefore, further research is needed before CBT can be used in the long-term.CBT has been demonstrated to be effective in the treatment of depression and anxiety, with well-maintained effects over a 3-month follow-up period48. Traditional CBT usually proceeds through face-to-face sessions with a professional in an individual or small-group format and therefore requires significant manpower, time, and cost65. Internet-based CBT programs is a promising therapeutic alternative that can spread widely within a very short period. They are more accessible and effective than traditional face-to-face interventions in terms of manpower and cost66. Internet CBT may provide access to standardized, evidence-based therapy without physical and/or geographical barriers67. It has been reported that internet CBT can achieve comparable outcomes to face-to-face CBT for mild to severe anxiety and depression in the general population68. Therefore, internet CBT has potential to revolutionize the delivery of CBT, improving the accessibility and availability of CBT content for cancer survivors.It's worth noting that, among the included literatures, several studies were based on internet CBT69. Although we applied strict inclusion and exclusion criteria to minimize heterogeneity, there were still high levels of heterogeneity found, which may be attributed to the different methods used to deliver CBT. A subgroup analysis was then used to analyze the potential sources of heterogeneity. The analysis revealed that the geographical location and treatment time were not sources of significant heterogeneity. Importantly, a treatment time of more than 6 weeks was associated with the treatment effect of CBT on both depression and anxiety. Thus, a treatment time of more than 6 weeks is recommended to ensure the efficacy of CBT. Specifically, the subgroup analysis was only performed on the post-treatment changes, since there were fewer than five included studies that conducted 3-, 6-, and 12-month follow-ups. Therefore, the effects of follow-up deserve further attention. Taken together, these findings support recommendations for the use of CBT in survivors of cancer.The methodological quality of the included articles herein was moderate; thus, the findings may have the potential to serve as a basis for clinical practice guidelinesThis study has several strengths. A wide range of databases were searched without restrictions on time scales or language. Strict inclusion and exclusion criteria were used to minimize heterogeneity. The high level of heterogeneity may be attributed to the differences in how CBT was delivered. Study selection and quality assessment were independently completed by two reviewers. The control group was limited to TAU, which can objectively evaluate the intervention effect of CBT. Additionally, the methodological quality of the included studies was moderate, and the control of selection bias, reporting bias, and loss-to-follow-up bias was reasonable. Importantly, although there was significant publication bias for some outcome indicators, the results of both the trim-and-fill method and the one-by-one elimination method suggested the high stability of the pooled results.This study has some limitations, which might have influenced the results. First, the heterogeneity of the included studies was large, and no significant source of heterogeneity was found in the subgroup analysis. Second, the CBT intervention approaches were inconsistent among the included studies, which is an important source of clinical heterogeneity. Currently, there is no appropriate quantitative method to evaluate the impact on the results of the meta-analysis. Finally, for some outcome indicators, the number of included studies was small, and the sensitivity analysis results were unstable, requiring more large-sample studies to verify the results.70. It has been suggested that behavioral interventions are valid for quality of life in cancer patients, and CBT is moderately efficacious for anxiety, depression, and stress symptoms72. Our study described a statistically significant effect of CBT on depression and distress among cancer survivors, and the results concluded that CBT was an effective intervention in improving depression and distress in cancer survivors during the intervention period and until 6 months of follow-up. Current interventions are often face to face and specialist led. The present mata-analysis included several studies based on internet CBT48, which has potential to revolutionize the delivery of CBT, improving the accessibility and availability of CBT content for cancer survivors. For future studies, it is necessary to address whether intervention effects appear after a continuous intervention.Depression and anxiety are highly prevalent concern, affecting cancer survivors and patients. A suite of interventions incorporating cognitive, behavioral, and educational components has been developed for depression and other psychological symptomsThis systematic review provided a detailed summary of the evidence on the effect of CBT interventions on depression and anxiety among cancer survivors and evaluated dynamic data at 3–12 months of follow-up. Compared with TAU, CBT significantly improved the depression and anxiety scores of the cancer survivors, and this improvement was maintained until the 6-month follow-up. It is recommended that more large-sample, high-quality RCTs be conducted for verification.Supplementary Information.


In Australia, breast cancer is one of the most common cancers affecting women. Between 1987–1991 and 2012–2016, the five-year survival rate improved from 75% to 91%. The increased chance of survival due to early detection and treatment interventions has resulted in more women living with the diagnosis. This qualitative study was designed to analyse the journey of breast cancer survivors, their experience of psychological distress and changes in quality of life (QOL) due to the increased prevalence amongst Australian women. In-depth interviews were conducted; they lasted over 45 min and comprised 15 participants. The main topics discussed were knowledge of breast cancer prior to diagnosis, psychological distress, QOL and experience of use of healthcare services. The results showed that the process of diagnosis, undergoing treatment and isolation post-treatment resulted in high amounts of psychological distress. A reduction in QOL was also experienced due to treatment and medication side effects, fatigue, cognitive changes, and body-image perception. These findings can assist researchers in providing evidence-based frameworks for policy changes and for further investigation into effective healthcare interventions. Breast cancer is one of the most common causes of cancer-related deaths in women globally. It occurs when abnormal cells in the breast grow uncontrollably. It is more common among women; however, a small proportion of men also are affected by breast cancer . After dFor BCS, common issues range from treatment side effects , financiStudies have indicated that BCS experience mental health issues as soon as they are diagnosed with cancer, during treatment and survivorship. Two main concerns within psychological distress have been identified for BCS: mental health issues and distress surrounding cognitive function. One-fourth of breast cancer patients will develop anxiety and depression at some point in the breast cancer journey . Those aQOL is an individual’s perception of their position in life, in the context of the culture and value system they live within along with their goals, expectations, standards and concerns . It is cWithin the literature, there is insufficient focus on the qualitative experience of Australian BCS from diagnosis to survivorship. Most of the literature available is based on quantitative studies, with limited research being available on the experiences of BCS. This research is an attempt to fill this gap. There has also been a focus on mental health and cognitive disorders such as struggles with depression and increased anxiety; However, there is a need for a greater understanding of the progression of these issues in Australian BCS throughout their entire BC journey.This research aims to understand the journey undergone by BCS diagnosed with breast cancer from diagnosis to survivorship. Furthermore, it explores the challenges experienced by the BCS due to physical changes, financial hardship, emotional distress and social isolation The Australian healthcare system is unique due to the country’s cultural diversity and different demographics. Understanding the experience of specifically Australian women with breast cancer is essential, as it will allow healthcare providers to understand the experiences of BCS in greater depth within the cultural context. This, in turn, may help facilitate greater sensitivity when treating their patients and assist in developing strategies and policies for BCS.This cross-sectional exploratory research is based on a qualitative research method. It aims to understand the journey undergone by women, diagnosed with breast cancer, from diagnosis to survivorship. Further, it explores the challenges experienced by the BCS due to physical change, financial hardship, emotional distress and social isolation.Eligible participants were BCS; they were aged 35 years and above, living in Sydney and had been diagnosed for at least a year. A total of 15 women with breast cancer were recruited for the study. Participants were excluded if they had been diagnosed less than one year ago to ensure all participants had completed their treatment. Participants that were diagnosed greater than 11 years prior were also excluded as they may not clearly recollect their early experience of diagnosis. Multiple strategies were used to recruit participants including snowball and convenience sampling, social media and community organisation advertising. For example, through the assistance of the organisation Pink Hope, a preventative health charity, we acquired participants using flyers. Advertising on social media gained the most traction, with participants sharing and passing on information to other survivors. Before recruitment commenced, ethics approval was obtained from the University of Sydney Human Research Ethics Committee (25 August 2021). The participants were also presented with the “Participant Information Statement” to ensure the study had informed consent and that participation was entirely voluntary and anonymous. The data were also saved in OneDrive and password-protected, and only researchers had access. These in-depth interviews were conducted over 45 min with 15 BCS. The first author participated in two days of training prior to the interviews commencing.This specific qualitative method was chosen to ensure that the full experience of BCS was explored effectively. In particular, QOL was measured subjectively rather than using established measurement tools. Quantitative measurement of QOL qualifies experience’s on a scale rather than exploring participants’ experiences which was important for this study. In the in-depth interviews, the interviewer led the BCS through a series of open-ended questions to establish the experience of breast cancer diagnosis, treatment and living with the diagnosis . The intA thematic analysis was conducted by researchers on the interviews . FirstlyThe main themes identified within this study were emotional and psychological distress throughout the journey of BCS, a reduction in QOL seen through social changes and physical symptoms and access to health services.The sociodemographic background of the study participants is presented in Participants were asked to recount the knowledge they had of symptoms, diagnosis and treatment of breast cancer prior to their diagnosis. Three participants had a family history of breast cancer and were more likely to be informed about breast cancer. Symptoms identified by the participants were lumps, swelling, sensitivity and pain in the breast. Around 66.7% of participants had heard of a mammogram before, and 40% knew of breast self-examination (BSE). The most common treatment identified was chemotherapy, with 73.3% reporting prior knowledge see . Some ofParticipants were asked, “How did you find out you had breast cancer?” The three main methods of diagnosis were finding a breast lump through self-examination, noticing changes in their breasts and through ultrasounds and mammograms. Approximately 40% mentioned that, initially, they dismissed the symptoms as being hormonal or something less serious See .Of these 15 participants, the most common sources of treatment reported were chemotherapy, radiation and surgery. Out of the total participants, 86.6% had chemotherapy and 53% had radiation, and all the participants underwent surgery (the majority received a mastectomy 66.6%). Side effects from these treatments and the preventative medications were also highly reported to impact QOF See .The study participants were asked to share any experience they had of psychological or emotional distress. Open-ended questions were used to assist participants in outlining their experience during diagnosis, treatment and post-treatment. Responses were categorised under the broad themes and presented below:Most participants (46%) went into a state of shock when they received their diagnosis, with three of the fifteen participants reporting a memory loss or blurred memories of the moment and four others reporting a trauma response .Participant 010 described the experience as:“My whole world just collapsed. And I think I just sat in his room for like 20 min wailing, feeling like I was gonna be sick.”Three of the fifteen participants reported crying, while four mentioned moving into “survival mode” to attack the problem pragmatically. Participant 008 stated that: “First question was, out of my mouth was what are we doing about it? Tell me what to do next…I was very practical, very pragmatic.”Of the 15 BCS interviewed, 13 went through at least one round of chemotherapy, either pre- or post-surgery. About 40% of participants reported a feeling of losing their identity, and 33% reported feeling helpless. For example, participant 015 stated that:“Chemo is terrible ’cause you lose not just your hair, you lose your eyelashes and your eyebrows, you lose absolutely everything…you just go grey, and again, it is the treatment that makes you sick… I found it overwhelming at times, I was quite emotional.”After treatment had been completed, several BCS reported a lack of direction and support, which caused psychological distress. Due to the continuing side effects of medications, menopause and the abrupt nature of ending treatment, 40% of BCS report of feeling abandoned and isolated.“I have had such a long time of treatment and now, I feel like I am going into this open water of not as much intensity.” (P010)Participant 011 also described the inability to deal with long-term medication side effects that caused considerable distress in many BCS.“There is always an end in sight…you have the surgery, and then you want clear margins, and you get your diagnosis…You know how many treatments of chemotherapy you are having over a period of time, You know how many treatments of radiation you are having over a period of time. So, once you get through all of that they put you on this medication, which the side effects don’t end…There is no end in sight.” (P011)A common phrase repeated amongst participants was “scanxiety” (3 participants), which describes the feeling of panic and stress before a check-up and scan. BCS also report a hyper awareness of aches and pains and how they jump to the conclusion of cancer quickly (46%). Four BCS described this anxiety as always being in the back of their minds and as constant stress. Participant 008 especially struggled with this stress and described her experience:“Biggest thing that I battle with all the time, it’s always there. It may not rear its ugly head every day, but it is always at the back of your mind, always.” (P008)Open-ended questions were asked about the impact of breast cancer on the QOL of the study participants. These questions focused on daily activities, sleep, fatigue, cognition, physical body image and sexuality. The three main themes that contributed to changes in QOL were physical symptoms, support network issues and finally accessibility to services.Several common symptoms impacted the QOL of BCS. These included the inability to sleep, increased fatigue, chemo fog, vaginal dryness and changes in body image. Almost all BCS reported having issues with the perception of their bodies. The majority reported embarrassment of their bodies, particularly how they look in front of others, feeling unattractive to partners and a reduction in self-esteem. Five of the study participants highlighted concerns with the reconstructions, while three BCS outlined how not having nipples contributed to this issue. Participant 006 linked her issues with body image to her relationship with her husband and her sexuality.“Now it is just very obvious I don’t have nipples, but they are just it looks like I’ve been massacred. And my husband is a bit sad about it all [chuckle]. Unfortunately, men are very…They’re quite visual creatures, unfortunately, in my experience, from what I’ve seen, but he’s very understanding, and I think it’s more the problem of the menopause, which is why sex life is dwindling.” (P006)Some BCS did report that cutting off their own hair before it fell out was a way to regain some control.“I did make a pre-emptive strike to cut off my hair, but not straight away, ’cause I used to have really long, curly hair, and I thought, Well, that’s something…Like I think a lot of women, something you can control.” (P007)Difficulties sleeping were reported by 66% of the BCS, while the other four participants had no issues with sleeping. Four BCS mentioned that hot flushes and side effects from menopause are the reason for this poor sleep, whereas two others associated poor sleep with an overactive mind. Three BCS use sleeping tablets and melatonin to get to sleep.“So not very good sleep to begin with and the chemo, I couldn’t sleep, I couldn’t…I just felt sick the whole time. Trying to sleep when you’re feeling nausea, wasn’t fun, so it was very difficult trying to sleep and then getting up and smells really affected me.” (P014)Fatigue not only impacts BCS during chemotherapy but lasts for years post-treatment. Three women reported that they feel like they have less energy, and two others say they have issues with maintaining work-hour requirements. On average, fatigue was worse during treatment, and now most BCS have reported improvements. Participant 009 was one of many BCS who experienced issues returning to work due to fatigue. “I would say for the first three years the fatigue is really, really tangible, very hard to, I guess, to sustain things for a long period of time…I found working, going back to work, even though it was a couple of days a week at first, were exhausting. Now, I still, even now, I still don’t have the physical, I guess, stamina that I used to have.” (P009)Cognitive changes impact self-confidence and workability. BCS have reported feeling like they can’t remember words and suffer from chemo fog and short-term memory loss. Four of these participants are worried about these cognitive changes impacting their working life. This issue was highlighted by participant 002, who stated:“As well, so I think once I got back into that, I felt like my brain came back online, but before that, It’s like I could. Sometimes I couldn’t even find the words to say, and I was worried. I’m like how am I gonna go back to work and have these conversations with families? And you know, I sound dumb pretty much.” (P002)Bodily changes due to menopause, medication side effects and changes in self-esteem have been seen to reduce BCS ability to be intimate. For varying reasons, from the experience of dryness and pain to a lower libido, 60% of the participants reported some change in their sex lives. Participant 009 describes her struggle with getting hormone replacement therapy to reduce symptoms and improve her ability to be intimate.“I had a very healthy sex life with my husband before any of this happened. Now it is non-existent. Not fun, not wanting to. But it is extremely painful. It doesn’t…I can’t obviously, can’t take HRT, I have tried. I have begged, I have screened, I have fought with doctors, I’ve been shut down at every turn.” (P009)Another participant outlined the steps she has taken to improve her sexual functioning.“Firstly, you don’t really feel like it, that’s for sure. But then afterwards, I think because of menopause, you’ve dryness and discomfort, definitely suffering from both of those. But because of my involvement volunteering with The Mater, I was lucky enough in those groups…So, she talked us through the option of laser in your cervix to get that sort of moisture back. But I…So we need to use lubricant now because it’s never really got back to 100% normal.” (P008)Support system changes were identified in the breast cancer survivors’ relationships with their children, husbands, friends and family members. These changes not only impacted them emotionally during the time of treatment but have also had lasting effects post-treatment. Most of these BCS (80%) were married and had children, and a majority of them reported that their husbands were extremely supportive.“He was very supportive. I was very lucky. I you know on being on breast cancer support group pages that I so many stories of relationships breaking down and you know divorce and all the rest of it. But yeah, no I was very lucky he was 100% in it with me.” (P002)A few BCS did outline issues with children’s behaviour or difficulties amongst the extended family unit. Participant 014 in particular noted the difficulties within a family unit. “My little girl was quite young at the time, so she didn’t really know what was going on, but her behaviour started becoming quite bad during it all…So it was difficult for the older kinds, but they all worked so they threw themselves into work and study and friends and kind of like, I felt like they ignored me a lot.” (P014)Seven out of the fifteen participants’ social networks shifted during their journey. Three BCS highlighted their desire for privacy throughout this time, while three others mentioned that they felt forgotten. Six BCS specifically mentioned that they felt disconnected and distant. Alternatively, 33% of BCS reported not feeling isolated and completely supported by their community, family and friendsFor participant 008, it came as a surprise as to who stepped up and who stepped back.“I felt like my network went into the washing machine and some people went down the drain, and others who came out lovely and fluffy; they are my posse. I’d trust my life with them. It’s quite amazing the people who step away…But I had a couple of very, very close friends who are not in my inner circle anymore, and just stepped away.” (P008)BCS in both the public and private sectors reported financial distress throughout their journey see . Out of “My husband had to take time off because he had to return to his work. The cancer therapy helped us pay half the bill, which they do because of the stress that comes on between a family and then the kids trying to go to school, go to work, and then your husband’s gotta look after the little one, cook, clean and wash.” (P012)There were also reports that post-treatments, due to financial constraints, BCS were not able to access services to improve their QOL.“Everything that’s come after it is virtually out of pocket so that I can’t afford to seek the therapy that I actually really need on a regular basis.” (P007)During treatment, interactions with the medical staff and ease of using services contributed to the overall QOL of BCS. One woman mentioned that she felt “like everyone was treating me like a queen. It was great. I’m like everyone so nice to me because they know I’ve got cancer” (P002), whereas another mentioned that during treatment she had a few issues with communication that led to further anxiety.“Oh, you’ve got more of a chance of it coming back somewhere else than in the other breast”, and I remember thinking, “Did you just hear what you just said?” They just…I know it’s hard for them and they need to be separate emotionally, but they also need to remember that they’re dealing with people and they’re dealing with people’s lives”As mentioned previously, there was a drop-off in support after active treatment. Here, BCS reported that they had difficulty getting help for the side effects of medications.“They don’t give you any way to manage those symptoms of what you’re gonna go through on the medication. They don’t identify things that you can go, “Oh, that’s what that is, and this is how I can treat it, how to avoid it.” They just kind of ignore the fact that you have side effects from it, or they say, “You know, I’ve seen people worse off, so you’ve got it okay.” (P011)This study revealed that participants frequently reported psychological distress and a reduction in QOL. This aligns with the previous literature, where issues of financial hardships , comorbiPsychological distress is the emotional suffering associated with stressors and demands that are difficult to cope with daily. The results from this study illustrate that the significant points of psychological distress along the journey of BCS are receiving the diagnosis during treatment and, finally, the process of survivorship. The most commonly endorsed stressors include chemotherapy trauma (46%) and loss of identity (40%). The anxiety of reoccurrence was noted by all survivors, with three of the fifteen participants reporting that it no longer concerns them. The literature has observed that BCS levels of anxiety and depression decrease over time, which contradicts the findings of our study where it has increased . The incParticipants’ QOL was explored by discussing how certain indicators, identified from the literature review, have impacted participants’ QOL. The significant concerns derived from these interviews were physical symptoms of BC, changes in support systems for BCS and poor body-image perception.Poor body image is associated with mastectomies and breast reconstruction surgery . AlthougSleep and fatigue are both factors contributing to the reduction in QOL. Several BCS reported insomnia, trouble staying asleep and extreme fatigue throughout the day. There was a common trend of fatigue and sleep issues being more prevalent during treatment and then improving as time went on, supported in the literature . There wCognitive changes were linked to memory loss and reduced capacity for work for the majority of the study participants. Similar findings were reported in previous studies, where participants noticed language, memory, spatial ability and motor function changes . HoweverThe majority of participants were married and had children. This resulted in extensive conversations about relationship changes and social isolation. Most BCS reported that their husbands were highly supportive and a great help during this time. Only a minority mentioned relationship breakdowns and increased stress due to their partners. Multiple studies have illustrated the positive effect of supportive spousal relationships ,37, whicThe experience of using and accessing healthcare services was identified as a significant factor contributing to QOL. Within Australia, Medicare is the publicly funded universal health care insurance scheme that all Australians can access. In addition to this, private health coverage is also available to paying customers to cover the gaps in Medicare. These two services however still do not alleviate the entire financial burden of Breast Cancer treatments and services. Financial distress acted as a significant barrier to healthcare services for BCS . This reIn some cases, participants had to pick and choose the most needed services at a specific time rather than having access to all services that may improve their QOL. Although the majority did report that financially they were stable, all acknowledge the exorbitant costs of life-saving and life-enhancing treatments during survivorship. Breast reconstruction was a significant source of financial strain. It is not covered under Medicare, and as it is not considered a life-saving surgery, private health services often do not cover it.Treatment and communication by staff within the healthcare system had a significant impact on survivors’ experience and distress. Four of the fifteen BCS reported at least one issue of switching practitioners or feeling like they were not being heard. One of the most considerable contributions to distress during diagnosis was the communication of medical staff about the severity and course of action for treatments. Participants also highlighted how their health was now in their own hands after treatment, and there was no transition phase. Many felt abandoned and isolated by the shift in control as well as being at a loss as to how to manage their symptoms into the future. Most participants continued to take medication after their treatments to prevent cancer recurrence. These medications, however, had harmful side effects that BCS have had to learn how to manage by themselves. This, paired with financial restrictions, has resulted in a reduction in QOL.However, there are a few limitations of the study. The limitations of this study include social media and readiness bias. The effectiveness of social media recruitment resulted in a biased sample toward BCS who do not use or do not have access to social media. In addition, it also eliminates participants who are not yet ready to share their experiences as they are still dealing with the consequences of their disease.Fifteen BCS were interviewed to understand their journey from pre-diagnosis to survivorship. The average participants were aged 35–45, had at least one child, were married and were Australian. The most common issues mentioned throughout this study were the lack of interventions for medication side effects, changes in their body image and anxiety around cancer reoccurrence. There were also many accounts of how physical side effects from treatments have impacted their work and social and sexual lives.These findings are based on a qualitative study, with a small sample of 15 in-depth interviews; therefore, a generalisation of the study cannot be made. Due to the small number of participants and sampling error, there was also a lack of older participants from diverse backgrounds.This study has provided a preliminary basis for the experience of BCS and can expanded on in a larger study using quantitative methods to assess QOL and psychological distress. These findings have implications for policymakers and for the healthcare industry along with the importance of a survivor’s relationship with their healthcare team and their ability to access services, which was especially highlighted. It would be our recommendation to focus future studies on the experience of BCS from ages 35 to 45 including their diagnosis. Future studies should also include BCS of culturally diverse groups and older age cohorts.From this research, it is also clear that younger women should have access to free and convenient mammograms. Additionally, the experience of sexuality and early menopause is an area that needs to be examined to provide better services and support for survivors. Access to post-care services, links to support groups and information about medication side effects should be prioritised in order to increase survivors’ QOL.


BRCA mutations. A literature search was conducted in PubMed, Cochrane Library, and Embase. Studies concerning the effect of fertility treatments on breast cancer risk in genetically susceptible women were included. The fixed and random effects models were used to estimate the summary effects. Risk Of Bias In Non-randomized Studies - of Interventions instrument was used to assess the risk of bias in the included studies. A total of 5,282 studies were screened. Five cohort studies and three case-control studies were included. Breast cancer risk was not significantly increased by fertility treatments in general genetically susceptible women , women with a family history of breast cancer , or women with BRCA mutations . In subgroup analyses, there was no significant increase in breast cancer risk whether in BRCA1 mutation carriers , BRCA2 mutation carriers , or in the women treated with in vitro fertilization , clomiphene citrate  or gonadotropins . This is the first meta-analysis concerning the impact of fertility treatments on breast cancer risk in genetically susceptible women. Despite the finding that fertility treatment did not significantly increase breast cancer risk in genetically susceptible women, large prospective cohorts with more detailed information are required. Further investigations are needed to explore subtypes of breast cancer, genetic background of hormone-related breast cancer, and the association between BRCA mutations and the incidence of hormone receptor-positive breast cancer. Women with hereditary breast cancer factors are more likely to be infertile and tend to receive fertility treatments. The safety of fertility treatments that contain hormone-related medications for ovarian stimulation has gained wide attention; however, evidence of the safety of fertility treatments is limited. This study aims to assess the association between fertility treatments and the incidence rate of breast cancer in women with a family history of breast cancer or PROSPERO(CRD42021281336). Breast cancer is the most common malignancy in female adults worldwide and is a leading cause of cancer-related deaths . Women wThe fertility medications include CC (clomiphene citrate), gonadotropins and letrozole. CC is a selective estrogen receptor modulator and could inhibit the negative feedback of gonadotropin releasing, thus promoting estrogen production and inducing ovulation . GonadotBRCA1 or BRCA2 mutations are also important risk factors for breast cancer in an inherited way (BRCA mutations on ovarian reserve in women who present with lower serum anti-Müellerian hormone (AMH)  , 11. Del oocytes . Due to Despite multiple clinical studies and meta-analyses focused on the association between fertility treatments and breast cancer risk, and they have confirmed the safety of fertility treatments among general female population, there was no meta-analysis concerning the impact of fertility treatments on women with hereditary breast cancer factors –18. EvenBRCA mutations.Therefore, to investigate whether fertility treatments increase the risk of breast cancer in women with hereditary risk factors, we reviewed the current literature, including randomized controlled trials (RCTs), case-control and cohort studies, to assess the association between fertility treatments and the incidence rate of breast cancer in women with a family history of breast cancer or This study was conducted in accordance with the Meta-analyses of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guidelines , 24. TheBRCA mutations  who received fertility treatment were included in the study population. Fertility treatments encompassed assisted reproductive technology (ART), in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), and the use of ovarian stimulating drugs, such as CC, letrozole, and gonadotropins. The reference population included genetically susceptible women who did not receive fertility treatment. The endpoint was breast cancer diagnosis. There were no limitations on publication year or status. Case series or reports that enrolled fewer than 10 patients, studies with incomplete data or overlapping cohorts, and non-English language literature were excluded. Studies on patients diagnosed with breast cancer before receiving fertility treatments such as embryo or oocyte cryopreservation, were also excluded.Randomized controlled, cohort and case-control studies focusing on the association between breast cancer incidence rates and fertility treatments were considered. Women with a family history of breast cancer or Three electronic databases including PubMed, Cochrane Library, and Embase, were searched until September 1, 2021, to identify relevant studies. The MESH terms used in the search are as follows:  AND “Breast Neoplasm.” A detailed search strategy is presented in The titles and abstracts of the included studies were browsed by two independent reviewers (W.L. and L.X.). Duplicates were excluded in addition to studies that were inconsistent with the eligibility criteria mentioned above. After the initial screening, the full texts of potentially relevant studies were inspected and assessed for eligibility. We sent emails to six authors for additional information. We received responses from two authors, and one of the responders could not provide further information because our request was unmatched by her data. The other four did not respond, perhaps because the system was invalid or they were unreachable. Discrepancies were resolved by discussion between the two authors to reach a consensus.We generated an Excel worksheet with a frame of key information for analysis. Information was extracted as follows: general information of the study , study characteristics , and outcomes including odds ratio (OR), hazard ratio (HR), relative risk (RR), and raw data for further calculation. Two reviewers (W.L. and L.X.) independently collected data from the selected articles and resolved disagreements through discussion.2 was < 50%, moderate heterogeneity when I2 was ≥ 50% and < 75%, or high heterogeneity when I2 was ≥ 75%. Fixed-effects (inverse-variant) models were used to determine the summary estimate effects in the cases with low heterogeneity; random-effects (DerSimonian-Laird) models were used in the cases with moderate or high heterogeneity.The OR was used as a summary statistic for ORs, HRs, and RRs because the incidence rate was low. I² statistics with 95% confidence interval (CI) were used to evaluate the heterogeneity between studies. The result was classified as low heterogeneity when IBRCA mutation types, including BRCA1 and BRCA2, or types of fertility treatments, such as IVF, CC, or gonadotropins. Sensitivity analysis was conducted to assess whether the pooled estimates were stable. Stata 16.0 software  was used for the statistical analysis.Subgroup analyses were conducted according to Robvis was used to create a risk-of-bias plot (Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) instrument was used to assess the risk of bias in cohort studies and case-control studies by two independent reviewers (W.L. and L.X.) . Disagreias plot  , in women with a family history , or in women with BRCA mutations   Figure 2BRCA1 or BRCA2 mutations    Figure 3P=0.14, I2 = 0%)    Figure 4I2 = 0%) , 27, 28. 22.58%) , 28, 32.= 35.6%) , 28, 32.BRCA mutations. No evident effects of fertility treatments on breast cancer risk were observed among women with different types of BRCA mutations or women treated with IVF, CC, or gonadotropins.In this study, we observed that compared with population with similar genetic backgrounds who was not exposed to fertility treatments, the breast cancer incidence rate was not significantly increased by fertility treatments in women with a family history of breast cancer or In our study, there was no evidence to support that fertility treatments have an impact on breast cancer incidence in genetically susceptible women; this was consistent with the findings of most previous meta-analyses on the general female population, in spite of some controversies among the previous studies that breast cancer risk under fertility treatments was lower compared with women who gave birth  and high2 = 60.21%) was present in the five included studies concerning women with a family history of breast cancer, of which one study showed a notable increase in breast cancer risk by fertility treatments   positive tumors, and CDH1 mutations have been identified in bilateral lobular breast cancer (Moderate heterogeneity (I17–4.04) . In agre17–4.04) , it was  unclear , 35. Thet cancer –36. HoweBRCA mutations or separate mutations in BRCA1 or BRCA2. It is speculated that BRCA mutation carriers are not easily affected by hormone treatment due to the clinicopathological characteristics of BRCA-associated cancer. Triple negative breast cancer (TNBC) is more common in BRCA1 carriers. In most cases of BRCA1-associated cancer, the expressions of estrogen receptor (ER) and progesterone receptor (PR) were significantly lower (BRCA2 carriers rather than BRCA1 carriers (BRCA2 carriers showed high heterogeneity (I2 = 80.6%), which was probably caused by differences of sample sizes between the two studies (BRCA2 mutation carriers, while 326 BRCA2 mutation carriers with breast cancer were included in the study of Kotsopoulos (BRCA mutations and hormone-related breast cancer requires further study.No significant negative effect of fertility treatment was observed on women with ly lower . Howevercarriers . The eff studies , 28. In  studies , only thThe effects of IVF, CC, and gonadotropins were evaluated separately in this study. None of the treatments was observed to increase the risk of breast cancer. However, the effects of CC remain controversial. A meta-analysis demonstrated that breast cancer risk was increased by non-IVF therapy, of which the main fertility drug was CC . A cohorThere are some limitations in this study. Eight studies included in this analysis were non-randomized observational studies, which contained three retrospective cohort studies, two prospective cohort studies, and three case-control studies. A high proportion of retrospective studies may have caused serious recall bias. Randomized trials concerned the impact of fertility treatments on breast cancer risk were not suitable based on ethical considerations. And cohort studies with large sample sizes were lacking.Apart from study size and design, confounding factors were the main sources of high discrepancies among the included studies. Multiple confounding factors that heckled the assessment were adjusted by baseline matching, multivariable regression, or stratification. The discrepancies would be better addressed if all confounding factors such as age at menarche, parity, oral contraceptive use, subfertility, breast cancer subtypes and history of mastectomy were fully presented or adjusted in each study. Moreover, in most studies, patients with hereditary factors were not the target population, and information on genetically susceptible patients was not fully recorded or analyzed. Therefore, several studies were excluded.The follow-up duration is important for the interpretation of the findings. A short period of follow up duration might cause a loss of record of breast cancer occurrence. Only three studies provided median or mean follow-up duration ranging from 9.69 to 30 years , 30, 32.BRCA mutations. Large prospective cohort studies with more detailed information such as fertility treatment regimens, history of mastectomy, and follow-up years are required. Further investigations are needed to explore subtypes of breast cancer, genetic background of hormone-related breast cancer, and the association between BRCA mutations and the incidence of hormone receptor-positive breast cancer.In conclusion, the breast cancer incidence rate was not significantly increased by fertility treatments in women with a family history of breast cancer or The original contributions presented in the study are included in the article/LW and XL designed the study. LW and XL performed database search, data extraction, and quality evaluation. XL, JY, and RP performed data analyses. XL, LW, and HZ drafted the manuscript. All authors contributed to the article and approved the submitted version.We would like to thank Dr Ruqiya Pervaiz for kindly providing additional information, as detailed in the manuscript. We would also like to thank the corresponding authors who replied to our request for additional information. Thank Dr. Rui Wang for providing instructional advice.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.


A risk-stratified approach to breast cancer screening has gained international interest as a mechanism to better balance the benefits, harms and costs of screening programmes. The aim of our agenda setting meeting was to identify key uncertainties to resolve in order to implement a risk-stratified breast screening programme within England. Findings from a 5-year programme of research assessing the feasibility of such an approach in England were presented before individual discussion groups and an open plenary session regarding what preparation needs to take place. Key findings highlight the need to further develop risk modelling to ensure equity of access to breast cancer risk assessment and ensure a risk-stratified programme is cost-effective. Other issues highlighted related to capacity and capability of the health services to offer an integrated risk assessment pathway that is accessible. Attendees identified ways in which risk-stratification could be implemented to minimise inequity of access to screening.It is now possible to accurately assess breast cancer risk at routine NHS Breast Screening Programme (NHSBSP) appointments, provide risk feedback and offer risk management strategies to women at higher risk. These strategies include National Institute for Health and Care Excellence (NICE) approved additional breast screening and risk-reducing medication. However, the NHSBSP invites nearly all women three-yearly, regardless of risk. In March 2022, a one-day agenda setting meeting took place in Manchester to discuss the feasibility and desirability of implementation of risk-stratified screening in the NHSBSP. Fifty-eight individuals participated  with relevant expertise from academic, clinical and/or policy-making perspectives. Key findings were presented from the PROCAS2 NIHR programme grant regarding feasibility of risk-stratified screening in the NHSBSP. Participants discussed key uncertainties in seven groups, followed by a plenary session. Discussions were audio-recorded and thematically analysed to produce descriptive themes. Five themes were developed: (i) risk and health economic modelling; (ii) health inequalities and communication with women; (iii); extending screening intervals for low-risk women; (iv) integration with existing NHSBSP; and (v) potential new service models. Most attendees expected some form of risk-stratified breast screening to be implemented in England and collectively identified key issues to be resolved to facilitate this.  Breast cancer is the most common form of cancer in the UK with approximately 56,000 cases reported annually equating to 15% of all cancer cases . In addisome risk stratification, by only routinely inviting women aged 50–70 years where there is evidence of screening benefits, in addition to very high risk screening for example, due to genetic mutations or family history [Risk stratification has been proposed as a means of improving the ratio of benefits to harms, including costs to the healthcare system, of breast screening for some time . In othe history . AdditioTo allow risk stratification for breast cancer screening at a population-level, much research has focussed on improving risk prediction in the context of national breast screening programmes ,10. ModeInternational randomised trials in the US (WISDOM)  and EuroThus, there is a pressing need to resolve any uncertainties around implementation outside of a research setting, should these ongoing trials find that risk stratification is indeed effective in reducing cancer stage at diagnosis, and costs. This would allow the NHSBSP to adequately prepare for successful implementation of risk-stratified screening, addressing potential barriers such as staff training and IT system development. Non-UK countries have been considering how to implement a risk-stratified approach to breast cancer screening, mainly in Europe, Australia and Canada ,24,25,26Recent reviews have aimed to identify key research gaps regarding risk-stratified screening for breast cancer, notably one based on a consensus meeting of experts working on various Europe-wide projects on this topic (ENVISION) , and a sThe aims of the meeting were therefore to ascertain whether attendees with a significant profile in breast screening, breast screening related research and/or screening policy decision-making (a) think risk-stratified breast screening should be implemented and, (b) identify issues that would need to be resolved before implementation into the NHSBSP could proceed.A one-day agenda setting meeting was held (March 2022) in hybrid format in Manchester, England. This formed the final stage of the PROCAS2 National Institute of Health and Care Research (NIHR) Programme Grant evaluating the feasibility of risk-stratified breast cancer screening (BC-Predict)  specificTo begin the meeting, after introductions, four members of the PROCAS2 team  presented findings from the different programme work packages. The presentations provided: (i) an overview of PROCAS1, PROCAS2 and the main findings from the BC-Predict study; (ii) economic evaluation of risk-stratified breast screening; (iii) evaluation of the psychological impacts of breast cancer risk assessment provision and, (iv) suggestion of key implementation issues to consider. Following this, in one of seven discussion groups , attendees discussed what needs to happen over the next five years for risk-stratified breast screening to be implemented in England, given that the main findings from MyPeBS and WISDOM are expected within five years. Each group included at least one member of the PROCAS2 research team and was facilitated by a member from the wider breast cancer risk research group that led PROCAS2. Group allocation was pre-determined by one co-author (DPF) based on ensuring representation of the relevant disciplines/roles within each group. For example, each group had at least one member who was a breast imaging professional and one member of the UKNSC. To guide discussions, ten potential uncertainties see  were proThe first author listened to audio recordings of each discussion group and the plenary session whilst making notes in a single document to summarise the key points made. No formal transcription of recordings or coding took place. The notes document was used to produce descriptive themes based on the key topics that attendees discussed in groups and focussed on in the plenary session. All points raised in the meeting were captured within the descriptive themes, an approach which has been previously used in articles outlining agenda setting meetings and workshops ,35. The primary profession and not including the 7 facilitators: 20 academics, 15 clinicians, 5 screening operations/management (this includes members of UKNSC), and 11 in the cancer charity sector. Twelve attendees were present or former members of the UKNSC, UKNSC adult reference group (UKNSC ARG) and BSP Research Advisory Committee. Note that some individuals were both clinical academics involved in the UKNSC and/or NHSBSP operations. There were no health economists present aside from one co-author (KP).The attendees represented most disciplines relevant to risk stratified screening see  with theBRCA1/2 carriers. Overall, attendees agreed that a risk stratified approach to breast cancer screening should be the direction of travel in the UK, pending trial results. Reasons given for this included the anticipated benefits and anticipated lack of harms, as well as this approach already taking place in other programmes such as cervical screening and to a limited extent in breast screening with the very high-risk programme for The discussions captured are presented in relation to the following five descriptive themes: risk and health economic modelling; health inequalities and communication with women; extending screening intervals for low-risk women; integration with the existing NHSBSP and; potential new service models. Most attendees indicated that the risk models for breast cancer demonstrate good predictive value for breast cancer diagnosis in the majority of the white European population and the most common type(s) of breast cancer, particularly if they use a combination of genetic, mammographic density and self-report information. On the other hand, some attendees were concerned that it is difficult to define what discrimination is good enough without trials or accurate natural history models showing impact on women screened whilst others felt that discrimination would not be good enough should only one component, for example polygenic risk scores or mammographic density alone, be used to determine screening interval. Discussions around accuracy of the risk models as implementable tools centred on requiring adequate knowledge about the natural history of the disease; for example, ability to predict different sub-types of breast cancer, and whether the cancer is diagnosed in pre- or post-menopausal women. Secondly, all groups acknowledged that risk is not static but that there is a lack of evidence demonstrating how risk changes over time. Evidence gaps highlighted included the need for better evidence to decide (a) whether to provide women with short term, long-term or lifetime risk and (b) when risk should be reassessed. Linked with this, a concern raised by all groups related to the lack of validation for risk prediction in minority ethnic groups due to lack of available data and that some such groups; for example black African and black Caribbean women, have poorer breast cancer survival rates. However, some attendees expressed confidence that both issues were relatively tractable, noting that research is ongoing so it should be possible to resolve these issues in the near future. Nevertheless, attendees highlighted that it needs to be possible to access these groups in order to assess their risk and assumptions about development of the disease are continually being updated. All discussion groups acknowledged that there is no gold standard yet for objective breast density measurement or which imaging technique is best to use if there is high breast density. This was seen as important as it is likely to be a key component of both the risk assessment and screening higher risk women. Some also emphasised that in addition to future risk, it is necessary to decide what type of risk outcome to base risk-stratification on. This may include short-term  risk of any type of breast cancer, lifetime risk, risk of developing an interval cancer during allocated screening interval, or risk of breast cancer death. This decision will depend on what factors are used to calculate the risk, for example including a PRS score is more effective for estimating lifetime risk and breast density, shorter-term risk. The approach to assigning a risk of breast cancer to each woman will affect the economic impact of rolling out a risk-stratified programme. The cost of the risk prediction tool also needs to take account of the required healthcare professional resources to feedback results in a supportive environment. In addition, attendees discussed how adding genetic data to breast cancer risk models would increase the cost of risk prediction substantially. However, the additional predictive value of including genetic data at a population level is not yet known taking into account the different ethnic backgrounds of women offered breast screening. The current economic model presented at the meeting assumed the use of the Tyrer-Cuzick risk model with Volpara™ breast density measurement to assign breast cancer risk. It was acknowledged that to understand the relative cost effectiveness of adding in genetic data, expansion of the current economic model in a future study is required. The need to understand if, and how, to reduce the number of screens over the lifetime of women at low-risk of breast cancer, to free up resources for women at high-risk was also discussed. Before a risk-stratified programme is rolled out, it will be necessary to understand how to keep the programme cost-neutral by introducing risk-stratified screening.There was agreement that a risk-stratified approach to breast screening may exacerbate existing health inequalities or create new ones. In order to ensure equality of access to information about risk-stratified screening and minimise adverse impact on informed decision-making, attendees discussed different approaches to ensuring meaningful engagement across communities. This did not only focus on characteristics such as ethnicity but also on other groups of women who may already have pre-existing health conditions, including anxiety. Therefore, it was highlighted by some that proactively identifying these groups requiring additional care prior to the offer of risk assessment would ensure adequate support to engage with them and minimise negative consequences of providing risk information. It was agreed that there should be a minimum standard of accessible information to enable informed decision-making along the entire pathway however some groups may require additional ‘doses’, i.e., a greater level of intervention, to achieve the same level of engagement. Discussions concerning this mainly centred on providing personal interactions between the service and women given that this may require targeted approaches for different groups of women. Examples of such approaches included developing awareness raising initiatives with trusted community leaders; ensuring culturally appropriate translation of information, especially technical terms; considering the use of ‘pathway navigators’ or health practitioners and developing clear decision aids in multiple formats. The role of wider media campaigns was also discussed as an essential component of communication with women. This included considering that those with higher risk may be concerned about financial implications . Given that there may be access barriers related to technology and written information more generally, it was viewed as important to give women the choice about communication preferences. This related to the option of receiving support (another possible role for pathway navigators) to complete the risk assessment itself if self-report information is required and for making informed decisions  about preventive options such as risk-reducing medication.There was agreement that incorporating risk assessment into breast screening is likely to benefit women at moderate or high risk but concerns were raised about whether it is possible to safely extend screening intervals  for women at low risk of breast cancer. Establishing evidence that low-risk women are not at increased likelihood of breast cancer mortality if screening frequency is reduced was viewed as paramount before decision-makers are likely to consider this and both screening professionals and women willing to accept it. Similarly, attendees wanted to know more about whether women would accept a longer screening interval if found to be lower risk. Some discussion groups focussed on the possibility of the three-yearly screening interval changing to two-yearly, regardless of an individual woman’s risk. Current thinking around this relates to need for reducing the levels of interval cancers in the current NHSBSP and the criticism that the programme intervals are longer than in any other country. This led to considering a two-yearly interval for women at higher than population level risk whilst women at low-risk would remain on the current interval, to minimise both overdiagnosis and the potential fallout of ‘taking screening away’. On the flip side, if women at low-risk attend screening at longer intervals and are less likely to require further assessment, this will have a positive impact on service capacity, helping to maintain the roll out as cost-neutral. Additionally, it was acknowledged that other UK national screening programmes have implemented risk adapted screening such as extended intervals for women with HPV negative cervical screening results. Discussions about how to implement a risk-stratified approach within the current NHSBSP focussed on on-going challenges within the service which focussed on technology, pathway linkage and capacity issues. In addition, the groups acknowledged there may be a trade-off between using the best possible risk prediction model and feasibility of implementing it successfully within the NHSBSP.The current IT system, used to invite women every three-years, was viewed as outdated and inefficient . However, it was widely acknowledged that this is a top priority within the programme. Although newer, future proof technology is expected to be incorporated within the next five years, there was some scepticism about the timescales for this. It was highlighted that this will allow the flexibility required for a risk adapted programme, as well as other innovations that may take place in the lifetime of an IT upgrade. Although viewed as a complex task, existing service failsafe standards and processes can also be adapted in order to minimise potential error, e.g., ensuring the right women are invited to screening at the right time. However, changes to the programme in general also take a long time such as deciding whether to extend the screening age from 50–70 to 47–73 years . There was agreement that it was not yet clear how many women would require additional screening (in whatever format that may be) if identified as higher risk, which is required for infrastructure planning, but that it should be possible to estimate this using economic model-based methods. One attendee suggested this should be considered annually for each local service so that women can be invited for screening in a timely manner and that the service can accommodate it. It was acknowledged that women opt into the NHSBSP and need to also opt in to completing a risk assessment; it was not clear how this offer might negatively affect uptake, which has continued to decline in recent years. Equally, it was recognised that uptake would expand to include uptake of risk assessment and risk-stratification pathway in addition to uptake of mammograms. The current organisation of screening is linked to inviting all eligible women from specific GP practices within geographical areas to attend for screening, usually in mobile screening vans. It may however only be possible to offer risk-stratification at static sites, therefore the current invite process may need to change. However, all discussions about this were underpinned by the need for logistic planning, staff training and concern about lack of workforce overall. This predominantly related to limited numbers of radiographers within the current NHSBSP and difficulties with succession planning for this professional group, many of whom are approaching retirement. In addition, the need for appropriate staff to support the risk assessment process was highlighted. Attendees also recognised that women at higher than population risk will be the most likely group to require additional support from health professionals. However, there was a lack of consensus on which health profession would be best suited for this task, given that NHSBSP staff may not necessarily have the skillset or capacity to have these conversations, not all services have fully integrated family history, risk and prevention clinics and even though women may access primary care as a first port of call, GPs may not have the capacity or capability in terms of appropriate training. All groups considered alternative service models in settings at least partly outside the NHSBSP. Given that the ultimate aim is to detect cancer as early as possible in order to avoid death, two key aspects related to whether breast cancer risk should be assessed alongside risk of other diseases and the age at which risk assessment should be conducted.If the goal is to better inform women about their health, some identified that it may be a better idea to integrate risk assessment across several diseases using an integrated approach to cancer early diagnosis (or not just cancer). This was viewed as best delivered in the primary care setting rather than with an individual screening programme given that initiatives such as health checks at age 40 are offered to women via their GP. In addition, risk-stratified approaches are already currently in use for diabetic eye screening and cardiovascular disease and are now being implemented in cervical cancer screening programmes. Targeted lung health checks have also been piloted by NHS England and are currently under consideration by the UKSNC and polygenic risk scores are being deliberated for use in the bowel screening programme. Linked with primary care, several attendees suggested that women could be asked to provide a saliva sample at the time they have their cervical screening appointment in primary care, in order to identify higher risk women at an earlier age  as at the moment, risk-stratified breast screening would only occur when a woman is first assessed in the NHSBSP. However, groups were in agreement that as primary care are currently only indirectly involved in breast screening, it may be more feasible to initially focus on specific aspects of the pathway such as risk-reducing medication for higher risk women.Similarly, regardless of how the initial risk assessment is carried out, and given that higher risk women are already offered more frequent screening, there must be some involvement with the NHSBSP programme, especially to identify who to invite and when. In the immediate future, it might be possible to offer a simple screening questionnaire prior to a breast screening appointment  to assess interest in risk assessment and identify those who may have higher risk due to family history before providing all risk assessment questions with the mammogram invite or at the appointment itself. One group also identified the possibility of integration with community diagnostic centres, a new NHS England service in development, which could accommodate additional screening for those at higher risk. Lastly, a second opportunity to integrate breast cancer risk assessment, if using polygenic risk scores, was identified due to the growing interest by the Department of Health in the use of genetic information for health more generally, e.g., Our Future Health.This agenda setting meeting identified cautious enthusiasm for risk-stratified breast screening, and a willingness to engage with the challenges that this raises. The participants identified conceptual issues related to risk modelling and evidence requirements as well as practical objectives to prepare the NHSBSP and the healthcare system more widely for successful implementation of a risk-stratified national breast screening programme.The meeting included attendees from most of the relevant stakeholder groups, in particular, those who would be involved in the decision to recommend risk-stratified screening to the UK Government  and those responsible for implementing any change within the NHSBSP. Including those involved in healthcare policy decisions has previously been highlighted as an important aspect of preparing for implementation of risk-stratified screening in a Spanish study . The leaEarlier exercises to identify research gaps  and reviews also recognised that risk stratification is worthwhile to consider implementing for population-level breast screening and concluded that a combination of risk factors should be used to estimate breast cancer risk ,20. FurtThere was general agreement that it is indeed now possible to predict risk of breast cancer in women of screening age . Indeed,It was viewed as important and essential that a risk-stratified NHSBSP should not increase costs of the service. Some existing evidence suggests that a risk-stratified screening programme is likely to be cost-effective in England, but this did not include the use of genetic data . DespiteIt is unsurprising that there is concern regarding how a risk-stratified programme will be received considering that cancer screening is viewed overwhelmingly positively by the general public in the UK . DespiteThe current findings also highlight a major concern that a risk-stratified screening approach may heighten inequity of access for particular groups of women. This has been highlighted previously by Canadian health professionals . Given tThere was some consideration as to whether primary care could support risk-stratified breast screening, however, a recent review suggests that GPs are unfamiliar with breast cancer risk assessment tools and lack confidence in advising on risk reducing medication . Similarcurrently offer risk assessment and provide women with access to additional screening and risk-reducing medication [There is an immediate need to reduce the disparity in access to appropriate services that dication . This isdication . This wodication .Risk-stratified cervical screening, which has been recently implemented in Wales, will result in 5-yearly intervals for women testing negative for HPV, and 12-month recall for those who test positive. This shift from 3- to 5-yearly intervals for HPV-negative women age 25–49 has already been implemented in Scotland and is recommended in England by the UKNSC. Therefore, such approaches to cancer screening are already under consideration in the screening committee. The current NHSBSP has strict quality assurance standards which may be difficult to integrate with and monitor should aspects of a risk-stratified screening programme be managed out with their remit. These would also require reconfiguration for a risk-stratified service, especially to ensure there are no incidents where women are allocated to the wrong risk group or invited at an incorrect screening interval. It may therefore be most appropriate, and acceptable, to introduce risk assessment to identify women most likely to receive a breast cancer diagnosis in the first instance rather than simultaneously reducing screening intervals for low-risk women. This may alleviate some of the acceptability concerns raised in previous work with health professionals regarding extending screening intervals . It coulSeveral information gathering exercises should be undertaken for each screening site to identify a comprehensive picture of (i) local demographics of women eligible for the current NHSBSP in relation to ethnicity and socioeconomic position, (ii) effective local engagement interventions, and (iii) estimated numbers of women in each risk group category. Similar exercises could take place in the other UK nations, or as a collective approach to implementing risk-stratified breast screening. This is an approach being undertaken in Canada who also consider the socio-ethical and legal issues related to risk-stratified breast screening as part of their implementation research . Given tWhichever way the NHSBSP decides to proceed, this would need approval from the UKNSC first but should be closely linked with NHS England which will ultimately be responsible for implementing a risk-stratified programme. If this is introduced into the NHSBSP, it is important to implement in such a way that will facilitate evaluation of effectiveness for example, using a stepped wedge trial design.Long-term follow up of existing cohorts , or reassessment of risk where possible, would determine the predictive value of the risk models over time and develop an evidence base for how risk may change in the course of a woman’s screening period. Similarly, the outcomes of the AgeX trial  will be Albeit there is some existing UK evidence , there iThe need to consider how best to evaluate breast screening outcomes based on breast density, and how to assess it, has been identified in relation to the Australian national programme . The outWith the expectation that risk-stratified breast screening will become accessible to women in England, the main uncertainties and future research priorities have been identified that should be the focus of preparation for implementation. It will be crucial to ensure this new approach to breast screening does not widen health inequalities.