American Indian (AI) women face disproportionate rates of breast cancer mortality and cancer disparities. This study conducted qualitative research to assess perspectives of AI women towards breast cancer screening, knowledge, barriers, and needs about mobile web app–based education to promote breast cancer screening. This study, in collaboration with the Yankton Sioux Tribe (YST), followed a community-based participatory research approach and conducted two focus groups with a total of 22 YST women aged 40–70 years living on reservation in rural South Dakota. Each group consisted of 11 local professionals working in healthcare and social services and community members. A grounded theory was used for the qualitative analysis. A large portion of participants reported having prior knowledge about breast cancer and screening methods, yet lacked awareness of the detailed procedure and recommended guidelines. Competing priorities and cost of mammograms were noted as major barriers to screening. Participants wanted to learn—in a convenient and easy-to-understand manner—more about breast cancer and prevention from a credible source. Both groups were favorable toward novel educational tools, such as the mobile web app education, and cited potential health benefits, particularly for women aged 40s to 60s. Our findings highlighted the importance of creating effective, culturally tailored educational interventions built into programs specific to AIs to increase understanding about breast cancer screening and promote screening behaviors among AI women. Particular attention to how AIs’ culture, beliefs, and barriers are implicated in screening behaviors could help with developing culturally tailored health education tools for this population. Breast cancer is the most common form of cancer and the second leading cause of cancer death among women in the USA . RoughlyAmerican Indian and Alaska Native (AI/AN) women shoulder disproportionate rates of rising incidence, cancer death, and low survival due to breast cancer, resulting in cancer health disparities. These disparities remain persistent with no sustained improvement. Breast cancer remains the second leading cause of cancer death for AI/AN women. Although AI/AN breast cancer incidence is lower than the incidence in non-Hispanic White (NHW) women, AI/AN women exhibit the highest breast cancer mortality and lowest breast cancer screening rates in the USA –8. SizabEarly detection of breast cancer through regular mammograms can reduce breast cancer mortality up to 40% . HoweverMobile web app interventions are a new method with positive impact on constructive behavioral change; they have taken a primary place in numerous mobile health  research initiatives  –15. MobiThe goal of this qualitative formative study was (1) to assess community member knowledge, barriers, and educational needs about breast cancer screening among the Northern Plains AI women; and (2) to explore how to best design education communication tools for rural, geographically isolated AI women to improve breast cancer screening behaviors, such as a mobile web app educational intervention. There have been some regional studies on AI women’s viewpoints about breast cancer screening, yet none has been conducted in the Northern Plains , 21. ConThis study employed a community-based participatory research approach by building upon collaborative partnerships between the research team and the YST in SD. Our study entailed the creation of a community advisory board (CAB), which is a partnership with the local AI communities. The CAB consisted of eight individuals—AI healthcare professionals, social service providers, staff from the YST Bureau of Indian Services, and community and religious leaders—who guided us in all aspects of study development, implementation, and dissemination of research findings. The CAB convened quarterly to procure community support and involvement, provide important community insights about community concerns, assist in recruitment strategies, and ensure cultural relevance.Two focus groups were undertaken in October 2020 to (1) elicit knowledge, cultural beliefs, and attitudes about breast cancer screening and (2) identify barriers and motivators for screening with YST women aged 40 to 70 years. The focus groups led to a broader discussion of culturally normative perspectives and a greater exchange of ideas regarding the main study themes than would be generated solely through individual interviews. Institutional Review Board approvals were obtained from the University of South Dakota and the YST.N = 22; n = 11 for each group). Each group represented one of the main stakeholder categories: YST community members and YST local professionals with backgrounds in cancer and health management . Dividing participants into two focus groups was intentional to capture the potential differences in their knowledge and awareness about and exposure to breast cancer. By incorporating into the research design a broader discussion of culturally normative perspectives in two similar, yet distinct, groups, this study sought to lay the groundwork for the development of culturally tailored interventions in AI communities. Eligibility criteria for participation in the focus groups included those (1) who were self-identified AI women of the YST, (2) who were aged 40 to 70 years, and (3) who resided on the YST reservation in SD. The participant age range of 40 to 70 was selected based on the breast cancer screening guidelines of the American Cancer Society that recommended women to begin regular mammograms at age 45 or at 40 if women opt to start screening earlier  was ever discussed, you know, no one ever talked about breast cancer or anything like that. When I started hearing about it all these scary things, you can die from it and the serious things that were going on. I am afraid to go get the mammogram because I thought what if I have this, and that’s how scared I was.Most participants identified breast cancer risk factors and symptoms . Some participants attributed risk factors of breast cancer to modifiable behaviors , while others regarded risk factors to be an unavoidable consequence of family genetic history and age. Across all age groups, those who had a family member diagnosed with cancer were more willing to consider undergoing mammograms. Several participants expressed larger concerns that breast cancer might have been caused/exacerbated by a systemic factor, such as life stressors and environment. Participants varied in the emotions evoked by discussing breast cancer and screening, with most frequently expressing fear or worries about possible diagnosis of breast cancer. One woman said:Overall, the YST women noted favorable attitudes towards breast cancer screening. Knowledge about breast cancer screening differed by type of screening. Participants most frequently mentioned breast self-examination (BSE) followed by mammography. A clinical breast examination did not surface in the focus group discussions. A higher proportion reported practicing regular BSE and knowing about its procedure and recommended frequency than for mammography. Women also expressed conflicting views about the role of mammograms, with some believing that mammography could be an effective diagnostic tool to detect breast cancer early, and others believing that BSE could be as effective as mammograms in diagnosis of cancer. Several participants talked about their own experiences with mammograms with some reporting extreme pains, and others being only moderately bothered. Some women were reluctant to regularly get a mammogram because they believed that the mammogram would cause radiation exposure, which may also cause cancer. The need for more adequate information about the specific procedures of mammograms, screening guidelines, or recommended age and frequency was prominent across both groups.Participants from both groups agreed that they usually do not seek help from a doctor unless they have a family history of cancer or have signs or symptoms of breast cancer. Multiple themes emerged across the two groups pertaining to barriers for breast cancer screening: competing demands, cost, lack of health insurance, lack of availability of screening facilities in the geographical area, absence of transportation, cultural stigma, fear of mammography or possible results, opposite sex practitioners, privacy concerns, mistrust of medical systems, and discrimination and oppression.Most YST women indicated that due to preoccupation with multiple responsibilities of daily survival , they were unable to make time to see a doctor or travel for screening. Cost was frequently cited as another key barrier to screening across both groups. Most focus group participants had limited income and indicated a mammogram is too expensive, especially for those who do not have adequate health insurance coverage. A lack of mammography service emerged repeatedly across the two groups. Access to screening was also affected by availability of clinics, transportation, and healthcare providers in the community. Many YST women living on the reservation, where screening facilities do not exist, must travel substantial distances to receive screening services. Some participants do not have reliable transportation to a clinic. Frustrations about the inadequacy of existing healthcare coverages emerged in all focus groups. A few participants related anecdotal accounts of misdiagnosis of breast cancer after having mammograms or lack of communication from their healthcare providers. Several participants reported being embarrassed or uncomfortable discussing or touching such a private body part during a mammogram, particularly with an opposite sex practitioner. However, most women agreed that the sex of practitioners was less important than “a good doctor” who they can trust. The prominent themes across the two groups were general lack of resources to address their health needs and associated vulnerability. Participants described instances of discrimination exacerbated by historical trauma .Participants from both focus groups expressed strong agreement that the level of information about breast cancer and screening needs to be expanded. There was a variety of traditional and nontraditional approaches to promoting breast cancer screening discussed in the focus groups: grocery store bulletin boards, talking circles , brochure or pamphlets, educational DVD, media advertisements, campaigns, social media, and mobile reminders.It would be really helpful because this is how our world is nowadays. I don’t have the time to go into hospital about myself, but with an app, you can do all that you can get information, probably interact with a doctor or something all over the app. Our phones are everything, we bank from them, send messages, do our work from these phones, so our phones are really our life phone.Across all groups, AI women referred to the use of innovative technology, such as a mobile web app–based education intervention for breast cancer screening and exposure to video content, as an effective medium for information dissemination about mammography. Participants in both groups were generally favorable toward the mobile web app intervention, and noted a potential health benefit, especially for women in their 40s to 60s. Perceived benefits to participation in the mobile web app intervention included convenience (overcoming restrictions to place and time of delivery), flexibility by reducing traveling and waiting time, increased accessibility to important breast health information, real-time interaction, reducing stigma, personalized messages, and a global sense of helping community and future generations. As one woman in her mid-60s stated:The education everything has to do with our health, now I’m finding many elderly add me on Facebook...I see a couple of them and they are lonesome we are not supposed to hug or anything [due to COVID], so if you offer this app to them, that will give them something to do for their mental health and help them focus on their health at that time.One participant commented on the benefits of the mobile web app during the COVID era:A greater willingness to participate in the mobile web app intervention was associated with perceived direct benefits for participants or their communities, particularly benefitting future generations.Some people have a phone month to month and the next they don’t. What they did now is that the tribe can have free Wi-Fi, and what’s good about having free Wi-Fi is that many people who don’t have minutes, but they can use internet, Wi-Fi and apps. If they keep the Wi-Fi, that would be a good idea to promote the app. It takes grants and funds to secure the resource first.Some women had concern about the lack of internet availability, mobile phones, and connectivity issues; however, others argued that the use of technology including internet, smartphones, and tablets has rapidly increased and Wi-Fi connections have improved on the YST reservation. In both focus group discussions, availability of the mobile web app educational service to community members focused on needing greater resources and funds. One participant noted:Contents: Across both focus groups, participants referred to the use of culturally tailored and YST community–specific health education content as critical for the development/implementation of the mobile web app intervention. Participants identified a range of information that need to be included in educational messages, such as breast cancer, breast cancer screening guidelines and procedures, screening benefits, and access to screening services and resources on or near the reservation . Some participants desired statistics more relevant to them about incidence of breast cancer and survivorship in the YST community, which would possibly lead to greater participation in breast cancer screening. Participants spoke of the importance of contextualizing the “Indigenous holistic wellness approach” that is driven by sociocultural factors that influences health and health behaviors of AIs. Participants mentioned the integration of mind, body, and spirit, as well as one’s connection with oneself and others. For example, one woman in her 60s exemplified the Native way of the holistic wellness approach:We come in contact with and within our environment. It’s the balance of our emotional, spiritual, and physical, how we live on a daily basis, is really important to us, women we take care of our whole families, in order to take care of them, we need to take care of ourselves, our bodies, our mental awareness, so we can live our healthy lives, so a lot of those factors contribute to our wellness and our health.The importance of prevention and early education for younger generations was a theme across the two focus groups. Multiple participants expressed concern about a lack of education specific to younger generations. Some attributed it to the fact that they were not of the recommended screening age, or that healthcare providers might not have supplied information about breast cancer. Participants suggested that as younger people, perhaps not ready for screening, are more familiar with a novel technology than participants aged 40 to 70, they would be more likely to find the mobile web app intervention a useful tool that may increase awareness of breast cancer screening at an early age and undergo their mammography in the right time frame. Participants also suggested creating educational messages involving young girls and intergenerational connectedness to encourage future screening in the web app program.Structure: Most participants felt that the mobile web app education intervention for breast cancer screening should be developed in an easy-to-understand, simple, interactive, and engaging manner. Some participants indicated that reminders and visual materials  would be effective in the mobile web app intervention in prompting participation in breast cancer screening. Participants expressed different opinions regarding the duration of the mobile web app intervention; some desired a shorter period of 7 days, while others preferred a 2- to 4-week program. There was a wide variation regarding the frequency of receiving the educational messages: per day, per week, and per month. Most participants preferred to receive the messages during evening hours based on their work schedules or other commitments.The present study explored knowledge, barriers, and educational needs about breast cancer screening with a focus on the novel mobile web app intervention among 22 YST women aged 40 to 70 years residing on reservation in rural areas in SD.Our key finding indicated that novel education programs, such as the mobile web app intervention for breast cancer screening, which are culturally tailored and built into programs specific to AIs, can be a feasible, acceptable, and effective tool to improve participation in breast cancer screening among AI women. All participants desired additional education about breast cancer. Most participants indicated the high usage of internet technology and mobile phone–based apps to access health/mental health–related and non-health-related information and to maintain social connections. Participants were generally favorable toward the mobile web app education intervention, and noted a potential health benefit, particularly for women in their 40s to 60s. Participants wanted to learn more about breast cancer, screening methods, and prevention from a credible source  and in a convenient, easy-to-understand, and engaging manner. Results showed that interactive multimedia messages and visual materials  are more likely to capture AI women’s attention and to motivate them to engage.The YST women felt that the mobile web app education intervention should contain information relevant to Indigenous populations. They desired culturally tailored information, which would lead to more breast cancer screening. Cultural relevance entails (1) putting pictures and music related to the YST on the app, (2) providing statistics and information about local clinics for screening tests specific to the YST community, (3) incorporating the Indigenous holistic wellness approach, and (4) bolstering intergenerational connectedness and early education for younger generations. While most participants were comfortable with using the mobile devices, several noted issues concerning the availability and connectivity of Wi-Fi as a potential barrier that might hinder some women from participating in the mobile web app education intervention. Thus, intervention efforts should address concrete improvements in those areas that would significantly influence the ability to access educational resources. Comprehensive funding that builds infrastructure and encourages internet service providers to invest in rural and remote areas of reservations is critical to address healthcare and social needs.Most participants had prior generic knowledge about breast cancer screening, and agreed that mammography is crucial to the health of their community. Participants of this study were aged 40 to 70 and most had their own experiences with mammography or knew someone who had breast cancer. Despite the struggle for daily survival due to a lack of economic and social resources, participants placed a great value on the breast health of their community, especially if applied to the improvement of health of the younger generation. They expressed a strong interest in learning more about preventing the onset of breast cancer and breast cancer screening. Findings indicated that people would be more willing to receive breast cancer screening if they have had a personal experience of a family member affected by breast or other types of cancer; and they have a more favorable attitude toward the potential benefits of screening.One of the focus group discussions centered on barriers to accessing breast cancer screening. The most important barriers included competing priorities, high cost of mammography, lack of health insurance coverage, lack of availability of screening facilities in the geographical area, transportation, and culturally inappropriate screening services. Similar barriers have been found in prior studies . This stThis study has several limitations. The small number of participants with the use of convenience sampling was the major limitation to our study. Participants were women from the YST aged 40 to 70 who live in a small geographic location of the Northern Plains. The findings, therefore, cannot be generalized to AI groups in different tribes, regions, and ages. The complexities of health beliefs and behaviors should be taken into account, as well as the unique features of the YST group.Despite these limitations, this study contributed to the limited body of literature on AI women’s knowledge, beliefs, attitudes, barriers, and educational needs about breast cancer and screening for the disease. Identifying these themes provided guidance for designing the innovative mobile web app–based educational intervention multimedia messaging program, with particular attention to breast health literacy and cultural humility. To our knowledge, this is the first study to elucidate the Northern Plains AI women’s perspectives and experiences about breast cancer and screening to assess the educational needs and concerns. Given the widespread use of mobile technology, the mobile web app intervention provides a viable mode of service delivery that builds upon low-cost technology and enhances accessibility and sustainability of health intervention to help reduce cancer health disparities experienced in Indian country. While our study is region- and tribe-specific, it may have implications for other regional and tribal initiatives for breast cancer screening and health educational communication. Future investigation that tests the efficacy and cultural acceptability of these tools with various AI subgroups is warranted.


Both obesity and metabolic syndrome are linked to increased incidence of type 2 diabetes, cardiovascular disease (CVD), and cancers of the breast , and other obesity-related cancers. Over the past 50 years, the worldwide prevalence of obesity and metabolic syndrome has increased, with a concomitant higher incidence of associated co-morbidities and mortality. The precise mechanism linking metabolic syndrome to increased cancer incidence is incompletely understood, however, individual components of metabolic syndrome have been linked to increased breast cancer incidence and worse survival. There is a bidirectional relationship between the risk of CVD and cancer due to a high burden of shared risk factors and higher rates of CVD among cancer survivors, which may be impacted by the pro-inflammatory microenvironment associated with metabolic syndrome and cancer-directed therapies. The Women’s Health Initiative (WHI) is an excellent resource to study a dual relationship between cancer and CVD (cardio-oncology) with extensive information on risk factors and long-term outcomes. The purpose of this review is to provide an overview of research on cardio-oncology conducted utilizing WHI data with focus on studies evaluating both breast cancer and CVD including shared risk factors and outcomes after cancer. The review also includes results on other obesity related cancers which were included in the analyses of breast cancer, articles looking at cancer after heart disease (reverse cardio-oncology) and the role of Clonal Hematopoiesis of Indeterminate Potential (CHIP) as a shared risk factor between CVD and cancer. A summary of pertinent WHI literature helps to delineate the direction of future research evaluating the relationship between CVD and other cancer sites, and provides information on the opportunity for other novel analyses within the WHI. Over the past 50 years, obesity has increased in prevalence, with consequent increases in morbidity and mortality , 2. FromBoth obesity and MS have been linked to increased incidence of type 2 diabetes, cardiovascular disease (CVD), and cancers of the breast , endometrium, adenocarcinoma of the esophagus, kidney, liver, gallbladder, pancreas, ovaries, small intestine, thyroid, stomach, multiple myeloma and non-Hodgkin’s lymphoma –9. The pIn this review, we provide a summary of published studies within the Women’s Health Initiative (WHI) which focus on the area of “cardio-oncology” defined as intersection between cancer and CVD. The review focuses on the relationship between BC and CVD and includes studies evaluating shared risk factors and outcomes after cancer as well as “reverse cardio-oncology” investigating the risk of cancer among women with CVD. The review also covers the role of Clonal Hematopoiesis of Indeterminate Potential (CHIP) and risk of subsequent cancer , 14–67. The WHI includes an observational study (OS) and 3 clinical trials (CT) including the dietary modification trial (DM), the hormone therapy trial (HT) and the Calcium/Vitamin D trial (CaD). Participants could be included in one or more CT. Women were included in the OS if they were not eligible or not interested in participating in a CT. The WHI study included 161,808 postmenopausal women, aged 50-79 at enrollment, and as part of the protocol, detailed information on CVD, cancer risk factors and long-term outcomes were collected , 69. ParSeveral predisposing risk-factors and/or protective factors have been linked to CVD and cancer including physical activity, obesity, body composition, hypertension, diet, lipids, circulating cytokines and insulin resistance , 71. Tatrend <0.001) , with increasing quintiles of energy expenditure associated with lower risk (P <0.001) . In an a <0.001) . These f <0.001) . As suggObesity and body size are well-established risk-factors for CVD , 75 and Other studies have shown that both smoking and obesity are independent risk-factors for CVD  and cancIt has been proposed that the obesity - cancer association may be due to the fact that adipose tissue is metabolically active, secreting cytokines and adipokines, which play a role in breast tumorigenesis , 81. SupAdiposity is also associated with higher levels of endogenous estrogen and insulin, both of which are known to play a role in breast tumorigenesis , 83. In In an analysis of both anthropometric measures and physical activity in the OS and CT, women with the highest BMI quartile compared to the two lowest quartiles had a 1.35 and 1.39-fold higher risk of triple-negative-BC (TNBC) and estrogen receptor (ER)+ tumors, respectively .In an attempt to develop a more valid measure of body fat distribution, a WHI study assessed the relationship between body fat distribution and central obesity  using baOther studies evaluated the impact of weight change on BC risk. In one OS analysis weight loss (≥ 5%) at 3-years was associated with a significantly lower risk compared to stable weight (< 5% loss) , and weight gain was associated with a higher risk for TNBC  . SimilarLastly, in another analysis, both obesity and metabolically unhealthy categories were independently associated with increased BC risk, but the metabolically unhealthy obese (MUO) phenotype demonstrated the highest risk  . Also anIn conclusion, while obesity and body composition are known risk factors for CVD, WHI research also demonstrates the relationship between obesity, body composition and cancer risk and provides evidence that measures of body composition utilizing DXA provides a more refined method in which to investigate this relationship. In addition, the WHI biospecimen repository has enabled research further investigating the relationship between insulin, inflammatory cytokines, hormones and cancer risk.Hyperlipidemia is a known risk-factor for CVD , and itstrend=0.02) (trend<0.0003)  . Similarnd=0.02)  and BC (nd=0.02) . In anot<0.0003) . In anot<0.0003) . The WHIMetabolic Syndrome (MS) has been shown by others to be associated with higher risk of type 2 diabetes and CVD . In an aHypertension is a known risk factor for CVD . In a stIn another analysis of 2,272 women with BC hospitalized for HF,  the inciIn the WHI, several measures of dietary intake have been used to investigate the relationship between diet, CVD and cancer. An investigation of 131,833 women reported a 4% reduction in BC risk per unit increase in healthy lifestyle index (HLI) scores  based onThe WHI Dietary Modification (DM) CT randomly assigned 48,835 postmenopausal women to usual diet (60%) vs intervention (40%) that focused on reduction of total fat intake to 20% of energy intake, increased vegetable and fruit intake to 5-servings and grains to 6-servings/day. As measured by food frequency questionnaire (FFQ), at baseline, women consumed 32% or more of their total energy from fat (FFQ) , 97.Several DM analyses evaluated the relationship between dietary intervention, CVD and incident cancer risk , 27, 35.An analysis comparing two dietary instruments (4-day food records [FR] and FFQs) among women in the non-intervention DM arm, showed that the FR over the FFQ, was a preferred method of dietary assessment for all types of dietary fats . AnotherIn another OS analysis, various reductions in energy consumption were associated with lower risk of major incident CVD events and cancer. Specifically, a 20% reduction in total energy consumption (TEC) was associated with one-third lower risk, 20% increase in activity-related energy expenditure (AREE) one-fourth lower risk, and simultaneous TEC and AREE, a 50% lower risk . AnotherIn summary, results from the OS strongly support a relationship between fat and energy consumption and risk of CVD and cancer, including alternative measures of healthy eating and lifestyle including the HLI and CVH. These results however have not been replicated in the DM thought to be at least in part due to poor dietary compliance among participants randomized to the intervention , 22. Thepost-hoc analyses among women with subsequent diagnosis of BC demonstrated, fewer deaths after BC among women randomized to the intervention (low fat dietary intake) ,  intake) . Consist intake) . Lastly, intake) . This latrend<0.001) but not BC mortality (Ptrend=0.86)  . A similnd=0.86)  showed tIn another analysis of 156,262 women in the entire cohort, those that were normal-weight, with central obesity, compared with women that were normal-weight and no central obesity, had a higher risk of mortality due to CVD  as well as mortality due to cancer  . These ftrend=0.003) and all-cause mortality   and significantly higher BC-overall mortality , likely because of reduction in other causes of death (trend<0.001), but not BC-specific mortality   .In summary, WHI analyses support the notion that shared risk-factors representing lifestyle and body composition impact both cancer and CVD outcomes, largely due to risk-factor burden. It is important for investigators interested in both CVD and cancer outcomes to investigate the impact of lifestyle interventions known to modify these risk factors, which may improve outcomes from both cancer and CVD.While the increased risk of CVD in cancer survivors is well described for certain cancers , the terIn an analysis of 93,676 women assessing the association between baseline self-reported atrial fibrillation (AF) and incident invasive breast over 15-years follow-up, there was a 19% excess risk of subsequent BC among women with AF . While the excess BC risk was mitigated by baseline cardiac glycoside use, the use of glycosides was also independently associated with increased BC risk , but not CRC . In an aAging is associated with acquisition of somatic mutations in the absence of neoplasia, known as clonal hematopoiesis of indeterminate potential (CHIP), which has been linked to a higher risk of cancers as well as CVD , 65. In In summary WHI studies demonstrate a possible relationship between pre-existing CVD and increased cancer risk. In addition, CHIP is a shared risk-factor between CVD and cancer. More importantly, several clinical associations that are seen with breast cancer are also shared with CHIP. For example, CHIP has been associated with diabetes in several cohorts and heart failure in the TOPMed consortium (that included WHI data) . The comThis review provides an overview of published literature on shared risk-factors and outcomes between CVD and BC, highlighting a likely bidirectional risk and adding information to a recent over-arching summary of cardiovascular research in the WHI . The WHISR and MS developed the hypothesis, rationale, helped with data gathering, analysis, writing and editing. CD-C, RC, AB, KR, AV, KC, PD and VN helped with writing and editing the manuscript. All authors contributed to the article and approved the submitted version.


The combination of classic chemotherapy agents like anthracyclines with novel targeted medications has had a positive impact on women’s survival from breast cancer. GnRH analogues are primarily employed to temporarily suppress ovarian function in premenopausal women with hormone-receptor-positive (HR+) breast cancer. Despite their benefits, the true degree of their collateral effects has been widely understudied, especially when it comes to ischemic heart disease. This review aims at summarizing the current state of the art on this issue, with particular focus on the risk for cardiotoxicity associated with the combined use of GnRH analogues and anthracyclines. Breast cancer is one of the most frequent malignancies among women worldwide. In the United States, 297,790 new cases of breast cancer are estimated to be diagnosed in 2023, with an yearly increase in incidence of 0.5% . The likThe use of GnRH analogues usually determines several symptoms that resemble those elicited by menopause. As menopause is known to influence rates of cardiovascular risk factors and ischemic heart disease, the use of this drug class could impact negatively on cardiovascular health and especially on the risk of developing ischemic heart disease. This raises concerns regarding the administration of GnRH analogues in association with anthracyclines, which are known to induce myocardial dysfunction. This review aims at enunciating the effects of GnRH analogues on myocardial ischemia with special focus on a possible synergistic effect with anthracyclines.According to the ESMO Guidelines for Early Breast Cancer, ET is the therapeutic option of choice in early Luminal A type or Luminal B breast cancer, alone or in combination with chemotherapy .GnRH analogues are primarily employed to temporarily suppress ovarian function in premenopausal women with hormone-receptor-positive (HR+) breast cancer, especially in cases of severe disease burden . In 2018The use of anthracycline-based chemotherapy in breast cancer treatment has been associated with an increased risk of cardiovascular toxicities. GnRH analogues, on the other hand, are primarily used to induce OFS, which may indirectly impact cardiovascular health through changes in risk factors for ischemic heart disease. Still, they are generally considered to have a lower risk of cardiovascular toxicities compared with anthracycline-based chemotherapy. However, there are some important considerations related to cardiac health that should be taken into account when using GnRH analogues either alone or in combination with anthracyclines and that will be discussed in the following paragraphs. GnRH is a decapeptide produced in the hypothalamus that stimulates the peripheral release of luteinizing hormone (LH) and follicular stimulating hormone (FSH) by interacting with specific receptors localized on gonadotropin cells in the pituitary gland. LH and FSH have a final role in inducing the production and release of steroids in male and female gonads . GnRH isThe potential role of GnRH in the pathogenesis of malignancies of the reproductive tract, as well as its potential as a possible treatment pathway for such diseases, was first suggested by its detection in non-pituitary, both cancerous and non-cancerous tissues, i.e., ovaries, prostate, and myometrium. GnRH receptors have also been found in nearly 50% of breast cancer specimens, with a remarkable prevalence in TNBC, and invasive ductal carcinomas , whereas their expression in normal breast tissues is yet to be proved ,9.GnRH-related signal transduction in non-pituitary cells presents several differences with the one described in the pituitary gland , even thThe progressive unravelling of this complex variety of effects elicited by GnRH on extra-pituitary tissues has opened new promising roads for the treatment of several malignancies of the reproductive system, both in male and in female patients . These tAs previously mentioned, these drugs have shown significant benefit in the overall and disease-free survival rates in several studies. Two large scale trials, Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT), analyzed the role of pharmacological or surgical OFS in addition to tamoxifen or exemestane on prognosis of female breast cancer patients . OverallThe encouraging body of evidence competing GnRH analogues and breast cancer prognosis has led to the search and development of association drugs linking GnRH analogues with doxorubicin: AN-152  proved to be effective in animal models and relatively safe to be tested in phase II and III trials ,17. StilThe issue with toxicity is of remarkable importance when it comes to anticancer treatment, especially when it comes to the effect of these medications on cardiovascular health. With regards to breast cancer, anthracyclines are by far the most renown cytotoxic agents with major life-limiting cardiotoxic effects, which can appear quite early into treatment . These ep < 0.001) [Fertility status in women is known to influence the likelihood of developing insulin resistance and diabetes, and this relation seems to be time-dependent. A recent meta-analysis gathering data from 191,762 postmenopausal women across thirteen studies observed that patients reaching menopause before 45 years of age (early menopause) and those with premature ovarian insufficiency all had a higher risk of developing diabetes than those entering their menopause later in life . The pot< 0.001) ,27. The potential synergistic action of GnRH analogues in combination with other forms of ET, such as taxane and exemestane, should also be taken into account. In the ECOG trial, patients administered with chemotherapy in combination with goserelin alone or goserelin and tamoxifen, showed higher rates of diabetes than with chemotherapy alone . An adjuFuture research is warranted to shed light on this still-foggy association between GnRH analogues, chemotherapy, and insulin resistance. Development of diabetes mellitus is a strong predictor for adverse cardiovascular events in women, having a direct impact on both atherosclerosis progression  and micrThe fact that serum estrogen levels do influence lipid metabolism has been documented before, but this association appears to be far from linear. Estrogen has been found to directly interact with the hepatic cells and act as a regulating factor in the process of fatty acids oxidation and very-low-density lipoprotein production (VLDL). In this regard, it has been shown that, when compared with men, premenopausal women do present lower concentrations of VLDL molecules, which, however, present a higher density than those found in their male counterparts . This leThe possibility of a synergic effect on lipid metabolism of GnRH analogues and anthracyclines is still to be investigated, but, if proved, this phenomenon would further remark the importance of an adequate lipid-lowering approach in breast cancer women undergoing treatment. Rosuvastatin has already been studied in combination with doxorubicin, and benefits both in terms of oxidative stress reduction and dyslipidemia control were detected . Future In the ECOG trial , the addIn male patients undergoing treatment for prostate cancer, GnRH analogues have been associated with increased arterial stiffness, a phenomenon generally attributed to the fall of androgen’s protective influence on vasodilation . EstrogeAn increase in fat deposits has been subject to widespread research, especially on its association with worsening cardiovascular health. Obesity has been shown to be related with an increased risk of ischemic heart disease . ThroughAn increase in body weight has been widely observed following a breast cancer diagnosis and it is correlated with a poor prognosis. Although the possibility of a direct association between breast cancer treatment and obesity has not been proven universally , the useThe association between sex and ischemic heart disease is complex and multifaceted, and the need to better understand the social and biological factors involved in this relationship has gained increasing attention over the past years. Atherosclerosis, which is one of the main pathophysiological mechanisms underlying coronary artery disease and ischemic heart disease, appears to be less pronounced in women under 60 years of age when compared with men of similar age. Still, when considering the most severe form of myocardial infarction, ST-segment-elevation myocardial infarction (STEMI), there does not seem to be a significant difference in prevalence across sexes . On the An effect of sex hormones on the development and damage of atherosclerotic plaques can also be hypothesized. In a recent study by Segeers et al., it was observed that, although an overall analysis men and women presented comparable distribution of luminal plaque morphology, sex differences appeared when stratifying the population by age . WhereasAnother element that suggests a potential impact on ischemic heart disease of GnRH analogues is the fact that vasomotor symptoms like hot flushes are to date the most common adverse effect of this drug. A large meta-analysis of 10 studies that included 213, 976 women reported that the presence of this symptom and other menopausal symptoms was associated with an increased risk of coronary heart disease  ,71.p < 0.001), myocardial infarction , and sudden cardiac death  [From an epidemiology standpoint, GnRH analogues have demonstrated the risk of coronary heart disease   in men t= 0.004) . However= 0.004) . This co= 0.004) . p < 0.001) [Radiotherapy has too been linked to an increased risk of ischemic heart disease: in a case-control study conducted by Darby et al., it was observed that the rate of major coronary events increased by 7.4% for each adjunctive 1 Gy delivered to the heart  . The dev< 0.001) .Although there are no definite data on the role of anthracyclines in increasing risk for ischemic heart disease, and especially on their synergistic effects when used combination with GnRH analogues, the cardiotoxic effects of this drug class are renowned and well-documented. The main issue developed as a consequence of their use is hypokinetic cardiomyopathy, whose first description dates back to 1967 . As defiIn conclusion, despite being a promising adjunctive treatment option for younger female patients affected by breast cancer, GnRH analogues still do not have a fully characterized risk profile, especially when it comes to cardiovascular health. Their potential triggering action for the development of cardiovascular risk factors may induce higher rates of ischemic heart disease in the long run, further exacerbating the already-known cardiotoxic effects of anthracycline-based chemotherapy. Unfortunately, few studies have thoroughly investigated this possibility in women, and tailored randomized control trials with long follow-up are warranted to prove or dismantle evidence of this correlation. In the meanwhile, women treated with GnRH analogues for breast cancer should be involved in a strong primary prevention plan aimed at reducing the incidence of these collateral effects. Encouraging heart-healthy lifestyle changes, such as maintaining a balanced diet, engaging in regular physical activity, and avoiding smoking, is essential for premenopausal women undergoing OFS.


FGFR2) gene polymorphisms are highly related to the risk of breast cancer. However, no investigation has been carried out to determine the association of FGFR2 gene polymorphisms in the Bangladeshi population. Based on polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), this study was performed to evaluate the association of FGFR2  variants in 446 Bangladeshi women (226 cases and 220 controls). A significant association of the FGFR2 rs1219648 variant with breast malignancy was reported in additive model 1 , additive model 2 , the dominant model , the recessive model , and the allelic model . This investigation also explored the significant association of the rs2981582 variant with the risk of breast cancer in additive model 2 , the recessive model , and the allelic model . However, the FGFR2 rs2420946 polymorphism showed no association with breast cancer except in the overdominant model . Furthermore, GTT (p < 0.0001) haplotypes showed a correlation with breast cancer risk, and all variants showed strong linkage disequilibrium. Moreover, in silico gene expression analysis showed that the FGFR2 level was upregulated in BC tissues compared to healthy tissues. This study confirms the association of FGFR2 polymorphisms with breast cancer risk.Breast cancer is considered the most frequent cause of mortality from malignancy among females. Fibroblast growth factor receptor 2 ( Breast cancer is one of the most prevalent types of malignancy. The number of newly diagnosed patients identified was more than two million, approximately 11.7% of total cancer cases worldwide, in 2020. According to a report by GLOBOCAN, it is the fifth leading cause of morbidity  in the world . SeveralFGFR2) is a membrane-associated receptor tyrosine kinase responsible for transmitting a signal from fibroblast growth factors (FGFs). It is mapped on chromosome 10q26 and has a minimum of 22 members that serve numerous functions in cell proliferation and differentiation, growth, survival, and cell death. However, mutation of this gene leads to the proliferation and survival of tumor cells but also could suppress tumor growth [FGFR2 mutations enhance DNA damage signaling and p53-induced senescence [FGFR2 triggering is induced by FGFR2 missense mutations surrounding the third Ig-like domain. In contrast, those interiors in the tyrosine kinase domain generate oncogenic FGFR2 activation owing to the acquisition of ligand sovereignty [Fibroblast growth factor receptor 2  are located on intron 2 of chromosome 10 at different positions. SNP rs1219648 A > G is located in Chr10:121586676, whereas rs2420946 C > T is positioned in Chr10:121591810 and rs2981582 C > T is mapped in Chr10:121592803. These variants are predicted to enhance histone marks and motif changing. In addition to these functions, rs1219648 A > G and rs2981582 C > T are also speculated to be involved in GRASP QTL hitting. Previous studies also frequently showed that rs1219648, rs2420946, and rs2981582 are linked with the development of breast cancer in different ethnicities [FGFR2 may be a plausible mediator of breast cancer risk due to its role in signaling, the incidence of t cancer ,15. Therr [FGFR2 . Therefonicities ,15,17,18FGFR2 polymorphisms .The associations of these polymorphisms were found to be inconsistent in different ethnic groups; however, there is no such investigation on the Bangladeshi population. Considering this fact, the current case–control study was performed to clarify the potential relationship between breast cancer and three common This case–control study was conducted at the Pharmacogenomics and Molecular Biology Laboratory at Noakhali Science and Technology University, Bangladesh, and approved by the ethical committee of the National Institute of Cancer Research and Hospital (NICRH), Bangladesh (NICRH/Ethics/2019/446). Around 446 women participated in this study, including 226 breast cancer patients and 220 healthy individuals. A comprehensive questionnaire was used to collect patients’ demographic and clinicopathological data with informed written consent. Selection guidelines for healthy controls mentioned no indication of cancer and other diseases such as kidney, liver, and lung diseases. For the clinicopathological features of breast cancer patients, we mostly focused on age, marital status, BMI, histological type of cancer, progesterone receptor status, estrogen receptor status, human epidermal growth factor receptor 2 (HER2/neu) status, grade, tumor measurement, lymph node condition, nodal stage, and distant metastasis. All information was retrieved from the patient’s medical record with the assistance of a physician. The Helsinki Declaration and its further correction were followed during the study [2-containing sterile tube at −80 °C until DNA extraction. DNA extraction was conducted via an established method routinely used in our lab [Approximately 3 mL of blood was collected from all participants and stored in an EDTA-Na our lab . GenotypSNPs rs1219648, rs2420946, and rs2981582 were genotyped by using the PCR-based restriction fragment length polymorphism (RFLP) technique. A working mix was prepared for each sample by adding EmeraldAmp GT PCR Master Mix (2x) and two designed complementary primers (forward and reverse) at a suitable concentration. For PCR, 20 µL of this working mix and 1 µL of DNA sample were mixed in a PCR tube and then amplified at certain conditions. The gel electrophoresis (1% agarose) method was followed to analyze the desired PCR fragments. Digestion of PCR products of all three SNPs was performed with HinP1I  by incubation at 37 °C overnight. Digestion conditions and expected fragment lengths of all SNPs are listed in 2) test was used to evaluate the Hardy–Weinberg Equilibrium (p < 0.05. ORs were adjusted (aOR) for BMI, age, marital status, family history, smoking status, OCP history, age at menarche, age of menopause, and drinking status for all genetic models except the allele model. In addition, targeted variants were compared with several clinicopathological characteristics. Meanwhile, the p-value was corrected by using Bonferroni correction, where the significance level was measured at p < 0.017 [The chi-square  was observed between cases and controls in terms of family history. Most subjects were overweight (28.76) or obese (30.51%). In addition, invasive ductal carcinoma (57.08%) and grade 2 (57.96%) types of cancer were the most common among the participants. Moreover, a higher percentage of them were recognized with a positive nodal status (64.16%) and Mx metastasis condition (75.22%).FGFR2 rs1219648, rs2420946, and rs2981582 polymorphisms with the risk of breast cancer in the Bangladeshi population. As presented, this study identified a greater percentage of homozygote genotypes of the FGFR2 rs1219648 variant in controls. In contrast, a higher percentage of heterozygotes and mutant homozygotes of this SNP was observed in patients. As a result, a significant association of these genotypes with breast carcinoma was identified in various association models, including additive model 1 , additive model 2 , the dominant model , the recessive model , and the allelic model . Unlike the first variant discussed above, a greater percentage of heterozygotes of the FGFR2 rs2420946 variant was observed in controls. However, no substantial relationship was observed in any genetic inheritance models for this polymorphism except the overdominant model . Again, mutant homozygotes of the rs2981582 variant were more prevalent in cases compared to healthy individuals. As is presented, this study illustrated the significant association of this SNP with an elevated risk of breast cancer in additive model 2 , the recessive model , and the allelic model .p < 0.0001) depicted an enhanced risk of breast cancer, whereas the ATT  and ATC  haplotypes showed a protective association. Moreover, this study also illustrated the linkage disequilibrium (LD) of all SNPs in the breast cancer cases and controls (2 = 0.624); rs1219648 and rs2981582 , and rs2420946 and rs2981582 .Furthermore, the haplotype-based analysis revealed a significant association of the GTT, ATT, and ATC haplotypes with breast cancer. The GTT haplotype  status, grade 2 cancer, and positive lymph node status of patients. The genotype distribution of this variant increased the breast cancer risk in patients with HER2-positive status ; however, it showed a protective association among those who had grade 2 cancer  and a positive lymph node status . In addition, patients identified with N1 nodal status showed a link with breast cancer  compared to the N0 nodal status of patients in terms of the rs2420946 polymorphism. Moreover, a protective correlation was also observed in patients with a positive lymph node status  in the case of the rs2981582 variant.We investigated the linkage of breast cancer risk with http://gepia.cancer-pku.cn/, accessed on 20 November, 2022) and UALCAN  databases to examine the FGFR2 mRNA expression levels in breast cancer. Breast cancer tissues had considerably more significant levels of FGFR2 mRNA expression than normal tissues (p < 0.01)  compared to Caucasians . On the other hand, moderate expression was observed in African Americans  (We used the GEPIA ( < 0.01) . We also× 10−12) . All thrFGFR2 mRNA expression for the studied SNPs  from the Genotype-Tissue Expression (GTEx) database  is shown in FGFR2 rs1219648 polymorphism in breast tissues (p = 0.20) depending on the genotype. In the case of the FGFR2 rs2420946 and FGFR2 rs2981582 polymorphisms, the expression levels in breast tissues were also reported to be non-significant between the genotypes .The analysis of genotype-based FGFR2 polymorphisms  in the Bangladeshi population. This is the first study in Bangladesh that has looked at the association of FGFR2 polymorphisms with breast cancer and observed a significant outcome. The increased incidence of cancer in recent years has had a devastating impact on the physical, mental, and social lives of human beings, making it one of the major problems of the century. The most common type of cancer in women worldwide is breast cancer, and this alarming condition has been associated with the most cancer-related deaths among women [This case–control study was performed to clarify the association between breast cancer and three common ng women . This isng women ,26.FGFR2 gene belongs to the tyrosine kinase receptor family, which is involved in multiple signaling pathways in tumorigenesis through apoptosis, differentiation, and cell growth [FGFR2 intron 2 location and modulated the interaction of two transcription factors named Oct-1/Runx2 and C/EBPb. Consequently, increased FGFR2 gene expression in both cell lines and breast tissues occurred [FGFR2 rs1219648 polymorphism with breast cancer risk in all determined genetic models, including additive model 1 , additive model 2 , the dominant model , the recessive model , and alleles . Studies conducted in different ethnic and regional populations, such as North Indian, American, Turkish, Arab, and Kazakhstani populations, also revealed the association of rs1219648 with BC risk [The l growth . Variousoccurred . As is o BC risk ,29,30.p = 0.010), the recessive model , and allele models . Siddiqui et al. found an association of the TT allele of the FGFR2 rs2981582 polymorphism with an increased BC risk in North Indian women [FGFR2 rs2420946 polymorphism showed no significant association with breast cancer except in the overdominant model . A previous study conducted among Jewish and Arab Israeli BC populations also described the genetic variations of the FGFR2 gene (including rs2981582 and rs2420946) as a risk factor for breast cancer [In addition, our study demonstrated the significant relationship between the rs2981582 variant and breast cancer in terms of some genetic models, including additive model 2  were associated with breast cancer risk. Additionally, Liang Jie et al. demonstrated that breast cancer in Chinese women mainly occurred in the premenopausal stage [Furthermore, several case–control studies were conducted in Mexican, West Siberian, South American, Chinese, Iranian, Australian Caucasian, and Jordanian Arab women to determine the correlation between rability ,34,35,36al stage . Howeveral stage . They obFGFR2 gene with the risk of breast cancer development [FGFR2 polymorphisms and ER/PR/HER2 subtypes of breast cancer [p = 0.025) with BC risk was observed in the case of the rs1219648 variant. In addition, this variant also showed an increased risk of breast cancer with grade 2 cancer (p = 0.006) and positive lymph nodes (p = 0.043) in patients. Meanwhile, rs2420946 and rs2981582 only showed an association with N1 nodal status (p = 0.002) and positive lymph nodes (p = 0.004) accordingly.Liang et al. conducted a case–control study in Southern Han Chinese women and confirmed the association of genetic variation of the elopment . Moreovet cancer . Our stu2 = 0.624); rs1219648 and rs2981582 , and rs2420946 and rs2981582 . The GEPIA and UALCAN databases revealed that breast cancer tissues possess greater levels of FGFR2 mRNA expression than normal tissues (p < 0.01). Significantly lower expression of FGFR2 in Asians (p = 2.83 × 10−4) was observed compared to Caucasians (p = 8.79 × 10−1). On the other hand, moderate expression was observed in African Americans (p = 2.09 × 10−12).Furthermore, the haplotype-based analysis demonstrated a significant association of GTT, ATT, and ATC haplotypes with breast cancer. In addition, this study illustrated the LD of all SNPs in the breast cancer cases and controls, with the LD between rs1219648 and rs2420946 (D’ = 0.931, rFGFR2 gene other than novel SNPs. Secondly, the comparatively small sample size of participants does not represent the whole scenario of all breast cancer patients in Bangladesh. Thirdly, there may be other factors, such as gene–environment interactions, which were not evaluated. Despite these limitations, this study has provided a clear indication of the relationship between FGFR2 gene polymorphisms and the risk of breast cancer development in the Bangladeshi population.Notably, there were some limitations in our study that must be acknowledged and overcome in future research. Firstly, we only investigated three available SNPs of the FGFR2 genetic polymorphisms are significantly associated with breast cancer in Bangladeshi women. Different clinicopathological variables, such as HER2 status, cancer grade, and lymph node status, may have an impact on genetic polymorphisms that may be collectively associated with breast cancer risk. More research with a large sample size is suggested to confirm the findings of this study.Our study found that


Electrically-assisted bicycles (e-bikes) are a means through which to increase individual physical activity (PA) and overcome some commonly reported barriers to engaging in conventional cycling. Fatigue is a common side effect to breast cancer treatment, and the rate of PA engagement drops significantly following a breast cancer diagnosis. The aim of this qualitative study was to examine perceptions of e-cycling as a means of increasing PA in this population. Twenty-four participants (mean age = 57.88 (standard deviation 10.8), 100% female) who have had a breast cancer diagnosis, completed two semi-structured interviews via Zoom. One interview was conducted prior to an e-bike taster session and a second, after the session. Taster sessions were conducted by certified cycling instructors in the community. Interviews were conducted between December 2021 and May 2022. Data were transcribed verbatim and analyzed thematically using NVivo 12 software. An inductive and deductive approach to analysis was adopted. Five themes were generated: (1) Perceived role of e-bikes during treatment, (2) The relationship between e-bikes and fatigue, (3) Cancer-specific considerations, (4) Is e-cycling ‘enough’?, and (5) Optimizing the intervention. Negative perceptions of e-bikes noted before the taster session were altered following riding an e-bike. The multiple levels of assistance made cycling manageable and less impacted by fatigue, thereby enabling individuals to re-establish previous cycling habits. E-cycling may be a suitable option to increase PA behavior amongst individuals being treated for breast cancer, with the potential to overcome many of the barriers of conventional cycling. Enabling this population to trial an e-bike elicits positive physical and psychological responses that may help to promote future engagement. Cancer is one of the leading causes of mortality worldwide, totaling approximately 10 million deaths in 2020 . There aCancer places great economic burden on society, with the cost of breast cancer chemotherapy alone mounting to over GBP 248 million, yearly [Physical activity (PA) has been identified as a highly effective, non-pharmaceutical intervention known to complement other breast cancer treatments and modify recurrence rates . The benIn addition, in oncology, PA engagement is recognized to improve both psychological and physiological functions, including the potential to mitigate common side effects such as incidence of fatigue, impaired health-related quality of life (HRQL), mental health decline, and reductions in physical health .It is important to note that an individual’s willingness and their physical and psychological responses to PA can vary depending on the type of treatment they are receiving. A cross-sectional study of 37 breast cancer patients revealed that patients were more likely to experience perceived difficulty engaging in PA if they had undergone more than three types of cancer treatment, in comparison to patients that experience no perceived difficulty  [Despite the known benefits of PA and the intention to increase their PA participation once diagnosed, the number of women meeting national PA guidelines is low . It is dIn 2012, a cohort study revealed that only 48.3% of breast cancer patients met the PA guidelines of 10 metabolic equivalent (MET) hours/week . While tThere are several perceived barriers to PA engagement during breast cancer treatment, including physical, psychosocial, environmental, and organizational factors . PhysicaSmith-Turchyn and colleagues’  qualitatEmery and colleagues’  researchElectrically-assisted bicycles  have been identified as a means through which to increase PA, providing at least moderate intensity PA . ElectriFor older adults, e-cycling is reported as being preferable over conventional cycling due to the reduced physical exertion required on an e-bike, leading to reduced feelings of fatigue following a cycling journey . Use of 2 (95% CI −0.020 to −0.0002) lower per additional day of e-cycling per month. Additionally, maximal power output increased for both untrained men and women  following six weeks of active commuting on an e-bike [Associations have been identified between e-bike use and physiological parameters. A longitudinal study by Dons and colleagues  found thn e-bike . Furthern e-bike . As suchThe aim of this research was to examine perceptions of e-cycling amongst individuals who have had a breast cancer diagnosis.What are the perceived barriers and facilitators to e-bike usage during breast cancer treatment?When, during cancer treatment, is perceived to be optimum for introducing e-cycling?Does the implementation of an e-bike taster session elicit changes in perceptions of e-cycling during breast cancer treatment?Based on this aim, the following research questions were developed:Due to the novel exploration of e-cycling during cancer treatment, a qualitative approach was identified as the most appropriate research method to identify initial perceptions and insights.Two one-to-one semi-structured interviews were conducted with each participant; one before an e-bike taster session (referred to as Interview One) to gather the participants’ initial thoughts of e-cycling, and one post the e-bike taster session (referred to as Interview Two) to identify whether e-cycling opinions had changed. Semi-structured, one-to-one interviews were used due to their ability to keep the interview focused whilst still providing flexibility for the researcher to explore pertinent ideas that may be raised during the conversation . InterviTwenty-four interviews were conducted for Interview One. Following this, five participants were no longer contactable and did not complete the e-bike taster session or Interview Two. Four participants did not require a taster session due to already owning an e-bike. As such, fifteen participants completed the taster session and nineteen completed Interview Two.All data collection was conducted by a female researcher, KMW (MSc). KMW was completing their MSc in Nutrition, Physical Activity and Public Health at the University of Bristol at the time of the study.Participants were eligible to take part in the study if they have had a breast cancer diagnosis. Metastatic cancer is prominent amongst breast cancer patients, therefore individuals with secondary cancer were included . ParticiA convenience sampling technique was used based on the aforementioned inclusion criteria. Participants were recruited via a Bristol-based charity, Penny Brohn UK. Advertisements were placed in two instalments of the monthly newsletters and emails were sent to a consenting mailing list. Additional social media adverts were promoted via Breast Cancer Now, on platforms including Facebook and Instagram. All advertisements contained the researcher’s contact details.The recruitment reach through Penny Brohn UK was 281 via email mailing list and 4800 via monthly newsletter. From this, 34 individuals expressed initial interest in the study (approximately 0.7% of those reached), were sent the participant information sheet (int), and were presented with a link to an online demographic survey. The demographic survey collected data which allowed the researcher to screen individuals for eligibility; a consent form for the survey was also attached which participants were asked to sign and date electronically.In total, 29 out of 34 who were sent the PIS completed the demographic survey. Of these 29, one was not eligible for the study due to not having a breast cancer diagnosis, and four dropped out due to personal reasons unrelated to the study. Data collection and analysis were conducted in parallel, therefore participant recruitment continued until saturation was met . Data saSeparate interview guides were developed for use during Interview One and Two . The aveInterviews were conducted by the primary researcher, KMW. Informal, ice-breaker questions commenced the interviews followed by open-ended questions with probing questions included ad hoc, depending on the participant’s response, with the intention to deepen or expand on a point if necessary . Pilot iE-cycling is a recently popularized mode of PA, therefore it could not be assumed that participants had engaged in e-cycling previously . To ensuTaster sessions were conducted by qualified instructors at Life Cycle, a Bristol-based charity. A full safety briefing was delivered and safety equipment, such as high-visibility jackets and helmets, were provided on request. Participants were given an introductory ride on the e-bike around a Bristol park with a cycle path, which included both flat and hilly routes to ensure maximum exploration of the e-bike. Participants were given the autonomy to switch between levels of assistance and were provided with advice and support on how best to use the e-bike.Ethical approval was obtained via the University of Bristol, School for Policy Studies Research Ethics Committee .Descriptive statistics were extracted from the demographic survey and presented in Interview recordings were held securely on the University of Bristol server until transcriptions were complete, after which they were deleted. All identifiable information was removed or anonymized during the transcription process and each participant was assigned an anonymous identification code.Thematic analysis was used and guided by Braun and Clarke’s  six stepTranscripts were read repeatedly by KMW to ensure the researcher was familiar with the data. Following data familiarization, segments of text were highlighted, and initial codes were derived inductively and deductively . KMW and a second coder (TJC) independently coded three transcripts. These three transcripts were selected by KMW to reflect diverse responses. The researchers met to discuss and refine the codes and a coding framework was developed. The remaining transcripts were coded by KMW, who revisited previously coded transcripts as required if new codes were identified. Codes were organized into categories based on their content through discussion between KMW and the second coder. From these categories sub-themes and higher order themes were generated.To adhere to the quality criteria for all qualitative research, credibility, transferability, dependability, and confirmability were all considered , therefoFive overarching themes were generated from a combination of Interview One and Two: (1) Perceived role of e-bikes during treatment, (2) The relationship between e-bikes and fatigue, (3) Cancer-specific considerations, (4) Is e-cycling ‘enough’?, and (5) Optimizing the intervention .Participants explained that e-bikes could play a significant role in overcoming barriers to cycling that are present following a diagnosis. For some participants, despite having a history of regular cycling, they were no longer able to participate because of their treatment due to factors such as reduced energy, weakness, fatigue, and lacking motivation:P.20: “I liked cycling, but it was hard work. Yeah. And, and now, now that I’m diagnosed and I’m on medication, I don’t think I could do it. I’m just exhausted after physical activity.”, multiple cancer diagnoses, undergoing treatment)Yet, the prospect of an e-bike was appealing, with the electric motor offering the required assistance to get participants back into their previous cycling habits:P.16: “I don’t use my push bike very much at all. I was reluctant to get on it I think for a long time because I hadn’t got the energy levels to do that. So yes, I think an e-bike definitely would help, knowing that you know I’ve got the power behind me.”Participants discussed that an e-bike would facilitate an improvement in cycling performance, providing the ability to cycle further, faster, and with more confidence. Most prominently, the e-bike was perceived to overcome the inability to cycle up hills, due to strength reductions and deterioration in cardiovascular fitness that result from treatment:P.2: “It makes it more do-able, you’d be able to go further distances and hills wouldn’t put you off. So you didn’t, you wouldn’t have to be as fit to cycle with them.”One participant compared up-hill e-cycling to feeling the same as cycling a conventional bike on a flat road, emphasizing that the electrical assistance allowed them to overcome their fear of hills:P.5: “Then we went up on a hill and of course she told me that I can use a higher program to help, then it was just like same like I was going on a straight, you know, it was like cheating almost, feeling that I’m cheating because that’s not the reality.”Cycling was often described as a social sport, with participants enjoying a leisurely ride with their families, friends, or community cycling groups. However, this was often diminished once treatment started, having a negative impact on the participants, both socially and psychologically:P.14: “My partner, and my daughters would go out riding bikes. But I, I wouldn’t go I couldn’t go because I, you know, I just hold them up, I couldn’t keep up with them.”Yet, the e-bike was positively described as a way to overcome this barrier, due to the electrical assistance allowing for increased duration, thereby boosting their confidence to keep up with their peers and enhancing enjoyment:P.20: “There’s lots of people that are using e-bikes to like, so that they can carry on cycling with their partner because their partner is so much fitter and faster than them.”There were several physical benefits of e-cycling described by participants both pre- and post-taster session , such asP.6: “It’s just a wonderful feeling on an e-bike, the freedom the bike gives you, the wind in your hair and going through the countryside is just glorious, and just be able to continue to do that I think is really really important.”Many participants also described the benefit e-cycling will have to their treatment response. In particular, the e-bike was commonly associated with alleviating the stress of both a diagnosis and when undergoing treatment:P.15: “I was very stressed to begin with, not quite knowing where it was all going. And, yeah, to me exercise is a way of releasing stress very definitely, and I think e-cycling is perfect in that way, even more than walking for me.”For some, the taster session raised concerns that introducing e-cycling during treatment could lead to added stress, particularly amongst participants with limited cycling history and a fear of road cycling:P.5: “I guess, because it’s a kind of stress for me that I’m afraid of the traffic. And it was a stress for me to even just, you know, we mostly used the bike road but there were other bikers, there were there were other pedestrians.”Often, negative perceptions of e-bikes noted before the taster session were altered following a trial on the e-bike, with participants stating that cycling was “easier” than expected and a more “tolerable” mode of PA, thus making them more inclined to e-cycle in the future.Many participants reported a loss of identity or feeling like their cancer defines them. Yet, the prospect of an e-bike provided a sense of independence that they had been lacking since receiving their diagnosis:P.16: “Having the e-bike gives you that security but allows you to have the exercise as well, and and the independence, because otherwise you’re relying on someone else drive you or you have to try and park the car.” For some, their diagnosis meant they were no longer able to drive. As such, the e-bike would provide a mode of travel that is quicker and more practical than walking:P.21: “I can’t drive so, I could use the e-bike for exercise and also if I ever wanted to sort of get to a shop or something and you know use it for that, that kind of thing.”P.20: “I was surprised. I just didn’t feel exhausted. I think I was expecting it to take more out of me.”The fear of not getting home due to tiredness once setting off on a conventional bike ride was enough to deter people from cycling completely. However, the use of an e-bike was assumed to address this problem:P.10: “If I cycled an hour there then that’s also an hour back. But with an e-bike, I feel like you just, you’ve that extra assistance so less worry about getting back, so then you just go a little bit further, I think. I’d be encouraged to go to places that you wouldn’t on a push bike.”Yet, anxieties were still raised post-taster session at the thought of the e-bike battery running low or stopping completely, thus leaving participants hesitant about cycling too far:P.8: “If you went on a route that is, like, I’m only choosing this route because I’ve got an electric bike so I know I can make it and then the bike breaks and then you’re like, oh what now.”Although some participants expressed a desire to e-cycle when fatigued, others stated it would be detrimental to their health if they exerted themselves too much:P.15: “You have to be very careful not to overdo it, because it’s quite exciting to get on an e-bike, you know, and you think oh I’ll have a go, but it’s easy to do too much and suffer from it.”Emphasis was placed on the importance of conserving energy for treatments and therefore not participating in e-cycling on days of high fatigue:P.14: “If I lacked energy, I wouldn’t use an e-bike, I would be trying to conserve my energy for areas where I would need that energy.”As a result of a lumpectomy or mastectomy, the restrictions in the arm and armpit were feared to limit the ability to hold the handlebars on the e-bike. However, the taster session appeared to eliminate this concern:P.9: “I thought maybe, you know, the slight weakness I have in my right arm because of the removal of the lymph node might have affected it, but that wasn’t a problem.”For some, it was the strength in the arm that appeared most preventative:P.19: “I don’t think I had the strength in my hand or my arm to hold on and maintain a rigid arm. That was quite difficult.”E-cycling was sometimes described as a “bumpy ride”, with potholes or uneven road surfaces often inducing high, uncomfortable impact onto the bike and the rider. Some participants expressed concerns regarding this impact when undergoing treatment:P.17: “It wasn’t the exercise as much as the sort of the slight pummeling you get by going on the road on a small thing. So I guess that’s what would stop me using them at points when I was having chemo.”As a result, it was suggested that an individual’s stage of cancer should be considered when prescribing e-cycling as a mode of PA:P.20: “I think it’s something you’d, if you’re gonna recommend it you to people with stage 4 you’d have to take it on board, you’d have to find out more about their physical condition and assess if it’s suitable for them, I think.”Yet, participants recognized that the e-bike is no more prone to pummeling when compared to a conventional bicycle:P.18: “I tend to sort of like stand up on the pedals if I know there’s a bump coming or try and avoid it, or whatever. But it’s no more of an issue than it is with an ordinary bike.”Following the taster session, a few participants reported that they expected the e-bike to be a strenuous form of PA that was potentially unmanageable, however, the taster session changed their perceptions:P.20: “The fact that we we went on this this bike ride we got back, and I just didn’t feel exhausted. I think I was expecting it to take it more out of me.”Others’ preconception was that e-cycling may not have provided any form of PA due to the assistance. However, following the taster session, e-cycling was perceived as being of sufficient intensity to provide a sufficient workout:P.19: “I think it was more than I expected because you still feel as though you’re cycling. You don’t feel as though everything’s doing the hard work for you. You feel that you’re having exercise, but just having that extra push when you needed it.”Participants stated that the bike ride raised their heart rate sufficiently, worked their leg muscles, and induced muscle soreness the following day; all of which were claimed to be an indication of a good amount of physical exertion without the expense of fatigue:P.21: “But I was still puffed out when we got to the top, I had to have a little breather. You know I had the full support on I did still need a bit of a breather.”Multiple assistance levels allowed participants to alter their exertion depending on how they were feeling, which was reassuring when experiencing fluctuations in energy and motivation during treatment:P.15: “So because I’m feeling fairly fit at the moment, I only had it on the eco level. So, yeah, even though it’s an e-bike, you can choose your level so that’s why it would be quite good because you could sort of tailor it to different people and how that person feels at the time”Some participants were willing to cycle with little or no assistance to ensure they made the most of the workout:P.7: “Once I finally got used to motor I turned it right down, because I wanted it to be part of my daily exercise.”However, the weight of the e-bike was frequently presented as a barrier to e-cycling , and theSome participants claimed the e-bike played a type of “psychological trick” on them and their willingness to cycle. Despite feeling tired and fatigued, participants suggested they would be more inclined to cycle an e-bike rather than a conventional bike, despite potentially exerting the same amount of energy:P.13: “It could have a psychological effect because you know you wouldn’t maybe go out on a normal bike, because of how you’re feeling yet you’d go out on an e-bike and end up actually doing the same amount of effort.”The opinion of whether e-cycling was possible during specific treatments varied greatly between participants, with only one common conclusion: it is solely down to the individual:P.1: “In general, whether you’d be able to do it with cancer treatments is individual because everyone is so different and everyone’s regime is different.”Regardless of whether cycling throughout breast cancer treatment was seen as beneficial, most participants suggested not to promote an e-bike at the start of the cancer journey, following diagnosis:P.20: “It’s not when you’re first diagnosed, because it was just like you couldn’t even think something new.”However, P.7 suggested using the e-bike as soon as possible following diagnosis to set the patient up best for the treatment that follows:P.7: “The reasons they need it before is so that they can use it to improve their fitness, because the more fit you are before your surgery, the quicker recovery when you come out for chemotherapy.”Regarding surgery, it was popular to assume that the e-bike would not be used until the individual had recovered physically from the surgery. The recovery time appeared to depend on the type of surgery administered:P.9: “I guess it depends what surgery you have. If you’ve just had a lumpectomy, you probably could get onto a bike relatively soon.”Typically, post-surgery was claimed to be an ideal time to present an e-bike. In particular, the e-bike was described to act as a distraction away from the disease and the upcoming treatments :P.6: “It would have been the mindfulness of distracting me from all those dark thoughts and all that gloom and you feel like you haven’t got the future. So anything that takes you away from that.”E-cycling during chemotherapy presented the most controversial opinions. For some, despite chemotherapy being an exhausting time, they were confident they could continue using an e-bike depending on the week the chemotherapy was administered:P.13: “Week one, I wouldn’t be able to go for it. But then on week two and three, I was feeling perfectly well, or getting to the stage where I had enough energy to go for it.”However, the prospect of e-cycling at any stage during chemotherapy seemed impossible for some:P.15: “I think chemo affects the brain too and they have that they say, you know that you have brain fog or kind of things and the dizziness and and all kinds of things which is probably not the very ideal time to go on a bike.”The main concern for e-cycling during radiotherapy was due to time commitments, rather than the treatment itself. The time necessary to attend appointments every day appeared to frequently result in fatigue, which then acts as a barrier to using the e-bike.P.17: “So, the tiredness wasn’t from the radiotherapy, it was more from the driving to the appointment, you know going to and from the appointment every day.”The other barrier to e-cycling during radiotherapy was the skin burns:P.13: “You get radiotherapy burns. Would I have cycled with them? I don’t know, maybe.”Presenting the e-bike post treatment as a method to aid recovery seemed optimal amongst patients:P.20: “That sort of rehabilitation, that rebuilding yourself because after being poisoned and, you know, cut open and radiated, you know it’s a lot for your body to go through.”The e-bike was promoted as a method to return to “normal life”; a way of putting the cancer in the past.This is the first qualitative study to explore perceptions of e-cycling amongst individuals who have had a breast cancer diagnosis. With the aid of a 1-h taster session, this research highlighted the intention and desire for PA engagement during breast cancer treatment, with the e-bikes providing a promising method to overcome perceived barriers to physical exertion. Participants frequently referred to the “ease” of e-cycling, and its ability to re-introduce previous cycling habits that were disenabled because of their diagnosis and treatment. Reservations and considerations were reported regarding specific treatment side effects and the appropriate timing to introduce an e-cycling intervention. The findings of this research can be used by healthcare professionals when prescribing sustainable and manageable physical activity interventions alongside treatment. The emergence of themes and their alignment with current literature are considered below to determine the relevance and significance of e-cycling during breast cancer treatment.During pre-taster session interviews, it was evident that most participants recognized an e-bike’s image and usability, though were yet to consider its benefits for use during breast cancer treatment. Nevertheless, the prospect of e-cycling was desirable in the present study, with many participants claiming the taster session solidified their expectations that e-cycling would be an easier alternative to conventional cycling, allowing for increased distance and speed due to the electric motor. This aligns with previous research findings amongst e-bike owners in the Sacramento, California area, whereby the notion of increased distance inspired their purchase, with many participants disposing of their previously used conventional bicycles . It is pParticipants expressed their perceived importance of PA during treatment through discussion of current exercise patterns. Following the e-cycling taster session, participants described the bodily fatigue and muscular soreness they experienced the next day, as well as the respiratory requirements of e-cycling. Previous research has confirmed the reduction in exertion from an e-bike, but also its suitability for individuals with physical limitations as a result . JohnsonFurthermore, frequent reference was made to the ability to cycle up a hill because of the electric motor, something which previously deterred individuals from getting on a bike. This reinforces previous research that recognized hills as a key barrier to conventional cycling and a key facilitator of e-cycling ,51. A 20Interestingly, participants discussed the desire to turn the electric motor off entirely when cycling on flat terrains. It was perceived that, during the taster sessions, participants felt the need to “push themselves, which consequently resulted in them working harder than anticipated due to the weight of the e-bike. This was described as “psychological trickery”, whereby the absence of the electric motor in fact promoted more intense PA and a greater sense of achievement. This is consistent with previous literature which explained that a perceived sense of achievement is a key facilitator to PA engagement during breast cancer treatment, in a study protocol where exercise instructors and continuous remarks of praise were used as a method to increase exercise self-efficacy . With paEnhancing the psychological benefits is important for improving long-term adherence to e-cycling and PA overall . ResearcMost participants shared their relationship with fatigue during their treatment. Although fatigue was presented as a key barrier to conventional cycling, especially regarding hills and non-flat terrains, many suggested they would still engage in e-cycling when they would consider themselves too fatigued to engage in other, more strenuous types of PA. However, some days, such as during weeks of chemotherapy, e-cycling was deemed “impossible” or “unsuitable” due to the need to conserve energy. This supports previous research which identified a decrease in PA engagement when undergoing adjuvant chemotherapy, as well as significant decreases in energy expended through PA .The greatest concern regarding fatigue was the fear of the e-bike battery running low and therefore cycling home with no assistance. Although advancements in technology mean that e-bike battery life is extending, this does not come without an increase in price . Fears rDespite listing extensive benefits and facilitators to e-cycling, participants were quick to identify limitations and barriers to this mode of PA. As e-bikes are a large financial investment, with prices increasing depending on the make and model , particiProspectively, the initial investment for an e-bike would be eliminated if e-bikes were used within a future intervention amongst cancer patients, as the equipment costs would be covered by research funding. However, investment must be considered when looking to induce long-term e-cycling habits, when participation in research studies is complete. A survey study conducted in Norway found that higher perceived benefits and familiarity with e-bikes were positively related with the intention to buy an e-bike . HoweverA key reported facilitator and, consequently, benefit of e-cycling was the social opportunities that e-cycling provides. Frequently, individuals highlighted that an e-bike would allow them to cycle alongside peers and family, something they had not been capable of since their diagnosis. Rey-Barth and colleagues  found thFears regarding physical limitations resulting from surgery, such as restricted use of the affected arm, are common in literature investigating the barriers to PA during breast cancer treatment. Participants in Sander and colleagues’  study rep = 0.02) in a study where 68 breast cancer patients undertook regular supervized, moderate-intensity, aerobic, and resistance exercise [Uncertainty was displayed when deciding if e-cycling would be manageable and maintainable during other breast cancer treatments, in particular the cyclic nature of chemotherapy doses. Parallel to previous research, exercise adherence was reported lower during chemotherapy in comparison to radiotherapy  to reduce or eliminate negative treatment side effects   and recuFuture researchers can be confident that breast cancer patients support the prospect of e-cycling during treatment and would be keen to partake if the opportunity was presented to them when undergoing treatment. Researchers must recognize that introducing an e-bike immediately after a cancer diagnosis could be detrimental, yet an optimal time to intervene is highly dependent on the individual. Participants in this study valued the taster session to gain a better understanding of the e-bike usability and practicality. Therefore, the implementation of an e-bike taster session will be essential when looking to recruit participants for a future e-bike intervention. Barriers to e-cycling predominantly surrounded initial investment, therefore it is imperative to ensure external funding is secured to cover costs of the e-bike if recruiting for a future intervention. Additionally, knowledge of how to access an e-bike once study involvement has concluded would contribute to long-term e-cycling engagement amongst cancer patients.To address the limitations of the present study, future research should aim to gather perceptions from a more ethnically diverse population to reduce disparities in healthcare research. Additional further research should qualitatively assess the motivations, facilitators, and barriers behind buying an e-bike during a cancer diagnosis. Understanding these factors may assist with prolonging e-cycling engagement throughout cancer treatment and beyond.This qualitative study provides novel insights to the perceived usefulness and practicality of e-bikes during breast cancer treatment. It is presented that individuals who have had a breast cancer diagnosis recognize the importance of engaging in PA during treatment and believe e-cycling is a suitable mode to overcome common barriers to conventional cycling, such as fatigue and physical exertion. There are both physical benefits of e-cycling, such as its suitability for individuals with a cancer diagnosis, and psychological benefits, such as fresh air and the influence to work harder than anticipated. However, worries regarding battery life and theft were prominent, and the initial financial investment deterred some participants from potentially purchasing an e-bike. An optimal time to introduce an e-bike intervention was difficult to discern for participants, as cancer treatment is explained to be highly dependent on the individual. Overall, e-cycling was deemed an appropriate mode of PA to engage in during breast cancer treatment. It suggests promise for increasing PA behaviors in this population, with the potential to overcome many barriers posed by conventional cycling. The positive physical and psychological responses associated with providing e-bike taster sessions in this population may help to promote future engagement.


Globally, an estimated 1% of the population identifies as transgender, with 2%–3% of individuals under the age of 25 identifying as transgender or gender diverse.Cancer is an understudied topic in transgender health due to paucity of available data.BOX 1Increased circulating estradiol levels from both endogenous and exogenous sources are associated with breast cancer risk in cis women; however, the evidence on the risk of breast cancer in transgender women is mixed. An analysis among United States (US) veterans found no increased incidence of breast cancer among 5135 transgender women who used estrogen compared to cisgender men.As androgens are thought to be the primary driver of prostate cancer it has been hypothesized that transgender women would have a lower risk of prostate cancer as many individuals use hormone therapy along with orchiectomy to reduce testosterone levels. Indeed, a study conducted in the Netherlands of 2260 transgender women who had undergone gender affirming care found a lower prostate cancer risk in transgender women compared to cisgender men (SIR: 0.20).Transgender persons may be at higher risk of certain cancers compared to cisgender persons, in part, due to an increased prevalence of infections like HIV.Transgender persons may be at higher risk for cancers due to coping mechanisms related to discrimination, stigma, and social isolation.Discrimination in healthcare settings has been documented as a major barrier to transgender people accessing care in both the US and the UK.Medical discrimination, among other factors, may even increase cancer outcome disparities. A study from the US reported that transgender adults with cancer had worse outcomes than cisgender adults with cancer.In summary, the prevalence of individuals reporting and seeking treatment for gender incongruence is growing globally. Therefore, there is an urgent need to explore cancer risk and cancer mortality in transgender persons as the incidence of certain cancers may be altered from that of cisgender persons. Given that many cancer risk factors are increased in this population, greater efforts are needed to ensure transgender adults undergo routine screening at the same rates as cisgender people. Finally, documenting transphobia and discrimination in healthcare is needed to provide interventions to clinicians in order to improve access to cancer prevention and care for all transgender individuals.The authors confirm that there are no conflicts of interest.