Despite the lack of statistical significance, likely due to the small sample size of the cohort, the present nested case–control study’s clinically significant effect size, dose–response, temporality, specificity, biological plausibility, consistency, coherence, and analogy with other research findings meet the criteria for inferred causality in observational studies, warranting further investigations. Furthermore, these findings suggest that a low-phosphate diet should be tested on patients with breast cancer.Research has shown that high amounts of dietary phosphorus that are twice the amount of the U.S. dietary reference intake of 700 mg for adults are associated with all-cause mortality, phosphate toxicity, and tumorigenesis. The present nested case–control study measured the relative risk of self-reported breast cancer associated with dietary phosphate intake over 10 annual visits in a cohort of middle-aged U.S. women from the Study of Women’s Health Across the Nation. Analyzing data from food frequency questionnaires, the highest level of daily dietary phosphorus intake, >1800 mg of phosphorus, was approximately equivalent to the dietary phosphorus levels in menus promoted by the United States Department of Agriculture. After adjusting for participants’ energy intake, this level of dietary phosphorus was associated with a 2.3-fold increased risk of breast cancer incidence compared to the reference dietary phosphorus level of 800 to 1000 mg, which is based on recommendations from the U.S. National Kidney Foundation, (RR: 2.30, 95% CI: 0.94–5.61,  As global populations increasingly transition to the risk factor profile of Western nations, “dramatic changes in lifestyle” are affecting the prevalence of risk factors for breast cancer and other cancers . For exaThe Lancet in 1996 [Inorganic phosphate (Pi) metabolism is regulated in the body with a sensitive network of endocrine hormones released by the kidney–bone–parathyroid–intestine axis . The acc in 1996 , suggestPhosphorus in the form of dietary phosphate is plentiful in the dietary pattern eaten by contemporary Western populations, including in Canada and the United States . Phospha, a MyPlate 2000-calorie daily menu that includes whole grains and fat-free milk provides approximately 1800 mg phosphorous [As the intake of nutrients like phosphorus rises above optimal levels for health, the increased concentration may eventually become toxic and even result in death . Althougsphorous , well absphorous .Three cups of fat-free milk, as recommended by USDA menu plans, supplies more than 700 mg of phosphorus, which is sufficient to meet adult requirements but provides only about 13% of calories in a 2000-calorie diet ; as a reThe purpose of the present study is to investigate associations of breast cancer incidence with discrete categories of dietary phosphate levels. Phosphate levels are based on dietary guidelines from U.S. health organizations and government agencies, and categories also include levels of phosphate associated with disease in the research literature. The hypothesis in the present study is that the relative risk of breast cancer incidence is more strongly associated with high levels of dietary phosphate compared to low levels of phosphate. The rationale for selecting the National Kidney Foundation (NKF) guidelines for dietary phosphate intake as the reference level in this study is based on numerous findings implicating chronic kidney disease as a risk factor for cancer, such as Lees et al. , Wong etThe present study used a nested case–control design to conduct a secondary analysis of cohort data from the Study of Women’s Health Across the Nation (SWAN) . SWAN isPublicly available data from SWAN used in the present study were collected from baseline interviews and examinations of physical, psychological, biological, and social factors, followed up with 10 annual visits (1997–2007). Food frequency questionnaires (FFQs) were administered to collect dietary data at baseline and at visits 5 and 9. In the present study, each of the 74 breast cancer cases, who self-reported breast cancer during annual follow-up visits, were matched with four controls randomly selected from the cohort, totaling 296 controls consisting of women with similar ages (42–52 years) who were followed over 10 annual assessments. Four controls per case is recommended to increase statistical power in a case–control study, with beyond four matched controls generally leading to negligible increases in power . A list Although an odds ratio is most often used in case–control studies to measure the ratio of disease prevalence between exposed and unexposed groups, the present case–control study is nested within a cohort and measures disease incidence or an incidence rate ratio between exposed and unexposed groups, which is represented in the present paper as a risk ratio .“The numerator of an incidence proportion or rate consists only of persons whose illness began during the specified interval. The numerator for prevalence includes all persons ill from a specified cause during the specified interval regardless of when the illness began” .p-values were calculated to four decimal places using online MedCalc Software Ltd. [p < 0.05.Additionally, odds ratios in cohort studies overestimate the risk ratio . Relativare Ltd. . StatistData of dietary phosphorus intake collected at baseline from food frequency questionnaires (FFQ) were cumulatively averaged with FFQ data collected in visits 5 and 9 according to the cumulative average method used by Wallace et al. . SpecifiDietary Assessment Primer of the National Cancer Institute (NCI) [Additionally, the adjustment method from the te (NCI)  was usedTo analyze breast cancer risk ratios, energy-standardized dietary phosphorus intakes of participants were grouped into six discrete categories, each spanning 200 mg of phosphorus (P), with 800 to 1000 mg of P as the reference category to which the other five categories were compared. As mentioned in the introduction, the reference category is based on NKF guidelines for P dietary intake . The fouInterestingly, nine cases initially reported unadjusted dietary P levels below 800 mg , which was reduced to two cases <800 mg of P after standardization. Among controls, 62 women initially reported unadjusted dietary P levels below 800 mg which was reduced to eight controls after standardization. Standardization appeared to reduce the proportion of initially reported dietary P levels <800 mg more so in cases (2 out of 9 or 22.2%) than in controls (8 out of 62 or 12.9%). The standardized mean P intakes for cases and controls in our study  are below P levels in MyPlate recommendations (~1800). This suggests that MyPlate recommendations may not be attainable for many people. Additionally, p-value is non-significant at 0.07.2 of 0.9341, indicating a strong correlation between increasing dietary P levels and breast cancer risks.p = 0.07). A curvilinear regression line of risks for breast cancer incidence shows a strong correlation with exposure to higher levels of dietary P; R2 equals 0.9341.To the best of the authors’ knowledge, the present study is the first to report an increased risk of self-reported breast cancer incidence associated with a high dietary P intake. Compared to the lowest P intake level in this nested case–control study from the SWAN cohort of middle-aged females, exposure to the highest P intake of >1800 mg is associated with a 2.30 relative risk of breast cancer incidence, although this effect is not statistically significant  will probably not have been measured with the same accuracy and consistency throughout. It may also be problematic if the diagnosis of the disease or outcome changes with time”.Additionally, the nested case–control design of this study has certain limitations common to observational studies:Nevertheless, among epidemiological observational studies, the nested case–control design ranks high, providing the advantage of observing disease incidence within a cohort .Other study limitations include the reliance on cohort participants to self-report breast cancer incidence, which may be prone to inaccuracies and information bias, unless credible proof of diagnosis is presented to verify the diagnosis. Study limitations also include standardization of self-reported dietary intake from FFQ data. Although standardization is intended to provide a more realistic estimation of dietary intake to improve validity of the study, standardization cannot estimate actual dietary intake levels, and adjustments are based on averages rather than individual caloric needs of women. More accurate dietary information can be obtained using intervention studies with controlled feeding of participants—which can be very expensive. Furthermore, researchers have found a correlation between dietary phosphate intake and phosphate excreted in 24 h urine collection, which has potential use as a biomarker to estimate dietary phosphate intake in clinical studies . HoweverFinally, potential confounding factors were not controlled in this observational study, such as exposures to environmental carcinogens, including alcohol and tobacco, and other risk factors like obesity, low physical activity, and family history of breast cancer . PhosphoFor future research on cancer therapies, Kuang et al. wrote, “our simulation results show that if an artificial mechanism (treatment) can cut the phosphorus uptake of tumor cells in half, then it may lead to a three-quarter reduction in ultimate tumor size, indicating an excellent potential of such a treatment” . FurtherRisk factors for breast cancer include the Western diet, which is high in the essential mineral P. Research has shown that higher amounts of dietary P are associated with disease and mortality. The present nested case–control study measured risk ratios of dietary P levels associated with self-reported breast cancer in middle-aged women from the SWAN cohort. Results in ten annual follow-up visits found that the highest dietary intake of P was associated with a clinically significant 2.30 relative risk of breast cancer incidence compared to the lowest intake level recommended by the U.S. NKF to treat chronic kidney disease. The highest level of P intake is within the approximate range promoted by the USDA. Evidence supports the criteria to infer breast cancer causation from high dietary P intake in observational studies, and further studies with larger cohorts are warranted. Additionally, clinical and preclinical studies with breast cancer patients should test the effect of a low-phosphate diet already in use for patients with chronic kidney disease.


The incidence of breast cancer in South Africa is increasing, with rural South African women presenting with advanced stages of the disease. A woman’s breasts are a symbol of her womanhood; they also constitute a social definition of her femininity. Women with breast cancer in rural South Africa are heavily stigmatized and suffer from various sociocultural interpretations of the disease. Breast cancer is frequently interpreted in rural South Africa as a symbol of witchcraft, sin, and punishment, and traditionally, it is treated by offering animal sacrifices, consumption of herbs, and prayer to ancestors. Using care-seeking behaviour theory as the theoretical framework, we intend to explore the sociocultural factors influencing breast cancer screening practices among rural South African women. A qualitative exploratory study was conducted using semi-structured interviews with 22 rural South African women selected by purposive sampling. Thematic analysis was used to analyse the data. The study identified four sociocultural factors influencing women’s practices of breast cancer screening in rural South Africa, including psychological factors, habits, beliefs, and perceptions of healthcare. Women in rural South African communities have deep-rooted traditional beliefs and practices regarding breast cancer. Consequently, this influences women’s preventative health behaviours regarding breast cancer screening. The development of culturally appropriate health education programs involving traditional healers and influential community leaders is essential to increasing the number of women being screened for breast cancer in rural South Africa. Breast cancer is not only the most diagnosed cancers worldwide, but it is also the leading cause of cancer death in over 100 countries . The majThe burden of cancer is disproportionately felt in low- and middle-income countries (LMICs), where the majority of new cancer cases and 70% of cancer deaths occur . The impGlobally, low breast cancer screening rates can be attributed to a lack of knowledge, a lack of awareness, cultural influences, and socioeconomic factors. Women’s knowledge of breast cancer screening varies across nations probably due to their cultural beliefs and socio-economic levels . The curThis study utilized the care-seeking behaviour (CSB) theory as a theoretical framework. This theory was originally developed to explain and predict preventative health behaviours . The CSBAffect: refers to a feeling of anxiety that may result from embarrassment or a diagnosis and these affectual concerns may lead to individuals refraining from performing preventative health behaviours ,22.Habit: refers to the way one acts when one is experiencing symptoms  .Belief: reflects the overall value or importance of CSB . Most stNorm: consists of the perception of morally acceptable behaviour towards seeking health care . The CSBThis paper presents the findings of a qualitative study conducted between August and October 2022. This study examines the sociocultural factors that influence the practice of breast cancer screening among rural South African women living in the iLembe District of KwaZulu-Natal (KZN). The district is divided into four local municipalities (areas): Mandeni, KwaDukuza, Ndwedwe, and Maphumulo . We chosThe study sample included South African women living in the iLembe District of KZN. Participants were recruited from four clinics in the district located in different areas. Participants within these clinics were presented with a research information sheet and asked to consent to participate in the study. This study employed a purposive sampling technique to select participants who were South Africans of African descent, living in the rural iLembe district in KZN province, aged 20 to 60, and who consented to participate in the study. Following the explanation of the research information sheet and the successful recruitment of participants, a written consent was obtained, and then the interview process commenced. This study included 22 participants as a result of data saturation.Data were collected at four healthcare facilities (clinics) in the iLembe district of KZN between August 2022 and October 2022. It was found that these healthcare facilities served a large sample of the population. Therefore, it was the most suitable option. The duration of each interview ranged from 30 to 40 min. Interviews were conducted in a designated area within the clinic to ensure confidentiality. Interviews were carried out in English, however a translator was available for participants to speak in their native language of isiZulu if they desired. To gain a deeper understanding of the sociocultural factors influencing breast cancer screening among South African rural women, a semi-structured, one-on-one interview approach was employed. Please refer to The researchers read the interview transcripts repeatedly to identify meanings and patterns, as well as to make preliminary observations.Upon reading and understanding the transcripts, initial codes are developed and written. From the codes, the researchers develop a series of categories and subcategories from which themes are derived. The process is repeated continuously to ensure that all possible codes have been recorded.Once all codes have been identified across the data set, the researchers identify overarching themes. Some of these codes are subsequently classified as primary themes, others as sub-themes, and some are discarded.Based on the supporting data, the researchers further categorize or merge the themes.The themes and supporting data from the interviews are then summarized.In light of the study’s data extracts, the researchers draw conclusions that confirm the prevalence of the theme.Transcripts of the interviews were transcribed verbatim by one of the researchers, with participant names replaced with codes to ensure confidentiality. Thematic analysis was chosen as the method of data analysis. The purpose of this was to provide an in-depth overview and description of the data comprehensively and interpret various aspects of the research topic. Thematic analysis consists of six stages :The reseAs suggested by Lincoln and Guba, this study was evaluated according to four criteria for establishing the trustworthiness of qualitative research: credibility, dependability, confirmability, and transferability. A high level of credibility was achieved as a result of extensive engagement with the participants. A record of the raw data collected during each interview was kept for future reference to ensure reliability. An audit trail detailing data collection, analysis, and interpretation was used to establish confirmability. The transferability of this study was achieved by providing detailed descriptions of the research setting and methods, thus confirming the authenticity and validity of the study. This allows for future research to be based on the findings.Ethical clearance was obtained from the Institutional Research Ethics Committee (IREC 157/22) at the Durban University of Technology for this study. The gatekeeper’s permission was obtained from the KZN Department of Health and the iLembe District Manager. A consent form was signed by all participants to participate in this study and to permit the researchers to record the interviews. All responses were kept anonymous and confidential. During the interview, the participants’ names were not used, but a number was assigned to each based on their order of interview. P1 was the first person interviewed, followed by P2 up to P22. Data were stored electronically and password protected.The supporting extracts of the interviews revealed a number of themes related to the theoretical framework (CSB). The data were analysed and themes were formulated by two of the researchers. Four themes were identified as influencing the practice of breast cancer screening among rural South African women. As part of the CSB theory, the construct “affect” is identified as the theme of “psychological influences,” which suggests feelings of fear, stigmatization, social support, and attitude. To better understand this construct, participants were asked to describe how they would feel if they discovered a lump in their breast. Moreover, follow-up questions involved exploring their comfort level with discussing their breast health with family, friends, and community members. The second construct, “habit”, was identified as a theme of “preventative healthcare habits”. In order to understand rural South African women’s healthcare habits, these women were asked about their habits when experiencing medical symptoms. As a result, the interviewer was prompted to explore further the various habits mentioned in the study. Thirdly, the construct of “belief” was identified as a theme of “breast cancer beliefs”. In drafting the questions, consideration was given to the existing literature as well as the theoretical framework of this study. Therefore, participants were asked to describe their traditional or cultural understanding of breast cancer and the treatment options available to them. Lastly, the construct “norm” was applied to the theme of “healthcare perception”. To better understand the perception of healthcare at a community level, participants were asked whether women are encouraged to practice BSE across the community. The findings of each of the four themes mentioned will be presented in the following sections.Breast cancer screening among rural South African women is influenced by four factors: fear, cultural stigmatization, social support, and attitude. When it comes to breast cancer and discovering a lump in the breast, most women express fear.“I will be heartbroken. As you can see my breast is small, imagine if I can find the lump. I will be scared.”(P8).“…. cancer is something that you should be afraid of. It’s not just a disease, it’s very dangerous.”(P18).The fear of breast cancer is often attributed to the belief that the disease is incurable and fatal.“This illness is like we scared to have it because we think that it’s not curable, and you’re going to die.”(P3).Additionally, participants frequently referenced the concept of stigmatization in their responses to the interview questions. According to several participants, South African women diagnosed with breast cancer are heavily stigmatized by other Africans. It is therefore less likely that women will engage in breast cancer screening or discuss it with others. The following excerpt illustrates some of the reported stigmatization:“They will mistreat her. They will see her as a different person like she’s not qualified to be a woman.”(P2).“When I say community, I mean women. Ladies! She will be such a shame. To males, no one will ever want to marry her and with her family, she’ll be a disgrace.”(P10).Interestingly, some participants said women with breast cancer or breast cancer symptoms are stigmatized and compared to HIV-positive individuals.“When you start losing weight and you look sickly, they go around talking about you, that you’ve contracted AIDS.”(P13).Consequently, this leads to the factor of social support. It was agreed by participants that South African women’s preventative health behaviours are greatly affected by the social support they receive from their families, friends, and communities. The likelihood of women being able to communicate their breast-related concerns is higher when they have a good support network. A positive response was noted by some participants when asked about how easy it is to discuss breast problems with family and friends:“It’s easy to talk to them, they understand.”(P4).Additionally, the majority of participants expressed a favourable attitude regarding their willingness to practice BSE and to participate in breast cancer programs in their respective communities.“I want to learn more. I want to know more.”(P3).“Yes, I will go because I will learn more, and I will understand more about breast cancer.”(P11).It cannot be overstated how important it is to understand women’s healthcare habits, particularly when one is experiencing a medical condition. To gain a better understanding of women’s preventative healthcare behaviours regarding breast cancer screening, we sought to understand habits. The one-on-one interviews conducted with African women revealed that they have three distinct healthcare habits, namely seeking healthcare services, self-treatment options, and traditional practices. Several participants reported that they would consult a healthcare facility if they had a breast-related problem or any other health-related problem, indicating their confidence in the healthcare system.“Obviously I will go to the clinic to seek medical help.”(P6).There were, however, several participants who indicated that they would not visit a health facility and would rather practice self-treatment options. Self-treatment options for medical symptoms included non-prescription pain medications found in their local shops, as well as turmeric roots and ginger.“I will just make what the people tell me I must make and drink, like ginger, fresh turmeric roots.”(P12).“If it’s something painful, I get some painkillers and use them and see if the pain goes away.”(P20).Other participants indicated that they would engage in traditional practices based on their religious beliefs. The traditional prayer herbs sought from traditional healers in their communities were consumed in this manner. Furthermore, participants reported that they may need to participate in slaughter ceremonies of animals and pray to their ancestors, as prescribed by traditional healers.“I use traditional herbs.”(P2).“If you get sick, they will consult your late grandfathers….. Maybe they will say, maybe we have to slaughter a cow.”(P3).Participants’ beliefs regarding breast cancer emerged as a dominant theme during the interview process. Two distinct factors were identified under this theme, namely healthcare beliefs and traditional beliefs. Several participants indicated that they would consult a health facility if they were experiencing breast-related problems or if they had any other medical concerns. It was determined that these participants had demonstrated an understanding of the concept of breast cancer and BSE earlier in the interview process. As a result, they held strong healthcare beliefs.“Breast cancer is where you have carcinogens or cancer in your breast or where you have a tumour in your breast.”(P13).“Healthcare provider first. Because they’re able to run the test, more tests to see what’s wrong with you.”(P18).Additionally, there were a substantial number of participants who held strong religious or traditional beliefs regarding breast cancer. Participants reported several traditional interpretations of breast cancer. Among these were those that believed breast cancer was the result of witchcraft, punishment, or sin.“Mostly, they think of witchcraft. They think maybe you are cursed, maybe something you’ve done, something in the past that you are not supposed to do now and God is punishing you, things like that.”(P20).Some women, however, believed that breast cancer signified the ‘cutting’ of a woman’s breast.“Cut your breast completely.”(P20).This theme sheds light on individuals’ morally righteous beliefs regarding health behaviour in terms of seeking health care, as well as their willingness to act on those beliefs. There were three factors found to influence health care perception, namely personal norms, social norms, and interpersonal norms. Personal norms explored participants’ perceptions of seeking medical care and how they understand and perceive BSE. In this study, it was revealed that a few participants were confident in practicing BSE. However, other participants were unsure of how to perform this screening procedure correctly. In addition, some participants indicated that they had sought out information about breast health concerns through the use of mass media, such as Google.“I don’t know if I’m doing it the correct way. That’s the problem.”(P5).“I Google and search, and they asked what kind of bra I am wearing. So, I wrote, I wear a bra with the underwire and they say you must stop wearing and try to wear the one that is comfortable with no wire. So, I went for those bras and the pain stops.”(P3).Social norms reflect society’s perception of preventative healthcare and breast cancer screening. It was found that a lack of awareness and knowledge of breast cancer screening was prevalent among family, friends, and the community.“They know nothing about it.”(P1).In addition, it was found that traditional beliefs play a significant role in how society interprets breast cancer.“They only believe in traditional things. So, it’s not easy to talk to them. And some will just treat you like you’re cursed or something.”(P2).All participants agreed, however, that raising awareness of breast cancer screening among family, friends, and communities would encourage more women to undergo screenings.“They will understand if there was someone to explain to them what breast cancer is and how it is cured.”(P2).“They will understand if there could be someone to explain to them what breast cancer is.”(P3).“Teach them, have a meeting, give health education it’s the only way we can help them.”(P6).Observations of interpersonal norms revealed the understanding between individuals regarding the necessity of seeking medical attention. The participants reported that women who were encouraged to practice breast cancer screening were more likely to do so.“If we have someone who know about it, like for instance, I know about the examination. So, if I teach my family obviously they will practice it.”(P1).This study explores the sociocultural factors that influence breast cancer screening among rural South African women. Furthermore, we explored breast cancer perceptions from a sociocultural perspective at a community level and identified challenges and potential opportunities associated with breast cancer screening in rural South Africa. Based on the research findings presented in this paper, psychological influences, habit, belief, and healthcare perception were identified as sociocultural factors influencing breast cancer screening among rural South African women.Participants expressed a fear of death due to the misconception that breast cancer is incurable. According to a previous study, women who have been diagnosed with breast cancer feared a mastectomy and death. This prevented them from consulting their physicians or reporting to a health centre . AdditioIt has been found in a previous study that women with preventative habits are 4.8 times more likely to adhere to screening recommendations, such as mammograms, than women without such habits . As a reTraditional beliefs and practices play a significant role in breast cancer screening among rural South African women. A common interpretation of breast cancer is that it represents witchcraft, sin, and punishment. It is commonly treated by sacrificing animals, consuming herbs, and praying to ancestors. According to a study conducted in Nigeria, breast cancer is the result of evil spirits, curses, or promiscuity and can only be cured spiritually . Even thSeveral other studies suggest that women who are knowledgeable about breast cancer awareness may not practice breast cancer screening because of social factors that may influence their health-seeking behaviour . In ruraThe present study focused solely on sociocultural factors that influence breast cancer screening in rural South Africa. There may be other factors influencing breast cancer screening in rural South Africa, such as traditional healers’ and tribal leaders’ perceptions of healthcare. Future studies should explore these factors in greater detail. Furthermore, the findings of this study should not be construed as representative of all African women in South Africa. Rather, we present a snapshot of the narratives provided by a small sample of rural South African women, and our analysis reflects their viewpoints. It should be noted that although participants responded to the interview questions in English, their native language is isiZulu. There is a possibility that participants may not have understood the interview questions in their entirety.This study suggests that sociocultural factors influence rural South African women’s preventative health behaviours and breast cancer screening practices. Furthermore, it was understood that rural South African women’s willingness to participate in breast cancer screenings was largely dependent on social support, traditional beliefs, and practices. In addition, it was found that South African rural women have a variety of preventative healthcare habits, which may contribute to further delays in seeking medical treatment. Moreover, this study suggests that rural South African women are more likely to present at a later stage due to fear, cultural stigmatization, and embarrassment as a result of a lack of social support from family and friends. Enhancing community engagement and breast health education are essential to improving the detection of breast cancer in rural South African communities. Although the present study acknowledged the role of traditional healers in breast cancer treatment, it did not examine their role in breast cancer screening. Therefore, future research should examine the role of traditional healers in the screening and prevention of breast cancer in rural South African communities. Additionally, there is a need for culturally sensitive breast cancer campaigns, involving key stakeholders, like traditional healers, tribal leaders, school educators, and local health facilities, who are trusted by the community.


Breast cancer survivors are living longer due to early detection and advances in treatment and are at increased risk for second primary cancers. Comprehensive evaluation of second cancer risk among patients treated in recent decades is lacking.We identified 16,004 females diagnosed with a first primary stage I-III breast cancer between 1990 and 2016 (followed through 2017) and survived ≥ 1 year at Kaiser Permanente (KP) Colorado, Northwest, and Washington. Second cancer was defined as an invasive primary cancer diagnosed ≥ 12 months after the first primary breast cancer. Second cancer risk was evaluated for all cancers  using standardized incidence ratios (SIRs), and a competing risk approach for cumulative incidence and hazard ratios (HRs) adjusted for KP center, treatment, age, and year of first cancer diagnosis.Over a median follow-up of 6.2 years, 1,562 women developed second cancer. Breast cancer survivors had a 70% higher risk of any cancer (95%CI = 1.62–1.79) and 45% higher risk of non-breast cancer (95%CI = 1.37–1.54) compared with the general population. SIRs were highest for malignancies of the peritoneum , soft tissue , contralateral breast , and acute myeloid leukemia /myelodysplastic syndrome . Women also had elevated risks for oral, colon, pancreas, lung, and uterine corpus cancer, melanoma, and non-Hodgkin lymphoma (SIR range = 1.31–1.97). Radiotherapy was associated with increased risk for all second cancers  and soft tissue sarcoma , chemotherapy with decreased risk for all second cancers  and increased myelodysplastic syndrome risk , and endocrine therapy with lower contralateral breast cancer risk . Approximately 1 in 9 women who survived ≥ 1 year developed second cancer, 1 in 13 developed second non-breast cancer, and 1 in 30 developed contralateral breast cancer by 10 years. Trends in cumulative incidence declined for contralateral breast cancer but not for second non-breast cancers.Elevated risks of second cancer among breast cancer survivors treated in recent decades suggests that heightened surveillance is warranted and continued efforts to reduce second cancers are needed.The online version contains supplementary material available at 10.1186/s13058-023-01647-y. There are nearly 4 million breast cancer survivors in the US, and this number is increasing due to an aging population and improvements in breast cancer survival . During Here we evaluated second cancer risk among a large retrospective cohort of breast cancer survivors diagnosed between 1990 and 2016 (followed through 2017) within an integrated US health care delivery system with long-term follow-up and comprehensive treatment data. Our study utilizes systematically ascertained data on radiotherapy, chemotherapy, and endocrine therapy to examine second cancer risk that cannot be addressed with Surveillance, Epidemiology, and End Results (SEER) registry data due to the known under-ascertainment of treatment and availability of initial treatment only . A comprn = 4,658 between 1990 and 2008), Colorado , or Washington . Eligible women were KP members who survived and remained at risk for second cancer for at least 1 year. We excluded women diagnosed with a first breast cancer at age < 20 years (n = 1) or ≥ 85 years (n = 563), in situ  or metastatic disease (n = 204), unknown stage (n = 72), and those not treated with surgery (n = 90)  Breast Cancer Survivors Cohort is a retrospective cohort of women diagnosed with a first primary unilateral breast cancer at three KP sites: Northwest  databases, including date of birth, race, ethnicity, body mass index (BMI), and smoking status. BMI was calculated from height and weight measurements within 1 year before to 1 year after first breast cancer diagnosis and supplemented with chart review to fill in missing data. Smoking status was obtained at first breast cancer diagnosis through 1 year after diagnosis from social history records of EMRs and supplemented using ICD-9 , ICD-10 , and procedure codes . Cancer diagnoses and tumor characteristics were obtained from cancer registries . Breast cancer tumor characteristics included stage, laterality, histologic type, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. Chemotherapy and endocrine therapy data were obtained from KP electronic pharmacy records and included information on specific drug names and dispensing dates. Data on chemotherapy were supplemented with information from tumor registries to capture patients that could have been treated outside of KP (< 4%). Endocrine therapy and chemotherapy were evaluated for the entire follow-up period. Radiotherapy was obtained from KP tumor registries and included the first course of therapy only.n = 144) were censored at date of diagnosis to reduce potential misclassification of a recurrence as a second cancer. Analyses for contralateral breast cancer excluded women who underwent a contralateral prophylactic mastectomy . Since myelodysplastic syndromes were not ascertained in SEER until 2001, analyses for these events were restricted to 2001–2017.Second cancer was defined as an invasive primary cancer diagnosed ≥ 12 months after the first primary breast cancer diagnosis. Second cancers were primarily identified according to the ICD-O-3 site and morphology codes , smoking , and clinicopathological characteristics of the first breast cancer, including stage , histology , and ER/PR status did not change the results; therefore, the more parsimonious model was used. Models examining endocrine therapy were restricted to first ER-positive breast cancers. HRs estimated with Cox proportional hazard regression are reported in the supplement. Due to a potentially longer latency period between treatment and second cancer risk, we also examined associations restricted to 5-year survivors.To further examine the association between treatment and second cancer risk, we used Fine and Gray regression with time since index date as the time scale to estimate subdistribution hazard ratios (HRs) accounting for competing events , and adjp-values < 0.05 were considered statistically significant and tests were two-sided. Analyses were performed using SEER*Stat 8.3.9 and Stata 16 .All The mean age at first breast cancer diagnosis was 60.7 years  and the mean year of diagnosis was 2003  . SIRs for second cancer were particularly elevated (SIRs ≥ 2.00) for women diagnosed with a first breast cancer at a younger age, and after a stage III breast cancer, ER-negative breast cancer, or ER-positive breast cancer without endocrine therapy. Although second cancer risk remained elevated regardless of latency, risk was higher 5 + years after diagnosis . SIRs for second non-breast cancer were attenuated compared to SIRs for all second cancers, particularly for ER status, year of diagnosis, and receipt of endocrine therapy, but otherwise patterns of risk remained similar.Breast cancer survivors had significantly higher risk for all second cancers and non-breast cancers compared with the general population  , soft tissue sarcoma , peritoneal cancer , and myelodysplastic syndrome     and soft tissue sarcoma  (Table This study presents a comprehensive evaluation of second cancer risk among 16,004 breast cancer survivors diagnosed and treated within an integrated health care delivery system from 1990–2017. Despite advances in breast cancer treatment, our results demonstrate that breast cancer survivors continue to have an elevated second cancer risk, and risk varied by first breast cancer characteristics and treatment. This elevated risk is consistent with prior studies among patients with older treatment regimens –13. FurtSite-specific second cancers have been extensively studied in breast cancer survivors over the past four decades. Consistent with previous studies, we found elevated risk for malignancies of the contralateral breast –46, coloOur finding that breast cancer survivors have an over three-fold increased risk of contralateral breast cancer is likely related to hormonal, genetic, and other shared risk factors that predisposed women to develop the first breast cancer . AlthougThe relative risk of soft tissue sarcoma in breast cancer survivors compared to that expected in the general population was over three-fold in our study. Soft tissue sarcoma risk was particularly elevated among younger women and associated with radiotherapy. The association between radiotherapy and soft tissue sarcoma has been well-reported among breast cancer patients treated with older treatment regimens , 49–53. Risks of myelodysplastic syndrome and acute myeloid leukemia were also particularly elevated in our study, and we observed a three-fold increased risk of myelodysplastic syndrome associated with chemotherapy. Prior studies suggest that these elevated risks are likely related to chemotherapy , 55–58 aStrengths of our study include a large cohort of breast cancer survivors within an integrated health care delivery system, which systematically captures aspects of care including cancer treatment and long-term follow-up. Radiotherapy and systemic treatments in SEER are for initial treatment only and even this is known to be under ascertained and classified as “no/unknown” for a large proportion of the population , 59. TheBRCA1/2 and other mutation carrier status, and history of hysterectomy and oophorectomy. Additional studies examining the role of treatment with other shared etiologic factors, including genetic, lifestyle, and reproductive factors, are warranted to determine the primary and independent factors driving an increased risk of second cancer. It is possible that heightened medical surveillance may have contributed to elevated second cancer risks, particularly within the first 5 years after a breast cancer diagnosis. However, we found markedly elevated risks 5 + years after diagnosis which suggests that the late effects of treatment, as well as other shared etiologic factors, play an important role. Statistical power was limited to detect associations with smaller effect sizes for some site-specific second cancers, particularly among stratified models. Further, it is possible that some of the observed statistically significant associations in our study may be due to chance. Finally, our study included primarily non-Hispanic white women, and our results may not be generalizable to other races and ethnicities. Future studies among more diverse study populations are needed.Our study also has several limitations. Although we had comprehensive cancer and treatment information, our study lacked data on family history of cancer, as well as reproductive and genetic factors, including This study found an elevated risk of second primary cancers in a large cohort of breast cancer survivors diagnosed and treated within an integrated health care delivery system. Our findings reflect contemporary US treatment practices and highlight the importance of heightened surveillance for second cancers among breast cancer survivors treated in recent decades. Observed second cancer risks, particularly for increased risk of soft tissue sarcoma after radiotherapy and myelodysplastic syndrome after chemotherapy, and decreased risk of breast cancer with endocrine therapy, warrant further investigation to mitigate carcinogenic effects and improve endocrine therapy initiation and adherence. Continued efforts are needed to identify prevention strategies to reduce second cancer risk in breast cancer survivors.Additional file 1. Risk of second primary cancer among women in the Kaiser Permanente Breast Cancer Survivors Cohort: Tables S1–S9 and Figures S1–S2.


Epidemiological studies suggest a bidirectional association between atrial fibrillation and breast cancer. This study aimed to conduct a meta-analysis to elucidate the prevalence of atrial fibrillation among breast cancer patients, and the bidirectional association between atrial fibrillation and breast cancer.PubMed, the Cochrane Library, and Embase were searched to identify studies reporting the prevalence, incidence, and bidirectional association between atrial fibrillation and breast cancer. The study was registered with PROSPERO (CRD42022313251). Levels of evidence and recommendations were assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE).2 = 98%). Atrial fibrillation was also significantly associated elevated risk of breast cancer . Grade assessment shown low certainty of the evidence for the risk of atrial fibrillation and moderate certainty of the evidence for the risk of breast cancer.Twenty-three studies  involving 8,537,551 participants were included. Among patients with breast cancer, the prevalence of atrial fibrillation was 3%  and the incidence was 2.7% . Breast cancer was associated with increased risk of atrial fibrillation  and breast cancer (moderate certainty). Cartoon depicting the association between atrial fibrillation and breast cancer. Breast cancer is the most frequent cancer amongst women worldwide, accounting for about 24.5 percentage of all cancers . Thanks Atrial fibrillation, the most common arrhythmia, is an important cause of embolism and death from cardiovascular diseases, with a global prevalence of approximately 2–4%. Age is a strong risk factor for the incidence of atrial fibrillation. The prevalence of atrial fibrillation tends to increase with the increase in human life expectancy . One stuRecently, many epidemiological studies have shown an increased risk of new-onset atrial fibrillation in women with breast cancer –15, whilhttps://www.crd.york.ac.uk/PROSPERO/ -registration number- CRD42022313251). This meta-analysis was performed according to the PRISMA 2021 guideline for systematic review and meta-analysis /American Heart Association (AHA), European Society of Cardiology (ESC) were also reviewed. The search MeSH items and keywords were as follows: (“Breast Neoplasms” [Mesh] OR “breast cancer” OR “breast cancers” OR “breast tumors” OR “breast tumors” OR “mammary Cancer” OR “mammary cancers” OR “mammary gland cancers” OR “mammary gland cancer”) AND  OR . The detailed search strategy is shown in Eligible studies were as follows: (1) clinical trials or observational studies  reported the prevalence or the incidence of atrial fibrillation in patients with breast cancer. (2) studies assessed the association between atrial fibrillation and breast cancer expressing with Relative Risk (RR)/HR and corresponding 95% CI or that can be calculated. For the incidence of atrial fibrillation or cancer, we only included cohort studies or the case cohort designed data. (3) studies assessed the association between atrial fibrillation and mortality in patients with breast cancers. Two authors (X-L and X.D-Y) independently reviewed the articles for eligibility. Any discrepancies were discussed until consensus.Accordingly, studies that met the following criteria were excluded: (1) Studies that specifically looked at the influence of breast cancer-related treatments  on atrial fibrillation, as anticancer treatment was linked to atrial fibrillation incident by the previous studies –31. (2) The information was extracted from each study, including first author, publication year, country, mean age, study design, data source, follow-up, prevalence or incidence of atrial fibrillation or breast cancer, atrial fibrillation diagnosis, breast cancer diagnosis, sample size, any subgroup, effect size, and adjustments. Three author (X.D-Y and X-L Z.Q-T) extracted data. For studies that reported the prevalence of atrial fibrillation or breast cancer, the Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the study quality. The Newcastle-Ottawa quality scale (NOS) was used to quantify the quality of studies reporting association between breast cancer and atrial fibrillation. A score of JBI > 16 or NOS > 6 was regarded as acceptable quality.We used a random-effect model to summarize the estimates and 95% confidence intervals (CIs). For incidence of atrial fibrillation or breast cancer, the exact binomial (Clopper–Pearson) method was used to calculate 95%CI . Estimat2) statistic   . PublicaP < 0.10 . For theE method , 38. Twoin vitro studies or irrelevant studies based on the screening of titles/abstracts, 58 reports remained for full-text review. Thirty-six full-length studies were excluded for the following reasons: (1) reviews or editorials (n = 10); (2) did not include the target population (n = 12); or (3) did not include the target outcomes (n = 13). The excluded studies are listed in As shown in According to the JBI critical appraisal checklist, 17 studies , 39–47 t2 = 99.99%)  .P for subgroup difference = 0.028) (P = 0.15), sample size (P = 0.76) or number of atrial fibrillation cases (P = 0.47)  was highest among breast cancer patients in the Americas (5%), followed by Asia (1.7%), and Europe (0.9%) (= 0.028) . Older (= 0.028) . Moreove= 0.028) . The pre= 0.028) . However = 0.47) .2 = 99.90%)  .2 = 98%).A total of five articles , 13, 14 2 = 0%).Five articles –20 reporAccording to the predefined criteria, subgroup analysis was not performed due to the limited number of studies.P > 0.1), and Begg's test (both P > 0.1) showed no significant publication bias in risk of atrial fibrillation, risk of breast cancer and incidence of atrial fibrillation, even though funnel plots are not recommended when the number of articles included is limited (N < 10). However, funnel plots, Egger's (p < 0.05), and Begg's tests (p < 0.05) for the prevalence of atrial fibrillation suggest publication bias. Sensitivity analysis by omitting each study indicated that our results were stable and reliable, with a range from 1.31 (95% CI: 1.01 to 1.69) to 1.56 (95% CI: 1.32 to 1.83) for the risk of atrial fibrillation and 1.16 (95% CI: 1.12 to 1.21) to 1.21 (95% CI: 1.15 to 1.29) for the risk of breast cancer (As shown in t cancer . For thet cancer .2 = 98%), downgrades were given. Ultimately, the risk of atrial fibrillation was evaluated as low certainty, and the risk of breast cancer was evaluated as moderate by the GRADE tool  , 41 repoOur study showed a 43% increased risk of atrial fibrillation in patients with breast cancer compared to those without breast cancer. There is accumulating evidence that breast cancer is closely related to the incidence of atrial fibrillation. Several mechanisms have been proposed to explain this association. First, previous studies have confirmed that the increased risk of atrial fibrillation in cancer patients may be related to the systemic inflammatory state caused by cancer. Inflammation has been considered a vital mechanism involved in the initiation and maintenance of atrial fibrillation . InflammOur study showed an 18% increased risk of breast cancer in patients with atrial fibrillation. The current study can only show the association between breast cancer and atrial fibrillation but cannot prove a causal relationship. It is speculated that the bidirectional relationship between the two diseases may be related to common risk factors, especially the procoagulant state, as thrombin is a drivers of both atrial fibrillation and breast cancer . In addiOur research is somewhat pioneering. Two previous meta-analyses reported an increased risk of cancer diagnosis within 90 days in patients with newly developed atrial fibrillation, but these studies focused on all malignancies rather than specific tumor subtypes , 72. A rThe overall prevalence (3%) of atrial fibrillation among breast cancer patients was similar to that of the general population; however, subgroup analysis showed an increased prevalence of atrial fibrillation among breast cancer patients >65 years of age (8.6%). Given the overall low prevalence of atrial fibrillation among breast cancer patients, screening for atrial fibrillation in breast cancer patients and screening for breast cancer in patients with atrial fibrillation are not currently recommended , althougOur systematic review and meta-analysis had several limitations. First, all the studies included were observational and could not prove causality. However, a bidirectional relationship between breast cancer and atrial fibrillation was found in cohort rather than case-control studies. Most cohort studies were retrospective cohort studies; therefore, reverse causality may still exist, and more prospective studies are needed. Second, most of the studies we included featured female breast cancer patients, and a considerable number of studies included very few male breast cancer patients. Since we could not contact the researchers to obtain the original data, we included these individual male patients. Third, atrial fibrillation is known to contribute significantly to the incidence of stroke. However, none of the studies we included reported an outcome event for stroke; more studies are needed to clarify the outcomes, especially stroke, in patients with atrial fibrillation and breast cancer.Atrial fibrillation is not uncommon in patients with breast cancer, and there is an increased risk of atrial fibrillation in breast cancer patients and vice versa. In addition, breast cancer patients with atrial fibrillation had increased all-cause mortality. GRADE assessment indicated low certainty for the risk of atrial fibrillation and moderate certainty for the risk of breast cancer. More studies are needed to determine whether screening for breast cancer in patients with atrial fibrillation is necessary.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.RQY contributed to the study concept and design and revised the draft. XDY, QWH, and XL performed the search strategy and contributed to database research, acquisition of data, and statistical analyses. All the authors participated in data analysis, reviewed, and approved the final manuscript.


Exposure to certain chemicals in the environment may contribute to the risk of developing cancer. Although cancer risk from environmental chemical exposure among general populations is considered low compared to that in occupational settings, many people may nevertheless be chronically exposed to relatively low levels of environmental chemicals which vary by such various factors as residential area, lifestyle, and dietary habits. It is therefore necessary to assess population-specific exposure levels and examine their association with cancer risk. Here, we reviewed epidemiological evidence on cancer risk and exposure to dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFASs), cadmium, arsenic, and acrylamide. Japanese are widely exposed to these chemicals, mainly through the diet, and an association with increased cancer risk is suspected. Epidemiological evidence from Japanese studies to date does not support a positive association between blood concentrations of DDT, HCH, PCBs, and PFASs and risk of breast or prostate cancer. We established assessment methods for dietary intake of cadmium, arsenic, and acrylamide using a food frequency questionnaire. Overall, dietary intakes of cadmium, arsenic, and acrylamide were not significantly associated with increased risk of total cancer and major cancer sites in the Japan Public Health Center-based Prospective Study. However, statistically significant positive associations were observed between dietary cadmium intake and risk of estrogen receptor-positive breast cancer among postmenopausal women, and dietary arsenic intake and risk of lung cancer among male smokers. In addition, studies using biomarkers as exposure assessment revealed statistically significant positive associations between urinary cadmium concentration and risk of breast cancer, and between ratio of hemoglobin adducts of acrylamide and glycidamide and risk of breast cancer. Epidemiological studies of general populations in Japan are limited and further evidence is required. In particular, studies of the association of organochlorine and organofluorine compounds with risk of cancer sites other than breast and prostate cancer are warranted, as are large prospective studies of the association between biomarkers of exposure and risk of cancer. Environmental factors play an important role in the causation of a majority of human cancers. “Environmental factors” are generally recognized as everything that is not specifically genetic in origin, including tobacco smoking, alcohol consumption, diet and nutrition, infectious agents, radiation, sunlight, exposure to environmental chemicals, and so on. In Japan, the greatest contributing factors to cancer in 2015 were infectious agents and active tobacco smoking, followed by alcohol drinking –6. In adSince the amounts of chemicals in air, water, food, and soil are typically much lower than those in the work environment, cancer risk from environmental chemical exposures among general populations is thought to be low compared to the risk in occupational settings. Nevertheless, even though exposure is likely low, large numbers of people are affected, in accordance with residential area, lifestyle, and dietary habits. It is therefore necessary to assess population-specific exposure levels and to examine their association with cancer risk.Here, we review epidemiological studies among Japanese, focusing on environmental chemicals to which Japanese are widely exposed, mainly through diet, and are suspected of being associated with increased risk of cancer. This evidence is presented as ‘p,pʹ-DDT and smaller amounts of other compounds such as o,pʹ-DDT, p,pʹ-DDD (dichlorodiphenyldichloroethane) and o,pʹ-DDE (dichlorodiphenyldichloroethylene) , 4342, 4In addition to epidemiological studies among highly exposed populations, a population-based prospective cohort study in the US found a statistically significant positive association of prediagnostic serum PFOA concentration, which was comparable with the general population, with the risk of renal cell carcinoma . MoreoveRecently, we measured serum concentrations of 20 PFAS congeners using samples from a hospital-based case–control study in Nagano Prefecture, Japan, and found a statistically significant inverse association of 17 of 20 PFAS congeners and risk of breast cancer . Table 3Cadmium is found at low concentrations in the Earth's crust, mainly as the sulfide in zinc-containing mineral deposits, and is widely but sparsely distributed through natural activities, such as volcanic activity, weathering and erosion, and river transport. It has also been widely dispersed into the environment through mining, smelting and refining of nonferrous metals, industrial emissions, and incineration of municipal waste . Other than occupational exposure, the major source of cadmium exposure in general populations is foods, in addition to tobacco smoking, since cadmium contained in soil and water can be taken up by certain crops and aquatic organisms and accumulate in the food chain .Although a well-known health effect of chronic exposure to cadmium is renal dysfunction, IARC classified cadmium and cadmium compounds as carcinogenic to humans Group 1) based on sufficient evidence for an increase in lung cancer risk, mostly from studies in occupational settings  used for the JPHC Study, and evaluated the validity of the FFQ in estimating intake by comparing 24-h urinary excretion of cadmium with dietary cadmium intake estimated from the FFQ . Spearmap = 0.032). Furthermore, a hospital-based case–control study in Gifu Prefecture, Japan measured urinary cadmium concentration using spot urine samples collected from 153 breast cancer cases and 431 matched control subjects [The estrogenic properties of cadmium have focused attention on their role in the etiology of breast cancer . As descsubjects . A statisubjects , 70, addArsenic is used in industrial processes such as nonferrous smelting, wood preservation, glass manufacturing, production and application of arsenic-based pesticides, and electronics. Inhalation is the primary route of exposure to arsenic in the workplace . ArsenicRegarding the health effects of long-term exposure, IARC classified arsenic and inorganic arsenic compounds as carcinogenic to humans Group 1) based on epidemiological studies which showed increased risk of lung, skin, and urinary bladder cancer due to exposure to arsenic through inhalation in the workplace or drinking water contaminated with high levels of inorganic arsenic (Table  based onhijiki (Hizikia fusiforme) contains inorganic arsenic, and concerns over a potential effect on cancer risk have been raised given its relatively common consumption among seaweeds by Japanese [In Japan, a historical cohort study was conducted in an arsenic-polluted area in which well water was polluted by liquid waste containing inorganic arsenic from a dye factory . ResultsJapanese .hijiki, seaweeds, rice, and vegetables to total arsenic intake were 32%, 28%, 20%, 16%, and 1%, respectively, while the contributions of hijiki, rice, seaweeds, seafood, vegetables, and fruits to inorganic arsenic intake were 50%, 35%, 5%, 4%, 3%, and 2%, respectively. We investigated the association of dietary arsenic intake with risk of total and site-specific cancer based on 10.9 years of follow-up data for 90,378 Japanese men and women aged 45–74 years in the JPHC Study [We developed a validated method for estimating dietary arsenic intake based on the FFQ used in the JPHC Study . From a HC Study . OverallFor site-specific cancers, no statistically significant association was observed for total arsenic intake among both men and women  based on sufficient evidence in experimental animals for the carcinogenicity of acrylamide . Given that acrylamide is primarily metabolized by phase I enzymes such as cytochrome P450 2E1 (CYP2E1) to the epoxide metabolite, glycidamide, which is likely to play an important role in the carcinogenicity [We examined the association of dietary acrylamide intake with risk of site-specific cancers using data from the 5-year follow-up survey of the JPHC Study –93. No sgenicity , 81, HbGgenicity .Fig. 3SuWe reviewed epidemiological studies of DDT, HCH, PCBs, PFASs, cadmium, arsenic, and acrylamide, to which Japanese populations are widely exposed. DDT, HCH, PCBs, and PFASs were detected in blood samples from general populations in Japan. Epidemiological evidence did not support positive associations between blood concentration of DDT, HCH, PCBs, and PFASs and risk of breast and prostate cancer. We established assessment methods for the dietary intake of cadmium, arsenic, and acrylamide using an FFQ. Overall, dietary intake of cadmium, arsenic, and acrylamide was not significantly associated with increased risk of total cancer and major cancer sites in the JPHC Study. However, a statistically significant positive association was observed between dietary cadmium intake and risk of estrogen receptor-positive breast cancer among postmenopausal women, and between dietary arsenic intake and risk of lung cancer among male smokers. In addition, studies using biomarkers as exposure assessment revealed statistically significant positive associations between urinary cadmium concentration and risk of breast cancer, and between HbGA/HbAA ratio and risk of breast cancer. Since the number of epidemiological studies in general populations in Japan is limited, further accumulation of evidence is required, with particular focus on the following: the association of organochlorine and organofluorine compounds with risk of cancer sites other than breast and prostate cancer; and large prospective studies of the association between biomarkers of exposure and risk of cancer. For the latter, collaboration among relevant researchers to ensure that epidemiological studies incorporate precise biologic sample-based exposure assessment will be essential.


Do patient-clinician discussions about breast density vary by women’s sociodemographic characteristics?In this telephone survey study of 770 women, most women reported that clinicians asked questions about breast cancer risk (88%), discussed mammography results (94%), and answered patient questions about breast density (81%); fewer women indicated that clinicians asked about worries or concerns about breast density (69%), future breast cancer risk (64%), or other screening options (61%). Non-Hispanic Black women were asked about breast cancer risk more often, and Hispanic and Asian women as well as those with low literacy were less likely to have questions or worries or concerns addressed.This study suggests that unaddressed worries or concerns and unanswered questions among Hispanic and Asian women as well as those with low literacy are areas for improvement. Breast density notifications advise women to discuss breast density with their clinicians, yet little is known about such discussions.To examine the content of women’s reports of breast density discussions with clinicians and identify variations by women’s sociodemographic characteristics .dense breasts or breast density. Results were analyzed from a subsample of 770 women reporting a conversation about breast density with their clinician after their last mammographic screening. Statistical analysis was conducted in April and July 2023.This US nationwide, population-based, random-digit dial telephone survey study was conducted from July 1, 2019, to April 30, 2020, among 2306 women aged 40 to 76 years with no history of breast cancer who underwent mammography in the prior 2 years and had heard the term Survey questions inquired whether women’s clinicians had asked about breast cancer risk or their worries or concerns about breast density, had discussed mammography results or other options for breast cancer screening or their future risk of breast cancer, as well as the extent to which the clinician answered questions about breast density.P = .04). Asian women less often reported being asked about their worries or concerns , and Hispanic and Asian women less often reported having their questions about breast density answered completely or mostly . Women with low literacy were less likely than women with high literacy to report being asked about worries or concerns about breast density , that mammography results were discussed with them , or that their questions about breast density were answered completely or mostly .Of the 770 women  whose results were analyzed, most reported that their clinicians asked questions about breast cancer risk (88% [670 of 766]), discussed mammography results (94% [724 of 768]), and answered patient questions about breast density (81% [614 of 761]); fewer women reported that clinicians had asked about worries or concerns about breast density (69% [524 of 764]), future risk of breast cancer (64% [489 of 764]), or other options for breast cancer screening (61% [459 of 756]). Women’s reports of conversations varied significantly by race and ethnicity; non-Hispanic Black women reported being asked questions about breast cancer risk more often than non-Hispanic White women (odds ratio [OR], 2.08 ; In this survey study, although most women reported that their clinicians counselled them about breast density, the unaddressed worries or concerns and unanswered questions, especially among Hispanic and Asian women and those with low literacy, highlighted areas where discussions could be improved. This survey study examines the content of women’s reports of breast density discussions with clinicians as well as variations in these discussions by women’s sociodemographic characteristics. Dense breast notifications accompany mammography results and provide information about breast density aimed at increasing women’s understanding of associated risks. Most notifications recommend that women with dense breasts discuss their personal risk with their physicians to foster more informed decisions about future and supplemental breast cancer screening.3Dense breast tissue increases the risk of breast cancer and reduces the sensitivity of screening mammography.5 and little is known about the content of the conversations that do occur. By understanding women’s experiences of such conversations, including whether they confer relevant information about breast cancer risk and screening options or address patients’ questions and concerns—all necessary components for shared decision-making—we can identify strengths and address potential deficits. As prior research showed that women who belong to minoritized racial and ethic groups and with lower literacy were often less knowledgeable or aware of breast density’s risks,4 we hypothesized that women’s conversations with clinicians might also vary similarly.However, prior research shows that less than half of women in the general population have conversations with their clinicians about breast density,9 and the Health Belief Model.11 The research was deemed exempt in the category of survey research by the Boston University Medical Campus institutional review board; however, a consent statement read to prospective participants provided options to decline or continue. This study followed the American Association for Public Opinion Research (AAPOR) reporting guideline.Using a telephone survey, we assessed women’s reported experiences of conversations with their clinicians about breast density. Survey content was based on existing literature, prior studies,4 In brief, structured telephone surveys from the survey firm SSRS included questions within the SSRS Omnibus survey, a national, weekly, dual-frame bilingual random-digit dial telephone survey using landlines and cell phones, conducted in English and Spanish. Our questions were included in the Omnibus survey from July 1, 2019, to April 30, 2020. We identified a representative sample of US women 40 to 76 years of age meeting the following eligibility criteria: (1) had undergone mammography within the prior 2 years, (2) had no personal history of breast cancer, and (3) had heard the term dense breasts or breast density. Eligible participants were also invited to participate using a prescreened callback sample from prior Omnibus waves to increase participation of Hispanic, Black, and Asian women; women with less than a high school education; and those living in less populous nonnotification states. A third group of eligible participants were recruited from a sample specifically modeled by SSRS to reach Asian American women. The AAPOR cooperation rates  from each sampling approach; the overall cooperation rate was 85% (2306 of 2718). This analysis was conducted among the 770 of 2306 women in the sample (33%) who reported having had a conversation about breast density with their clinician after their last mammographic screening.We conducted a cross-sectional, national, random-digit dial telephone survey study using a sampling approach detailed previously.We queried participants about their most recent discussion with their clinician regarding breast density. As detailed in the eAppendix in 13 To assess and control for breast cancer risk factors as covariates, we asked each woman whether she had a first-degree relative with a diagnosis of breast cancer or had ever had a breast biopsy.We assessed whether or not respondents lived in a state mandating DBNs, sociodemographic characteristics including age , educational level , income , and race and ethnicity ]). We assessed literacy, defining low literacy as either having less than a high school education or reporting sometimes, often, or always needing assistance to complete forms using the validated Single Item Literacy Screener.2 analyses assessing associations between each dependent variable and each of the sociodemographic variables listed. We then conducted separate multivariable binary logistic regression analyses, evaluating associations among each dependent variable and all of the sociodemographic variables and breast cancer risk factors simultaneously. We excluded educational level from multivariable models due to its inclusion in the health literacy measure and collinearity with income. All analyses were conducted with the statistical analysis software IBM SPSS Statistics, version 27 (IBM Corp). Statistical significance was defined at 2-tailed α = .05. Post hoc comparisons in bivariate analyses were Bonferroni corrected for multiple comparisons.Statistical analysis was conducted in April and July 2023. We first conducted bivariate χ21 = 13.58; P < .001), be younger , have a lower annual income level , to have a lower level of literacy , and to have a prior breast biopsy . They were also more likely than those not in the analytic sample to be of other race (10% [77 of 770] vs 5% [83 of 1535]) and less likely to be non-Hispanic White (41% [317 of 770] vs 48% [741 of 1535]) .Among the analytic sample (770 of 2306 [33%]), most women (630 [82%]) lived in states mandating DBNs . ApproxiP < .05). Non-Hispanic Black women more often reported being asked questions about breast cancer risk (92% [187 of 204]) than Hispanic women (82% [101 of 124]) (P < .05). Similarly, multivariable results revealed that non-Hispanic Black women were 2.08 times more likely to report questions about breast cancer risk than non-Hispanic White women  (P = .01) or prior biopsy .Overall, 88% of women (670 of 766) said that their clinician had asked questions about breast cancer risk . In bivaP = .04) . In multP < .05) (P = .002)  (P < .05) (P = .02) (P < .05) (P = .03)  indicated their clinician had asked about worries or concerns about breast density. In bivariate analyses, women who were aged 65 years or older reported receiving fewer questions about worries or concerns (58% [129 of 223]) compared with younger women  , and thi = .002) . In biva = .002) , althougP = .09) . In bivaP < .05) . This paP = .02) . Women wP < .05)  and multP = .03) .P < .05) (P = .001) (P < .05) (P = .02)  said their clinician discussed their mammography results. However, bivariate analyses revealed this was less common among women with low literacy (88% [136 of 155]) compared with women with high literacy (96% [588 of 613]) (P < .05) . This as = .001) . HispaniP < .05) . SimilarP = .02) .P < .05)  (P = .01).Overall, 61% of women (459 of 756) indicated their clinician had discussed other options for breast cancer screening. In bivariate analyses, women aged 50 to 64 years were more likely (65% [231 of 353]) to report such discussions than women aged 65 years or older (55% [119 of 217]) (P < .05) , althougP = .28) . In multOverall, 64% of women (489 of 764) indicated that their clinician discussed future risk of breast cancer. We found no differences by any sociodemographic characteristics or breast cancer risk factors in either bivariate or multivariable analyses .P < .05) (P = .02) and Asian women  were less likely than non-Hispanic White women to indicate their clinician had answered all of their questions about breast density (P < .05) (P = .004)  indicated their clinician had mostly or completely answered their questions about breast density, but such reports varied by women’s race and ethnicity. In bivariate analyses, non-Hispanic White women were more likely (86% [270 of 315]) than non-Hispanic Black women (79% [160 of 203]), Hispanic women (74% [89 of 120]), or Asian women (70% [33 of 47]) to say their clinician had answered their questions (P < .05) . This pa density . Women wP < .05) , and thi = .004) .5 Findings newly revealed that these women were more likely to be members of historically marginalized groups, including lower income or literacy levels or women of minority racial and ethnic groups. Among women reporting such conversations, most indicated that clinicians asked about breast cancer risk, discussed mammography results, and answered questions about breast density. However, women less frequently reported that clinicians had asked about worries or concerns about breast density or discussed future risk of breast cancer or other options for breast cancer screening.As one of the first studies, to our knowledge, to examine women’s reports of the frequency and content of clinician-patient breast density discussions, we examined whether or how such discussions might vary by women’s sociodemographic characteristics. Overall, only approximately one-third of women surveyed reported such a conversation, similar to other studies.14 The single prior study we located regarding the content of women’s discussions with physicians about breast density found no differences between the proportion of non-Hispanic White and non-Hispanic Black women who reported talking with their physicians about breast density notifications,5 but those results did not characterize the discussions’ content.Women’s reports of these discussions varied significantly by race and ethnicity. Non-Hispanic Black women  more often reported being queried about breast cancer risk, but Hispanic and Asian women were less likely to report being asked about worries or concerns or having their questions about breast density answered completely or mostly. Although our data do not provide an explanation for this observed difference, clinician behavior may be influenced by the evidence of elevated breast cancer mortality among young Black women in particular.15 but our data do not allow us to examine this. Perhaps the information given was less comprehensible to women with low literacy, as prior research shows that some clinicians struggle with providing understandable information to such patients.16 Regardless, our findings suggest that women with low literacy want more or different information to meet their needs.Women’s reported breast density discussions with clinicians varied significantly with literacy level. Women with low literacy less frequently reported being asked about worries or concerns about breast density or that their mammography results were discussed with them and less frequently felt their questions were answered completely or mostly. This finding highlights a mismatch between patients’ informational needs and material shared by clinicians; one possibility is that clinicians limit the information offered to patients when discussing breast density due to assumptions about the ability of patients with low literacy to understand information about screening or its consequences,Clinician questioning and counseling did not vary by state DBN legislation status, suggesting that the legislation either was associated with broad or no nationwide outcomes or that other clinician education has generally been associated with care. We are unable to determine this with our data given the single time point of measurement. Clinician questioning and counseling almost never varied by women’s age or income. As might be expected, women with risk factors  were more likely to report being asked questions about breast cancer risk; the latter group was also more likely to indicate that their clinician discussed other options for breast cancer screening. Women with a family history of breast cancer could have a heightened sensitivity to the topic, which could in turn have increased recall of discussions of breast cancer risk, although we were unable to examine this possibility directly.20 so additional education about the risks of breast density may support clinician knowledge and effective counseling on this topic. Inconsistent insurance coverage of supplemental screening and the absence of a widely agreed-on evidence base21 or guidelines regarding supplemental screening to guide counseling at the time these data were collected may have inhibited such counseling and the incorporation of recommended shared decision-making, which could improve the quality of conversations.22 The limited clarity regarding supplemental screening may undergird these shortcomings, as clinicians may eschew addressing ambiguous topics. However, the unaddressed worries or concerns and unanswered questions, especially among historically marginalized women, highlighted areas where discussions could be improved. In many situations, it is appropriate for clinicians to not discuss breast density or supplemental screening depending on the woman’s overall risk profile or other pressing clinical concerns. Despite some reassuring findings regarding appropriate differential counseling by patient race and ethnicity, other results echo prior research documenting racial and ethnic variations in processes of care25 and provide new evidence of differential processes by patient literacy.Our findings suggest that when discussions about breast density do occur, over half of women’s clinicians are addressing relevant related topics. Shortfalls in addressing breast density may be a function of clinicians feeling ill prepared,26 may have influenced counseling since then. Despite such limitations, women’s reports represent the most efficient method to assess the content of the conversations.This study had several limitations. We were able to examine the content of discussions only among the women who had had such discussions, and these women differed in several ways from the national sample. Without clinical assessments of breast density, we were unable to determine whether breast density was a clinically significant or appropriate topic for clinicians to address in their discussions with women. Moreover, women’s self-reports of their discussions might be influenced by recall bias, and we did not have data on the length of time that elapsed between the mammography and these conversations. Although language barriers may have been an issue, without data on language we could not address this possibility in the analysis. In addition, we report results of a large number of statistical tests among correlated dependent variables, which warrants caution when interpreting significant findings. Future research efforts are needed to test the generalizability of observed associations, particularly those of smaller effect size. Care processes are not structured such that women are prompted to return to their clinician after mammographic screening (most see them before), so women reporting these discussions could have different health care use patterns relative to those who did not report conversations about breast density with their clinicians. They could have also been more concerned and sought out conversations, but our data did not allow us to examine these possibilities. Although the United States Preventive Services Task Force has not issued new guidelines for supplemental screening for women with dense breasts since this study was conducted, the American College of Radiology guidelinesTaken together, the results of this survey study provide some positive outcomes assessments when clinician-patient conversations about breast density do occur in that most patients report their clinicians are discussing potential breast cancer risk factors and mammography results and answering questions about breast density. However, these results also suggest potential areas for improvement as only a minority of our national sample reported such discussions, and when they occurred, there were limited conversations about other options for breast cancer screening, future breast cancer risk, or queries about patient worries or concerns about breast density. Efforts to improve cultural competency, shared decision-making, and counseling skills, especially when guidelines for care for women with dense breasts become more widespread, can potentially help close the remaining gaps in conversations about breast density.