The goal of this study was to estimate the risk of thyroid cancer following a diagnosis of breast cancer and to identify (therapeutic and genetic) risk factors for the development of thyroid cancer after breast cancer. We followed 10,832 breast cancer patients for a mean of 14 years for new cases of thyroid cancer. Of the 10,832 women with breast cancer, 53 (0.49%) developed a second case of primary thyroid cancer. The ten-year risk of thyroid cancer was higher in women who carried a CHEK2 mutation (1.5%) than in women who carried no mutation (0.9%). In Poland, following a diagnosis of breast cancer, the risk of thyroid cancer is increased four times, but is increased nine times in women who carry a CHEK2 mutation.p = 0.38) for those with a CHEK2 protein-truncating mutation and 2.75  for those with a CHEK2 missense mutation.The goal of this study was to estimate the risk of thyroid cancer following breast cancer and to identify therapeutic and genetic risk factors for the development of thyroid cancer after breast cancer. We followed 10,832 breast cancer patients for a mean of 14 years for new cases of thyroid cancer. All women were genotyped for three Polish founder mutations in BRCA1  and four mutations in CHEK2 . Information was collected on chemotherapy, radiotherapy, hormonal therapies, and oophorectomy. Of the 10,832 women, 53 (0.49%) developed a second primary thyroid cancer. Based on Polish population statistics, the expected number was 12.4 (SIR = 4.3). The ten-year risk of developing thyroid cancer was higher in women who carried a CHEK2 mutation (1.5%) than in women who carried no mutation (0.9%). The age-adjusted hazard ratio for developing thyroid cancer was 1.89 (0.46–7.79;  The number of survivors of breast cancer is increasing worldwide due to wide-scale screening programs and effective therapies . A diagnWomen with breast cancer are offered a range of therapies, including radiotherapy, chemotherapy, hormonal therapies (tamoxifen and aromatase inhibitors), and oophorectomy. It is not clear if any of these treatments impact the risk of thyroid cancer. The studies that have looked at radiotherapy conclude that the risk of thyroid cancer is not increased ,7,8. It p < 0.001). Approximately 6% of breast cancer patients in Poland carry a CHEK2 mutation. We have estimated that a CHEK2 mutation increases the risk of breast cancer by 2.5 times and the risk of thyroid cancer by 3.3 times [The positive association between breast and thyroid cancers suggests a possible common genetic susceptibility in some cases. PTEN mutations predispose women to Cowden Syndrome (which features both thyroid cancer and breast cancers) . CHEK2 i.3 times ,15. WomeWe enrolled 10,832 breast cancer patients from throughout Poland in the cohort study. Patients were diagnosed in oncology centers in Bialystok, Bielsko-Biala, Bydgoszcz, Gliwice, Kielce, Koszalin, Krakow, Lublin, Lodz, Olsztyn, Opole, Poznan, Rzeszow, Szczecin, Warszawa, Wroclaw, and Zielona Gora between 1996 and 2014. The clinical information collected included the age of diagnosis, year of breast cancer surgery, lymph node status, tumor size, histopathology, estrogen-receptor status, HER2 status, use of chemotherapy, radiotherapy, hormonal therapy, oophorectomy, and prior history of cancers. In some centers, only women diagnosed under age 50 were recruited (6755 women were diagnosed at or below age 50 and 4114 women with breast cancer diagnosed at or above age 50). Patients with a prior diagnosis of thyroid cancer were excluded from the current analysis (40 patients). All patients signed informed consent to use their blood samples for DNA analysis. The study was presented to the Ethics Committee of the Pomeranian Medical University in Szczecin, Poland, but the project did not require the Ethics Committee’s approval.The DNA of peripheral blood lymphocytes of patients was examined for the presence of four founder mutations in the CHEK2 gene, using standard molecular biology techniques. We genotyped three founder mutations in BRCA1  using a multiplex-polymerase chain reaction (PCR) assay. These three founder BRCA1 mutations constituted 82% of all identified BRCA1-mutation carriers (303/370 patients) in a large series of 1018 Polish women with hereditary breast cancer who were fully sequenced . The 538® Real-Time PCR 480 System . The 1100del C mutation was detected using the forward primer Chk2delC_F GGCAGACTATGTTAATCTTTTTATTTTATGG, the reverse primer Chk2delC_R CAAGAACTTCAGGCGCCAAGT, and two probes: Chk2delC HEX-TTTAGATTACTGATTTTGGGC-BHQ1 and Chk2wt 6-FAM- TTAGATTATGATTTTGGGCAC-BHQ1. The IVS2 + 1G > A mutation was analyzed using the forward primer Chek2_IVS_F ACCGAACATACAGCAAGAAACACTT, the reverse primer Chek2_IVS_R TGACCAAATTACCAGCTCTCCTAGA, and two probes: Chek2_IVS_M HEX-CGGATTTTCAGGATAGGTA-NFQ and Chek2_IVS_wt 6-FAM-TCGGATTTTCAGGGTAGGTA-NFQ. The I157T missense variant was detected using the forward primer Chek2_Mis _F TGTTCTCTATTTTAGGAAGTGGGTCCT, the reverse primer Chek2_Mis _R AAGGTTCCATTGCCACTGTGAT, and two probes Chek2_Mis _M HEX-CTTCTATGTATGCAATGTAAG-BHQ1 and Chek2_Mis _WT 6-FAM-CTTCTATGTATGCAGTGTAAG-BHQ1. The large deletion of exon 9 and 10 of the CHEK2 gene was genotyped using the multiplex-PCR reaction. In detail, two primer pairs were designed specifically for genotyping a large deletion of exons 9 and 10 in a multiplex PCR. The first pair  flanked the breakpoint site in intron 8. The second pair  flanked the breakpoint site in intron 10. In mutation-negative cases, only two PCR fragments of 379 and 522 bp were amplified from the wild-type allele. The forward primer of the first pair and the reverse primer of the second pair amplified an additional PCR product of 450 bp in deletion-positive cases.We also genotyped the four most frequent CHEK2 mutations in the Polish population: Three protein-truncating mutations  and one missense mutation (I157T), which is a missense substitution of an isoleucine for threonine in exon 3 . In a stPatients were followed from the date of diagnosis until the first instance of thyroid cancer, death from any cause, or date of last follow up. The annual risk of thyroid cancer was calculated as the ratio of thyroid cancer events to the total person–years of follow-up. We compared the observed number of thyroid cancers to the expected number of thyroid cancer cases using data from female age-specific thyroid cancer incidence rates in Poland.The 10- year actuarial risk of thyroid cancer was calculated using the Kaplan–Meier method. In a multivariable model, we estimated the adjusted hazard ratios for the development of thyroid cancer according to the age of diagnosis and treatments received . Oophorectomy was modeled as a time-dependent variable. We also included the presence of a CHEK2 mutation and a BRCA1 mutation in the Cox proportional hazards model.Among 10,792 breast cancer patients, 53 patients (0.48%) developed thyroid cancer in the follow-up period. The majority of thyroid cancers were papillary carcinomas (45), but there were also three cases of follicular and two cases of medullary carcinoma . The median time from breast cancer diagnosis to thyroid cancer diagnosis was 6.3 years. The characteristics of the women with and without thyroid cancer are presented in The annual rate of thyroid cancer in the cohort was 54 per 100,000 per year  Based onMoreover, 914 breast cancer patients (8.3%) carried a CHEK2 mutation  and 502 breast cancer patients (4.6%) carried a BRCA1 mutation.Among the 914 women with a CHEK2 mutation, there were 10 thyroid cancers observed, versus 1.04 expected (SIR = 8.7). Eight of the CHEK2 mutations were missense and two were truncating. The annual risk of thyroid cancer was 114 per 100,000 per year in those with a CHEK2 mutation . The cump = 0.38) for those with a CHEK2 protein-truncating mutation and was 2.75  for those with a CHEK2 missense mutation. We did not see an increase in the risk of thyroid cancer associated with radiotherapy. We saw a borderline significant decrease in the risk of thyroid cancer associated with prior chemotherapy (HR = 0.52 (0.28–0.97); p = 0.04).The univariable and multivariable hazard ratios for the development of thyroid cancer are presented in In this large cohort study, we estimated the risk of thyroid cancer in women with a previous diagnosis of breast cancer. There were 53 new cases of thyroid cancer in the cohort for an average annual risk of 0.5% per year. The risk did not vary by age of diagnosis or by attained age. Based on the Polish National Cancer Registry, the expected number of thyroid cancer cases was 12.4 (SIR = 4.3) ). Previop = 0.009). Overall, 10 of the 53 cases of second primary thyroid cancer (19%) could be attributed to carrying a CHEK2 mutation. We have previously estimated that a CHEK2 mutation increases the risk of thyroid cancer by 3.3 times over the general population [In our cohort, the most significant predictor of thyroid cancer was the presence of a CHEK2 mutation. In our study, 10 of 914 CHEK2 mutation carriers developed thyroid cancer  that predispose CHEK2 carriers to breast cancer also predispose them to thyroid cancer.We did not see an increase in the risk of thyroid cancer in our cohort associated with radiotherapy, consistent with previous studies ,7,8. We It has been suggested that lifestyle factors and environmental factors might contribute to the risk of thyroid cancer among breast cancer patients . ProposeThere are several other limitations to this study. We assumed that all thyroid cancers were independent cancers (and not breast cancer metastases). We did not have details on the clinical presentation of thyroid cancers nor the treatments they received. For a substantial proportion of women, data on ER and HER2 were missing. We sought founder mutations only, as these account for greater than 80% of the BRCA1 and CHEK2 mutations in the Polish population, but we may have missed a number of mutation carriers ,17. It wThese results suggest that screening for thyroid cancer among breast cancer patients with a CHEK2 mutation might be warranted. Routine thyroid ultrasonography detects thyroid nodules in 8% of breast cancer patients ,23. It iThe risk of thyroid cancer in women with a (truncating or missense) mutation in CHEK2 is approximately nine times that of the general population of Poland. Approximately 19% of thyroid cancers after breast cancer are attributable to CHEK2 mutations.


This first assessment of the dose–response relation between LAN and breast cancer supports a positive association in selected subgroups, particularly in premenopausal women.Breast cancer is the most common malignancy in women and the second leading cause of cancer death overall. Besides genetic, reproductive, and hormonal factors involved in disease onset and progression, greater attention has focused recently on the etiologic role of environmental factors, including exposure to artificial lighting such as light-at-night (LAN). We investigated the extent to which LAN, including outdoor and indoor exposure, affects breast cancer risk. We performed a systematic review of epidemiological evidence on the association between LAN exposure and breast cancer risk, using a dose–response meta-analysis to examine the shape of the relation. We retrieved 17 eligible studies through September 13, 2021, including ten cohort and seven case–control studies. In the analysis comparing highest versus lowest LAN exposure, we found a positive association between exposure and disease risk , with comparable associations in case–control studies  and cohort studies . In stratified analyses, risk was similar for outdoor and indoor LAN exposure, while slightly stronger risks were observed for premenopausal women  and for women with estrogen receptor (ER) positive breast cancer . The dose–response meta-analysis, performed only in studies investigating outdoor LAN using comparable exposure assessment, showed a linear relation up to 40 nW/cmThe online version contains supplementary material available at 10.1186/s12942-021-00297-7. Breast cancer is the most common cancer in women in both developed and undeveloped countries . In ItalIn 2007, the International Agency for Research on Cancer (IARC) defined night-shift work as ‘probably carcinogenic to humans’ i.e. belonging to category 2A , due to Two recent meta-analyses summarized data on the association between LAN and breast cancer risk, investigating the effects of the highest vs. the lowest LAN exposure categories , 22. SinWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement  to perfoThe research question was configured according to PECOS statement , Outcomes, and Study design): “Is exposure to light-at-night, as assessed through indoor and outdoor exposure to lighting sources, positively associated with risk of breast cancer in non-experimental studies?” and “Is there a dose–response association between LAN and breast cancer incidence?” . AccordiTwo authors reviewed all titles and abstracts independently, and any conflicts were resolved with the help of third author. For each included study, we extracted information about design, population size and characteristics, country, study period and years of follow-up, risk estimates  along with their 95% confidence interval (CI) of breast cancer, adjustment factors, type of exposure assessment, and dose of exposure.We assessed the quality in the included studies by using the Risk Of Bias In Non-randomized Studies of Exposures (ROBINS-E) tool . We clasWe performed a meta-analysis comparing breast cancer incidence in the highest versus lowest levels of LAN exposure using a restricted maximum likelihood random effect model, which bases estimates on a likelihood function calculated from a transformed set of data . AdditioBesides the overall group, we also performed stratified analyses according to menopausal status , body mass index-BMI (< 25 and ≥ 25), estrogen receptor-ER status (ER + and ER–) of cases, and type of LAN exposure (outdoor and indoor). Furthermore, we explored the role of possible effect modifiers, by dividing the studies according to the country-specific estimated annual sunshine hours  into the2 statistics, and by carrying out stratified analyses whenever possible such as for LAN exposure assessment method, menopausal status, participants’ weight , and ER status. We used Stata software , namely its ‘meta’ and ‘drmeta’ routines, for data analysis.We assessed the potential for small-study bias using funnel plots for studies reporting highest versus lowest exposure, and by performing Egger’s test , 38 and Overall, of the 494 individual studies identified after removal of duplicates, we excluded 465 studies due to title and abstract screening, and 13 additional studies after full-text evaluation, leaving 17 studies eventually fulfilling inclusion criteria  [Table 2/sr) , 44, 52.2/sr) . Indoor Risk of bias assessment . In subgroup analyses Table , we founEight studies assessed breast cancer risk among both pre and postmenopausal women at the moment of diagnosis, while one was restricted to postmenopausal women only. The summary RR was slightly stronger among premenopausal women  than postmenopausal women   and 1.07 (95% CI 0.92–1.23), respectively  group  UV-B irradiance levels . Conversely, there was no association between LAN and breast cancer risk in countries with low UV-B irradiance (< 0.58 W/m2).With regard to confounding factors, solar UV-B radiation is thought to be protective for breast cancer development. The inverse association between cancer risk and UV-B radiation was hypothesized for the first time by the Garland brothers in 1980  who theoferation . Across feration –72. A reWe considered another confounding factor that also correlates with UV-B radiation and could influence the outcome risk: the influence of annual sunshine hours , 74. We 2/sr the curve flattened in women with ER + disease but still increased in the ER − subgroup.Our results are relatively consistent with two previous meta-analyses , 22, witOur review has some strengths and limitations. Firstly, we used a newly developed meta-analytic tool for exploring the full shape of the dose–response, enabling us to assess the shape of the relation between LAN exposure and breast cancer risk over a wide range of exposure and across population subgroups. Our approach also yielded some indications of the threshold exposure levels that can increase breast cancer risk. Moreover, we systematically used the most adjusted model from each included study, thereby accounting for major confounders of the association.Nonetheless, we acknowledge that some summary estimates are still statistically unstable due to the low number of studies still characterizing some subgroups. In addition, we could not rule out that unmeasured confounding was still likely in the investigated studies, and therefore influenced the findings. An example of such potential identified confounder could be the possibility that air pollution is heavier in urban areas, where the highest levels of LAN exposure are also detectable. In particular, LAN exposure may correlate with higher levels of traffic-related pollutants, including noise, as indicated by its inverse correlation with greenness and green space diversity , 83. UnfOur review suggests a positive association between LAN exposure and risk of breast cancer, particularly in some subgroups, especially in premenopausal women, while few differences substantially emerged according to ER status, thus ongoing efforts to minimize LAN exposure might contribute to decrease human burden of diseases –87.


Baseline assessments were completed within 90 days of surgery. Measurements included accelerometers to measure PA and SB; a graded treadmill test with gas exchange analysis to measure cardiorespiratory fitness (VO2peak, the average aerobic fitness level was 26.6 ± 6 ml/kg/min. Average body fat was 43 ± 7.1%.At baseline, the 1528 participants’ mean age was 56 ± 11 years, 59% were post-menopausal, 62% had overweight/obesity, and 55% were diagnosed with stage II or III disease. Based on device measurements, study participants spent 8.9 ± 1.7 h/day sedentary, 4.4 ± 1.2 h/day in light-intensity activity, 0.9 ± 0.5 h/day in moderate-intensity activity, and 0.2 ± 0.2 h/day in vigorous-intensity activity. For those participants who reached VOWe have established a unique cohort of breast cancer survivors with a wealth of data on PA, SB, and HRF obtained through both direct and self-reported measurements. Study participants are being followed for at least ten years to assess all outcomes after breast cancer. These data will inform clinical and public health guidelines on PA, SB, and HRF for improving breast cancer outcomes.The online version contains supplementary material available at 10.1007/s10552-021-01539-6. In 2020, approximately 27,700 Canadian women were diagnosed with breast cancer and 5,100 died from the disease [Despite improved survival rates, life after breast cancer remains challenging given the multimodal therapy that is sometimes difficult and prolonged, resulting in negative effects on the long-term health and well-being of breast cancer survivors. After breast cancer treatments, survivors face increased risks of recurrence, second cancers, cardiac dysfunction, weight gain, bone loss, lymphedema, arthralgias, cognitive dysfunction, menopausal symptoms, fatigue, and psychosocial distress –7.Observational epidemiologic studies have shown that self-reported physical activity either before or after a breast cancer diagnosis is associated with improved survival outcomes . A recen2). A systematic review [The primary health-related fitness parameter  that has been examined for its association with breast cancer survival is body mass index  Study cohort that was specifically designed to address these gaps in knowledge regarding the role of physical activity, sedentary behavior, and health-related fitness in breast cancer survivors from diagnosis to end-of-life [Most observational studies have captured physical activity by self-report and included only limited measurements of sedentary behavior and health-related fitness. These studies have not measured changes in exposures over time. We previously described our -of-life . We also-of-life . The aimA description of the AMBER study design and methods has previously been described , 16. We The AMBER study includes measurements at four time points: baseline, 1-, 3-, and 5-year post-diagnosis. The first three sets of assessments included questionnaires, blood collection, one or two days of in-person health-related fitness testing, and week-long device-based measures of physical activity and sedentary behavior. Only questionnaires are being completed at the 5-year follow-up assessment. The goal was to have participants complete baseline assessments within 90 days of surgery and/or prior to initiating adjuvant systemic or local treatments. Due to personal circumstances, some participants were allowed into the cohort if they had completed up to two cycles of chemotherapy or ten fractions of radiation therapy. Using this approach, we were able to accommodate more participants after determining that women were still willing and able to complete baseline assessments after the start of their treatments. In a subset of women who received neoadjuvant treatment, the goal was to complete baseline assessments prior to initiating chemotherapy but always before the third cycle of chemotherapy.Baseline Health Questionnaire asked participants about their sociodemographic characteristics, menstrual, reproductive, and medical history, exogenous hormone and medication use history, family history of cancer, and lifetime smoking and alcohol use histories. In addition, the Canadian adaptation of the US National Cancer Institute’s past year Diet History Questionnaire II (CDHQ-II) [Past Year Total Physical Activity Questionnaire (PYTPAQ) [General Health Questionnaire that measured patient-reported outcomes including health-related quality of life, symptoms , psychosocial outcomes , facilitators and barriers to physical activity, and sedentary behavior were completed [Baseline Health Questionnaire, all other questionnaires are being completed at each follow-up time point.Four sets of questionnaires were completed at baseline. The CDHQ-II) , the Pas(PYTPAQ) , and a Gompleted –29. ExcePhysical activity and sedentary behavior were further assessed at baseline with 1- and 3-year follow-ups using the waist-worn ActiGraph GT3X + ®  and the thigh-worn activPAL® inclinometer . Participants wore these devices for seven consecutive days and completed an Activity Monitor Log to record when the devices were worn (and removed) each day.2peak, and recovery heart rate); and upper and lower body muscular strength  and endurance .Health-related fitness assessments were performed by certified exercise physiologists using standardized testing protocols and the same equipment at both sites have been previously described . The assArm volume was assessed using the Perometer® . Cancer-related lymphedema was considered present with a ≥ 200 ml volume difference between the affected and unaffected arms [shoulder range of motion  indicate a limitation if the difference in range of motion between the affected and unaffected arm exceeds 10°. Self-reported arm function was assessed using the Disabilities of the Arm, Shoulder and Hand scale (DASH) [Upper body functioning and lymphedema were assessed by self-report in the baseline questionnaire and by direct measurements performed by exercise physiologists. ted arms . Measuree (DASH) . Upper aAMBER study participants were asked to provide a 60-ml fasted blood sample at baseline and 30-ml fasted blood samples at 1- and 3-year follow-up. A standardized protocol for blood collection, processing, shipping, and storage is followed for the collections at both sites. We have 20 aliquots per person per blood draw  available for assays. The aliquoted blood samples are stored in ultralow (− 86 °C) freezers in the ACRB facility in Calgary. Blood collections were done predominantly pre-surgery in Calgary through the ACRB and postsurgically in Edmonton given the timing of recruitment there.form® or Blaise® with data verification, cleaning, and analysis done in STATA (version 16) or SAS (version 9.4). Databases in Access® are used for tracking the cohort and for the health-related fitness assessments. Caloric and nutrient intakes from the CDHQ-II are estimated using Diet*Calc [All self-reported questionnaire data were captured in either TELEiet*Calc . MET valiet*Calc  to deriviet*Calc . Sedentaiet*Calc . For theDescriptive analyses  were estimated for all baseline questionnaires, health-related fitness, as well as device-based and self-reported measures of physical activity and sedentary behavior data. Data from the questionnaires were used to further categorize participants into clinically meaningful groups where possible. Menopausal status was determined based on age and a series of questions about the menstrual cycle. Participants were considered post-menopausal at baseline if (1) their period stopped naturally or due to medical treatment, such as surgery, hormone replacement therapy, radiation, or chemotherapy or (2) if they were taking hormone replacement therapy and were > 55 years of age. The burden of co-morbid conditions was estimated using an adapted version of the Charlson Comorbidity Index . Individn = 4,740; 43%), having an ineligible disease stage , medical/age issues  , living outside the catchment areas in Calgary and Edmonton (> 200 km from centers) , having a language barrier , already completed too much adjuvant treatment , or other issues . We recruited 1,528 of 3,673 eligible (42%) into the study. The most common reasons for refusal were being overwhelmed/too sick , not interested , and living out of town/distance . From the sample, 884 were recruited in Calgary and 644 in Edmonton , illness or musculoskeletal problems, such as knee pain or ankle injury , or complications related to treatment or surgery . The remaining HRF tests were completed by at least 83% of participants with tests having a > 90% completion rate. The HRF assessment completion rates were similar between the two centers except for upper body strength and endurance measures that were completed at a lower rate in Calgary because these participants were recruited into the cohort closer to the time of surgery compared to Edmonton. Baseline HRF assessments were completed after initiation of chemotherapy in 274 (18%) of participants of which 250 had completed one cycle and 24 two cycles of treatment. Likewise, 82 (5%) study participants completed their baseline assessments after starting their radiation treatment with a maximum of 10 fractions.Supplementary Table 1 provides details on the baseline assessment completion rates overall and by center for all data collected from the AMBER participants. In total, 1,388 (90.8%) participants attempted the treadmill test and 1,287 (84.2%) completed the test sufficiently to obtain a direct (76.2%) or estimated (8.0%) measure of VOBaseline Health Questionnaire and the remaining questionnaires were completed by 95% of participants.The baseline assessment completion rates for lymphedema, upper arm function, peripheral neuropathy, and blood collection were over 98% and comparable between centers. Blood samples were obtained from 98.9% of participants with predominantly pre-surgical bloods in Calgary (81.9%) and post-surgical bloods in Edmonton (87.6%) because of the difference in the timing of recruitment between centers. All participants completed the Useable data, defined as ≥ 10 h of wear time/day, were obtained from 95.4% and 94.3% of participants for the ActiGraph GT3X + ® (95.4%) and activPAL® devices.On average, the AMBER study participants were 54.9 years old SD = 10.8), predominantly White (87%), married or common-law (75%), well educated (44% with university undergraduate degree or higher), had relatively high family incomes , an average of 1.7 live births (SD = 1.2), were mainly post-menopausal (58.7%), and nearly a third (29%) had a first-degree family history of cancer  Table . The canMost AMBER participants never smoked (56.7%) with 36.8% reporting being ever smokers (defined as smoking at least 100 cigarettes at some point in their lives) and 6.4% were current smokers  was 26.6 ml/kg/minute (SD = 6). Their flexibility, as assessed with the sit and reach test, was 27.4 cm (SD = 9.9). They completed an average of 29 (SD = 29) curl-ups on the test for abdominal endurance. Their combined right and left grip strength was 55 kg (SD = 12) and upper body strength as indicated by the chest press predicted 1-RM was 27.9 kg (SD = 7.9). Their lower body strength assessed by the leg press predicted 1-RM was 74.6 kg (SD = 24.4).AMBER participants’ average cardiopulmonary fitness , flexion (21.8%), and horizontal abduction (12.9%).Physical activity and sedentary behavior measures from both the self-report and accelerometry-derived measures are presented in Table The AMBER Study is a unique breast cancer survivor cohort with 1,528 women recruited between 2012 and 2019. Participants have provided detailed and comprehensive self-report and direct measurements of a wide range of exposures shortly after diagnosis (baseline) and again at 1-, 3-, and 5-year follow-up. These participants will be followed for at least an additional five years for all cancer survival outcomes.Initial recruitment into the cohort required seven years to achieve the target sample size of 1,500 women. The final sample is 10% of all Albertan women who were diagnosed with breast cancer during this period. The eligibility requirements for this cohort study reduced the available sample size for recruitment to 3,673 breast cancer patients (25%) of which 42% were recruited into the AMBER cohort. This recruitment rate is similar to comparable breast cancer survivor cohort studies, including the Pathways Study , Health,For those women who did participate, we had high baseline completion rates for all the assessments. In AMBER, we achieved 99.9% baseline completion for anthropometric measurements which is comparable to the 84%–100% rate reported in other breast cancer cohorts –39. We hWe compared our population to the base population of breast cancer survivors in Alberta and the USA, as well as to other breast cancer survivor cohorts in the USA to assess the generalizability of the AMBER cohort study. The most recent publication of the age and stage distribution of women diagnosed with stage I to III breast cancer in Alberta between 2016 and 2017  reportedAMBER participants, who were on average 55 years at diagnosis, were somewhat younger than the base population of female breast cancer survivors in Alberta  as well 2 which classified them as overweight and 27.9% of the cohort had obesity (BMI ≥ 30) at baseline. Their average body fat percentage of 43.1% was above the recommended range for women between the ages of 35 and 55 years (23%–38%) and for women over the age of 56 years (25%–38%) [The rate of 6% for current smokers in AMBER was comparable to the rates reported in other breast cancer cohorts (7%–9%) , 39 but 25%–38%) . Partici25%–38%) .2peak) of AMBER participants was borderline fair according to age- and sex-specific norms for maximal and submaximal exercise tests [very good, the mean score of 25 for curl-ups would classify participants’ abdominal muscular endurance as excellent and the mean score of 27.4 cm for the sit and reach test would classify participants’ low back and hip flexibility as fair according to age- and sex-specific norms [With respect to health-related fitness at baseline, the average cardiorespiratory fitness level , the exclusion of lower stage (< T1c) breast cancer, the standardized and direct measurements of outcomes that are repeated at three time points during follow-up, and our high measurement completion rates. While we have achieved excellent internal validity of the cohort, there are some limits to the external generalizability of the sample given the relatively homogeneous demographic, medical, and behavioral profiles of study participants. Initial publications from our cohort study will describe the baseline patient-reported outcomes and their associations, the physical activity, sedentary behavior, and health-related fitness measures. The cohort follow-up is planned to continue for at least another eight years to describe the associations of these measures with long-term outcomes, including recurrence and survival.Supplementary file1 (docx 14 KB)Below is the link to the electronic supplementary material.


Our study is aimed at exploring the knowledge and personal practice of breast cancer screening among female community pharmacists in Jordan.  A cross-sectional survey was carried out using a nonrandom sample selection method for pharmacists in community pharmacies.  A total of 551 female pharmacists completed the questionnaire. The mean age of pharmacists was 29.1 ± 7.3 years (range 21–67), and most have bachelor degrees in pharmacy (89.1%). The mean score of knowledge of breast cancer signs and symptoms was 4.2 ± 1.5 out of 6 points (range 0–6). The mean score of knowledge of risk factors was 7.6 ± 1.9 out of 12 points (ranging from 2–12). The mean score for knowledge of screening guidelines was 2.8 ± 0.9 out of 4 points (range 0–4). Overall, 452 pharmacists (85.8%) had acceptable knowledge while 75 pharmacists (14.2%) had poor knowledge of breast cancer. Pharmacists surveyed were aware of the different screening methods of breast cancer. The percentage of pharmacists who has performed breast self-examination (BSE), clinical breast examination (CBE), and mammography was 46.6%, 16.5%, and 5.4%, respectively. The most common reason for the lack of BSE and CBE performance was the absence of breast symptoms. Not being at the age recommended for mammography was the most common reason for not undergoing this screening method. Knowledge and practice of screening methods were influenced by age, years of experience, geographic region, personal history of breast cancer, and educational level among community pharmacists.  This study revealed some gaps in the knowledge of breast cancer among female community pharmacists. The practice of the different screening methods was suboptimal, and variable reasons were indicated for the low uptake of these screening methods. Community pharmacists need to practice preventive behaviors to a satisfactory level to encourage women in the community to adopt similar behavior. Breast cancer is the top cancer in women in both the developed and the developing world . It accoEarly diagnosis of breast cancer is a potentially beneficial way to control the disease and reduce mortality . Breast Healthcare workers are a direct source of medical information for the public and are essential contributors to promoting breast cancer awareness among their communities , 8. CommA limited number of studies have been conducted to evaluate the knowledge and practice of breast cancer screening methods among healthcare professionals in Jordan. Therefore, this study was conducted to assess the knowledge and screening practices of breast cancer among female community pharmacists in Jordan. The study is also aimed at identifying motivators for the screening behavior for the early detection of breast cancer.A descriptive cross-sectional design was carried out among female pharmacists in community settings over the different directorates in Jordan. Pharmacists who have a bachelor's degree in pharmacy (BPharm) or a higher educational degree were eligible to participate in this study. The study was approved by the Institutional Review Board committee of Jordan University of Science and Technology (JUST) (research number 20180026).Convenience sampling was used to recruit community pharmacists. Pharmacists were approached by a trained research assistant who explained the purpose and procedures of the study. Pharmacists who agreed to participate in the study were handed out the questionnaire and requested to fill it in while the research assistant was available. This approach allows for consistency in answering any raised issues during data collection and improves response rate. The average time to complete the questionnaire was 5-10 minutes.n = 25). Feedback and comments by the pilot group resulted in minor edits to the study tool, which was considered to improve the clarity of the survey items. Data from the pilot sample was excluded from the final analysis. The study tool was composed of three parts: (1) demographic and practice characteristics, (2) knowledge of breast cancer, and (3) practice of breast screening methods. The internal consistency reliability coefficients (Cronbach's α) calculated for knowledge and screening items were 0.711 and 0.853, respectively.A structured, self-administered questionnaire was used to collect responses. The questionnaire was developed and modified by the researchers based on previous literature and was administered to participants in the English language –17. The https://www.cancer.org). Each “Correct” response was scored 1 point, and each “Incorrect” and “I do not know” responses were both scored zero points. Six signs and symptoms were included in this part. Pharmacists who scored 0–3 points were considered to have poor knowledge of breast cancer signs and symptoms, while those with 4–6 points were determined to have an acceptable level of knowledge. Twelve items were listed on knowledge of risk factors of breast cancer. Participants who correctly recognized 7 out of the 12 stated risk factors were determined to have acceptable knowledge of risk factors while participants who identified 6 or fewer risk factors would have poor knowledge. Four items were listed on breast cancer screening representing the ACS 2017 recommendations [Demographics included items such as age, marital status, level of education, personal and/or family history of breast cancer, and years of practice. The second part of the questionnaire assessed knowledge of breast cancer signs and symptoms, risk factors, and screening guidelines with answer options of “Correct,” “Incorrect,” and “I do not know.” Breast cancer signs and symptoms, as well as risk factors, were reported according to the ACS . Pearson's Chi-square test of independence was applied to assess associations between categorical variables. Differences between groups were determined by independent student t-test for two-group comparisons or one-way analysis of variance (ANOVA) followed by Tukey HSD post hoc test for multiple group comparisons. Bivariate correlation analysis was performed to test for correlations between continuous variables. All p values were two-sided, and differences were statistically significant at p < 0.05.Data analysis was performed using IBM SPSS statistical package . Descriptive statistics were used to report study variables. Continuous variables are presented as mean ± standard deviation, and categorical variables are presented as frequency and percentages  reported that their oncology education at the undergraduate level was inadequate. Most pharmacists  never attended continuous educational activities related to cancer awareness in the last two years. Other demographic and practice characteristics are shown in The mean age of community pharmacists was 29.1 ± 7.3 years (range 21–67). Most participants were single (56.7%) and had a BPharm (89.1%) . More thn = 447, 81.6%). Less than half of the participants (46.7%) recognized that a painful mass is not a typical finding in breast cancer  correctly indicated obesity as a risk factor for breast cancer. The mean score of knowledge of risk factors was 7.6 ± 1.9 points (ranging from 2–12). Most pharmacists (71.2%) had an acceptable level of knowledge of risk factors.The majority of pharmacists correctly recognized the age of a patient (78.2%), a positive family history of the disease (97.6%), and genetic causes (93.2%) as risk factors for breast cancer . Neverthn = 457, 83.1%) correctly responded to the statement that “Women ages 45 to 54 years should be screened annually with mammography.” The mean score for pharmacists' knowledge of screening guidelines was 2.8 ± 0.9 points (range 0–4). Among the participants, 159 pharmacists (28.9%) had poor knowledge, while 391 pharmacists (71.1%) had acceptable knowledge of screening guidelines.Regarding knowledge about breast cancer screening, most pharmacists (89.3%) correctly indicated that screening with mammography reduces breast cancer mortality . Our resn = 452, 85.8%) had acceptable knowledge.The overall mean score for pharmacists' knowledge of breast cancer signs and symptoms, risk factors, and screening guidelines was 14.6 ± 3.01 out of a maximum score of 22 points (range 5–22). The majority of pharmacists  and risk factors (p = 0.001). Although the number of working hours per shift was negatively correlated with all four scores of knowledge, none of these reached statistical significance    . The mea= 0.038) . Similarp = 0.003). In this regard, a greater proportion of pharmacists with the PharmD degree (92.9%) had an acceptable knowledge of risk factors compared to each of BPharm (68.9%) and those with graduate studies (81.3%) (p = 0.021) and screening guidelines among community pharmacists (p = 0.028) (Associations between breast cancer knowledge with demographic and practice characteristics of pharmacists are shown in  (81.3%) . The geo= 0.028) .n = 128, 50.8%) performed BSE after menstruation while a smaller number performed BSE during and before menstruation . Regarding CBE, 442 pharmacists (80.5%) were aware of this screening tool. A small proportion of pharmacists had CBE performed by a healthcare professional . Four hundred and sixty pharmacists (83.6%) were aware of mammography as a screening tool for detecting breast cancer. Sixty-one pharmacists were 40 years or older of whom 25 pharmacists had mammography performed.Concerning the personal practice of female pharmacists, 520 pharmacists (94.4%) were aware of BSE, and 257 (46.6%) had performed BSE. Among pharmacists who performed BSE, 68 (26.4%) performed BSE monthly, 20 (7.8%) did it twice yearly, 12 (4.7%) performed it once yearly, and 149 (57.8%) performed BSE irregularly when it comes to mind. Half of the pharmacists (The motivators for performing each of the screening methods are shown in n = 369) had never done CBE. The most common reasons for not considering CBE included the absence of breast symptoms (54.1%), negative family history of the disease (26.0%), lack of time (23.0%), and feeling of anxiety (13.0%)  for not considering BSE . Notably (13.0%) . Most ph (13.0%) . Other r (13.0%) .p = 0.001 and p < 0.001, respectively, p < 0.001) and mammography (p = 0.011) compared to single respondents (p < 0.001). This study also showed a significant association between the overall level of knowledge of breast cancer and BSE practice (p < 0.001). The type of pharmacy, oncology education, and continuous medical education was not significantly associated with screening practice in this study (data not shown).Screening practice was influenced by the age of the pharmacist. A greater proportion of pharmacists at age 45 or older had CBE and mammography compared to younger pharmacists  is a simple, quick, noninvasive, and inexpensive procedure for the early detection of breast cancer among women , 16. BSEAwareness campaigns and believing in the usefulness of BSE for the early detection of breast cancer were the most reported reasons for practicing BSE among community pharmacists in this study. In other studies, however, the commonest reasons reported by female healthcare workers practicing BSE were for the early detection and the fear of developing breast cancer . ReasonsClinical breast examination (CBE) is the inspection of a female's breasts by a trained healthcare professional, such as a breast surgeon, a family physician, or a breast care nurse, to recognize different types of abnormalities in the breast . Only 16Mammography is the only screening modality that has been proven to reduce breast cancer mortality based on multiple randomized clinical trials . It is tIn the present study, the motivators for considering mammography were the presence of breast symptoms and a recommendation by a healthcare provider. Alternatively, the perceived benefit that mammography enables early detection of breast cancer was the main motivator to perform mammography by female healthcare workers in another study . SeveralIn this study, breast cancer knowledge was influenced by age and years of experience among community pharmacists. The level of knowledge was improved among pharmacists in South regions, postmenopausal, and those with PharmD degrees. Screening practice was influenced by age, marital status, the geographic area for respondents, and the presence of a family or personal history of the disease. Older pharmacists had better knowledge and practice screening methods to a greater extent than younger ones. Pharmacists who have a personal or family history of breast cancer also practiced these methods more than others. In a study by Soylar et al., age and family history of any cancer type were significantly correlated to the practice of cancer screening methods . KnowledMost studies published on breast cancer knowledge and the screening behavior involved medical doctors, resident doctors, nurses, paramedics, midwives, and other health care professionals. Nevertheless, community pharmacists were largely underrepresented in the literature. It is worth mentioning that a previous study conducted among community pharmacists in Jordan revealed adequate knowledge along with positive attitudes and willingness of pharmacists to participate actively in promoting awareness on breast cancer . TherefoThis study has a few limitations. First, the self-reported information is subject to social desirability bias. Second, the questionnaire was distributed using nonrandom sampling. Convenience sampling might trigger selection bias and further limit the generalizability of the results. However, we are hopeful that the high response rate achieved in this study would mitigate the bias that may be caused because of the sampling applied.To the best of our knowledge, this is the first study to assess the practice of breast cancer screening among female community pharmacists in Jordan. This study revealed the gaps in the knowledge of breast cancer among pharmacists especially regarding modifiable risk factors that can be altered to reduce the risk of breast cancer among women. Improving the knowledge of signs and symptoms and risk factors is mandatory in the curricula of undergraduate studies and through continuing medical education events and activities. While the female pharmacists in this study were aware of breast cancer screening methods and guidelines, this was not reflected in their practices. The practice of the different screening methods was inadequate, and variable reasons were indicated for the low uptake of these screening methods. Community pharmacists need to perform the preventive behaviors themselves to a satisfactory level to encourage women in the community to adopt similar behavior.


TP53 gene , also known as the Li–Fraumeni syndrome, have a very high (70–100%) lifetime risk of developing cancer and at younger ages. Carriers are also prone to develop secondary tumours due to irradiation. Current guidelines recommend surveillance programmes within studies and the use of non-irradiation modalities such as whole-body MRI (WB-MRI). In 2016, the Swedish TP53 study (SWEP53) started inclusion, offering a surveillance program including WB-MRI. With this study, we aimed to describe the rate, anatomical distribution of malignant, indeterminate, and benign imaging findings as well as the associated further workup generated by the baseline WB-MRI in adult study participants. Our study identified the need of further workup in 19/61 participants, of whom three patients had a new cancer. WB-MRI appears to be a valuable surveillance strategy in families with hTP53rc syndrome. Individuals who are born with a disease-causing variant of the TP53-related cancer syndrome (hTP53rc), commonly referred to as the Li–Fraumeni syndrome (LFS), is studied in a prospective observational nationwide multi-centre study in Sweden (SWEP53). The aim of this sub-study is to evaluate whole-body MRI (WB-MRI) regarding the rate of malignant, indeterminate, and benign imaging findings and the associated further workup generated by the baseline examination. Individuals with hTP53rc were enrolled in a surveillance program including annual whole-body MRI (WB-MRI), brain-MRI, and in female carriers, dedicated breast MRI. A total of 68 adults ≥18 years old have been enrolled to date. Of these, 61 fulfilled the inclusion criteria for the baseline MRI scan. In total, 42 showed a normal scan, while 19 (31%) needed further workup, of whom three individuals (3/19 = 16%) were diagnosed with asymptomatic malignant tumours . Forty-three participants were women, of whom 21 had performed risk-reducing mastectomy prior to inclusion. The remaining were monitored with breast MRI, and no breast tumours were detected on baseline MRI. WB-MRI has the potential to identify asymptomatic tumours in individuals with hTP53rc syndrome. The challenge is to adequately and efficiently investigate all indeterminate findings. Thus, a multidisciplinary team should be considered in surveillance programs for individuals with hTP53rc syndrome.A surveillance strategy of the heritable  TP53 variant have a lifetime risk of 70–100% [TP53-related cancer syndrome (hTP53rc) rather than LFS [Carriers of a disease-causing germline  70–100% . During TP53rc are at risk of developing cancer at considerably younger ages (median age 25 years) than non-carriers, and up to 50% of all carriers develop a tumour before the age of 30 [TP53-carriers are more prone to develop multiple primary cancers [Individuals with hge of 30 ,5. Breasge of 30 . TP53-ca cancers . The pot cancers ,9,10 whiTP53rc would likely benefit from surveillance to facilitate early detection of tumours in a potentially curative stage. In 2016, Villani et al. [Persons with hi et al.  publisheTP53 variant, reported a 7% detection rate of new, localized primary cancers [TP53 variants. To our knowledge, there are as yet no other ongoing studies in the Scandinavian countries, but studies with WB-MRI are reported in Australia [A previous meta-analysis of baseline WB-MRI as a cancer screening tool, including 578 carriers of a pathogenic  cancers . The rea cancers  makes WBustralia , Brazil,ustralia , Great Bustralia , the Netustralia , France ustralia , and theustralia ,19. So fTP53 study (SWEP53), which aims to improve the clinical care of families with hTP53rc syndrome. The details of the SWEP53 study protocol have previously been described [The reported participants have been enrolled for WB-MRI within the Swedish escribed .The aim of this report is to evaluate baseline WB-MRI regarding the distribution and rate of radiological findings in terms of malignant, indeterminate, and benign lesions and the associated further workup generated by this surveillance strategy. TP53 variants were invited to participate in SWEP53 from 1 April 2016. Those who had performed their baseline WB-MRI by 1 May 2021 were included in this study. Inclusion was performed at the six cancer genetic units in Sweden, i.e., at the University Hospital in Umeå, Uppsala University Hospital, Karolinska University Hospital (Stockholm), Linköping University Hospital, Sahlgrenska University Hospital (Gothenburg), and Skåne University Hospital (Lund). Individuals were identified as carriers of a disease-causing TP53 variant by one of these four testing procedures: (1) through gene panel testing within the clinical workup of participants with a suspected hereditary breast cancer, (2) through gene panel testing within a national research study aiming at identifying novel high risk genes for breast cancer, (3) targeted testing of TP53 due to multiple primary cancers or family history fulfilling the Chompret 2015 criteria [TP53 variant previously identified in the family. Written informed consent was obtained prior to inclusion. Ethical permission was obtained by the regional ethical review board in Stockholm with approval number 2015/1600-3 with the amendments 2017/1527-32 and 2018/1690-32. Exclusion criteria were individuals with general contraindications to MRI, any co-morbidity that precludes treatment of a cancer found in the surveillance program, or an ongoing intensive cancer treatment, where priority was given to clinical examinations.Individuals with pathogenic or likely pathogenic germline criteria , or (4) The WB-MRI was defined as the baseline if it was either the first scan performed after study inclusion or, in some cases, a clinically performed WB-MRI prior to the inclusion date. The surveillance program included WB-MRI, a separate brain MRI, and in women with no previous bilateral risk-reducing mastectomy (RRM), breast MRI and breast ultrasound. All study participants were informed of the risk of possible secondary workup due to findings detected by the radiological and/or clinical examinations. The yearly WB-MRI examinations were intended to cover the whole body from the skull base to the feet . The SWEThe study sites were provided with a protocol , and we The evaluation of findings on whole-body MRI were single- or double read by radiologists and depending on need, local resources, and routines also separately evaluated by a neuro- and breast radiologist. For the purpose of reporting the findings on baseline WB-MRI, benign lesions were defined as those that were judged to be obviously benign on the MRI (and/or on prior imaging) requiring no further additional work-up. The clearly benign findings were handled as they would have been treated in a clinical setting. Findings referred to as indeterminate were those that required a further investigation to state whether benign or malignant. Malignant findings were defined as a new primary tumour, previously undiagnosed recurrence, or metastatic disease. Multiple lesions within the same organ (such as multiple liver metastases) were regarded as one finding.Clinical data were collected from the medical records, including information on family history of cancer, previous cancer diagnosis and age at onset, findings at WB-MRI, and any subsequent workup. A typical workflow was inclusion at the site by an oncologist or a clinical geneticist. Physical evaluation and referral for WB-MRI followed, and results of the imaging were managed by the referring physician in accordance with established clinical procedures. The radiological reports and results of the workups from each participating site were then reviewed by the central site at Karolinska University Hospital in Stockholm. All data presented are observational. Data are presented as numbers and proportions. The mean age for the whole study population was 39 years (range 18–74 years old). Out of the 61 individuals, 32 had a previous history of tumour diagnosis prior to study inclusion . Breast cancer was the most common (23 participants with 27 breast cancer diagnoses). A total of 18 individuals had had 21 other tumour types. Tumour onset ranged from 4 months to 71 years of age. Thirteen participants had previously had more than one different type of malignancy by the time of study inclusion .By 1 May 2021, a total of 68 adult participants had been included nationally in SWEP53, of whom 61 adults had performed their baseline scans . A total of 30 new lesions  were ideOverall, 9 of the 30 lesions (30%) that required further workup were malignant. All nine were identified in three individuals (3/61 = 5%): one participant had a new primary cancer, another had disseminated disease, and the third had a recurrent cancer. All patients were asymptomatic at the time of inclusion. Of the 21 indeterminate findings , Table 2In all 61 individuals, a total of 58 benign imaging findings were found, defined as benign by the radiologist without any need for further workup. The most common benign findings after further work-up were in the brain  and in the liver . TP53 variants showed that one-third of carriers had indeterminate imaging findings on baseline WB-MRI requiring further workup. Of these, all except one resulted in benign results. Of note, the rates of both indeterminate and benign imaging findings were higher than malignant findings, which were, in total, 9/88 lesions (10%) identified in 3/61 (5%) of all participants. A meta-analysis by Ballinger et al. in 2017 [TP53 variants from 13 different cohorts who underwent baseline WB-MRI, reported 7% new malignancies. In contrast with our study, Ballinger et al. only included new localised cancers as new malignancies, whereas we defined previously unknown metastatic cancers and recurrences as malignant findings. We found new, non-metastatic malignancies in 1/61 (1.6%), thus lower than Ballinger et al. This is likely not due to age differences, as the mean age in our study group was 39 years  and 41 years  compared to Ballinger et al., who reported a mean age of 33 years. However, our cohort was smaller (61 compared to 578), and thus, the estimate should be interpreted with caution. We also included both persons with a classical LFS tumour spectrum and individuals from families with predominantly hereditary breast cancer. This could possibly have led to a lower detection rate due to an overall lower tumour risk for cancers other than breast cancer. In addition, we did not detect any cases of breast cancer in the 22 women who had not undergone RRM. This is not surprising, as the women were previously offered annual breast surveillance with breast MRI and ultrasound according to national guidelines. The fact that one patient had disseminated disease but a normal clinical examination highlights the difficulties in detecting cancer solely through clinical check-ups. We had a detection rate of 31% of indeterminate imaging findings requiring further investigation. In the meta-analysis by Ballinger et al. [The results from this cohort of individuals with germline disease causing  in 2017 , comprisr et al. , the “far et al. . TP53 alterations. Instead of viewing the study participants as healthy individuals, perhaps the radiologists should consider them “patients with an unknown cancer” to minimize the risk of disregarding or overlooking potential malignant findings. Although we had a defined study protocol for WB-MRI, some local adaptations were made due to different technical platforms, which led to slightly different anatomical coverage and imaging protocols. Since both soft-tissue sarcomas and osteosarcomas often occur in the limbs ,23, it iTP53rc individuals with, for example, predominantly hereditary breast cancer from WB-MRI surveillance, and thereby reduce the risk of unnecessary workup. However, the benefits of repeated WB-MRI and risk stratification, potentially based on genotype–phenotype characterisations, is still under evaluation. Therefore, we suggest that all germline TP53 carriers should be surveilled with WB-MRI in accordance with the ERN GENTURIS guidelines independent of family history [In the future, it may be reasonable to exclude hTP53-related cancer syndrome may detect asymptomatic cancers. Benign and indeterminate imaging findings that require further work-up are more common than cancer. A multidisciplinary approach and a clinical infrastructure to manage these findings is needed to ensure adequate management.Whole-body MRI in individuals with heritable


Among the women with breast cancer, no correlations were found of baseline BMD with tumor size or grade, nodal involvement, or breast cancer stage. We concluded that women with newly diagnosed breast cancer tend to have higher BMD than women with similar characteristics but without breast cancer. This implies that BMD might be considered a biomarker for breast cancer risk.Estrogen may have opposing effects on health, namely increasing the risk of breast cancer and improving bone health by increasing bone mineral density (BMD). The objective of this study was to compare dual-energy X-ray absorptiometry (DXA) BMD between women newly diagnosed with breast cancer and matched controls without breast cancer. Women newly diagnosed with breast cancer treated between April 2012 and October 2017 were prospectively enrolled. A control group was established of women with negative mammography or breast ultrasound, matched 1:1 by age, body mass index, parity, and the use of hormone replacement therapy. All those included had DXA BMD, and lab assessments at enrollment. Of 869 women with newly diagnosed breast cancer, 464 signed informed consent. Of the 344 who completed the study protocol, 284 were matched to controls. Overall, the mean age was 58 years. Compared to the control group, for the breast cancer group, the mean vitamin D level was lower (48.9 ± 19.0 vs. 53.8 ± 28.8 nmol/L,  Estrogen is central for the maintenance of bone integrity; its deficiency leads to accelerated bone loss and decreased bone mineral density (BMD), and a propensity for osteoporotic fractures2. BMD has been suggested as a marker for lifetime estrogen exposure, and thus may aid in predicting breast cancer risk3. High endogenous estrogen levels have been shown to be associated with increased risk of breast cancer (particularly hormone receptor-positive breast cancer)4. Reducing estrogen levels  has been shown to reduce the risk of breast cancer recurrence5.The incidences of both breast cancer and osteoporosis increase following menopause16. In a retrospective study of over 14,000 women who performed dual-energy X-ray absorptiometry (DXA) BMD, we found that future breast cancer risk adjusted for age and body mass index (BMI)) was doubled in women in the highest tertile compared to the lower tertiles of femur neck and total hip BMD Z scores17. In contrast, other studies found no association between BMD and breast cancer risk in either pre or postmenopausal women23. In a meta-analysis published during the past decade, which included over 70,000 postmenopausal women, high hip and spine BMD was found to be a risk factor for developing breast cancer. This supports the conclusion that higher BMD confers higher breast cancer risk15.Several observational studies have shown an association of higher BMD with increased breast cancer risk irrespective of other risk factors24. Findings on the association of 25 OH-vitamin D levels and the risk of breast cancer are conflicting26. A review by Bauer et al., including nine prospective studies with a total of 11,656 women, found that postmenopausal  breast cancer risk was decreased by 12% for each 5 ng/mL increase in 25(OH)D level between 27 and 35 ng/ml27. Similar observations of an inverse “dose–response” relation between 25(OH)D levels and breast cancer risk were also found in additional meta-analyses29.In addition to estrogen exposure, several other factors, including vitamin D levels, may influence BMD and breast cancer risk. Low vitamin D levels may lead to reduced bone mineralization and therefore lower BMDWe conducted a prospective matched cohort study with the primary objective of assessing BMD in women with newly diagnosed breast cancer, and comparing to matched controls.Between April 2012 and March 2016, 869 women newly diagnosed with breast cancer were referred to the oncology department of our institute. Figure p = 0.834), mean BMI , and the use of hormone replacement therapy (HRT) (27.5%) did not differ statistically between the groups; this was expected, since these were the parameters used for matching. Although the participants were matched by parity, this parameter was lower in the breast cancer than control group . Ninety-seven percent of those with breast cancer and 100% of the control group were of Jewish origin. Rates of prior use of anti-osteoporotic medications in the two years prior to enrollment were collected from electronic medical records only for women insured by Clalit Health Services (70% of the participants in the breast cancer group and 97% of those in the control group), and were similarly low in the two groups. Considering only those with available blood tests, mean creatinine, eGFR, and parathyroid hormone (PTH) levels did not differ statistically between the two groups. Compared to the control group, for the breast cancer group, mean 25-OH vitamin D levels were lower ; and a higher proportion had a vitamin D level below 50 nmol/L (54.4% and 46.3%) (p = 0.071).Baseline characteristics of the women in the case and matched control groups are presented in Table 2 and as T and Z scores. Compared to the control group, for the breast cancer group, higher mean values were observed of femoral neck Z score , total hip BMD , T score , and Z score . Mean values of the lumbar spine BMD, and T and Z scores did not differ statistically between the case and control groups (Table T score < −2.5): at the femoral neck (12 (4.2%) vs. 4 (1.4%), p = 0.073); total hip (9 (3.2%) vs. 8 (2.8%), p = 1.0); and the lumber spine (33 (11.6%) vs. 25 (8.8%), p = 0.332).Results of DXA–BMD according to site, for the 284 women with breast cancer, and the 284 matched controls are presented in Table n = 344) are presented in Table 2. Most (67.2%) never smoked, 74.7% were postmenopausal, 27.7% used postmenopausal HRT, 24.4% reported having a previous fracture. The median number of pregnancies was three; 68% reported breastfeeding after every delivery. Fifty-three per cent were of Ashkenazi Jewish ancestry, 37% were Sephardic Jews, and 3% were Bedouin Arabs. The duration of unopposed lifetime estrogen exposure was calculated at 14.3 ± 4.4 years. The mean vitamin D level was 47.2 ± 19.2 nmol/L , while the mean creatinine, eGFR, and PTH levels were within the normal range. Characteristics of breast cancer including: histologic type and grade, tumor-node-metastasis (TNM) stage, and immunohistochemistry (IHC) positivity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) are presented in Table 2), T score, or Z score in any of the three sites examined, with various parameters of breast cancer including: tumor size and grade, hormone-receptor status, nodal involvement, and disease stage.Baseline characteristics of women with breast cancer , with mortality.The median follow-up of breast cancer patients was 51.9  months. As of June 30, 2018, 25 breast cancer patients had died. A Cox regression analysis found no association of DXA BMD, or 17. The current study showed a higher mean femoral neck DXA Z score and total hip BMD, and also higher total hip Z and T scores among women with breast cancer than among matched controls without breast cancer. These findings were despite a significantly lower mean vitamin D level among those with breast cancer. Since the women with breast cancer were matched to the control group according to prior HRT use, our study suggests that bone integrity and breast cancer risk might be linked by factors not related to estrogen. Spine DXA measurements were not different between the breast cancer and control groups. Among the women with breast cancer, DXA BMD was not found to be associated with breast cancer characteristics at diagnosis including tumor size or grade, nodal involvement, disease stage, or hormone receptor status. Nor was DXA BMD associated with mortality among the women with breast cancer.This prospective case-control trial confirmed the association we found between higher BMD and breast cancer risk in our retrospective analysis22. A meta-analysis was conducted of 70,878 postmenopausal women from eight prospective cohort and two nested-control studies. For women in the highest vs. the lowest category of hip and spine BMD, the relative risks of developing breast cancer were 1.66 and 1.82, respectively15. The current report of DXA BMD results in women with incident breast cancer compared to matched controls concurs with observations on bone mass in a matched pair analysis of 242 women with newly diagnosed breast cancer in the Marburg breast cancer and osteoporosis trial (MABOT) study13. There, bone density, as assessed with quantitative ultrasonometry (QUS) at the heel, revealed higher speed of sound and stiffness index T- and Z-scores in women with incident breast cancer than in healthy controls, even after post-matching for possible confounding variables of estrogen exposure. In the MABOT II trial, the same group of researchers studied 402 postmenopausal and 88 premenopausal women with breast cancer, and matched controls, using QUS and DXA BMD. Similar to the initial report, significantly higher values were found in all DXA BMD and QUS parameters of postmenopausal women, but not in premenopausal with breast cancer, compared to controls14. A similar observation was apparent in our study population; higher BMD was found in BC patients above age 50 compared to controls but not in the younger population. In the MABOT II trial BMD was higher at all three sites  while in our study higher BMD in BC patients was found only in total hip BMD, T and Z scores and femoral neck Z score, but not in the spine, although there was a trend for higher BMD T score and Z score in the spine that did not reach statistical significance. These differences may be explained by the larger size of the MABOT II trial, since in our study spine BMD tended to be higher in BC but this did not reach statistical significance. If our findings are substantiated by other research then possibly a study design using HRpQCT that can evaluate for cortical thickness (in the arm and the tibia) could examine this question in cases and controls, but this is beyond the scope of the study.Our results corroborate several studies that reported higher incidence of breast cancer in postmenopausal woman with higher BMD19. Both our cohort and that of the MABOT studies assessed younger women, mean age 57–59 years. This may explain the discrepancy between observations, as additional parameters may affect BMD in older age women, and thus confound the association between BMD and incident breast cancer.Our findings and those of the MABOT studies contrast with a case control study that found non-significantly different BMD at all sites  between 79 postmenopausal women aged 65 years and older, who had been recently diagnosed with breast cancer, and 158 age-matched controls with normal mammograms14.Lifetime unopposed estrogen exposure may have confounded our findings, such that longer exposure may have led to better BMD while increasing the risk for breast cancer. However, since we did not collect relevant data for calculating this parameter in the control group, we cannot draw conclusions regarding higher BMD as a risk factor for breast cancer, independent of lifetime estrogen exposure. Notably, in the large MABOT II study, the higher BMD in the breast cancer group could not be explained by differences in years of lifetime estrogen exposure, age at menarche, or duration of HRT use30. Moreover, a prospective study of 1504 women aged 75 years and older reported a greater risk of death during 7 years follow up for those in the highest than the lowest tertile at all skeletal sites 31. The younger age and the shorter length of follow up of the women with breast cancer in our cohort may partially explain the discrepancy in findings.We did not find associations of DXA BMD with breast cancer characteristics at diagnosis, including tumor size or grade, nodal involvement, disease stage, hormone receptor status, or survival. Notably, during 6.5 years of follow up of a large cohort of elderly women (mean age 70.6 years) who performed single-photon absorptiometry BMD, those with high BMD had an increased risk especially for advanced breast cancer (stage II or higher)25. Taken together, these findings imply an independent association of BMD with breast cancer risk, which is not mediated by vitamin D levels.We report higher total hip BMD among women with breast cancer compared to a control group, despite lower mean vitamin D levels. In multiple studies and meta-analyses, low vitamin D levels were found to be associated with increased risk of breast cancerA main strength of this study is the unique structure of the breast cancer clinic in our institution, which serves a diverse and large population. This made patient recruitment more feasible, and thus enabled adequate case control matching and uniform blood testing. Since all the breast cancer patients were recruited in a single center, thorough characterization of disease features was possible for all the participants. The prospective nature of our study and the use of DXA BMD upon the diagnosis of breast cancer are also unique to our study. In contrast, most studies stratified the future risk of developing breast cancer according to DXA BMD group. Our in-house mammography and BMD units enabled greater standardization of these tests. Another strength of our study is that we matched women with breast cancer to a control group according to postmenopausal HRT use. This mitigates the possibility that the higher BMD in the breast cancer group resulted from greater use of HRT, and suggests that bone integrity and breast cancer risk might be linked by factors other than estrogen effect.32. Investigation of BMD in patients receiving NAC is warranted. The ethnicity of our population was over 90% Jewish, of either European (Ashkenazi) or North-African/Asian (Sepharadi) origins. The findings in our population are probably relevant for European and American populations as shown by the similarity of the order of prevalence of the different types of cancers in the USA and Israel34. In addition, we were unable to calculate lifetime estrogen exposure in the control group, and therefore the possibility of estrogen exposure as a confounder could not be assessed. Exercise and physical activity level may impact BMD and potentially breast cancer risk but unfortunately, we did not collect this demographic information in BC and controls. Finally, our sample size did not enable stratifying by menopausal status at breast cancer diagnosis; this may have affected our results.Our study has several limitations. We did not exclude women who were treated for osteoporosis during or within the two years prior to study entry, and this may have affected BMD. We addressed this issue after the study ended and found low rates of prior bisphosphonate treatment, which were similar in the breast cancer and control groups. We excluded patients who received neoadjuvant chemotherapy (NAC), used primarily during years of the study to enable breast conserving surgery, and therefore may have skewed our cohort to earlier stage disease with a better prognosis and a higher percentage of HR positive cases. Standard-of-care NAC is currently administered not only to facilitate breast conservation therapy but also to patients with HER2 positive or triple negative subtypes of breast cancer with tumors 2 cm or larger in order to individualize post-surgical therapy on the basis of pathologic response to NACZ scores, and total hip BMD, Z, and T scores, among women diagnosed with breast cancer than among matched controls without breast cancer, despite significantly lower mean vitamin D levels in the former. DXA BMD parameters were not found to be associated with breast cancer characteristics at diagnosis. In addition, DXA BMD was not associated with mortality among women with breast cancer.In conclusion, our prospective case-control study showed higher femoral neck DXA The study was conducted at Soroka University Medical Center, and approved by the institutional review board: IRB # SOR11-189. Prior to participation, women with breast cancer and women in the healthy control group signed informed consent forms.35. Soroka University Medical Center is a regional medical center for a population of ~700,000, and serves nearly 1.2 million as a tertiary hospital. This includes the provision of mammographic screening and breast cancer treatment.Israel has operated a comprehensive breast cancer early-detection program since the early 1990s, in the context of comprehensive universal national health care coverageInclusion criteria for the study group were age 18 years and older and a diagnosis of breast cancer. Women were recruited at their first visit to the oncology department following surgery for breast cancer. Radiotherapy and chemotherapy prior to screening were exclusion criteria. The control group was recruited at the mammography unit following a breast mammography or breast ultrasound that was reported as normal. Exclusion criteria for the study and control groups were oncologic diseases other than breast cancer, bone diseases other than osteoporosis, autoimmune diseases (i.e. rheumatoid arthritis and systemic lupus erythematosus), and chronic steroid therapy.2, parity ±1 birth, and the use of postmenopausal hormone replacement therapy (HRT).Women in the breast cancer and control groups were matched by age ±5 years, BMI ± 5 kg/mThe primary objective of this study was to compare BMD between women newly diagnosed with breast cancer and matched healthy women with no radiologic evidence of breast cancer.−1.154 × age−0.203 × 0.742.During the first visit, the following data were recorded: body weight and height, demographic data, and past medical history. The latter included postmenopausal HRT, smoking habits, menstrual cycle status, parity and past breastfeeding. Blood samples were taken for measurement of vitamin D levels, parathyroid hormone (PTH), thyroid stimulating hormone (TSH), creatinine, calcium, phosphorous, albumin, complete blood count, and C-reactive protein. Estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease (MDRD) GFR equation: 186 × serum creatinineBMD was performed one year before or up to 3 months after enrollment for the breast cancer group, and one year before or after enrollment for the control group. BMD was measured by DXA using a Prodigy densitometer .2), T-score (standard deviation from the mean for young women), and Z-score (standard deviation from the mean for age-matched women adjusted for body mass). Z and T scores were calculated according to the Lunar-Prodigy manufacturer’s internal database, and based on data of The National Health and Nutrition Examination Survey III.BMD was assessed at the lumbar spine, femoral neck, and total hip; and expressed as bone density  HER2 immunostaining, tumor tissues were submitted for chromosome in situ hybridization or fluorescent in situ hybridization testing. Participants were classified into four subtypes by IHC staining results: luminal A- ER and/or PR positive and HER2 negative; luminal B- ER and/or PR positive and HER2 positive; HER 2 positive- ER negative/PR negative/HER2 positive; triple negative- ER negative/PR negative/HER2 negative. (Women with HER2 2+ results and unknown chromosome in situ hybridization/fluorescence in situ hybridization status were regarded as HER2 negative).® 25 OH Vitamin D TOTAL Assay ([REF] 310600). The results were expressed as nmol/l, normal range: 75–250 nmol/L.Vitamin D status was reported when available. Vitamin D levels were determined by measuring patients’ serum 25-hydroxyvitamin D (25(OH)D) levels by chemiluminescent immunoassay technology, LIAISONPTH status was reported when available. PTH was measured using the intact-PTH test . This test is based on a chemiluminescent reaction in two sites on the molecule. PTH levels were reported in pg/mL; normal range: 14–72 pg/mL.Anti-osteoporotic medications used in the two years prior to enrollment were identified by the Anatomical Therapeutic Chemical Classification System codes and collected from the electronic medical record, which were accessible for participants insured by Clalit Health Services. Medications included oral bisphosphonates (ATC codes M05BA04 and M05BA07), injected bisphosphonates (M05BA03 and M05BA08), vitamin D analogs (A11CB and A12AX), and calcium supplements .Lifetime estrogen exposure was calculated only for the breast cancer group, and was based on self-reported data, using the following equation:36.Total menstrual period/2 [total menstrual duration = menopause age–(menarche age + parity*9 months + miscarriage*3 months + breastfeeding duration + pill use duration)]χ2-test or Fisher’s exact test, as appropriate. For continuous variables, the independent sample T-test or the Mann–Whitney U test was applied, as appropriate. Pearson’s correlation was used to assess bivariate relations. To further examine associations of BMD with tumor size, tumor grade, nodal involvement, and breast cancer stage, we performed multivariable linear regression models, adjusted for estrogen exposure, BMI, and bisphosphonates received in the previous 2 years. Variables were tested for multicollinearity. Survival analysis by DXA results was done using Cox regression models, while adjusting for age and breast cancer stage. All p values are based on 2-tailed tests of significance. Variables were considered significant at p < 0.05. Statistical analysis was performed with IBM SPSS version 24.Categorical data were expressed as numbers and percentages. Continuous data were expressed as means ± standard deviations or medians , depending on the normality of the data. Parametric model assumptions were assessed using normal plot. For categorical data, univariable comparisons were made using Further information on research design is available in the Reporting Summary Checklist


Our data fit the hypothesized SEM model well (Goodness of fit index (GFI) = 0.91, adjusted GFI (AGFI) = 0.89, comparative fit index (CFI) = 0.91, root mean square error of approximation (RMSEA) = 0.05, standardized root mean residual (SRMR) = 0.06, and Chi-square/df = 2.01). Three PMT subconstructs  were significantly associated with screening intention. Knowledge, social status, and medical history had significantly indirect associations with screening intention through the mediating effect of PMT subconstructs. Considering the utility of PMT, intervention programs might be more effective based on the subconstructs of PMT, especially to improve self-efficacy, perceived severity, and knowledge, reduce response cost, as well as targeting specific demographic groups.Despite the significance of early detection of breast cancer through screening, the screening uptake in China remains relatively low. Protection motivation theory (PMT) suggested by Rogers is one of the theories concerning threat appeal. This study aimed to apply the protection motivation theory (PMT) in predicting breast cancer screening intention. In this cross-sectional study, a sample of Chinese urban women was recruited using the convenient sampling method from five communities in Wuhan. Data were collected using a self-report questionnaire that included demographic variables, knowledge about breast cancer, six PMT subconstructs, and screening intention. We used the structural equation modeling (SEM) to identify the predictor factors associated with screening intention. Of the total sample ( Breast cancer is the most common cancer and the leading cause of cancer-related death in women worldwide. According to the latest data released by the International Agency for Research on Cancer (IARC), breast cancer has surpassed lung cancer as the most common cancer globally, with 2.3 million new cases in 2020 . More thThe early detection of breast cancer could significantly reduce mortality and the disease burden ,4. MammoHealth behavior theory can help to explain and alter the disproportionately low rates of screening . The heaProtection motivation theory (PMT) was proposed by Rogers based on HBM in 1975 . It is aNumerous studies have been conducted to investigate the factors that may affect women’s participation in breast screening ,33,34, bThis study aimed to determine the predictor factors associated with breast cancer screening intention among urban Chinese women, and identify the associations of PMT subconstructs with screening intention. The goal of our study was to provide an evidence base for designing intervention strategies for breast cancer screening in the future.A cross-sectional survey was conducted in 2020. This study is part of the Cancer Screening Program in Urban China (CanSPUC). This project was organized by the National Health and Family Planning Commission. Since 2012, screening programs for the five major types of cancer  have been carried out for risk factor investigation, high-risk population assessment, cancer screening, and health economics assessment. Our study was a breast cancer screening intention survey when screening high-risk groups at baseline. The high-risk population was identified by the Harvard Cancer Risk Index to calculate an individual risk score for breast cancer exposure, which included history of benign breast disease, family history of breast cancer, age at menarche, childbirth history, reproductive age, and breastfeeding history . The relThis study was conducted in Wuhan, the capital city of Hubei Province, an important central city in mainland China. Participants were selected using the convenient sampling method from five communities. All eligible participants who resided in the sampled communities were invited to participate in the study through WeChat (version 8.0.11) by staff of the community neighborhood committees. The inclusion criteria were as follows: (a) Aged 40–74 years and (b) willing to participate. Women with a history of breast cancer or suspected breast cancer were excluded. The study focused only on women aged 40–74 years, because epidemiological evidence demonstrated that the peak onset age for breast cancer in Chinese women is between 40 and 50 years, and women with an average risk of breast cancer should begin mammography at 40 years old . A totalData were collected in September and October, 2020. The survey was administered by trained graduate students from Wuhan University. After consent was obtained, data were collected through person-to-person interviews in the community health service center settings using pencil and paper questionnaires that had been pilot-tested, which took approximately 15 min. To minimize bias, all investigators received two-day professional training before distributing the surveys. The completed questionnaires were checked, verified, and recalled by the trained data collectors on the spot.The demographic variables included age (in years), education , marital status , occupation , history of benign breast disease (yes/no), and family history of breast cancer (yes/no). For the subsequent SEM analysis, education and occupation were merged into a latent variable called “social status”. Education was categorized into four scores . Occupation was categorized into five scores . The total score of “social status” was obtained by adding up the score of education and occupation, which ranged from 2 to 9. Similarly, history of benign breast disease and family history of breast cancer were merged into a latent variable called “medical history”. Each item was rated as “yes” (1 point) or “no” (0 point) and the points were combined to obtain a total score of “medical history” ranging from 0 to 2.The knowledge of breast cancer scale consists of 3 subscales. Knowledge of risk factors included seven items and was assessed by asking women to select “yes” or “no” to whether the items could increase the risk of breast cancer. Knowledge of symptoms included five items and was assessed by asking women whether the items were breast cancer signs. Knowledge of breast cancer screening included three items and assessed whether women were aware of mammography screening. For knowledge of breast cancer, each correct answer was given one point, with a maximum of 15 points.The Breast Cancer PMT Scale was developed by the authors based on a literature review and expert consultation. The reliability and validity of the scale were confirmed among Chinese women . The iteThe 17 items of the Breast Cancer PMT Scale were measured on a five-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). The mean score of each PMT subconstruct was computed from the individual items, and higher score represents a greater perception about that subconstruct.One item was used to assess screening intention by asking “Are you willing to participate in breast cancer screening in the future?” using a five-point scale ranging from 1 (very unwilling) to 5 (very willing). For our analyses, we integrated screening intention scores of “4” and “5” into “Yes”, which represented intention to participate in breast cancer screening; meanwhile, scores “1” to “3” were integrated into “No”, indicating no screening intention.t-tests. Pearson’s correlation was used to assess the relationship between the PMT constructs and screening intention. The structural equation model (SEM) was employed to assess the relationship between variables, and data model fitting was assessed using the following indexes: Goodness of fit index (GFI) > 0.9, adjusted GFI (AGFI) > 0.9, comparative fit index (CFI) > 0.9, root mean square error of approximation (RMSEA) < 0.08, standardized root mean residual (SRMR) < 0.05, and Chi-square/df < 5.0. The statistical significance level was set at p < 0.05. IBM SPSS statistics for windows (version 25.0) and Amos (version 21.0) were used for all analyses.Data were double entered in EpiData (version 3.2) after checking them manually. Errors identified by comparing the double data entries were resolved by referring to the paper records. We used descriptive statistics to summarize the sociodemographic characteristics of the study sample. Comparisons between groups were determined using the Chi-square or n = 412), 86.65% expressed the willingness to screen for breast cancer in the future. More than half (52.18%) of the participants were over 60 years old, and the majority (94.17%) were married. Approximately half (50.48%) of the participants had less than a senior high school education, and 47.57% were industrial/commercial/services workers. Of the whole sample, 65.53% had no personal history of benign breast disease, and 95.15% had no family history of breast cancer.The sociodemographic characteristics of the study sample are presented in t-tests showed that the knowledge score of breast cancer was significantly higher among those women with screening intention than those without (p < 0.05).r = 0.27, p < 0.01), fear arousal , response efficacy , response cost , and self-efficacy .As shown in p < 0.05), response cost , and self-efficacy  were significantly associated with breast cancer screening intention. Perceived severity measures the perceived negative consequences from breast cancer, response cost measures the perceived costs associated with breast cancer screening, and self-efficacy measures the perceived ability to take part in breast cancer screening.p < 0.05) and self-efficacy , while it was significantly negatively associated with response cost . In other words, knowledge can promote screening intention by increasing the perceived severity and self-efficacy, as well as reducing response cost.Of the four external factors, knowledge of breast cancer was indirectly associated with screening intention mediated by three significant PMT subconstructs. Knowledge was significantly positively associated with perceived severity  and self-efficacy , while medical history was significantly associated with response cost .Lastly, social status and medical history had indirect associations with screening intention mediated through different PMT subconstructs. Social status was significantly associated with perceived severity  and social status (education and occupation) were associated with various PMT subconstructs. For example, medical history was indirectly associated with screening intention mediated through response cost, so there was a lower probability of mammography among women with a medical history. One possible explanation is that fatalism is more common in women with a medical history . PreviouAs breast cancer remains an increasingly serious public health issue in China, understanding women’s screening intention and behavior is the key step to form tailored breast cancer screening and prevention strategies. The present study confirmed the important role of PMT in cancer screening interventions, which may be useful for healthcare workers to implement theory-guided strategies to increase the possibility of taking up screening. Importantly, we identified PMT constructs in the promotion of screening uptake, such as self-efficacy, perceived severity, and response cost, which should be considered targets for future intervention of breast cancer screening. More attention is also needed for women with a family history of breast cancer and history of benign breast disease. Moreover, popularizing knowledge about breast cancer is another strategy to promote screening participation for women.This study has several limitations. First, it was a cross-sectional design, so no causal relationships could be inferred, and longitudinal studies are required to further confirm our findings. Second, this study only included respondents from Wuhan, so the results cannot be generalized to other regions in China, a country with more than 1.4 billion citizens with diverse socioeconomic and cultural backgrounds. Future research should include larger samples and replicate and expand this work in urban settings. Lastly, although the reliability of the total PMT scale was acceptable, the Cronbach’s α coefficients for two PMT subconstructs were less than satisfactory: perceived risk (Cronbach’s α = 0.37) and fear arousal (Cronbach’s α = 0.66). Thus, the reliability of these two subconstructs should be improved in future research.Despite these limitations, this study examined the PMT’s predictive validity for breast cancer screening intention among Chinese urban women. It identified that self-efficacy, response cost, perceived severity, and knowledge as well as some demographic factors were significant predictors of breast cancer screening intentions. The findings of this study provide new data supporting more effective interventions to increase the uptake of breast screening.