Study On The Appropriate Breast Cancer Screening Technologies And Optimization Strategies For Chinese Women

ObjectivesFocusing on the bottlenecks faced by breast cancer screening in China,firstly,to systematically review current breast cancer screening guidelines and summarize corresponding recommendations in different countries,to provide the latest authoritative evidence for developing screening strategies in China.Secondly,to evaluate and compare the screening performance of three methods(including automated breast ultrasound[ABUS],handheld ultrasound[HHUS],mammography[MAM]),and the different combined strategies,to explore the optimal screening strategies for Chinese women at average risk;to analyze the appropriate biopsy strategies to reduce unnecessary biopsies of US 4a masses by supplementing the second-look MAM adjunct to US(HHUS or ABUS).Thirdly,to identify the frequency and related factors of loss or delay in the follow-up of screening abnormalities based on the real-world breast cancer screening program.Materials and methods1.Systematic review of global guidelines for breast cancer screening:"Breast cancer/breast neoplasms","mass screening/early detection",and"guidelines/recommendations" were searched as keywords in MEDLINE,EMBASE,Web of Science,Scopus,China National Knowledge Infrastructure(CNKI),WanFang Data from the date of creation to 1st May 2023 for breast cancer screening guidelines.All literature was independently examined by two experienced reviewers,and the core information was extracted to summarize the screening methods,age,and intervals for average-risk women and high-risk women,respectively.2.Effectiveness of breast cancer screening techniques and optimization strategies:Women aged 45-64 were recruited for breast cancer screening in six hospitals in China from 2018 to 2022.All participants underwent HHUS,ABUS,and MAM.The most severe suspicious finding among the three methods was taken for the referral.We simulated different screening algorithms based on three screening methods and compared their performance stratified by age and breast density.McNemar’s test assessed differences in the cancer detection rate(CDR),the false-positive biopsy rate,sensitivity,and specificity of different strategies.In addition,based on a multi-center evaluation study of ABUS for breast cancer detection compared with HHUS and MAM,we recruited women aged 40-69 years who underwent HHUS,ABUS,and MAM from 2016 to 2017 at five high-level hospitals in China.Logistic regression analysis assessed image variables correlated with false-positive lesions in US category 4a.Unnecessary biopsies,invasive cancer(IC)yields,and diagnostic performance among different biopsy strategies(integrated MAM to US 4a)were compared.3.Current status of follow-up management of real-world breast cancer screening program:A retrospective cross-sectional study was conducted based on case data from the four national breast cancer screening program sites from 2018-2021 for the 35-64 years old screening population,using a typical case study approach to investigate the current status of breast cancer screening follow-up management in the pilot sites.The study also compared the follow-up and timeliness rates of breast cancer screening programs in different pilot sites and applied logistic regression to analyze the factors influencing women’s missed and delayed follow-up.Results1.Systematic review of global breast cancer screening guidelines:A total of 26 guidelines issued between 2010 and 2022 in 11 countries or regions were identified for further review.For average-risk women,most of the guidelines recommended biennial mammographic screening for those aged 40-74 years.For women at higher risk,there was a consensus among most guidelines that annual MAM or annual MRI should be given,and the screening should begin earlier than the average-risk group.2.Effectiveness of breast cancer screening techniques and optimization strategies:19,171 participants aged 45-64 years(51.46±4.61)were included at the six sites from Feb 2018 to Aug 2022,of whom 76.47%were women with dense breasts.A total of 1,134 cases(5.92%)with the most severe diagnostic result of BI-RADS category 4-5 were detected by HHUS,ABUS,and MAM.72 cases were detected.The screen positive rates were higher for HHUS and ABUS than for MAM(all p<0.001).The differences in CDRs,sensitivity,and AUC values between HHUS and ABUS were not statistically significant(all p>0.0167).Compared to MAM alone,both MAM-negative plus HHUS and ABUS increased CDRs(3.66‰ vs 2.69‰,3.66‰ vs 2.69‰,all p<0.001).There was no significant difference in cancer yields between the two integration strategies.Compared with the current strategy of the National Breast Cancer Screening Program(NBCSP)(integrated MAM with HHUS BI-RADS 0 and 3),CDR,sensitivity,and AUC values were lower for other strategies(including MAM alone,HHUS alone,integrated MAM with HHUS-positive results,and integrated MAM with ABUS-positive results)while increased specificity and PPV3(all p<0.001).Parallel strategy(MAM and HHUS),integrated HHUS with MAM-negative results,and integrated MAM with HHUS-negative results strategies had higher screen positive rates and false positive biopsy rates than the current strategy(all p<0.001)while the differences between CDR were not statistically significant.In addition,the CDR and sensitivity of the current strategy were better than or equal to the other strategies among different age and breast density groups.Based on the head-to-head comparative study in five tertiary hospitals in China from Feb 2016 to Mar 2017,the false-positive rate of category 4a in ABUS was almost 65.81%,which was similar to HHUS(67.55%).For ABUS,compared to the current scenario,unnecessary biopsy rate was reduced without affecting IC yields when changing biopsy thresholds by adding MAM(BI-RADS 3.4,and 5)for US 4a in the total population(p<0.001;p>0.05).Notably,the IC yields of the new biopsy thresholds were not inferior to the current scenario for HHUS in women with less dense breasts(p=1.000)and those with palpable masses(p=0.063)while with a lower unnecessary biopsy rate(p<0.001).3.Current status of follow-up management of real-world breast cancer screening program:303,085 women aged 35-64 years who participated in the organized breast cancer screening program among four sites between 2018 to 2021 were included analysis.Both Boluo(site A)and Liling(site B)have one-stop screening services implemented by county-level maternal and child health centers,while only US and diagnostic MAM are available at maternal and child health centers in Ordos(site C).clinical breast examination and US are provided by each community health center and district-level maternal and child health centre in Shunyi(site D),with referrals to district-level maternal and child health centers for those requiring diagnosis(MAM and histopathological examination).The follow-up rate for the whole procedure between HHUS and the diagnostic tests varied among site A,site B,site C,and site D,with 98.04%,79.82%,23.37%,and 56.06%,and the timeliness of follow-up(≤60 d)among the total participants showed 77.85%,59.76%,21.02%,and 52.06%,respectively.Higher education level(high school and above)were contributing factors to follow-up or the timeliness of follow-up among women with abnormal results while older age(45-64 years),no previous history of breast disease,no previous screening,and premenopause were at risk factors(all p<0.05).ConclusionsGlobally,most guidelines recommended biennial mammographic screening between 40 and 74 years for average-risk populations and annual MAM or annual MRI starting from a younger age for high-risk populations.There is an urgent need to explore the development of screening guidelines based on high-quality clinical research evidence from localized clinical practice in China.The screening performance of the current breast cancer screening strategy of NBCSP(integrated MAM with HHUS categories 0 and 3)was better than or equal to the other strategies and it is suitable for application in the Chinese population.In addition,ABUS had the potential to be applied to average-risk women in China.Loss of follow-up on women with abnormal screening results was mostly attributed to inadequate and unconnected follow-up care service.By strengthening the integrated service system and focusing on the follow-up of delayed vulnerable groups,the accessibility and adherence rate of screening to the target population can be improved.This study can provide related evidence for policymakers to develop the appropriate screening strategy,to help promote the quality of breast cancer screening,especially in low-resource areas.