Transgender women experience gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. Transgender people undergo different surgical procedures and receive sex steroids hormones to reduce psychological distress and to induce and maintain desired physical changes. A search of the existing literature dedicated to hormone regimens used for treating male to female patients, their impact on breast tissue  and breast cancer risk provided the available information for this review. An evaluation of breast cancer risk is complicated because of the heterogeneity of administered treatments and a lack of long-term follow-up studies.Transgender women experience gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. Transgender people undergo different surgical procedures and receive sex steroids hormones to reduce psychological distress and to induce and maintain desired physical changes. These persons on feminizing hormones represent a unique population to study the hormonal effects on breast development, to evaluate the risk of breast cancer and perhaps to better understand the precise role played by different hormonal components. In MTF  patients, hormonal treatment usually consists of antiandrogens and estrogens. Exogenous hormones induce breast development with the formation of ducts and lobules and an increase in the deposition of fat. A search of the existing literature dedicated to hormone regimens for MTF patients, their impact on breast tissue (incidence and type of breast lesions) and breast cancer risk provided the available information for this review. The evaluation of breast cancer risk is currently complicated by the heterogeneity of administered treatments and a lack of long-term follow-up in the great majority of studies. Large studies with longer follow-up are required to better evaluate the breast cancer risk and to understand the precise mechanisms on breast development of each exogenous hormone. Transgender people experience gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity ,2,3,4. TThe female transgender landscape is heterogeneous in terms of populations and particularly complex in terms of treatments and follow-up ,13,14. TThe mammary gland develops through several distinct stages ,25,26.In humans, the earliest breast development occurs prenatally, is hormone independent and does not differ between sexes ,24. MorpProgesterone, in conjunction with GH and IGF1, also affects the development of the breast during puberty and thereafter ,39,40. TThe development and functional differentiation of the mammary gland represents a fantastic and highly complex morphogenetic process involving interactions between key hormones and multiple growth factors ,43,44  have been published ,18,51,52Hormone replacement therapy has become a cornerstone for the management of gender dysphoria in transgender patients. In transwomen, the major aim of hormone therapy is to better align their physical and psychological features with a more feminine expression phenotype . Sex horSupplementation with estrogens lowers testosterone concentrations because of negative feedback on the hypothalamic-pituitary gonadal axis. Conjugated estrogens and synthetic estrogens are not recommended because it is not possible to monitor their blood concentration and these drugs increase the risk of thromboembolism ,45,55. AMany patients will require the addition of an antiandrogen medication to inhibit testosterone production or to block the androgen receptor ,59,60.Different androgen receptor blockers can be used. Flutamide, which is administered in patients with prostate cancer, can be used at doses of 50–75 mg/day and is known to generate gynecomastia development. Spironolactone blocks androgens from binding to their receptors and increases both total and free estrogen levels, resulting in antiandrogenic properties. The drug is used at a dose of 100 to 200 mg/day with a maximum of 400 mg/day. Cyproterone acetate was used in MTF patients at doses of 50–100 mg/day, has stronger anti-androgenic effects than spironolactone, but can induce severe side effects such as depression and meningioma, so it is no longer recommended in transwomen .The place of progesterone remains controversial: a possible role to increase breast growth has not been demonstrated and the association of progesterone with estrogens increases the risk of cardiovascular diseases.GnRH (gonadotropin-releasing hormone) agonists are commonly prescribed in adolescents to block pubertal development ,61.The precise concentration that results in adequate feminization with the lowest risk of complications is not currently known ,62,63.Physical changes observed include softening of the skin, mood changes, decrease in libido and erections, fat redistribution at the hip, and growth of breast tissue . Up to 2The main side effects of taking estrogens are-An increased thromboembolic risk ;-Liver disorders;-Lipid abnormalities;-Depression and suicidal risk, which are high among transgender patients ,52,65,66-Breast cancer risk ,20,23,67The most commonly used drugs are presented in Benign breast lesions observed in male-to-female patients are essentially reported in case reports, except for data published in the Amsterdam Cohort . TherefoThe long-term effects of pharmaceuticals used for feminization in transwomen have not yet been sufficiently studied ,72.There is a certain parallelism between substitution treatments for cisgender women and feminization hormone treatments for transwomen. Nevertheless, some differences can be noted. Substitution treatments already have a long history ,74,75,76On the contrary, for endocrine treatments in transgender women, information is lacking, as there are no randomized studies. Some cohort studies are available but long-term follow-up is currently lacking. In Anglo-Saxon countries, conjugated estrogens are still regularly used, whereas European countries prefer natural compounds . To obtaConcerning the risk of breast cancer induced by feminization treatments, it should be noted that the doses used in transgender patients are higher than the doses used as replacement therapy in cisgender women .The issue of treatment duration has only been raised in a few publications and should be the subject of future studies.In the nationwide cohort study performed in the Netherlands, 2260 transwomen received gender-affirming hormone treatment. Fifteen cases of invasive breast cancer were identified ; this was 46-fold higher than in cisgender men  but lower than in cisgender women  ,82. The -GAHT is sometimes administered before surgical removal of birth-sex gonads, so the patient may have elevated serum levels of both masculinizing and feminizing hormones ,84.-Schedules of GAHT can vary widely by individual patient, with differences in the levels of hormones. These differences complicate the studies on the role of GAHT on breast cancer risk ,82,85.-As a general rule, the duration of GAHT in transwomen will far exceed the recommended duration of HRT in ciswomen, and this duration criteria needs to be taken into account and analyzed.Comparison between gender-affirming hormone therapy (GAHT) for transwomen and hormone replacement therapy (HRT) for cisgender women highlights the following differences:The transgender community is a particularly fragile community that is often discriminated against and does not always have access to quality health care ,85,86. AThere are currently no international established cancer screening guidelines for transgender patients at any point in their transition process ,13,22,23Breast cancer screening guidelines in cisgender women are an evolving area of medicine ,95,96. RScreening should be based on shared decision making, and patients and providers may want to start screening at an earlier age in patients with a significant family history ,94.BRCA1/2 mutations, etc.) [That is the reason Maglione et al. recommend screening based on risk factors  .On the contrary, Gooren et al. do not recommend screening for transwomen ,101. AccBrown et al. recommend similar screening to that in ciswomen: a mammography every two years between the ages of 50 and 69 .Therefore, the systematic review conducted by Hartley et al. could not make a universal recommendation due to the large number of case reports, the lack of meta-analysis, the significant variation in hormone treatment, the wide variability in treatment uptake and the lack of long-term follow-up .More recently, a cohort study was conducted in the Netherlands by the Medical University of Amsterdam in response to the increasing number of transwomen.As a result of this study, it is recommended that transwomen undergoing hormonal treatment for at least 5 years be followed up in a similar way to ciswomen .This recommendation is also applied in other countries. For example, in the Belgian hospital UZ Gent, which specializes in the treatment of transgender people, it is recommended to screen transwomen who have been on hormonal treatment for more than 5 years. This recommendation is also followed in Canada . Recomm.This review highlights the difficulties of establishing and measuring breast cancer risk among transgender women. It confirms the need to register as many transgender patients as possible and to carry out cohort studies with precise data on hormone treatments and long-term follow-up ,84,104.


Breast cancer is the most common malignant tumor in Chinese women, and its incidence is increasing. Regular screening is an effective method for early tumor detection and improving patient prognosis. In this review, we analyze the epidemiological changes and risk factors associated with breast cancer in China and describe the establishment of a screening strategy suitable for Chinese women. Chinese patients with breast cancer tend to be younger than Western patients and to have denser breasts. Therefore, the age of initial screening in Chinese women should be earlier, and the importance of screening with a combination of ultrasound and mammography is stressed. Moreover, Chinese patients with breast cancers have several ancestry-specific genetic features, and aiding in the determination of genetic screening strategies for identifying high-risk populations. On the basis of current studies, we summarize the development of risk-stratified breast cancer screening guidelines for Chinese women and describe the significant improvement in the prognosis of patients with breast cancer in China. In China, the incidence of female breast cancer continues to increase, thus endangering women’s health2. Breast cancer screening is an important method for secondary prevention. It facilitates early detection, diagnosis, and treatment of breast cancer, and effectively improves patient survival and prognosis4. Western countries began to standardize the breast cancer screening process earlier than China and have already established many screening guidelines for breast cancer13. However, the screening rate in women in China is much lower than that in Western countries, and a national screening program in China is difficult to establish14. Additionally, breast cancer shows clear differences according to ancestry: Chinese women have unique breast cancer risk factors, breast structure features, and characteristics of breast cancer onset16. Therefore, standard evidence-based screening guidelines suitable for Chinese women are needed to guide and promote breast cancer screening in China.Breast cancer is the most common malignant tumor worldwideIn this review, we systematically discuss the epidemiological and population characteristics of breast cancer in China. The risk factors and genetic features of Chinese patients are summarized. Furthermore, we elucidate the establishment of screening guidelines suitable for Chinese women.1. Among women, breast cancer accounts for 1 in 4 cancer cases and causes 1 in 6 cancer-related deaths. Globally, 1 in 18 women develops breast cancer in her lifetime17. Breast cancer also substantially influences Chinese society. GLOBOCAN 2020 included morbidity and mortality information for breast cancer from 23 Chinese cancer registries. In China, breast cancer is the cancer type with the highest incidence in women, with 416,371 new cases and 117,174 deaths in 2020, accounting for 18% of new cases and 17% of deaths worldwide, respectively18.Breast cancer incidence and mortality have increased in recent years. According to the Global Cancer Observatory (GLOBOCAN) 2020 estimates of cancer incidence and mortality, female breast cancer has become the most commonly diagnosed cancer and the fifth leading cause of death among all cancers, with an estimated 2.3 million new cases and 685,000 deaths per year24, we plotted the changes in breast cancer incidence and mortality in recent years in the United States and China. As illustrated in Figure 1, the incidence of female breast cancer has plateaued and is slowly increasing in the United States. One explanation for this finding is that widespread breast cancer screening with mammography at the end of the last century has reached a plateau in the United States5. The decrease in the use of hormone replacement therapy after menopause has also contributed to the stabilization of the incidence25. Besides, mortality due to breast cancer in the United States began to decrease with the standardization and popularization of breast cancer screening, as well as advances in treatment . Compared with those in the United States, the breast cancer incidence and mortality rates in China continue to rise . Therefore, China must establish a standardized breast cancer screening and early diagnosis system for early detection of breast cancer to reduce mortality.The United States and China have distinct trends in breast cancer incidence and mortality. Using nationwide statistics of cancer incidence and mortality from the International Agency for Research on Cancer and National Central Cancer Registry of China26. The former peak is greater, thus resulting in a young median age of onset. According to the GLOBOCAN 2020 estimates, the median age of onset in China is 50–54 years, which is much younger than the 60–64 years in Europe and the United States 27. An earlier median age of onset suggests that more women have breast cancer at younger ages in China. Consequently, patients require longer follow-up and treatment periods, and have fewer healthy life years, thus increasing the disease burden for both individuals and society. Therefore, Chinese women must start breast cancer screening at an earlier age to enable early detection of suspicious lesions, improve prognosis, and reduce the burden of disease.Compared with patients with breast cancer in Europe and the United States, Chinese patients have distinct features in the age of onset. Our previous research has revealed 2 age peaks of breast cancer onset in China: one at 45–55 years of age and the other at 70–74 years of ageIn summary, the incidence and mortality of breast cancer in Chinese women has been increasing, and the median age of onset is young, thus suggesting that breast cancer screening in Chinese women must be standardized and started earlier. The specific risk factors leading to these onset characteristics in Chinese women are also worthy of exploration.16. Since the family planning policy was enacted in the 1970s, the national total fertility rate (TFR) decreased dramatically from approximately 6 in the 1960s to 1.22 in 2000. The TFR has since increased to approximately 1.3, owing to relaxation of the policy28. The fertility rates in Northeast China, Beijing, and Shanghai are lowest, with a TFR of only approximately 0.7. Correspondingly, the incidence of breast cancer in Northeast China is highest: the age-standardized incidence rate by the world standard population (ASIRW) is 35.4/100,000, whereas the total ASIRW is 28.7/100,000. In addition, significant differences in TFR exist between urban and rural areas 29. The ASIRW of breast cancer is also significantly higher in urban than in rural areas 2. Therefore, according to both the temporal and spatial distribution, the decline in fertility rate is accompanied by an increase in breast cancer incidence. Moreover, the incidence of breast cancer is higher in regions with significantly lower fertility rates, thus suggesting that the decline in fertility rate is an important reason for the increase in breast cancer incidence in China. In addition to policy restrictions, later ages at marriage and postponement of childbearing are important reasons underlying the decrease in the TFR. Late marriage and pregnancy in China are attributed to the lifestyle changes resulting from the rapid development of Chinese society since the 21st century. Women who have more education, have higher labor participation, and pursue career development may choose marriage and pregnancy at older ages30. Therefore, these women have lower fertility rates and higher incidence of breast cancer, particularly in large cities such as Beijing and Shanghai.In China, a significant factor underlying the rapid increase in breast cancer incidence in recent decades is the decrease in the fertility rate among women33. In addition, hormone replacement therapy and oral contraceptives contribute to the development of breast cancer, but their effects are not as substantial as those of reproductive factors34. Moreover, risk factors associated with diet, obesity, and exercise, which have been recognized as crucial contributors to the increased incidence of breast cancer in Western countries, warrant more attention in China35. Recent data have shown a substantial increase in the prevalence of obesity in China in recent years and indicated that a “meat-sweet pattern” diet increases breast cancer risk in postmenopausal Chinese women37.In contrast, some risk factors in China are similar to those in Western countries, including reproductive and hormonal factors, as well as dietary factors. Early menarche, late maternal age at the birth of the first or last child, and long intervals between menarche and the birth of the first or last child are all associated with higher breast cancer risk, particularly in premenopausal women, whereas a lower rate of breastfeeding and late menopause are important risk factors for postmenopausal womenIn conclusion, breast cancer has distinct prevalence characteristics and risk factors in China. Consequently, targeted screening and early diagnosis strategies must be established for Chinese women.Table 1.Screening for breast cancer mainly relies on imaging techniques, most importantly mammography, ultrasound (US), and magnetic resonance imaging (MRI). The features, advantages, limitations, and performance of these imaging techniques are summarized in 53. Mammography has developed rapidly in recent decades, and digital mammography (DM) has gradually replaced conventional screen-film mammography.Mammography, the most widely used screening technique for breast cancer, provides a two-dimensional projection image of the breast. In general, mammography is performed with craniocaudal and mediolateral views of each breast54. Many meta-analyses have confirmed the efficacy of mammography. Since the application of mammography, the breast cancer mortality rate has decreased by approximately 20% in women over 40 years of age, and the effect is particularly significant in the older population, with a decrease of greater than 30% in women over 60 years of age55. However, limitations of mammography have also been observed. The sensitivity of mammography is relatively lower for women of young age with dense breasts49. In addition, overdiagnosis might increase with the increasing diagnostic rate of breast cancer in younger women with the widespread use of mammography56.Because of its recognized ability to enable the diagnosis of breast cancer, as well as its high sensitivity to microcalcifications in early breast cancer, convenience, and economical clinical application, mammography is now the most important method for the screening and early diagnosis of breast cancer, and the preferred method in various guidelinesMany new techniques have been developed and popularized in clinical practice to further improve the sensitivity and specificity of mammography, and minimize overdiagnosis.57. With postprocessing algorithms, 2D mammogram images are reconstructed from tomosynthesis images in synthetic mammography, which is equivalent to DM.DBT, also called 3D mammography, acquires a series of stacked images while the X-ray tube is pivoted in an arc in a plane aligned with the chest wall58. In DBT, compared with DM, the cancer detection rate is relatively higher in patients with high breast density or heterogeneous density60. Screening examinations with DBT are associated with a higher cancer detection rate and sensitivity, as well as a lower recall rate, thus decreasing false-positive rates and overdiagnosis61. In general, DBT may be a better choice than DM for breast cancer screening.This 3D imaging substantially decreases tissue stacking, thus enabling the discovery and localization of lesions hidden in high-density glands62.Although DBT performs better than DM for breast cancer screening, researchers have not conclusively determined whether DBT can replace DM, owing to its higher costs, radiation dosages, and acquisition and interpretation times63. The high-energy and low-energy images are postprocessed to generate the final recombined image of enhanced lesions in the breast.CEM is another emerging mammography technique that uses intravenous iodinated contrast agents to improve the visualization of tumor neovascularity. Dual-energy digital mammography provides a low-energy image, similarly to DM, and a high-energy image to detect the signal from the contrast agent45. CEM is only slightly less sensitive than MRI, but it provides higher specificity and a positive predictive value, as well as a similar ability to assess lesion size and disease extent66. Thus, in the future, CEM may be used as an alternative to MRI in breast cancer screening for women with moderate-to-high risk.With CEM, abnormal anatomical signs and the blood supply within lesions can be observed in the recombined images. Therefore, screening with CEM significantly increases the cancer detection rate in patients with dense breasts, and has a significantly higher sensitivity and specificity than screening with DM. No added benefit of using supplementary US examination has been shown68. In addition, the limitations of 2D mammography images still apply, because some deep breast lesions cannot be visualized63.However, compared with conventional mammography, CEM has several disadvantages, including a greater radiation dose and risk of adverse reactions to contrast agents69. Beyond conventional linear US, several advanced imaging techniques have been used to improve diagnostic ability. Color and power Doppler are important complementary tools for evaluating lesion vascularity. The demonstration of irregular branching vascularity and a greater number of peripheral vessels raises suspicion of malignant lesions71. US elastography can detect changes in the elasticity of soft tissues resulting from specific pathological processes. Higher lesion stiffness corresponds to a greater probability of malignancy72. In clinical practice, US is used mainly for supplementary screening in women with dense breasts and negative mammogram findings, and for localizing lesions identified by mammography or MRI for puncture biopsy74.Hand-held ultrasound (HHUS) is commonly used to examine breast diseases. One major advantage of US is its ability to distinguish breast cysts from malignant solid masses, thus helping avoid unnecessary biopsies69. In addition, US lacks standardized techniques and is time consuming. The diagnostic ability of US depends on the experience and ability of technologists, who must recognize lesions and thoroughly evaluate them through real-time scanning75.However, US also has limitations. First, the ability of US to indicate the nature of calcification is inferior to that of mammography76. ABUS separates the acquisition step from interpretation, thereby prolonging the interpretation time. However, ABUS is less dependent on the technologist’s experience than HHUS, and computer-aided detection software for ABUS has been developed for ease of interpretation77. ABUS has high sensitivity and specificity comparable to or better than that of HHUS, and it outperforms HHUS in the detection of architectural distortions82. Therefore, ABUS may be a promising early screening method replacing HHUS, particularly in settings lacking skilled technologists.Automated breast ultrasound (ABUS) is an advanced ultrasonography technique with high-frequency broadband transducers that provides 3D reconstructed images based on 3–5 views of each breast83.MRI is the most sensitive imaging technique for breast cancer screening. During the examination, women lie in the prone position with the breasts hanging free in the recesses of the coil, to allow the breast tissue to spread and minimize motion artifacts induced by breathing84. Time-signal intensity curves are highly valuable in assessing benign and malignant lesions, because malignant lesions exhibit a fast initial phase and rapid washout85. Ultrafast breast imaging is an advanced method that captures the fast early enhancement of malignancies within shorter acquisition times86. T2-weighted imaging performs well in revealing edema, a potential sign of malignancy87. Malignancies also show decreased water diffusion in diffusion-weighted imaging compared with normal tissue, thus leading to a higher signal intensity and a lower apparent diffusion coefficient88. In summary, multiparametric breast MRI provides high accuracy for the diagnosis of breast disease, and it has a better ability to detect invasive cancer than ductal carcinoma in situ84. Moreover, breast MRI can be used for multiplanar imaging of the breast, which specifically displays both the anatomical structure and the lesions. Small lesions and multiple scattered lesions are relatively easier to observe in MRI images, thus avoiding missed detection. Compared with DM alone or in combination with US, MRI substantially improves the sensitivity and cancer detection rate, and decreases interval cancers, particularly in women with dense breasts89.The MRI approach currently used for breast cancer screening is multiparametric breast MRI, which provides better differentiation between benign and malignant lesions. T1-weighted contrast-enhanced sequences are the basis for MRI protocols to illustrate vascularity within lesions50. Therefore, MRI is currently clinically used for breast cancer screening in women at high risk to avoid missed tumors90. Long examination times and high costs are also important factors limiting the wide application of MRI in breast cancer screening. Abbreviated MRI, an emerging technique, uses a shorter image acquisition and interpretation time, thus increasing the availability of breast MRI and decreasing costs91.However, the high sensitivity of MRI may come at the cost of low specificity and a high false-positive rateAs described, the various breast cancer screening techniques each have their own advantages and disadvantages, along with different detection abilities and indications. Therefore, standard evidence-based screening guidelines are needed to guide screening strategies for different populations.The formulation of breast cancer screening guidelines requires data support from many studies to determine the screening techniques, the initial age of screening, and the frequency of screening. On the basis of the results of many large-scale screening studies conducted in Europe and the United States, several institutions have developed breast cancer screening guidelines.10. However, other guidelines provide more conservative recommendations. The WHO and the European Breast Guidelines provide similar recommendations that women 50–69 years of age undergo biennial mammography screening12. The European Breast Guidelines also suggest biennial or triennial mammography screening for women 45–49 years of age and triennial mammography screening for women 70–74 years of age12. The U.S. Preventive Services Task Force (USPSTF) recommends biennial mammography screening for women 50–74 years of age. For women 40–49 years of age, mammography screening may yield false-positive results resulting in unnecessary biopsies and a higher risk of overdiagnosis. Therefore, the USPSTF recommends that women who place higher value on the potential benefits than the potential harms may choose to begin biennial screening at ages of 40–49 years13.For women with an average risk of breast cancer, among these guidelines, the American Cancer Society (ACS) breast cancer screening guidelines provide more active recommendations. The ACS strongly recommends that women start mammography screening annually at age 45 and transition to biennial screening at age 55 or continue screening annually. They also recommend that women 40–44 years of age be given the opportunity to begin screening92. Moreover, both the USPSTF and the European Breast Guidelines conclude that insufficient evidence supports that additional screening with DBT, HHUS, or ABUS for women with dense breasts provides benefits outweighing the added costs. However, the European Breast Guidelines suggest DBT for women recalled for suspicious lesions on a mammogram13.Regarding the selection of screening techniques, all these guidelines recommend mammography screening alone for women at average risk. The ACS and USPSTF recommend against breast self-examination for breast cancer screening, because evidence remains insufficient to assess the additional benefits and harms beyond mammography screeningBRCA germline mutation, women with a first-degree relative with a known BRCA germline mutation, and women with an over 20% lifetime risk of breast cancer, on the basis of risk estimation models11. Commonly used models for predicting an individual’s risk of breast cancer include BRCAPRO and BOADICEA, which focus primarily on family history and genetic factors, and the Tyrer-Cuzick and Gail models, which include classic risk factors93. Other conditions considered to be associated with a high risk of breast cancer include radiation to the chest at an age younger than 30 years; diagnosis of Li-Fraumeni, Cowden, or Bannayan-Riley-Ruvalcaba syndrome; and a personal history of breast lesions that are either malignant or benign95.In contrast, the ACS recommends breast MRI screening for women with a high risk of breast cancer. Annual mammography and MRI screening are recommended starting at 30 years of age for women with In summary, improved screening techniques, updated study evidence, and more detailed risk stratification will help establish better breast cancer screening guidelines.14. Clinicians lacked standard screening guidelines to guide their screening selection. However, Chinese women have significantly smaller and denser breasts than white women, particularly women younger than 50 years97. Because previous studies have found that higher breast density affects the sensitivity and screening efficacy of some screening techniques, screening strategies suitable for Chinese women must be established.In Chinese clinical practice, the selection of imaging-based screening was subjectively performed by clinicians referring to the screening strategies of Western countries, the breast features and personal history of patients, and facility conditions of hospitals99. Mammography is sensitive to microcalcification, but the sensitivity decreases significantly with increasing breast density. Lesions without calcification may be masked by dense fibroglandular tissue100. Compared with mammography, dense fibroglandular tissues are hyperechoic, and most lesions are hypoechoic on ultrasonograms. Therefore, US is not affected by higher breast density101. US may help identify the presence of an associated mass with suspicious calcification; its boundary, size, and shape; and the benign or malignant properties of lesions. US may also detect lesions on the edge or deep inside the breast, which may be missed on mammograms102. Rougher lesion margins and a lower lesion/glandular tissue stiffness ratio are often associated with lesions identified on ultrasonograms but not on mammograms103. Many international studies have shown that additional US with mammography for women with dense breasts improves sensitivity and increases the detection rate of cancer, particularly small, early-stage and lymph node-negative invasive cancer108. A randomized controlled trial in Japan has demonstrated that screening with mammography and ultrasonography has a significantly higher sensitivity than mammography alone (91.1% vs. 77.0%), with an incremental cancer detection rate of 1.7 per 1,000. Accordingly, the early diagnosis rate is increased, and interval cancer is decreased107. However, additional US screening may also decrease the specificity and increase the false-positive rates. This outcome is associated with indications for the selection of US98. A unified standard of indications for screening with US is not yet available.US can be used as an adjunct to mammography in screening women with dense breasts110. Table 2 summarizes the results of several other studies on combined US and mammography screening for breast cancer in China114, all showing higher sensitivity for mammography plus US. Together, these findings indicate the effectiveness of supplementary US in Chinese women. However, this greater sensitivity comes at the cost of lower specificity and a lower positive predictive rate. The lower specificity may result from the separate interpretation of the mammogram and US images, which also leads to a higher recall rate. A combined assessment helps improve specificity107.Because Chinese women generally have smaller and denser breasts than women in Western countries, the FUSCC conducted a study to evaluate whether the combined use of US and mammography might be more suitable for Chinese women. A total of 14,464 women 35–74 years of age participated in this Shanghai Society-based Breast Screening Program. All participants first underwent a clinical examination, and those with positive results and all women 45–69 years of age underwent biennial mammography and US screening. US was found to be most sensitive in women younger than 45 years, whereas mammography performed better in older women. The combined use of US and mammography increased the sensitivity from 67.3% of mammography alone to 79.3%, particularly in hormone receptor-positive breast cancer. In addition, the study concluded that mammography plus US screening for women 45–69 years of age and mammography alone for women older than 70 years is a more cost-effective screening strategy. Given the large population and limited resources in China, clinical breast examination (CBE) is an effective screening method for younger womenIn summary, the combined use of US and mammography can be a suitable strategy for Chinese women, particularly younger women and women with dense breasts. For women 45–69 years of age, this choice is a better and more cost-effective method. The screening guideline established in China have taken the above factors into account and recommend that women 45–69 years of age with average risk should undergo biennial mammography, and supplementary US screening after mammography should be performed in women with dense breasts. CBE is an effective method for early screening in Chinese women. More detailed screening strategies are discussed in the following sections.BRCA1/2 germline mutations are the most frequent germline mutations found in breast cancer and are present in approximately half of all patients with a family history of breast cancer115. BRCA1 germline mutation carriers have a 37.9% cumulative risk of developing breast cancer by the age of 70 years, and the risk is 36.5% for BRCA2 germline mutation carriers, which is approximately 10 times higher than that in the general population116. Table 3 summarizes different germline mutation frequencies of most frequently mutated genes between breast cancers in Chinese and white patients. Among all patients with breast cancer, approximately 5% carry BRCA1/2 germline mutations, and this percentage is similar in Chinese and white patients with breast cancers126. BRCA2 germline mutation is more frequently detected than BRCA1 in Chinese patients with breast cancer122. Approximately 3% of patients carry other germline mutations. PALB2 is present at a relatively high frequency of 1%118. ATM and CHEK2 are mutated more frequently in white breast cancer patients120. However, RAD51D germline mutation is more frequently present in Chinese patients and is particularly enriched in K91fs variants129. In addition, RAD51D germline mutation confers an increased breast cancer risk: carriers have a 20% cumulative risk of developing breast cancer by 80 years of age130. PTEN germline mutation is relatively rare in the Chinese population and is not recommended for genetic testing125.Genetic screening is another important method for screening breast cancer. A screen of germline mutations is useful to identify populations at high risk of developing breast cancer. BRCA1/2 mutation testing to better recognize possible BRCA germline mutations in patients with breast cancer and to alert affected relatives. The study has identified 5 risk criteria: TNBC, male breast cancer, bilateral breast cancers, early onset of breast cancer (diagnosed in patients younger than 40 years of age), and a family history of breast or ovarian cancer. Genetic testing is strongly recommended for patients with both a family history and either bilateral breast cancer or male breast cancer, as well as for patients with family history of at least 3 affected relatives. Moderate recommendations have been provided for patients with any 2 of 5 risk criteria or patients with family history of at least 2 affected relatives, and low recommendations have been provided for patients with any one of 5 risk criteria126. This pipeline has been applied in clinical diagnosis to recognize the genetic risk factors for patients with breast cancer and their relatives. Moreover, because its high cost makes DNA sequencing inaccessible for most people, FUSCC launched and developed an NGS panel called Fudan-BC panel, including 484 breast cancer-specific genes that are frequently mutated and are potential therapeutic targets in breast cancer. This panel aids in the preliminary detection of high-frequency germline mutations in more patients131.FUSCC has developed an NGS-based pipeline for Overall, the identification of the genomic characteristics and mutation profiles of breast cancer in China enables the identification of high-risk populations of breast cancer and the determination of indications for genetic testing. Moreover, genetic testing plays an important role in breast cancer risk stratification and screening.132. Therefore, a risk prediction model suitable for Chinese women is needed. FUSCC has developed a risk prediction model for breast cancer by analyzing information on various risk factors collected through a questionnaire, including family history and personal characteristics. This model has high predictive value, with an accuracy of 64.9%, a sensitivity of 79.0%, a specificity of 64.8%, and an area under receiver operating characteristic curve of 0.762133. Other researchers have built risk prediction models with an expected/observed ratio of nearly 1.0 and an area under the receiver operating characteristic curve exceeding 0.6135. These risk models could be applied for self-assessment and large-scale preliminary screening for breast cancer, but they would still require further improvement and exploration before being widely applied in clinical practice in the future.In addition to breast density and genetic factors, many other risk factors for breast cancer have been identified, as described above, including a history of benign breast disease. Stratification of these risk factors is important for the establishment of breast cancer screening strategies. The Gail model is widely used in Western countries. However, the predictive performance of this model in China is limited, because it may overestimate the risk in Asian women136. The recommended screening process is shown in Figure 3. Compared with other international guidelines, this guideline has several important features. First, because the peak age of breast cancer in Chinese women is younger than that in Western countries, the guideline recommends an earlier initial age of screening. Women 45–69 years of age with average risk should undergo biennial mammography, and women 40–44 years of age should undergo opportunistic screening. Second, because of the large population and limited resource settings in China, CBE is a preliminary screening method that can be used before imaging screening, particularly among women older than 50 years. The screening interval is biennial for women with an average risk of breast cancer. Moreover, the guidelines have additional recommendations for the use of US in breast cancer screening. Because of the high breast density in Chinese women, supplementary US screening after mammography in women with dense breasts is recommended. US is also recommended for women with a high risk of breast cancer but without genetic factors, such as US alone for women 40–44 years of age and US combined with mammography for women older than 45 years. This guideline also provides specific recommendations for women with high breast cancer risk. The guidelines divide high-risk women into 2 groups: those with a high-risk family history of breast cancer or pathogenic germline mutations, and those with other high-risk factors, such as a history of benign breast diseases or radiation therapy applied to the chest. MRI is primarily recommended for screening in the former group, whereas US and mammography screening are mainly recommended in the latter group, because this practice is more cost-effective138.According to the characteristics of breast cancer in Chinese women described above and with reference to international screening guidelines, the China Anti-Cancer Association has formulated breast cancer screening guidelines for Chinese womenThe establishment of breast cancer screening guidelines suitable for Chinese women has standardized the screening process in China, thereby improving the detection rate and early diagnosis of breast cancer, and the long-term survival rate of Chinese patients with breast cancer.Figure 4A). In addition, the number of patients undergoing breast-conserving surgery increased from 17.0% in 2008 to 28.3% in 2016, and the percentage of patients opting for reconstruction after mastectomy increased from 3.5% to 8.2% . Moreover, with the development of sentinel lymph node biopsy (SLNB), more patients can preserve axillary lymph nodes after biopsy. The percentage of patients undergoing only SLNB markedly increased from 6.9% in 2008 to 57.9% in 2016 . Importantly, the early detection of breast cancer and the use of less invasive surgical modalities have increased the long-term survival rates among patients. The 5-year overall survival rate of patients treated at FUSCC increased from 94.6% to 96.3%, and the 5-year disease-free survival rate increased from 85.9% to 88.5% (4E). In conclusion, standardized breast cancer screening reduces the burden of breast cancer treatment and substantially improves the survival and prognosis of patients with breast cancer.Breast cancer screening has important effects on the diagnosis and treatment of breast cancer. Through the standardized application of breast cancer screening methods recommended by the guidelines, the FUSCC has made substantial achievements in breast cancer screening and early diagnosis. The stage of cancer at diagnosis decreased from 2008 to 2016. According to the TNM staging system, the percentage of patients diagnosed with stage I disease increased significantly, from 30.5% to 39.4%  is another trend expected in future screening. AI systems can assist radiologists in image interpretation, thus substantially improving the accuracy. Many studies have shown that AI systems simultaneously improve sensitivity and specificity, decrease false-positive and false-negative rates, more accurately identify invasive cancer, and are robust for breast cancer screening145. Furthermore, AI systems may be used to predict the personalized risk of breast cancer. The assessment of personalized risk prediction is based on combined assessment of an individual’s risk factors and breast images149. This approach facilitates risk stratification for breast cancer screening and thus guides the use of appropriate screening methods for different women. In addition, with greater understanding of tumor molecular characteristics, some tumor genomic and epigenomic features may serve as biomarkers for breast cancer. In this regard, liquid biopsy to detect these features may become an important method for breast cancer screening151. Combined with advances in multiomics studies, breast cancer screening and recognition are expected to become more precise.Over the past 20 years, breast cancer screening in China has begun to receive attention and has gradually been standardized, thus enabling the achievements described above. In this development process, progress in science and technology has played a crucial role in promoting breast cancer screening. Updated screening techniques make breast cancer screening more accurate and convenient. Advanced mammography techniques such as DBT and CEM have substantially improved the sensitivity for detecting malignancies in dense breasts. ABUS has enabled US screening to become more convenient and universal. New MRI techniques have also simplified the MRI screening procedures. The advances in, and comprehensive use of, these screening techniques have greatly improved the sensitivity and specificity of cancer detection, and increased the accuracy of distinguishing benign from malignant lesions. Future technical progress is also expected to minimize the existing disadvantages, such as the harm due to use of radiation and contrast agents, to better benefit the public. The development of high-throughput sequencing technologies will allow for simultaneous sequencing of multiple pathogenic genes and even the whole exome or the entire genome of a patientChina is continually updating and refining breast cancer screening guidelines suitable for Chinese women. In addition to technological innovation, more large-scale cohort studies in the Chinese population are needed to obtain additional evidence and establish better screening strategies suitable for the Chinese population. Furthermore, standardized breast cancer screening will substantially increase the survival of patients with breast cancer in China and reduce mortality.Breast cancer screening and early diagnosis in China are being standardized and popularized. This review highlights the background and the establishment of breast cancer screening strategies in China. The unique demographic and genetic characteristics of breast cancer in China summarized in this review have provided an important basis for the Chinese breast cancer screening guidelines. This knowledge will help guide future related studies and further improvement of breast cancer screening guidelines in China. Evidence-based and standardized breast cancer screening programs will play important roles in improving the prognosis of patients with breast cancer.


The MyPeBS study is an ongoing randomised controlled trial testing whether a risk-stratified breast cancer screening strategy is non-inferior, or eventually superior, to standard age-based screening at reducing incidence of stage 2 or more cancers. This large European Commission-funded initiative aims to include 85,000 women aged 40 to 70 years, without prior breast cancer and not previously identified at high risk in six countries . A specific work package within MyPeBS examines psychological, socio-economic and ethical aspects of this new screening strategy. It compares women’s reported data and outcomes in both trial arms on the following issues: general anxiety, cancer-related worry, understanding of breast cancer screening strategy and information-seeking behaviour, socio-demographic and economic characteristics, quality of life, risk perception, intention to change health-related behaviours, satisfaction with the trial.At inclusion, 3-months, 1-year and 4-years, each woman participating in MyPeBS is asked to fill online questionnaires. Descriptive statistics, bivariate analyses, subgroup comparisons and analysis of variations over time will be performed with appropriate tests to assess differences between arms. Multivariate regression models will allow modelling of different patient reported data and outcomes such as comprehension of the information provided, general anxiety or cancer worry, and information seeking behaviour. In addition, a qualitative study (48 semi-structured interviews conducted in France and in the UK with women randomised in the risk-stratified arm), will help further understand participants’ acceptability and comprehension of the trial, and their experience of risk assessment.Beyond the scientific and medical objectives of this clinical study, it is critical to acknowledge the consequences of such a paradigm shift for women. Indeed, introducing a risk-based screening relying on individual biological differences also implies addressing non-biological differences  from an ethical perspective, to ensure equal access to healthcare. The results of the present study will facilitate making recommendations on implementation at the end of the trial to accompany any potential change in screening strategy.https://clinicaltrials.gov/ct2/show/NCT03672331Study sponsor: UNICANCER. My personalised breast screening (MyPeBS). Clinicaltrials.gov (2018) available at: Contact: Cécile VISSAC SABATIER, PhD, + 33 (0)1 73 79 77 58 ext + 330,142,114,293, contact@mypebs.eu.The online version contains supplementary material available at 10.1186/s12885-022-09484-6. Breast cancer is the leading cause of death among women worldwide . Breast Since the risk of developing breast cancer varies widely among women , risk-based approaches to breast cancer screening have recently emerged as promising cancer prevention strategies –9. TheseThe MyPeBS studyThis study is relevant to address the relative impact of risk-stratified screening for several reasons. First, it is a very large study, with 85,000 women to be randomised. Second, each of the countries in the MyPeBS study have a routine screening programme in which the study is inserted, and against which any additional benefits and harms of risk-stratified screening can be readily compared. Third, it takes place across six different countries with differing screening programmes, healthcare organisations, cultures and ethnic minority populations. Given this, any comparisons of the two approaches to screening will take into account these background factors, to allow the conclusions to be generalisable across countries, or to flag up where caution is needed in making generalisations.If they were to be implemented on a population scale, risk-stratified breast screening programmes would have to adhere to gold standards of the Wilson and Jungner criteria  and addiThe first objective of the research is to assess the emotional impact of risk communication on women. Amongst the potential harms of risk-stratified screening are undue increases in general anxiety or distress related to cancer. The results from a previous study assessing effects of breast cancer risk-stratification found little evidence for elevated distress, although risk information was communicated approximately three years after information on risk factors was elicited from participants . The preThe second objective aims to assess women’s comprehension of the information provided within MyPeBS, and their willingness to search for further information. One particular aim will be to test whether there is a correlation between women’s information comprehension level, information-seeking behaviours and their sociodemographic and socio-economic characteristics. As risk-based approaches rely on information and schedules that are more complex, it is essential that all decisions made in the context of screening programmes are informed and based on sound understanding of the information provided. Therefore, is it important to assess whether individuals have access to sufficient and clear information to decide to participate and to understand the proposed programme.The third objective is to analyse MyPeBS participants' socio-economic and demographic characteristics as well as quality of life, to assess whether they are representative of the social heterogeneity of the participating countries, and whether these characteristics influence screening perceptions, uptake and behaviours, such as compliance with the proposed breast cancer screening programmes. This relates to a more general aim stated in previous research  to identThe fourth objective is to assess perception of risk of breast cancer, and perceptions of efficacy and risks of prevention options , 25. UptThe fifth objective aims at measuring overall satisfaction with the trial, and the acceptability of the risk-based approach, should it be implemented at a population scale. First, it is necessary to assess if women are satisfied with this new screening proposal, and with the organisation of the clinical trial, whether they are in the risk-stratified arm or in the standard arm. Furthermore, it is critical to collect women’s feedback on the information and communication materials that they receive throughout the trial, in order to anticipate future needs raised by the large-scale implementation of this new strategy.We aim to compare women in the risk-stratified arm and in the standard arm of MyPeBS, on the following issues: (1) anxiety and cancer worry; (2) understanding of breast cancer screening strategy and information seeking behaviour; (3) socio-demographic and economic characteristics and quality of life; (4) risk perception and intention to change behaviour; (5) acceptability and satisfaction of the trial.In addition to the aforementioned issues which will be assessed globally and for each country, one further objective will be to compare the issues between countries. One of the strengths of the MyPeBS trial is the participation of six countries with specificities in terms of recruitment, local organisation of the trial and type of healthcare professionals involved. Adopting a comparative and contextualised perspective when analysing the results on acceptability of the trial, anxiety and cancer worry, understanding and information-seeking behaviours, equity, risk perception and intentions to change behaviour will offer a more nuanced view on the psychological and socio-economic issues at stake with risk-based approaches.In order to meet the described objectives, this work package was designed with two complementary methodologies: a quantitative approach with questionnaires administered to each woman participating in MyPeBS, and a qualitative study consisting of 48 semi-structured interviews conducted with women randomised in the risk-stratified arm in France and in the UK. The use of qualitative methods, in addition to quantitative measures, is recommended in guidance on process evaluation , as the The quantitative questionnaires will provide measures for the previously stated objectives, at various time points during the trial. Qualitative methods will help further investigate perceptions of risk-stratified screening and collect feedback on the trial from the participants. This qualitative work will give insight into how acceptable women found the process of being offered risk-stratified screening, and their experiences of participating in the trial.The multi-disciplinary structure of the research team  enriched the design of the methodology of this study. The methodology was reviewed and validated by the project’s executive committee and then approved by ethics committees in each participating country. Data collection and processing are compliant with the European General Data Protection Regulation.th July 2019 and inclusion is still ongoing.Women from the general population  aged 40 to 70 are eligible if they live in a participating area from one of the six participating countries. Women are either invited to participate by the organised breast screening programme structures in each participating country or by a healthcare professional, or she can self-volunteer; indeed, information about the study was disseminated in healthcare providers’ premises , in the media, and through health insurances’ newsletters. Candidates who are interested in participating in the trial and who are eligible with respect to the inclusion and exclusion criteria are registered and randomised via an online dedicated web platform , and receive a unique identification code that ensures anonymity of data treatment. The participants’ informed consent is obtained by the recruiter before any study-related procedures are performed. The first participant was included on 18For the qualitative substudy, participants who undergo risk-stratified screening in the MyPeBS trial are recruited by letters sent via screening centres in Manchester (UK) and in the regions of Paris and North of France (France). Study in the UK attempts to recruit a range of women from different levels of socio-economic status. Further informed consent is gained by the study researcher before participants take part in the qualitative study.Psychosocial questionnaires see Fig.  are admin = 24) and in the UK (n = 24). The aim is to recruit six women per risk group , in order to reach data saturation for each of those. Recruitment in France will be carried out with the help of Haut-de-France’s and Ile-de-France’s Regional centres for coordinating cancer screening (CRCDC). Recruitment in the UK will be carried out with help from the Manchester University NHS Foundation Trust (MFT). The interviews will provide an in-depth account of women’s views and experiences of the breast cancer screening programme and allow investigation of how healthcare systems and cultural differences affect acceptability of the proposition.For the qualitative study, the research team will conduct 48 semi-structured interviews with women in the risk-stratified arm of the trial, both in France  between the two experimental groups.Among the questionnaires selected, most are validated questionnaires previously used, some of them in different languages. Appropriate licences have been obtained.Several questionnaires were created to fit this study aims: the comprehension questionnaire, the information seeking-behaviour questionnaire and the satisfaction questionnaires were built according to previously described methodologies –29. WhenIn order to assess if increased distress is a harm of risk-stratified breast cancer screening, the research team will compare the levels of general anxiety and cancer-specific worry between women who receive risk-stratified screening and women who receive standard screening. Cancer-specific worry measures seem to be more sensitive to the effects of receiving risk information than more general measures of anxiety , 31. By The Lerman Cancer worry scale questionnaire has been used in similar studies evaluating cancer risk assessment and clinical programmes , 35. TheThere is also evidence that both general anxiety and cancer-related worry peak shortly after receiving information on cancer risk and then gradually decline , 31. ForAs levels of anxiety might be affected if women have their mammogram the day they fill in those questionnaires, information on whether or not a mammogram is planned on the day of inclusion will be collected.Patients' understanding of health information is a key issue in the exercise of their autonomy, and an ethical principle. This is why different texts—including legal, such as informed consent, or deontological, such as the code of medical ethics or the patient's charter—specify that the physician must provide the patient with a clear, fair and appropriate information on his or her health state, and on the investigations and care proposed. Providing information to the patient and ensuring that he or she understands is a necessary, even if not sufficient, condition for informed or shared decision-making to occur, and is a major public health issue, including in the case of breast cancer screening –38.For all of these reasons, we decided to assess the comprehension of the information provided in MyPeBS. A comprehension questionnaire was developed based on our previous studies , 39 and The comprehension questionnaire will be administered to women at three months and four years. In order to test if responses are not due to pure chance, a Q Cochran test will be used to assess this.Based on previous research conducted by our research team on French cancer survivors’ living conditions, we decided to explore women's information-seeking behaviours. This research showed that patients’ comprehension of information provided is related to their information-seeking behaviours . PatientOur questionnaire asks whether women searched for information in the first place, their reasons for doing so, and the type of information they looked for . Some questions also relate to breast cancer screening in general, and to risk-stratified breast cancer screening issues in particular.As this questionnaire was developed for use in this specific study, the questions were piloted  amongst the same group of ten women and with the same methods as the ones used for the comprehension questionnaire.The information-seeking behaviour questionnaire is administered at three months and four years to all participants of MyPeBS.As previously underlined, it is essential that all decisions made as part of breast cancer screening are informed and based on sound understanding of good quality information provided. A key element of understanding is how accurately women perceive their own risk of breast cancer following risk-stratified screening, and whether this has been improved, relative to standard screening. For these reasons, we will assess perception of risk of breast cancer, and perceptions of efficacy and risks of different prevention options, to assess the constructs of Protection Motivation Theory, a theory that aims to understand how risk information can translate into behaviour change or not . Uptake To estimate comparative risk and comparative severity scores, participants are asked to choose a category indicating their perceived risk of invasive breast cancer over the next ten years, compared to the population’s average (comparative risk). They are also asked to evaluate, if they were to get breast cancer, how severe they think this would be (comparative severity) on a five-point scale from lower to higher risk.The behaviour change questions evaluate three different behaviours relating to reducing breast cancer risk: improving diet, increasing physical activity and attending mammography appointments. Five-point scales are used to measure Response Efficacy (the perception of how much the behaviour would reduce the participant’s risk of breast cancer) and Self-Efficacy (how easy or difficult it would be to enact these behaviours). To calculate the intention to change behaviour scores, participants are asked three questions assessing their intention to change the three health-related behaviours on a five-point scale, from “strongly disagree” to “strongly agree” .To assess women’s quality of life, we use the EQ-5D licensed by EuroQoL research foundation. This European quality of life tool is a validated pre-scored multi-attribute health status scale that has been used in a wide range of populations and situations, including breast cancer screening –49. It iThe EQ-5D is administered at baseline and at four years to analyse and compare women’s quality of life between the two screening options, i.e. standard versus personalised breast cancer screening, and between groups of different risk levels. We will thus explore whether women who underwent risk-stratified screening have a better quality of life than women who underwent standard screening. Quality of life among different socio-economic subgroups will also be compared and related to breast cancer screening compliance, using both aggregated and unaggregated measures (i.e. considering the five dimensions of the EQ-5D separately) of quality of life, based on the responses to the EQ-5D questionnaire.This questionnaire is an evaluation of the overall satisfaction of women with their participation in the study, with the information provided and communication tools used, and with the overall organisation of the trial. The intention to participate in the study is assessed at one year and actualised at four years. Analyses will consider the dropout rate. The questionnaire is an adapted version of a satisfaction questionnaire on organisation of the screening process and the information received, validated by Bairati et al.  and currThe characteristics of women participating in MyPeBS versus those taking part in the current population-based screening programmes will be analysed and compared, in terms of socio-demographics  and socio-economic status. In particular, we will focus on social inequalities by using the nine items version of the Material Deprivation Index (MDI), keeping in mind that socio-economic deprivation is a well-established determinant for low uptake and low compliance to cancer screenings  includinThe MDI is an aggregated measure of deprivation validated in many European countries, based on the EU-SILC survey that has already been used to assess inequalities in cancer screening access . This inThe MDI score is calculated by scoring 1 if the person answers “no, I cannot afford it” to the item and then by summing all items (thus the MDI ranges between 0 and 9). A threshold value of three of the MDI is used to classify individuals into “material deprivation” and a threshold of is used to classify individuals into “severe material deprivation”.The impact of socio-demographics and deprivation levels on women's adherence to schedule during the trial will be analysed. Women’s socio-demographic and socio-economic characteristics will be analysed at baseline and four years and will be compared to the characteristics of women taking part in the current population-based screening.Participants will be asked about how acceptable they found the risk-stratified process, their understanding of the purpose of each phase, how they experienced receiving their risk category, if they would recommend this type of screening to their friends or family, and how the process could be improved. Demographic information to describe the sample of participants will be collected on the same occasion as the main interview. Interviews will last approximately one hour and will be conducted face-to-face, via telephone or video call, according to the Covid-19 sanitary situation and restriction measures.With the consent of participants, interviews will be audio-recorded and transcribed in the languages in which they were conducted, using an accredited transcription company, to ensure data security. Interviews conducted in French will then be translated into English, since it is the language used for the analysis. All transcribed interviews will be checked by the research team to ensure accuracy and to remove information that could allow the identification of interviewees.The quantitative analysis plan see  includesThe qualitative data will support the interpretation of findings from the quantitative data. It will use framework analysis, a form of thematic analysis that facilitates the handling of large qualitative datasets . It invoDissemination of the study results will include the publication of research papers. A more direct feedback to investigators and to participants is planned at various stages of the trial.st, 2021, 22,884 participants have been included and randomised in the trial and have completed baseline questionnaires. Inclusion for the qualitative study started in November 2021 in France and will start in March 2022 in the UK.As of December 31The Covid crisis resulted in a six-months suspension of trial enrolment as of March 2020, and still has a major detrimental impact on the recruitment, as successive epidemic waves continue to hinder both women and healthcare teams to participate in the study. Furthermore, when the enrolment reopened, one of the priorities was to reduce participants' time on site as much as possible. It was therefore decided to have women complete the first two questionnaires  at the inclusion site prior to randomisation, while the other questionnaires could be completed afterwards, either at the inclusion site or at home. This allowed the scientific requirements for assessing anxiety levels to be maintained prior to the start of the study, while adapting the conditions of inclusion to the health context.One point to note is that the French Ethics committee limited the range of questionnaires proposed to women in France, due to concerns around heightened anxiety after answering the STAI-6 (Q1) and Lerman cancer worry scale (Q2). These questionnaires, however, will be administered in the five other countries taking part in the trial.Along with investigating women’s perceptions of risk-based approaches and the socio-economic issues raised by this new form of screening, feedback is also needed on professionals’ perceptions of the MyPeBS trial and more generally on risk-based approaches. There is a dearth of research on clinicians’ views on implementing such approaches . With thBeyond the scientific and medical objectives of this clinical study, it is critical to pay attention to the consequences of such a paradigm shift for women on the one hand and for professionals on the other. Indeed, introducing a risk-based screening relying on individual biological differences also implies acknowledging non-biological differences  from an ethical perspective to ensure equal access to healthcare , 55. ThuAdditional file 1. N°1 list of Ethical Committees involved in MyPeBS. Additional file 2. N°2 list of study sites involved in MyPeBS.