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INTRODUCTION: Prophylactic antibiotic (PPA) usage is a common practice in breast cancer surgery. However, there is limited information on the global patterns of antibiotic usage in this setting. This study aimed to investigate the prevalence and preferences of PPA usage in breast cancer surgery among surgeons across different continents. METHODS: A multicontinental survey study was conducted among 295 surgeons who were actively involved in breast cancer surgery around the world. The survey collected information on PPA usage, preferred antibiotic choice, and factors influencing antibiotic prescribing patterns. RESULTS: The survey revealed that PPA usage was widespread, with an overall prevalence of 89% among respondents. Cephalosporins were the most preferred antibiotics for prophylaxis. Antibiotic usage was similar and high among surgeons practicing in Europe (90%), in Asia (87%), and in other continents (91%). Academic surgeons and those dedicating a larger portion of their practice to breast cancer surgery reported a more frequent use of PPAs. Surgeons with >25 y of practice had the lowest rate of PPA use. CONCLUSIONS: This multicontinental survey study highlights the high prevalence of PPA usage in breast cancer surgery among surgeons around the world, with cephalosporins being the preferred choice. Furthermore, academic surgeons and those specializing in breast cancer surgery were more likely to prescribe PPAs. These findings provide valuable insights into the current practices and trends in antibiotic usage in breast cancer surgery, emphasizing the need for further research and guidelines to optimize antibiotic stewardship in this surgical setting.
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OBJECTIVE: Breast cancer is the leading cancer in women in terms of incidence and mortality. The literature currently identifies several risk factors, some modifiable and others not. Because of its multifactorial nature, the combination of factors either increases or reduces the risk of cancer. Since 2004, the first commission's rapport of the French National Environmental Health Plan has recognized the significant impact of occupational exposure on the development of breast cancer. However, neither primary nor secondary preventive measures have yet been implemented in work environment. METHOD: Based on available literature, we reviewed current knowledge of breast cancer risk factors associated with occupational exposure. RESULTS: The risk factors identified were ionizing radiation, magnetic fields, certain endocrine disruptors, ethylene oxide and night shift work. CONCLUSION: Recognition of breast cancer as an occupational disease is complicated. In some cases, however, it may be possible, particularly in cases of multifactorial exposure. This work should help to raise awareness among employers and reinforce preventive measures in the workplace.
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BACKGROUND: Early hormone-positive breast cancers typically have favorable outcomes, yet long-term surveillance is crucial due to the risk of late recurrences. While many studies associate MMP-11 expression with poor prognosis in breast cancer, few focus on early-stage cases. This study explores MMP-11 as an early prognostic marker in hormone-positive breast cancers. METHODS: In this retrospective study, 228 women with early hormone-positive invasive ductal carcinoma, treated surgically between 2011 and 2016, were included. MMP-11 expression was measured by immunohistochemistry, and its association with clinical and MRI data was analyzed. RESULTS: Among the patients (aged 31-89, median 60, with average tumor size of 15.7 mm), MMP-11 staining was observed in half of the cases. This positivity correlated with higher uPA levels and tumor grade but not with nodal status or size. Furthermore, MMP-11 positivity showed specific associations with MRI features. Over a follow-up period of 6.5 years, only 12 oncological events occurred. Disease-free survival was linked to Ki67 and MMP-11. CONCLUSION: MMP-11, primarily present in tumor-surrounding stromal cells, correlates with tumor grade and uPA levels. MMP-11 immunohistochemical score demonstrates a suggestive trend in association with disease-free survival, independent of Ki67 and other traditional prognostic factors. This highlights the potential of MMP-11 as a valuable marker in managing early hormone-positive breast cancer.
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Neoplasias de la Mama , Humanos , Femenino , Supervivencia sin Enfermedad , Neoplasias de la Mama/diagnóstico por imagen , Antígeno Ki-67 , Metaloproteinasa 11 de la Matriz , Estudios Retrospectivos , Imagen por Resonancia Magnética , HormonasRESUMEN
Breast cancer is the most common female cancer in the world. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of formal breast self-examination (BSE) as opposed to breast awareness has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: The Commission of Senology (CS) of the Collège National de Gynécologie et Obstétrique Français (CNGOF) respected and followed the Grading of Recommendations Assessment, Development and Evaluation method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE versus abstention from this examination led to detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from clinical breast examination by practitioners from the age of 25, and from organized screening from 50 to 74 (strong recommendation). In the absence of data on the benefits of BSE in patients aged over 75, for those at high risk and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these categories wish to undergo BSE, information on the benefits and risks observed in the general population must be given, notably that BSE is associated with a higher number of referrals, biopsies, and a reduced quality of life.
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Neoplasias de la Mama , Autoexamen de Mamas , Detección Precoz del Cáncer , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Anciano , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Francia , Adulto , Ginecología , Obstetricia , Ginecólogos , ObstetrasRESUMEN
OBJECTIVES: Forums are a source of health information and exchange. They can be studied to determine patients' needs and improve caregivers' practices. The aim of this study was to identify the needs of breast cancer patients based on messages posted on a discussion forum. METHODS: Initial messages posted in 2021 on the Ligue nationale contre le cancer (LNCC) breast cancer forum were analyzed quantitatively. Message content was classified into three categories: testimonial, request for advice or request for medical opinion. The tone of the message (positive, neutral, or negative) was recorded. The temporality of the illness during which the patient expressed herself was defined. Analysis was carried out on the initial messages using the Chi2, Fisher, and Kruskal-Wallis tests, with a significance level of<0.05. RESULTS: In 2021, 640 initial messages posted on the LNCC forum dedicated to breast cancer were analyzed. Messages were posted by 312 authors, including 275 patients and 37 family members. Three main types of messages were identified: requests for medical advice (n=339), advice (n=164), and testimonials (n=137). Requests for medical advice elicited fewer responses than testimonials (P<0.001). A need for supportive care was identified in 42.8% of messages, mostly concerning social (17.3%) and psychological (13%) care. CONCLUSION: Our study revealed a need for more information especially regarding the social impact of the disease and the side-effects of treatment. The period of greatest need of information was the diagnostic waiting time. However, patients using discussion forums are not representative of all women with breast cancer and our results should not be generalized to all patients treated for breast cancer.
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Neoplasias de la Mama , Cuidadores , Humanos , Femenino , Persona de Mediana Edad , FranciaRESUMEN
OBJECTIVES: Upper limb lymphedema secondary to breast cancer treatment is the leading cause of lymphedema in France. Despite improved surgical practices and de-escalation of radiotherapy, the risk of lymphedema after breast cancer still affects 5-20% of patients, with this variation depending on the measurement method used and the population studied. Lymphedema has a negative impact on quality of life and body image, and their possible occurrence remains a major concern for all women treated for breast cancer. The Sénologie Commission of the Collège national des gynécologues et obstétriciens français (CNGOF) asked four specialists in breast surgery or lymphology to prepare a summary on the prevention, medical and surgical management of lymphedema after breast cancer treatment, and to discuss the medical and surgical innovations currently being evaluated. METHODS: This synthesis was based on national and international guidelines on the management of upper limb lymphedema after breast surgery and a recent review of the literature focusing on the years 2020-2023. RESULTS: From a preventive point of view, the restrictive instructions imposed for a long time (reduction in physical activity or the carrying of loads, air travel, exposure to the sun or cold, etc.) have altered patients' quality of life and should no longer be recommended. A good understanding of risk factors enables us to target preventive actions. Examples include obesity, a sedentary lifestyle, axillary clearance, radiotherapy of the axillary fossa in addition to axillary clearance, total mastectomy, taxanes or anti-HER-2 therapies in the adjuvant phase. Resumption of physical activity, minimally invasive axillary surgery, de-escalation of radiotherapy and breast-conserving surgical procedures have all demonstrated their preventive value. When lymphedema does occur, early management, through complete decongestive physiotherapy, can help reduce its volume and prevent its long-term worsening. CONCLUSION: Surgical (lymph node transplants, lympho-vascular anastomoses) and medical (prolymphangiogenic growth factors) approaches to lymphedema treatment are numerous, but require long-term evaluation of their efficacy and adverse effects.
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Neoplasias de la Mama , Linfedema , Humanos , Femenino , Neoplasias de la Mama/cirugía , Mastectomía/efectos adversos , Calidad de Vida , Mama , Linfedema/etiología , Linfedema/prevención & controlRESUMEN
OBJECTIVES: The indications and modalities of breast and axillary surgery are undergoing profound change, with the aim of personalizing surgical management while avoiding over-treatment. To update best practices for axillary surgery, four questions were selected by the Senology Commission of the Collège National des Gynécologues et Obstétriciens Français (CNGOF), focusing on, firstly, the definition and evaluation of targeted axillary dissection (TAD) techniques; secondly, the possibility of surgical de-escalation in case of initial lymph node involvement while performing initial surgery; thirdly, in case of surgery following neo-adjuvant systemic therapy (NAST), and fourthly, contra-indications to de-escalation of axillary surgery to allow access to particular adjuvant systemic therapies. METHODS: The Senology Commission based its responses primarily on an analysis of the international literature, clinical practice recommendations and national and international guidelines. RESULTS: Firstly, TAD is a technique that combines excision of clipped metastatic axillary node(s) and the axillary sentinel lymph nodes (ASLNs). The detection rate and sensitivity are increased but it still needs to be standardized and practices better evaluated. Secondly, TAD represents an alternative to axillary clearance in cases of metastatic involvement of a single node that can be resected. Thirdly, neither TAD nor ASLN alone is recommended in France after NAST outside of clinical trials, although it is used in several countries in cases of complete pathological response in the lymph nodes, and when at least three lymph nodes have been removed. Fourthly, as some adjuvant targeted therapies are indicated in cases of lymph node invasion of more than three lymph nodes, the place of TAD in this context remains to be defined. CONCLUSION: Axillary surgical de-escalation can limit the morbidity of axillary clearance. Having proved that TAD does not reduce patient survival, it will most probably replace axillary clearance in well-defined indications. This will require prior standardization of the method and its indications and contra-indications, particularly to enable the use of new targeted therapies.
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Neoplasias de la Mama , Escisión del Ganglio Linfático , Humanos , Femenino , Ganglios Linfáticos/cirugía , Neoplasias de la Mama/cirugía , Mama , Terapia Combinada , Respuesta Patológica CompletaRESUMEN
OBJECTIVES: Breast oncology genetics emerged almost 30 years ago with the discovery of the BRCA1 and BRCA2 genes. The evolution of analytical practices has progressively allowed access to tests whose results now have a considerable impact on the management of both female and male breast cancers. The Sénologie commission of the Collège national des gynécologues et obstétriciens français (CNGOF) asked five specialists in breast surgery, oncology and oncological genetics to draw up a summary of the oncogenetic testing criteria used and the clinical implications for the female and male population of the test results, with or without an identified causal variant. In the case of proven genetic risk, surveillance, risk-reduction strategies, and the specificities of surgical and medical management (with PARP inhibitors in particular) were updated. METHODS: This summary was based on national and international guidelines on the monitoring and therapeutic management of genetic risk, and a recent review of the literature covering the last five years. RESULTS: Despite successive technical developments, the probability of identifying a causal variant in a situation suggestive of a predisposition to breast and ovarian cancer remains around 10% in France. The risk of breast cancer in women with a causal variant of the BRCA1, BRCA2, PALB2, TP53, CDH1 and PTEN genes is estimated at between 35% and 85% at age 70. The presence of a causal variant in one of these genes is the subject of different recommendations for men and women, concerning both surveillance, the age of onset and imaging modalities of which vary according to the genes involved, and risk-reduction surgery, which is possible for women as soon as their risk level exceeds 30% and remains exceptionally indicated for men. In the case of breast cancer, PARP inhibitors are a promising new class of treatment for BRCA germline mutations. CONCLUSION: A discipline resolutely focused on understanding molecular mechanisms, screening and preventive medicine/surgery, oncology genetics is currently also involved in new medical/surgical approaches, the long-term benefits/risks of which will need to be monitored.
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Neoplasias de la Mama , Predisposición Genética a la Enfermedad , Femenino , Humanos , Masculino , Anciano , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Neoplasias de la Mama/epidemiología , Genes BRCA2 , Factores de RiesgoRESUMEN
OBJECTIVES: Breast cancer is the most frequent and deadly cancer among women. In France, 50% of adults are currently overweight, mostly as a result of a sedentary lifestyle. Numerous studies have highlighted overweight, obesity and lack of physical activity as risk factors for the occurrence and prognosis of cancers, particularly breast cancer. The aim of this study was to understand the extent to which physical activity can improve this prognosis, and what the pathophysiology is. METHODS: The Senology Commission of the Collège national des gynécologues et obstétriciens français (CNGOF) based its responses on an analysis of the international literature using a Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) methodology conducted on the PubMed database between 1994 and 2023. RESULTS: A total of 70 articles were selected, demonstrating the role of regular physical activity in reducing the risk of breast cancer occurrence and recurrence. This role in controlling carcinogenesis is mediated by metabolic factors such as leptin, adiponectin and insulin, sex hormones and inflammation. The signaling pathways deregulated by these molecules are known carcinogenic pathways which could be used as therapeutic targets adapted to this population, without replacing the essential hygienic-dietary recommendations. CONCLUSION: Physical activity has a protective effect on breast cancer risk and prognosis. We must therefore continue to raise awareness in the general population and promote physical activity as a means of primary, secondary, and tertiary prevention.
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Neoplasias de la Mama , Adulto , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , Sobrepeso , Mama , Ejercicio Físico , FranciaRESUMEN
OBJECTIVES: Breast surgery is the cornerstone of breast cancer treatment. Its indications and procedures are constantly evolving. To update best practices, four questions were submitted to the Senology Commission (SC) of the Collège national des gynécologues et obstétriciens français (CNGOF), covering the indications and modalities of tumor surgery: (1) initially, (2) following neoadjuvant systemic treatment, (3) in case of local recurrence, and (4) the quality and safety of care indicators applicable to this surgery. METHODS: The CNGOF SC essentially based its responses on the clinical practice recommendations and guidelines of the French Cancer Institute concerning invasive carcinomas of the breast. Exclusion criteria were carcinoma in situ, sarcoma and axillary surgery. RESULTS: To define the type of breast surgery, knowledge of four parameters is essential: the patient's level of risk, the presence of metastases, the size of the breast tumor and its focality (assessed by the clinical/mammography/ultrasound tripod). (1) In the case of initial management, the 6 indications for mastectomy are patient choice (particularly in case of high risk), contraindication to radiotherapy, inflammatory cancer (T4d), surgery with positive margins (after several surgical intervention), surgery that cannot be performed as a monobloc in the case of tumors with multiple foci, and poor expected aesthetic results. All other situations should be treated conservatively. (2) The same criteria apply after neoadjuvant systemic treatment, with conservative treatment still possible whatever the size (excluding carcinomatous mastitis) and focality of the initial tumor. (3) In case of local recurrence, total mastectomy is the reference treatment, with a second conservative treatment reserved for patients with no risk factors for a second recurrence, and no poor prognostic factors, after validation in a multidisciplinary meeting. (4) Four quality and safety indicators apply to breast surgery: it must be performed after obtaining a histological diagnosis, within less than 6 weeks of mammography, in a single surgery in over 80% of cases, and followed by local radiotherapy in the case of conservative treatment. CONCLUSION: The indications and modalities of breast surgery are evolving rapidly. To improve aesthetic results, oncoplastic techniques, immediate breast reconstruction, and preservation of the skin or nipple-areolar complex need to be further developed and evaluated in the long-term. These developments must necessarily be accompanied in France by a training policy for breast surgeons.
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Neoplasias de la Mama , Femenino , Humanos , Axila , Mama , Neoplasias de la Mama/cirugía , Mamografía , MastectomíaRESUMEN
OBJECTIVES: Breast cancer is the most common female cancer in the world. In France, over 60,000 new cases are currently diagnosed, and 12,000 deaths are attributed to it annually. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of breast self-examination (BSE) has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: the CNGOF's Commission de Sénologie (CS), composed by 17 experts and 3 invited members, drew up these recommendations. No funding was provided for the development of these recommendations. The CS respected and followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions concerning BSE, individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE compared with abstention from this examination led to the detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from a clinical breast examination (by the attending physician or gynecologist) from the age of 25, and from organized screening from 50 to 74 (strong recommendation). However, in the absence of data on the role of BSE in patients aged over 75, those at high risk of breast cancer and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these latter categories wish to undergo BSE, they must be given rigorous training in the technique, and information on the benefits and risks observed in the general population. Finally, the CS invites all women who detect a change or abnormality in their breasts to consult a healthcare professional without delay. CONCLUSION: BSE is not recommended for women in the general population. No recommendation can be established for women aged over 75, those at high risk of breast cancer and those previously treated for breast cancer.
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Objective: Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives. Materials and Methods: The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives. Results: Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy.In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials. Conclusion: Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women.
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PURPOSE: A considerable amount of valuable information is present in electronic health records (EHRs) however it remains inaccessible because it is embedded into unstructured narrative documents that cannot be easily analyzed. We wanted to develop and evaluate a methodology able to extract and structure information from electronic health records in breast cancer. METHODS: We developed a software platform called Onconum (ClinicalTrials.gov Identifier: NCT02810093) which uses a hybrid method relying on machine learning approaches and rule-based lexical methods. It is based on natural language processing techniques that allows a targeted analysis of free-text medical data related to breast cancer, independently of any pre-existing dictionary, in a French context (available in N files). We then evaluated it on a validation cohort called Senometry. FINDINGS: Senometry cohort included 9,599 patients with breast cancer (both invasive and in situ), treated between 2000 and 2017 in the breast cancer unit of Strasbourg University Hospitals. Extraction rates ranged from 45 to 100%, depending on the type of each parameter. Precision of extracted information was 68%-94% compared to a structured cohort, and 89%-98% compared to manually structured databases and it retrieved more rare occurrences compared to another database search engine (+17%). INTERPRETATION: This innovative method can accurately structure relevant medical information embedded in EHRs in the context of breast cancer. Missing data handling is the main limitation of this method however multiple sources can be incorporated to reduce this limit. Nevertheless, this methodology does not need neither pre-existing dictionaries nor manually annotated corpora. It can therefore be easily implemented in non-English-speaking countries and in other diseases outside breast cancer, and it allows prospective inclusion of new patients.
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Neoplasias de la Mama , Registros Electrónicos de Salud , Humanos , Femenino , Algoritmos , Estudios Prospectivos , Procesamiento de Lenguaje Natural , Minería de Datos/métodosRESUMEN
BACKGROUND: Epidemiological data indicate that the role of environmental factors on breast cancer (BC) incidence remains undetermined. Our daily life exposure to aluminium (Al) is suspected to influence BC development. This review proposes a state of the art on the association between Al and BC risk combined with a critical point of view on the subject. METHODS: We searched the PubMed database using terms related to Al and BC up to November 18, 2022. Reports were eligible if they were cohort or case-control studies or meta-analyses. FINDINGS: Six studies focused on the relationship between deodorant and antiperspirant use and BC incidence and didn't produce consistent results. Among 13 studies relating Al content in mammary tissues and BC risk, results are not unanimous to validate higher Al content in tumor tissues compared to healthy ones. We detail parameters that could explain this conclusion: the absence of statistical adjustments on BC risk factors in studies, the confusion between deodorant and antiperspirant terms, the non-assessment of global Al exposure, and the focus on Al in mammary tissues whereas a profile of several metals seems more appropriate. The clinical studies are retrospective. They were carried out on small cohorts and without a long follow-up. On the other hand, studies on cell lines have shown the carcinogenic potential of aluminum. Moreover, studies considered BC as a unique group whereas BC is a heterogeneous disease with multiple tumor subtypes determining the tumor aggressiveness. CONCLUSION: In light of the precautionary principle and based on the data obtained, it is better to avoid antiperspirants that contain Al. Deodorants without aluminum are not implicated in breast cancer, either clinically or fundamentally.
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Neoplasias de la Mama , Desodorantes , Humanos , Femenino , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Antitranspirantes/efectos adversos , Desodorantes/efectos adversos , Aluminio/efectos adversos , Estudios RetrospectivosRESUMEN
CONTEXT: Adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) is debated as benefits are inconstant. Molecular signatures for DCIS have been developed to stratify the risk of local recurrence (LR) and therefore guide the decision of RT. OBJECTIVE: To evaluate, in women with DCIS treated by BCS, the impact of adjuvant RT on LR according to the molecular signature risk stratification. METHODOLOGY: We conducted a systematic review and meta-analysis of five articles including women with DCIS treated by BCS and with a molecular assay performed to stratify the risk, comparing the effect of BCS and RT versus BCS alone on LR including ipsilateral invasive (InvBE) and total breast events (TotBE). RESULTS: The meta-analysis included 3478 women and evaluated two molecular signatures: Oncotype Dx DCIS (prognostic of LR), and DCISionRT (prognostic of LR and predictive of RT benefit). For DCISionRT, in the high-risk group, the pooled hazard ratio of BCS + RT versus BCS was 0.39 (95%CI 0.20-0.77) for InvBE and 0.34 (95%CI 0.22-0.52) for TotBE. In the low-risk group, the pooled hazard ratio of BCS + RT versus BCS was significant for TotBE at 0.62 (95%CI 0.39-0.99); however, it was not significant for InvBE (HR = 0.58 (95%CI 0.25-1.32)), Discussion: Molecular signatures are able to discriminate high- and low-risk women, high-risk ones having a significant benefit of RT in the reduction of invasive and in situ local recurrences, while in low-risk ones RT did not have a benefit for preventing invasive breast recurrence. The risk prediction of molecular signatures is independent of other risk stratification tools developed in DCIS, and have a tendency toward RT de-escalation. Further studies are needed to assess the impact on mortality.
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Pathological complete response (pCR) after neoadjuvant systemic treatment (NST) is an important prognostic factor in HER2-positive breast cancer. The majority of HER2-positive breast cancers are amplified at the HER2 gene locus, several genes are co-amplified with HER2, and a subset of them are co-expressed. The STARD3 gene belongs to the HER2 amplicon, and its role as a predictive marker was never addressed. The objective of this study was to investigate the predictive value of STARD3 protein expression on NST pathological response in HER2-positive breast cancer. In addition, we studied the prognostic value of this marker. METHODS: We conducted a retrospective study between 2007 and 2020 on 112 patients with non-metastatic HER2-positive breast cancer treated by NST and then by surgery. We developed an immunohistochemistry assay for STARD3 expression and subcellular localization and determined a score for STARD3-positivity. As STARD3 is an endosomal protein, its expression was considered positive if the intracellular signal pattern was granular. RESULTS: In this series, pCR was achieved in half of the patients. STARD3 was positive in 86.6% of cases and was significantly associated with pCR in univariate analysis (p = 0.013) and after adjustment on other known pathological parameters (p = 0.044). Performances on pCR prediction showed high sensitivity (96%) and negative predictive value (87%), while specificity was 23% and positive predictive value was 56%. Overall, specific, relapse-free, and distant metastasis-free survivals were similar among STARD3 positive and negative groups, independently of other prognosis factors. CONCLUSION: NST is an opportunity for HER2-positive cancers. In this series of over a hundred HER2-positive and non-metastatic patients, a STARD3-negative score was associated with the absence of pathological complete response. This study suggests that determining STARD3 overexpression status on initial biopsies of HER2-positive tumors is an added value for the management of a subset of patients with high probability of no pathological response.