6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7).

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking. Each guideline is accompanied by the level of evidence (LoE), grade of recommendation (GoR) and percentage of consensus reached at the consensus conferences. Updated diagnostic and treatment algorithms are also provided. The guidelines represent the best management options for patients living with ABC globally, assuming accessibility to all available therapies. Their adaptation (i.e. resource-stratified guidelines) is often needed in settings where access to care is limited.

Evaluation of SARS-CoV-2 interferon gamma release assay in BNT162b2 vaccinated healthcare workers.

To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies.

Breast cancer highlights from 2023: Knowledge to guide practice and future research.

This narrative work highlights a selection of published work from 2023 with potential implications for breast cancer practice. We feature publications that have provided new knowledge immediately relevant to patient care or for future research. We also highlight guidelines that have reported evidence-based or consensus recommendations to support practice and evaluation in breast cancer diagnosis and treatment. The scope of selected highlights represents various domains and disciplines in cancer control, from prevention to treatment of early and advanced breast cancer.

EUSOMA quality indicators for non-metastatic breast cancer: An update.

INTRODUCTION: Quality care in breast cancer is higher if patients are treated in a Breast Center with a dedicated and specialized multidisciplinary team. Quality control is an essential activity to ensure quality care, which has to be based on the monitoring of specific quality indicators. Eusoma has proceeded with the up-dating of the 2017 Quality indicators for non-metastatic breast cancer based on the new diagnostic, locoregional and systemic treatment modalities. METHODS: To proceed with the updating, EUSOMA setup a multidisciplinary working group of BC experts and patients' representatives. It is a comprehensive set of QIs for early breast cancer care, which are classified as mandatory, recommended, or observational. For the first time patient reported outcomes (PROMs) have been included. As used in the 2017 EUSOMA QIs, evidence levels were based on the short version of the US Agency for Healthcare Research and Quality. RESULTS: This is a set of quality indicators representative for the different steps of the patient pathway in non-metastatic setting, which allow Breast Centres to monitor their performance with referring standards, i.e minimum standard and target. CONCLUSIONS: Monitoring these Quality Indicators, within the Eusoma datacentre will allow to have a state of the art picture at European Breast Centres level and the development of challenging research projects.

Treatment and outcomes in breast cancer patients: A cross section study from the EUSOMA breast centre network.

INTRODUCTION: The present study was designed to describe tumour features and treatments for patients with breast cancer. It also aimed at assessing the risk of distant metastases in relation to biological profiles, disease stages and treatment. METHODS: Data were analysed from 81,882 patients in the EUSOMA database (disease stages at diagnosis 0-IV; median age 61 years; range 20-100 years). All patients were treated between January 2016 and December 2021 in 53 Breast Centres within the EUSOMA certification process in 13 European countries. Cases were classified as HR+ /HER2-, HR+ /HER2 + , HR-/HER2 + or HR-/HER2- and data were analysed accordingly. RESULTS: Univariable and multivariable analyses for distant metastases were conducted on a subset of 38,119 cases with information on whether or not they had developed them. Potential determinants included sub-group type, Ki67 value, disease stage, adjuvant systemic therapies and post-operative radiation therapy. In multivariable analysis, the HR-/HER2 + and HR-/HER2- sub-groups were associated with a higher risk of distant metastases than HR+ /HER2-. Ki67 > 20 % and advanced stage disease also carried a high risk. Radiation therapy emerged as a protective factor against distant metastases. CONCLUSIONS: Present results show a large patient database offers an information stream that can be applied to reduce uncertainties in clinical practice. Database parameters need to be updated dynamically for outcome monitoring. Molecular prognostic factors, gene-expression signatures, tumour-infiltrating lymphocytes and circulating tumoral DNA should be added.

Effects of exercise training on cancer patients undergoing neoadjuvant treatment: A systematic review.

OBJECTIVES: This systematic review aimed to analyze the effects of different exercise protocols on physical fitness (cardiorespiratory fitness, muscle strength, and body composition), quality of life, cancer-related fatigue, and sleep quality in patients with different types of cancer undergoing neoadjuvant treatment. DESIGN: Systematic review. METHOD: A comprehensive search of existing literature was carried out using four electronic databases: PubMed, Scopus, Web of Science, and Cochrane Library (published until October 19, 2022). All databases were searched for randomized controlled trials, quasi-experimental investigations, and pre-post investigations assessing the effects of exercise in cancer patients during neoadjuvant treatment. Excluded articles included multicomponent interventions, such as exercise plus diet or behavioral therapy, and investigations performed during adjuvant treatment or survivorship. The methodological quality of each study was assessed using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: Twenty-seven trials involving 999 cancer patients were included in this review. The interventions were conducted in cancer patients undergoing neoadjuvant treatment for rectal (n = 11), breast (n = 5), pancreatic (n = 4), esophageal (n = 3), gastro-esophageal (n = 2), and prostate (n = 1) cancers, and leukemia (n = 1). Among the investigations included, 14 utilized combined exercise protocols, 11 utilized aerobic exercise, and two utilized both aerobic and resistance training separately. Exercise interventions appeared to improve cardiorespiratory fitness, muscle strength, body composition, and quality of life, although many investigations lacked a between-group analysis. CONCLUSION: Despite limited evidence, exercise interventions applied during neoadjuvant treatment demonstrate promising potential in enhancing cardiorespiratory fitness, muscle strength, body composition, and overall quality of life. However, a scarcity of evidence remains on the effects of exercise on cancer-related fatigue and sleep quality. Further research with high-quality randomized controlled trials is warranted.

Evaluating the ability of an artificial-intelligence cloud-based platform designed to provide information prior to locoregional therapy for breast cancer in improving patient's satisfaction with therapy: The CINDERELLA trial.

BACKGROUND: Breast cancer therapy improved significantly, allowing for different surgical approaches for the same disease stage, therefore offering patients different aesthetic outcomes with similar locoregional control. The purpose of the CINDERELLA trial is to evaluate an artificial-intelligence (AI) cloud-based platform (CINDERELLA platform) vs the standard approach for patient education prior to therapy. METHODS: A prospective randomized international multicentre trial comparing two methods for patient education prior to therapy. After institutional ethics approval and a written informed consent, patients planned for locoregional treatment will be randomized to the intervention (CINDERELLA platform) or controls. The patients in the intervention arm will use the newly designed web-application (CINDERELLA platform, CINDERELLA APProach) to access the information related to surgery and/or radiotherapy. Using an AI system, the platform will provide the patient with a picture of her own aesthetic outcome resulting from the surgical procedure she chooses, and an objective evaluation of this aesthetic outcome (e.g., good/fair). The control group will have access to the standard approach. The primary objectives of the trial will be i) to examine the differences between the treatment arms with regards to patients' pre-treatment expectations and the final aesthetic outcomes and ii) in the experimental arm only, the agreement of the pre-treatment AI-evaluation (output) and patient's post-therapy self-evaluation. DISCUSSION: The project aims to develop an easy-to-use cost-effective AI-powered tool that improves shared decision-making processes. We assume that the CINDERELLA APProach will lead to higher satisfaction, better psychosocial status, and wellbeing of breast cancer patients, and reduce the need for additional surgeries to improve aesthetic outcome.

Skin deformation analysis for pre-operative planning of DIEAP flap reconstruction surgery.

Deep inferior epigastric artery perforator (DIEAP) flap reconstruction surgeries can potentially benefit from augmented reality (AR) in the context of surgery planning and outcomes improvement. Although three-dimensional (3D) models help visualize and map the perforators, the anchorage of the models to the patient's body during surgery does not consider eventual skin deformation from the moment of computed tomography angiography (CTA) data acquisition until the position of the patient while in surgery. In this work, we compared the 3D deformation registration from supine arms down (CTA position) to supine with arms at 90° degrees (surgical position), estimating the patient's skin deformation. We processed the data sets of 20 volunteers with a 3D rigid registration tool and performed a descriptive statistical analysis and statistical inference. With 2.45 mm of root mean square and 2.89 mm of standard deviation, results include 30% cases of deformation above 3 mm and 15% above 4 mm. Pose transformation deformation indicates that 3D surface data from the CTA scan position differs from data acquired in loco at the surgical table. Such results indicate that research should be conducted to construct accurate 3D models using CTA data to display on the patient, while considering projection errors when using AR technology.

The Lucerne Toolbox 2 to optimise axillary management for early breast cancer: a multidisciplinary expert consensus.

Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.

Augmented Reality in Breast Surgery Education.

Introduction: Augmented reality (AR) has demonstrated a potentially wide range of benefits and educational applications in the virtual health ecosystem. The concept of real-time data acquisition, machine learning-aided processing, and visualization is a foreseen ambition to leverage AR applications in the healthcare sector. This breakthrough with immersive technologies like AR, mixed reality, virtual reality, or extended reality will hopefully initiate a new surgical era: that of the use of the so-called surgical metaverse. Methods: This paper focuses on the future use of AR in breast surgery education describing two potential applications (surgical remote telementoring and impalpable breast cancer localization using AR), along with the technical needs to make it possible. Conclusion: Surgical telementoring and impalpable tumors noninvasive localization are two examples that can have success in the future provided the improvements in both data transformation and infrastructures are capable to overcome the current challenges and limitations.

The current role of nuclear medicine in breast cancer.

Breast cancer is the most common cancer in females worldwide. Nuclear medicine plays an important role in patient management, not only in initial staging, but also during follow-up. Radiopharmaceuticals to study breast cancer have been used for over 50 years, and several of these are still used in clinical practice, according to the most recent guideline recommendations.In this critical review, an overview of nuclear medicine procedures used during the last decades is presented. Current clinical indications of each of the conventional nuclear medicine and PET/CT examinations are the focus of this review, and are objectively provided. Radionuclide therapies are also referred, mainly summarising the methods to palliate metastatic bone pain. Finally, recent developments and future perspectives in the field of nuclear medicine are discussed. In this context, the promising potential of new radiopharmaceuticals not only for diagnosis, but also for therapy, and the use of quantitative imaging features as potential biomarkers, are addressed.Despite the long way nuclear medicine has gone through, it looks like it will continue to benefit clinical practice, paving the way to improve healthcare provided to patients with breast cancer.

Correction: Effectiveness of Secondary Risk-Reducing Strategies in Patients With Unilateral Breast Cancer With Pathogenic Variants of BRCA1 and BRCA2 Subjected to Breast-Conserving Surgery: Evidence-Based Simulation Study.

[This corrects the article DOI: .].

Effects of home-based exercise programs on physical fitness in cancer patients undergoing active treatment: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This systematic review and meta-analysis aimed to investigate the effects of home-based exercise on physical fitness (cardiorespiratory fitness, muscle strength, and body composition) in cancer patients undergoing active treatment. DESIGN: Systematic review with meta-analysis and Grading Recommendations Assessment, Development, and Evaluation of the evidence. METHODS: A comprehensive search of existing literature was carried out in four electronic databases: PubMed, Web of Science, Scopus, and PEDro. All databases were searched for randomized controlled trials assessing the effects of home-based exercise on physical fitness outcomes in cancer patients during active treatment. Multicomponent interventions (i.e., exercise plus diet/behavioral therapy) were excluded. The methodological quality of each study was assessed using the Revised Cochrane risk-of-bias tool for randomized trials. Meta-analytical procedures were performed when appropriate and standardized mean differences (SMD) were calculated. RESULTS: Twenty-eight randomized controlled trials (n = 2424 cancer patients) were included. Most of the interventions were conducted in breast cancer patients (n = 13) during the adjuvant treatment period (n = 17); 18 studies included a walking component in their home-based protocol. Home-based exercise was effective at improving the distance of the 6-minute walk test (k = 6; SMD = 0.321, p = 0.010). However, the results were no longer significant when performing sensitivity analysis based on exclusively walking (k = 1) and non-exclusively walking interventions (k = 5; SMD = 0.258; p = 0.072). No effects were found for muscle strength and body composition outcomes (p > 0.05). CONCLUSIONS: Regular home-based exercise programs are an effective strategy to improve 6-minutes walk test in cancer patients undergoing active treatment. Conversely, no alterations were found in muscle strength and body composition.

Effectiveness of Secondary Risk-Reducing Strategies in Patients With Unilateral Breast Cancer With Pathogenic Variants of BRCA1 and BRCA2 Subjected to Breast-Conserving Surgery: Evidence-Based Simulation Study.

BACKGROUND: Approximately 62% of patients with breast cancer with a pathogenic variant (BRCA1 or BRCA2) undergo primary breast-conserving therapy. OBJECTIVE: The study aims to develop a personalized risk management decision support tool for carriers of a pathogenic variant (BRCA1 or BRCA2) who underwent breast-conserving therapy for unilateral early-stage breast cancer. METHODS: We developed a Bayesian network model of a hypothetical cohort of carriers of BRCA1 or BRCA2 diagnosed with stage I/II unilateral breast cancer and treated with breast-conserving treatment who underwent subsequent second primary cancer risk-reducing strategies. Using event dependencies structured according to expert knowledge and conditional probabilities obtained from published evidence, we predicted the 40-year overall survival rate of different risk-reducing strategies for 144 cohorts of women defined by the type of pathogenic variants (BRCA1 or BRCA2), age at primary breast cancer diagnosis, breast cancer subtype, stage of primary breast cancer, and presence or absence of adjuvant chemotherapy. RESULTS: Absence of adjuvant chemotherapy was the most powerful factor that was linked to a dramatic decline in survival. There was a negligible decline in the mortality in patients with triple-negative breast cancer, who received no chemotherapy and underwent any secondary risk-reducing strategy, compared with surveillance. The potential survival benefit from any risk-reducing strategy was more modest in patients with triple-negative breast cancer who received chemotherapy compared with patients with luminal breast cancer. However, most patients with triple-negative breast cancer in stage I benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy or just risk-reducing salpingo-oophorectomy. Most patients with luminal stage I/II unilateral breast cancer benefited from bilateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. The impact of risk-reducing salpingo-oophorectomy in patients with luminal breast cancer in stage I/II increased with age. Most older patients with the BRCA1 and BRCA2 pathogenic variants in exons 12-24/25 with luminal breast cancer may gain a similar survival benefit from other risk-reducing strategies or surveillance. CONCLUSIONS: Our study showed that it is mandatory to consider the complex interplay between the types of BRCA1 and BRCA2 pathogenic variants, age at primary breast cancer diagnosis, breast cancer subtype and stage, and received systemic treatment. As no prospective study results are available at the moment, our simulation model, which will integrate a decision support system in the near future, could facilitate the conversation between the health care provider and patient and help to weigh all the options for risk-reducing strategies leading to a more balanced decision.

Immediate breast reconstruction uptake in older women with primary breast cancer: systematic review.

BACKGROUND: Postmastectomy immediate breast reconstruction (PMIBR) may improve the quality of life of patients with breast cancer, of whom older women (aged 65 years or more) are a growing proportion. This study aimed to assess PMIBR in older women with regard to underlying impediments (if any). METHODS: MEDLINE, Embase, and PubMed were searched by two independent researchers up to June 2022. Eligible studies compared PMIBR rates between younger and older women with invasive primary breast cancer. RESULTS: A total of 10 studies (2012-2020) including 466 134 women were appraised, of whom two-thirds (313 298) were younger and one-third (152 836) older. Only 10.0 per cent of older women underwent PMIBR in contrast to 45.0 per cent of younger women. Two studies explored factors affecting uptake of PMIBR in older women; surgeon-associated (usual practice), patient-associated (socioeconomic status, ethnicity, and co-morbidities), and system-associated (insurance status and hospital location) factors were identified. CONCLUSION: Uptake of PMIBR in older women is low with definable (and some correctable) barriers.

Targeted Axillary Dissection after Chemotherapy: Feasibility Study with Clip and Carbon Dye Tattoo - Neotarget Trial.

Background: Axillary staging in patients with complete response after neoadjuvant chemotherapy (NAC) is still controversial. Our objective was to test tattoo alone and subsequentially tattoo plus clip as markers in the targeted axillary dissection of ycN0 patients. Methods: Prospective cohort of cT1-T3, cN1 (proven histologically), M0 patients scheduled to receive NAC. Exclusion criteria were lobular histology, prior axillary surgery, and clinical N2/3. In cohort 1 this positive node (Neotarget node) was tattooed at diagnosis. If ycN0, a targeted axillary dissection was performed. After an interim analysis with negative results we changed the protocol in order to do a double marking procedure (Cohort 2): the positive node was clipped at diagnosis and after NAC a tattoo was done before surgery. Results: Thirteen patients in Cohort 1 and 18 patients in Cohort 2. Failure to identify the Neotarget node with multiple nodes retrieved in 9/13 (69%) of Cohort 1 patients. Also in 5/13 (38%) of Cohort 1 patients and 3/18 (17%) of Cohort 2 there was a failure to clearly identify tattooed nodes. In Cohort 2, clip identification by surgical specimen radiography allowed the identification of the tagged node in 17/18 (94,4%) of cases. The concordance between the clipped node and sentinel nodes was 16/18 (89%). Conclusions: The introduction of double marking by clipping the metastatic node and verifying their removal by surgical specimen radiography, using carbon ink as a tracer, allowed the identification of the metastatic node in 94% of cases, with a simple, reproducible, and easy-to-implement targeted axillary dissection procedure.

Urethra Sparing With Target Motion Mitigation in Dose-Escalated Extreme Hypofractionated Prostate Cancer Radiotherapy: 7-Year Results From a Phase II Study.

Purpose: To explore whether the rectal distension-mediated technique, harnessing human physiology to achieve intrafractional prostate motion mitigation, enables urethra sparing by inverse dose painting, thus promoting dose escalation with extreme hypofractionated stereotactic ablative radiotherapy (SABR) in prostate cancer. Materials and Methods: Between June 2013 and December 2018, 444 patients received 5 × 9 Gy SABR over 5 consecutive days. Rectal distension-mediated SABR was employed via insertion of a 150-cm3 air-inflated endorectal balloon. A Foley catheter loaded with 3 beacon transponders was used for urethra visualization and online tracking. MRI-based planning using Volumetric Modulated Arc Therapy - Image Guided Radiotherapy (VMAT-IGRT) with inverse dose painting was employed in delivering the planning target volume (PTV) dose and in sculpting exposure of organs at risk (OARs). A 2-mm margin was used for PTV expansion, reduced to 0 mm at the interface with critical OARs. All plans fulfilled Dmean ≥45 Gy. Target motion ≥2 mm/5 s motions mandated treatment interruption and target realignment prior to completion of the planned dose delivery. Results: Patient compliance to the rectal distension-mediated immobilization protocol was excellent, achieving reproducible daily prostate localization at a patient-specific retropubic niche. Online tracking recorded ≤1-mm intrafractional target deviations in 95% of treatment sessions, while target realignment in ≥2-mm deviations enabled treatment completion as scheduled in all cases. The cumulative incidence rates of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicities were 5.3% and 1.1%, respectively. The favorable toxicity profile was corroborated by patient-reported quality of life (QOL) outcomes. Median prostate-specific antigen (PSA) nadir by 5 years was 0.19 ng/ml. The cumulative incidence rate of biochemical failure using the Phoenix definition was 2%, 16.6%, and 27.2% for the combined low/favorable-intermediate, unfavorable intermediate, and high-risk categories, respectively. Patients with a PSA failure underwent a 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) scan showing a 20.2% cumulative incidence of intraprostatic relapses in biopsy International Society of Urological Pathology (ISUP) grade ≥3. Conclusion: The rectal distension-mediated technique is feasible and well tolerated. Dose escalation to 45 Gy with urethra-sparing results in excellent toxicity profiles and PSA relapse rates similar to those reported by other dose-escalated regimens. The existence of intraprostatic recurrences in patients with high-risk features confirms the notion of a high α/ß ratio in these phenotypes resulting in diminished effectiveness with hypofractionated dose escalation.

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy.

AIM: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. METHODS: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. RESULTS: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. CONCLUSIONS: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR.