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Breast cancer stands as the most frequently diagnosed cancer and the primary cause of cancer-related mortality among women worldwide, including Italy. With the increasing number of survivors, many are enrolled in regular follow-up programs. However, adherence to recommendations from scientific societies (such as ASCO, ESMO, AIOM) for breast cancer follow-up management varies in daily clinical practice across different cancer centers, potentially resulting in unequal management and escalating costs. To address these concerns, the Italian Association of Multidisciplinary Oncology Groups (AIGOM) orchestrated a Consensus on early Breast Cancer follow-up utilizing the Estimate-Talk-Estimate methodology. Following the identification of 18 Items and 38 statements by a select Board, 46 out of 54 (85.1%) experts comprising a multidisciplinary and multiprofessional panel expressed their degree of consensus (Expert Panel). The Expert Panel underscores the potential for the multidisciplinary team to tailor follow-up intensity based on the individual risk of recurrence. In selected cases, the general practitioner may be recommended as the clinical lead for breast cancer follow-up, both after completion of adjuvant treatment and at early initiation of endocrine therapy in low-risk patients. Throughout follow-up, and alongside oncologic surveillance, the expert panel advises osteometabolic, cardiologic, and gynecologic surveillance for the early detection and management of early and late treatment toxicities. Moreover, preserving quality of life is emphasized, with provisions for psycho-oncologic support and encouragement to adopt protective lifestyle behaviors., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None of the authors has any interests to report directly related to this manuscript. Outside the scope of this manuscript: Stefania Gori, Fiorenza De Rose, no conflict of interests to declare. Antonella Ferro, honoraria from Novartis, MDS, Daiichi Sankyo, Astra Zeneca, Ely Lilly, Gentili. Alessandra Fabi grants from Astra Zeneca (steering committee); consulting fees from Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Menarini; honoraria from Astra Zeneca, Roche, Lilly, Novartis, Gilead, Pfizer, Daiichi Sankyo Exact Sciences; travel grants from Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Menarini; advisory board from Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Menarini. Catia Angiolini, Giuseppe Azzarello, Maurizio Cancian, Michela Cinquini, Luca Arecco no conflict of interests to declare. Cynthia Aristei, grants from PRIN 2023, from the Ministry of University and Research. Project title “The microbiome in breast cancer therapy and its potential for pRobIOtics to improve treatment outcome. Acronym: BARRIO”. Daniela Bernardi, Laura Biganzoli, Anna Cariello no conflict of interests to declare. Laura Cortesi, report grants from Astra Zeneca, MSD, Pfizer; consulting fees and honoraria from Astra Zeneca, Gilead, MSD, Roche, Pfizer, Daijchii Sanchio, Novartis; travel grants from Gilead, Pfizer, Daijchi Sanchio; Advisory Board from Astra Zeneca, MSD, Novartis. Elisabetta Cretella no conflict of interests to declare. Carmen Criscitiello, grants from Seagen, Gilead; consulting fees and honoraria from Pfizer, Novartis, Lilly, MSD; Seagen, Daiichi Sankyo, Gilead, AstraZeneca, Roche. Ugo De Giorgi consulting fees from Amgen, Astellas Pharma, Astrazeneca, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck KGaA, MSD, Novartis, Pfizer; travel grants from Pfizer, Ipsen, Astrazeneca. Maria Carmen De Santis, Giuseppe Deledda, Massimo Dessena, Sara Donati, Arianna Dri, Gianluigi Ferretti no conflict of interests to declare. Jennifer Foglietta, honoraria from Novartis; travel grants from Roche, Sophos, Pfizer; Advisory Board from Menarini Stem Line. Davide Franceschini, Pierfrancesco Franco, Alessio Schirone no conflict of interests to declare. Daniele Generali, grants from LILT, University of Trieste, Novartis, Roche; consulting fees from Lilly, Novartis, Pfizer, Roche, Accord, Daiichi Dankyo; honoraria from Lilly, Novartis, Pfizer, Roche, Accord, Daiichi Dankyo, Astrazeneca, Istituto Gentili; travel grants from Roche, Menarini; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Mednote. Lorenzo Gianni, travel grants from Novartis, Lilly, Pfizer; Advisory Board from Astra Zeneca, Novartis, Seagen. Stefano Giordani, Giovanni Grandi, Maria Cristina Leonardi, Stefano Magno, no conflict of interests to declare. Luca Malorni, consulting fees from Menarini, Pfizer, Lilly, Novartis, Roche; travel grants from Roche, Menarini, Celgene, IT Health Fusion; Advisory Board from Novartis. Carlotta Mantoan no conflict of interests to declare. Federica Martorana honoraria from Lilly, Daychii-Sankyo, Pfizer, Astra-Zeneca, Novartis; travel grants from Gilead, Roche, Pfizer, Lilly; advisory board from Amgen. Icro Meattini consulting fees from Pfizer, Astra Zeneca, Daiichi Sankyo, Novartis, Eli Lilly, Seagen, Gilead, Menarini StemLine. Bruno Meduri, Laura Merlini, Federica Miglietta, Alessandra Modena, Fabrizio Nicolis, Isabella Palumbo, no conflict of interests to declare. Pietro Panizza honoraria and travel grants from Bayer AG. Francesca Angela Rovera, Piermario Salvini, Armando Santoro, Mario Taffurelli, no conflict of interests to declare. Angela Toss consulting fees and grants from Lilly, Pfizer, Novartis, MSD, Astrazeneca, Gilead, Seagen, Daiichi Sankyo; travel grants from Gilead, Daiichi Sankyo, Menarini, Astrazeneca. Paolo Tralongo, Monica Turazza, Matteo Valerio, Matteo Verzè no conflict of interests to declare. Patrizia Vici consulting fees from Lilly, Daiichi-Sankyo, Pfizer, MSD, Novartis; honoraria from EISAI, Daiichi-Sankyo, Lilly, Novartis, Pfizer; travel grants from Roche, Pfizer, Daiichi-Sankyo, Novartis, IPSEN; advisory board from Pfizer, Novartis. Claudio Zamagni no conflict of interests to declare. Giuseppe Curigliano advisory board from Roche, Novartis, Lilly, Pfizer, Astra Zeneca, Daichii Sankyo, Ellipsis, Veracyte, Exact Science, Celcuity, Merck, BMS, Gilead, Sanofi, Menarini. Giovanni Pappagallo no conflict of interests to declare. Alberto Zambelli consulting fees Pfizer, Lilly, Novartis, Roche, AstraZeneca, DaiichiSankyo, Seagen, ExactSciences, MSD, Gentili, Gilead; travel grants from Roche, DaiichiSankyo, AstraZeneca, Novartis; advisory board from Roche., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Women who have a mastectomy for breast cancer treatment or risk reduction may be offered different options for breast reconstruction, including use of implants or the woman's own tissue (autologous tissue flaps). The choice of technique depends on factors such as the woman's preferences, breast characteristics, preoperative imaging, comorbidities, smoking habits, prior chest or breast irradiation, and planned adjuvant therapies., Objectives: To assess the effects of implants versus autologous tissue flaps for postmastectomy breast reconstruction on women's quality of life, satisfaction, and short- and long-term surgical complications., Search Methods: We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registries in July 2022., Selection Criteria: We included studies that compared implant-based reconstruction with autologous tissue-based reconstruction following mastectomy for breast cancer treatment or risk reduction. The minimum eligible sample size was 100 participants., Data Collection and Analysis: Two review authors independently assessed risk of bias and extracted data using standard Cochrane procedures. We used GRADE to assess the certainty of the evidence., Main Results: Thirty-five non-randomised studies with 57,555 participants met our inclusion criteria. There were nine prospective cohort studies and 26 retrospective cohort studies. We judged 26 studies at serious overall risk of bias and the remaining studies at moderate overall risk of bias. Some studies measured quality of life and satisfaction using the BREAST-Q (scale of 0 to 100, higher is better). Implants may reduce postoperative psychosocial well-being compared with autologous tissue flaps (mean difference (MD) -4.26 points, 95% confidence interval (CI) -4.91 to -3.61; I² = 0%; 6 studies, 3335 participants; low-certainty evidence). Implants may reduce or have little to no effect on postoperative physical well-being compared with autologous tissue flaps, but the evidence is very uncertain (MD -1.92 points, 95% CI -4.44 to 0.60; I² = 87%; 6 studies, 3335 participants; very low-certainty evidence). Implants may reduce postoperative sexual well-being compared with autologous reconstruction (MD -6.63 points, 95% CI -7.55 to -5.72; I² = 0; 6 studies, 3335 participants; low-certainty evidence). Women who undergo breast reconstruction with implants versus autologous tissue flaps may be less satisfied with the breast, but the evidence is very uncertain (MD -8.17 points, 95% CI -11.41 to -4.92; I² = 90%; 6 studies, 3335 participants; very low-certainty evidence). This outcome refers to a woman's satisfaction with breast size, bra fit, appearance in the mirror (clothed or unclothed), and how the breast feels to touch. Women who undergo breast reconstruction with implants versus autologous tissue flaps may be less satisfied with the reconstruction (MD -5.96 points, 95% CI -10.24 to -1.68; I² = 62%; 4 studies, 1196 participants; low-certainty evidence). This outcome refers to whether the aesthetic outcome has met the woman's expectations, the impact surgery has had on her life, and whether she thinks she made the right decision to have the reconstruction. Implants may reduce or have little to no effect on the risk of short-term complications compared with autologous tissue flaps, but the evidence is very uncertain (risk ratio (RR) 0.80, 95% CI 0.63 to 1.03; I² = 91%; 22 studies, 34,244 participants; very low-certainty evidence). Implants may increase long-term complications compared with autologous tissue flaps, but the evidence is very uncertain (RR 1.56, 95% CI 1.09 to 2.22; I² = 94%; 17 studies, 26,930 participants; very low-certainty evidence). Implants may have little to no effect on the need for reintervention compared with autologous tissue flaps, but the evidence is very uncertain (RR 1.23, 95% CI 0.91 to 1.68; I² = 93%; 15 studies, 14,171 participants; very low-certainty evidence). Implants may reduce the duration of surgery compared with autologous tissue flaps, but the evidence is very uncertain (MD -125.04 minutes, 95% CI -131.41 to -118.67; I² = 0; 2 studies, 836 participants; very low-certainty evidence)., Authors' Conclusions: The findings of this review show that autologous tissue-based reconstruction compared with implant-based reconstruction may improve participant-reported outcomes such as psychosocial well-being, sexual well-being, and satisfaction with the reconstruction. There is also very uncertain evidence to suggest that autologous tissue-based reconstruction increases satisfaction with the breast and reduces the risk of long-term complications compared with implants. Implant-based reconstruction may be a shorter procedure, but the evidence is very uncertain. Despite the growing demand for breast reconstruction, the best technique has not been adequately studied in randomised controlled trials (RCTs), and the evidence provided by non-randomised studies is often unsatisfactory. There is no superior breast reconstruction technique for all women. Future research should focus on the definition of decisional drivers to guide an evidence-based shared decision-making process in reconstructive breast surgery., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different studies. We aimed to assess the prognostic value of ctDNA in patients with operable (non metastatic) BC., Materials and Methods: A systematic search of databases (PubMed/Medline, Embase, and CENTRAL) and conference proceedings was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS) and overall survival (OS) in patients with stage I-III BC. Log-hazard ratios (HRs) were pooled at each timepoint of ctDNA assessment (baseline, after neoadjuvant therapy, and follow-up). ctDNA assays were classified as primary tumor-informed and non tumor-informed., Results: Of the 3174 records identified, 57 studies including 5779 patients were eligible. In univariate analyses, ctDNA detection was associated with worse DFS at baseline [HR 2.98, 95% confidence interval (CI) 1.92-4.63], after neoadjuvant therapy (HR 7.69, 95% CI 4.83-12.24), and during follow-up (HR 14.04, 95% CI 7.55-26.11). Similarly, ctDNA detection at all timepoints was associated with worse OS (at baseline: HR 2.76, 95% CI 1.60-4.77; after neoadjuvant therapy: HR 2.72, 95% CI 1.44-5.14; and during follow-up: HR 9.19, 95% CI 3.26-25.90). Similar DFS and OS results were observed in multivariate analyses. Pooled HRs were numerically higher when ctDNA was detected at the end of neoadjuvant therapy or during follow-up and for primary tumor-informed assays. ctDNA detection sensitivity and specificity for BC recurrence ranged from 0.31 to 1.0 and 0.7 to 1.0, respectively. The mean lead time from ctDNA detection to overt recurrence was 10.81 months (range 0-58.9 months)., Conclusions: ctDNA detection was associated with worse DFS and OS in patients with operable BC, particularly when detected after treatment and using primary tumor-informed assays. ctDNA detection has a high specificity for anticipating BC relapse., Competing Interests: Disclosure GNM reports meeting/travel grants from AstraZeneca. EA reports consultancy fees/honoraria from Eli Lilly, Sandoz, and AstraZeneca; research grant to the institution from Gilead; meeting/travel grants from Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo, and AstraZeneca (all outside the submitted work). DMB reports full time employment at European Society for Medical Oncology since September 1, 2023; speaker’s engagement from Daiichi Sankyo/AstraZeneca; participation as medical research fellow in research studies with institutionally funded by Eli Lilly, Novartis, and F. Hoffmann-La Roche Ltd to Institut Jules Bordet; non-financial interest as member of the board of directors for Associaҫão de Investigaҫão e Ciudados de Suporte em Oncologia; non-remunerated prior leadership role as Portuguese Young Oncologists Committee Chair from Sociedade Portuguesa de Oncologia (all outside the submitted work). ALC reports leadership role at Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD; intellectual property for MEDSIR; a consulting role for Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, Exact Sciences, Seagen, and GSK; to be part of the speaker bureau for Lilly, AstraZeneca, and MSD; to receive research funding from Pfizer, Roche, Foundation Medicine, Exact Sciences, Pierre-Fabre, and Agendia; and travel compensation from Roche, Lilly, Novartis, Pfizer, and AstraZeneca. JC reports consulting/advisor role for Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp & Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, HiberCell, BioInvent, GEMoaB, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, and AbbVie; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo, AstraZeneca; research funding to the institution from Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F. Hoffmann-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, PIQUR Therapeutics, IQVIA, and Queen Mary University of London; stocks from MAJ3 Capital and Leuko (relative); travel, accommodation, and other expenses covered by Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead, and Merck Sharp & Dohme; patents ‘Pharmaceutical Combinations of A Pi3k Inhibitor And A Microtubule Destabilizing Agent’—Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde, WO 2014/199294 A (issued) and ‘Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy’—Aleix Prat, Antonio Llombart, Javier Cortés, US 2019/ 0338368 A1 (licensed). MI reports honoraria from Novartis and Seattle Genetics; research support to the institution from Natera Inc, Inivata, Roche, and Pfizer; and travel grants from Roche and Gilead. GP reports being part of the advisory board/speaker bureau for Roche, Bayer, AstraZeneca, Novartis, Illumina, and ADS Biotech; and grants from Candriam and Thermo Fisher. EA reports honoraria and/or being part of the advisory board for Roche/GNE, Novartis, Seagen, Zodiac, Libbs, Pierre Fabre, Lilly, and Astra-Zeneca; travel grants from Roche/GNE and AstraZeneca; research grant to the institution from Roche/GNE, Astra-Zeneca, and GSK/Novartis. SDC reports being on the speaker’s bureau for AstraZeneca; and on the advisory board for Pierre-Fabre, IQVIA, and MEDSIR. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Approximately 5-10% of unselected breast cancer (BC) patients retain a hereditary predisposition related to a germline mutation in BRCA1/2 genes. The poly-ADP ribose polymerase (PARP)-inhibitors olaparib and talazoparib have been granted marketing authorization by both FDA and EMA for adults with BRCA1/2 germline mutations and HER2-negative (HER2-) advanced BC based on the results from the phase III OlympiAd and EMBRACA trials., Methods: The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer addressed two critical clinical questions, adopting the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Evidence to Decision framework (EtD), to develop recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related triple-negative (clinical question 1) and hormone receptor-positive (HR+)/HER2- (clinical question 2) advanced BC., Results: Two studies were eligible (OlympiAd and EMBRACA). For both clinical questions, the Panel judged the benefit/harm balance probably in favor of the intervention, given the favorable impact in terms of PFS, ORR, and QoL at an acceptable cost in terms of toxicity; the overall certainty of the evidence was low. The panel's final recommendations were conditional in favor of PARP-inhibitors over single-agent chemotherapy in both HR+/HER2-and triple-negative BC. Finally, the Panel identified and discussed areas of uncertainty calling for further exploration., Conclusions: The Panel of AIOM BC Clinical Practice Guideline provided clinical recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related HER2-advanced BC by adopting the GRADE methodology., Competing Interests: Declaration of competing interest FM personal fee from Roche, Novartis and Gilead outside the submitted work. MVD: personal fees from Eli Lilly, MSD, Exact Sciences, Novartis, Pfizer, Seagen, outside the submitted work; CC: consultan-cy/advisory role/speaker bureau: Pfizer, Novartis, Lilly, Roche, Gilead, MSD, Seagen, outside the submitted work; FM: Fees for advisory board participation; Novartis, Astra Zeneca, Daiichi Sankyo, SeaGen, MSD, Pfizer, Roche, PUMA, outside the submitted work; LDM: grants from Eli Lilly, personal fees from Eli Lilly, personal fees from Novartis, personal fees and non-financial support from Roche, personal fees from MSD, personal fees and non-financial support from Pfiz-er, personal fees from Genomic health, personal fees from Pierre Fabre, personal fees from Daiichi Sankyo, personal fees from Astrazeneca, personal fees from Seagen, personal fees and non-financial support from Eisai, personal fees from Ipsen, personal fees from Gilead, outside the submitted work; AZ: fees for advisory board; Lilly, Novartis, Astra Zeneca, Daiichi Sankyo, SeaGen, MSD, Pfizer, Roche, ExactSciences; LB: honoraria, consulting or advisory role Astra-Zeneca, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Seattle Genetics; research Funding Celgene, Genomic Health, Novartis, all outside the submitted work; CM: personal consultancy fees from Bayer, Roche, Astrazeneca, Daiichi Sankyo, outside the submitted work., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice., Methods: A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach., Results: According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence)., Discussion: This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients' values. Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest to disclose., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Premenopausal women with hormone receptor-positive early breast cancer are candidates for adjuvant endocrine therapy, as recommended by the major international guidelines. To date, adjuvant endocrine options for premenopausal women include tamoxifen with or without ovarian function suppression (OFS) or an aromatase inhibitor with OFS. Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed, and the results of randomised clinical trials have been reported over the last years. Despite this evidence, the optimal algorithm for endocrine therapy for premenopausal women with hormone receptor-positive early stage invasive breast cancer shows open questions regarding the role of OFS in addition to tamoxifen and the optimal use of hormonal agents. The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer applied the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology on three critical questions on the choice of the adjuvant hormonal therapy in premenopausal breast cancer patients to summarise available evidence and to create recommendations to help physicians in their clinical practice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The development of premature ovarian failure and subsequent infertility are possible consequences of chemotherapy use in pre-menopausal women with early-stage breast cancer. Among the available strategies for fertility preservation, pharmacological protection of the ovaries using luteinising hormone-releasing hormone analogues (LHRHa) during chemotherapy has the potential to restore ovarian function and fertility after anticancer treatments; however, the possible efficacy and clinical application of this strategy has been highly debated in the last years. Following the availability of new data on this controversial topic, the Panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guideline on fertility preservation in cancer patients decided to apply the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology around the relevant and current question on the clinical utility of temporary ovarian suppression with LHRHa during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients. To answer this question, preservation of ovarian function and fertility were judged as critical outcomes for the decision-making. Three possible outcomes of harm were identified: LHRHa-associated toxicities, potential antagonism between concurrent LHRHa and chemotherapy, and lack of the prognostic impact of chemotherapy-induced premature ovarian failure. According to the GRADE evaluation conducted, the result was a strong positive recommendation in favour of using this option to preserve ovarian function and fertility in breast cancer patients. The present manuscript aims to update and summarise the evidence for the use of this strategy in light of the new data published up to January 2016, according to the GRADE process., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The general aim of this systematic review is to mitigate breast cancer (BC) overdiagnosis and overtreatment. The specific aim is to summarize available data on the occurrence and features of indolent invasive or in situ (DCIS) BC, and precisely survival of untreated cases, prevalence of occult cancers found in autopsies, frequency of regressive BC. PubMed, Embase and Cochrane Library were systematically searched up to 3/31/2014. Eligibility criteria were: cohort studies, case-control studies, uncontrolled case series assessing survival in women with a diagnosis of BC who did not receive treatment compared to treated women; case series of autopsies estimating the prevalence of undiagnosed BC; cohort studies, case-control studies, uncontrolled case series, case reports assessing the occurrence of spontaneous regression of BC in women with a confirmed histology diagnosis. Untreated BC: 8 cohort studies and 12 case series (3593 BC) were included. In three controlled cohort studies (diagnoses 1978-2006), the 5-years overall survival was 19-43%. Occult BC: 8 case series (2279 autopsies) were included. The prevalence of invasive BC undiagnosed during lifetime range was 0-1.5%, while for DCIS the range was 0.2-14.7%. Spontaneous regression: 2 cohort studies, 3 case reports, 1 case series included. In the cohort studies the relative risk of regression for screen detected compared with nonscreened BC was estimated as 1.2 and 1.1. It seems plausible that around 10% of invasive BC are not symptomatic during life, and that one fith of BC patients if untreated would be alive after 5 years. Around 1 of 10 screen-detected BC may regress according two studies., (© 2016 UICC.)

Background: Follow-up examinations are commonly performed after primary treatment for women with breast cancer. They are used to detect recurrences at an early (asymptomatic) stage. This is an update of a Cochrane review first published in 2000., Objectives: To assess the effectiveness of different policies of follow-up for distant metastases on mortality, morbidity and quality of life in women treated for stage I, II or III breast cancer., Search Methods: For this 2014 review update, we searched the Cochrane Breast Cancer Group's Specialised Register (4 July 2014), MEDLINE (4 July 2014), Embase (4 July 2014), CENTRAL (2014, Issue 3), the World Health Organization (WHO) International Clinical Trials Registry Platform (4 July 2014) and ClinicalTrials.gov (4 July 2014). References from retrieved articles were also checked., Selection Criteria: All randomised controlled trials (RCTs) assessing the effectiveness of different policies of follow-up after primary treatment were reviewed for inclusion., Data Collection and Analysis: Two review authors independently assessed trials for eligibility for inclusion in the review and risk of bias. Data were pooled in an individual patient data meta-analysis for the two RCTs testing the effectiveness of different follow-up schemes. Subgroup analyses were conducted by age, tumour size and lymph node status., Main Results: Since 2000, one new trial has been published; the updated review now includes five RCTs involving 4023 women with breast cancer (clinical stage I, II or III).Two trials involving 2563 women compared follow-up based on clinical visits and mammography with a more intensive scheme including radiological and laboratory tests. After pooling the data, no significant differences in overall survival (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.84 to 1.15, two studies, 2563 participants, high-quality evidence), or disease-free survival (HR 0.84, 95% CI 0.71 to 1.00, two studies, 2563 participants, low-quality evidence) emerged. No differences in overall survival and disease-free survival emerged in subgroup analyses according to patient age, tumour size and lymph node status before primary treatment. In 1999, 10-year follow-up data became available for one trial of these trials, and no significant differences in overall survival were found. No difference was noted in quality of life measures (one study, 639 participants, high-quality evidence).The new included trial, together with a previously included trial involving 1264 women compared follow-up performed by a hospital-based specialist versus follow-up performed by general practitioners. No significant differences were noted in overall survival (HR 1.07, 95% CI 0.64 to 1.78, one study, 968 participants, moderate-quality evidence), time to detection of recurrence (HR 1.06, 95% CI 0.76 to 1.47, two studies, 1264 participants, moderate-quality evidence), and quality of life (one study, 356 participants, high-quality evidence). Patient satisfaction was greater among patients treated by general practitioners. One RCT involving 196 women compared regularly scheduled follow-up visits versus less frequent visits restricted to the time of mammography. No significant differences emerged in interim use of telephone and frequency of general practitioners's consultations., Authors' Conclusions: This updated review of RCTs conducted almost 20 years ago suggests that follow-up programs based on regular physical examinations and yearly mammography alone are as effective as more intensive approaches based on regular performance of laboratory and instrumental tests in terms of timeliness of recurrence detection, overall survival and quality of life.In two RCTs, follow-up care performed by trained and not trained general practitioners working in an organised practice setting had comparable effectiveness to that delivered by hospital-based specialists in terms of overall survival, recurrence detection, and quality of life.