Health-Related Quality of Life After Nipple-Sparing Mastectomy: Results From the INSPIRE Registry.

INTRODUCTION: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is increasingly used for both breast cancer (TNSM) and risk reduction (RRNSM). The aim of the study is to report the results of the INSPIRE registry assessing health-related quality of life (HRQoL) comparing baseline and 1-year follow-up, regarding surgical indications and chemotherapy (CT) received. METHODS: INSPIRE is a prospective database including women undergoing NSM and IBR from 18 countries. HRQoL was measured using EORTC QLQC30 and QLQ-BR23 before surgery and after 1 year. RESULTS: A total of 677 women were included, of whom 537 (79.3%) underwent TNSM and 140 (21.6%) RRNSM: in total, 806 NSM (556 TNSM and 250 RRNSM). Nipple involvement was present in 7.73% of TNSM and incidental carcinoma in 1.2% of the RRNSM group. Out of the overall 537 patients with systemic treatment, 177 (32.96%) received neoadjuvant chemotherapy (NCT) and 118 (21.92%) adjuvant chemotherapy (CT). A total of 227 patients (28.16%) developed at least one complication postoperatively, 164 (29.5%) in the TNSM group and 63 (25.2%) in the RRNSM group. The TNSM group improved in global health status and emotional functioning after 1 year. No differences were found when comparing HRQoL at 1 year between patients who received NCT and those who received adjuvant CT. The RRNSM group showed improvement in HRQoL, with better emotional functioning and fatigue after 1 year. CONCLUSIONS: This registry reports HRQoL findings after NSM. The impact of CT on worse HRQoL is independent from its timing. Patients with RRNSM showed an improved HRQoL at 1-year follow-up. Discussion of HRQoL outcomes with patients will facilitate the informed decision-making when considering NSM.

Retrospective, Multicenter Analysis Comparing Conventional with Oncoplastic Breast Conserving Surgery: Oncological and Surgical Outcomes in Women with High-Risk Breast Cancer from the OPBC-01/iTOP2 Study.

INTRODUCTION: Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4). METHODS: Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. RESULTS: A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 ("ink on tumor") in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. CONCLUSIONS: Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI.

Sodium assessment in neonates, infants, and children: a systematic review.

Hyponatremia is a common disorder in childhood. The indirect and the direct potentiometry are currently the most popular techniques employed for sodium assessment, although discrepancies between the two techniques may be > 10 mmol/L. It is known that < 20% of the recently published articles report information about the technique used for sodium analysis, but no data are available on pediatric studies. This study aimed at investigating the laboratory technique employed for sodium measurement in studies conducted in childhood. A systematic literature search in PubMed, Embase, and Web of Science was undertaken to identify articles containing the word "hyponatremia" in the title between 2013 and 2020. Papers with < 10 subjects were excluded. A total of 565 articles were included. Information on the laboratory technique used for sodium analysis was more commonly (p = 0.035) reported in pediatric (n = 15, 28%) than in non-pediatric (n = 81, 16%) reports. The frequency of reports with and without information on the technique for sodium assessment was not different with respect to the study characteristics, the quartile of the journal where the paper was published, the country income setting, and the inclusion of neonates among the 54 pediatric studies.   Conclusion: Most pediatric papers do not report any information on the technique used for sodium analysis. Although international authorities have recommended the implementation of direct potentiometry, a low awareness on this issue is still widespread in pediatric research. What is Known: • Direct potentiometry and indirect potentiometry are currently employed for sodium analysis in blood. • Direct potentiometry is more accurate. What is New: • Less than 30% of pediatric articles provide information on the technique employed for sodium analysis in blood. • Indirect potentiometry is more frequently employed than direct potentiometry in pediatric studies.

Multidisciplinary blended learning to build a breast cancer specialist career: survey on the perspective of the first 2 cohorts of the ESO-ULM Certificate of Competence in Breast cancer (CCB).

BACKGROUND: Breast Cancer (BC) specialists need to acquire comprehensive knowledge, covering their own specialty and principles of related disciplines. Blended learning, the integration of online and face-to-face learning, is becoming more and more important in academic education and has added value during pandemics which limit face-to-face learning and residential training. In this context, the ESO-ULM Certificate of Competence in Breast Cancer (CCB) provides postgraduate multidisciplinary education and delivers an academic postgraduate title. The aim of this work is to investigate the degree of satisfaction of 42 participants to the first two editions of the programme and to assess if attending the programme entailed any professional gain. METHODS: An ad-hoc questionnaire was developed exploring 4 areas: participants' characteristics, administrative aspects, CCB Program syllabus and design, professional impact. RESULTS: The program was attractive for specialists of different disciplines from all over the world: > 90% of responders appreciated the curriculum set up and the quality of the teaching. Despite 64% of responders changed their clinical practice, only 33% could implement institutional changes. One third of the participants activated a collaboration with other colleagues and 64% used the CCB as a trigger to take part in other educational activities. Only 12% of the participants had the opportunity, after CCB, to visit other BC Units or to be involved in international research projects. More than half of the attendees profited from attending CCB in terms of promotions (16.7%), change of working institution (9.5%) or development of a more structured educational program at their home institutions (28.6%). CONCLUSIONS: Results provide interesting and stimulating considerations on the expectations and needs of training physicians and on what modern educational tools and formats can achieve. This paper can provide useful information to navigate through what the post-graduate training market is currently offering to develop a specific curriculum in modern multidisciplinary BC care but might not be applicable to other fields of multidisciplinary oncology.

Which laboratory technique is used for the blood sodium analysis in clinical research? A systematic review.

BACKGROUND: Circulating sodium is analyzed by flame spectrometry and indirect or direct potentiometry. The differences between estimates returned by the three techniques are often relevant. It is unknown whether peer-reviewed international publications focusing on this parameter provide information about the technique. Objectives of the study were to ascertain if information about the employed technique is provided. CONTENT: A search in the National Library of Medicine for articles whose title contains "hyponatr[a]emia" was performed. We restricted the search to clinical reports including 10 or more humans published in the 2013-2015 and 2017-2019 periods. Authors of papers not reporting the technique were contacted to obtain this information. The study design and journal quartile ranking of each article were also evaluated. SUMMARY: For the final analysis, we included 361 articles (2013-2015, n=169; 2017-2019, n=192). Information about the laboratory technique was given in 61(17%) articles. Thanks to our inquiry, we collected this information for 116(32%) further reports. Indirect potentiometry was the most frequently used technique, followed by direct potentiometry. Spectrometry was used in a small minority of studies. Study design, journal ranking and study period did not modulate the mentioned frequency. OUTLOOK: Most articles focusing on hyponatremia do not provide information on the laboratory technique. This parameter is nowadays analyzed by indirect or, less frequently, direct potentiometry. The figures are similar for high and low impact factor journals and for the 2013-2015 and the 2017-2019 periods. Many authors, reviewers and editors likely assume that the results of this parameter are not influenced by the technique.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

Functional characterization of epithelial ovarian cancer histotypes by drug target based protein signaling activation mapping: implications for personalized cancer therapy.

Epithelial ovarian carcinoma (EOC) is a deadly disease, with a 5-year survival of 30%. The aim of the study was to perform broad-scale protein signaling activation mapping to evaluate if EOC can be redefined based on activated protein signaling network architecture rather than histology. Tumor cells were isolated using laser capture microdissection (LCM) from 72 EOCs. Tumors were classified as serous (n = 38), endometrioid (n = 13), mixed (n = 8), clear cell (CCC; n = 7), and others (n = 6). LCM tumor cells were lysed and subjected to reverse-phase protein microarray to measure the expression/activation level of 117 protein drug targets. Unsupervised hierarchical clustering analysis was utilized to explore the overall signaling network. ANOVA was used to detect significant differences among the groups (p < 0.05). Regardless of histology, unsupervised analysis revealed five pathway-driven clusters. When the EOC histotypes were compared by ANOVA, only CCC showed a distinct signaling network, with activation of EGFR, Syk, HER2/ErbB2, and SHP2 (p = 0.0007, p = 0.0021, p < 0.0001, and p = 0.0410, respectively). The histological classification of EOC fails to adequately describe the underpinning protein signaling network. Nevertheless, CCC presents unique signaling characteristics compared to the other histotypes. EOC may need to be characterized by functional signaling activation mapping rather than pure histology.

Pyoderma gangrenosum following reduction mammoplasty: Systematic review of the literature and case report.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis that can develop at a surgical site. Diagnosis can be challenging at its presentation causing delays in appropriate treatment. The aim of this study is to review the current literature as well as to describe the clinical presentation, diagnostic pathway, and treatment of PG after reduction mammaplasty in order to define a standardized multidisciplinary diagnostic and therapeutic approach. In the future, this may ease early identification and prompt treatment, and eventually minimize severe morbidity and long-term sequelae. METHODS: The entire PubMed/Medline database was screened following the PRISMA guidelines to identify studies describing PG that have occurred after reduction mammoplasty. RESULTS: Twenty-eight articles including 31 patients reported a PG after breast reduction surgery between January 1988 and March 2022. Twenty-one (68%) patients presented with skin ulcerations, 14 (45%) with erythema, and 5 (16%) with vesicles. Out of the 30 cases that underwent bilateral surgery, 18 (60%) developed PG bilaterally. In 12 out of 31 patients, nipple-areolar complex (NAC) involvement was evaluated, though in 10 patients (83%) the NAC was spared. Of the 20 patients (65%) who underwent skin biopsies for histopathological examination, 18 (90%) showed neutrophilic infiltration of the dermal layers. All 31 patients (100%) showed rapid clinical improvement after the introduction of immunosuppressive therapy. CONCLUSIONS: PG can result in devastating skin alterations also after reduction mammoplasty, if misdiagnosed. However, it presents with constant yet unspecific local and general signs and symptoms that can be recognized to early initiate an appropriate pharmacological treatment.

Sleep and sleep disorders during pregnancy and postpartum: The Life-ON study.

OBJECTIVE: to prospectively assess sleep and sleep disorders during pregnancy and postpartum in a large cohort of women. METHODS: multicenter prospective Life-ON study, recruiting consecutive pregnant women at a gestational age between 10 and 15 weeks, from the local gynecological departments. The study included home polysomnography performed between the 23rd and 25th week of pregnancy and sleep-related questionnaires at 9 points in time during pregnancy and 6 months postpartum. RESULTS: 439 pregnant women (mean age 33.7 ± 4.2 yrs) were enrolled. Poor quality of sleep was reported by 34% of women in the first trimester of pregnancy, by 46% of women in the third trimester, and by as many as 71% of women in the first month after delivery. A similar trend was seen for insomnia. Excessive daytime sleepiness peaked in the first trimester (30% of women), and decreased in the third trimester, to 22% of women. Prevalence of restless legs syndrome was 25%, with a peak in the third trimester of pregnancy. Polysomnographic data, available for 353 women, revealed that 24% of women slept less than 6 h, and 30.6% of women had a sleep efficiency below 80%. Sleep-disordered breathing (RDI≥5) had a prevalence of 4.2% and correlated positively with BMI. CONCLUSIONS: The Life-ON study provides the largest polysomnographic dataset coupled with longitudinal subjective assessments of sleep quality in pregnant women to date. Sleep disorders are highly frequent and distributed differently during pregnancy and postpartum. Routine assessment of sleep disturbances in the perinatal period is necessary to improve early detection and clinical management.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

The optimal timing between neoadjuvant therapy and surgery of breast cancer: A brief systematic review of the literature.

Neoadjuvant therapy is a cornerstone of some early and locally advanced breast cancer treatment. The use of neoadjuvant chemotherapy, in fact, allows to obtain numerous advantages, including allowing a more conservative intervention, evaluating the in vivo response to therapy, modulating the intensity of subsequent treatments based on the degree of response to therapy and allowing to surgery with information on genetics. However, at the end of neoadjuvant cytotoxic therapy it is not possible to carry out surgery immediately, as a certain amount of time is required for recovery from toxicity, especially haematological, due to the systemic therapy itself. At the same time, it is intuitive that too much time must not pass between the end of neoadjuvant therapy and surgery. The goal of this systematic literature review is to summarize the most relevant literature data on this topic, selected and extracted according to the methodology of systematic reviews.

Electrical Impedance Spectroscopy for Ex-Vivo Breast Cancer Tissues Analysis.

This paper describes a cancer detection procedure based on customised electrical impedance spectroscopy (EIS) in breast cancer surgical samples and an analysis of its outcomes. A tissue analyser was developed to inject a low-amplitude alternating current with penetrating electrodes into breast specimens along a broad spectrum of frequencies. Experimental measurements were carried out on more than one hundred excised breast cancer specimens, with the goal of discriminating between the tumour and surrounding non-neoplastic tissue. The probe was inserted in different locations immediately after surgical excision in order to measure tissue impedance (modulus and phase). Electrical impedance varied significantly between neoplastic and surrounding non-neoplastic tissues, with a low standard deviation among the different measurements, confirming good reproducibility. Tumours could be discriminated from non-neoplastic tissues according to their impedance modulus value for high frequencies and phase value for low frequencies. Impedance also varied significantly in both non-neoplastic and tumour tissues depending on the patient's age and tumour characteristics, such as size and histological sub-type. EIS is able to discriminate between healthy tissue and cancer. Future developments of this technology could be exploited for intraoperative real-time evaluation of the transition zone between cancer and normal tissues.

Apolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer.

Tumor cells promote the recruitment of immunosuppressive neutrophils, a subset of myeloid cells driving immune suppression, tumor proliferation, and treatment resistance. Physiologically, neutrophils are known to have a short half-life. Here, we report the identification of a subset of neutrophils that have upregulated expression of cellular senescence markers and persist in the tumor microenvironment. Senescent-like neutrophils express the triggering receptor expressed on myeloid cells 2 (TREM2) and are more immunosuppressive and tumor-promoting than canonical immunosuppressive neutrophils. Genetic and pharmacological elimination of senescent-like neutrophils decreases tumor progression in different mouse models of prostate cancer. Mechanistically, we have found that apolipoprotein E (APOE) secreted by prostate tumor cells binds TREM2 on neutrophils, promoting their senescence. APOE and TREM2 expression increases in prostate cancers and correlates with poor prognosis. Collectively, these results reveal an alternative mechanism of tumor immune evasion and support the development of immune senolytics targeting senescent-like neutrophils for cancer therapy.

Management and Outcome of Young Women (≤40 Years) with Breast Cancer in Switzerland.

Background: An increase in breast cancer (BC) incidence in young women (YW) as well as disparities in BC outcomes have been reported in Switzerland. We sought to evaluate treatment and outcome differences among YW with BC (YWBC). Methods: YW diagnosed with stage I-III BC between 2000−2014 were identified through nine cancer registries. Concordance with international guidelines was assessed for 12 items covering clinical/surgical management, combined in a quality-of-care score. We compared score and survival outcome between the two linguistic-geographic regions of Switzerland (Swiss-Latin and Swiss-German) and evaluated the impact of quality-of-care on survival. Results: A total of 2477 women were included. The median age was 37.3 years (IQR 34.0−39.4 years), with 50.3% having stage II BC and 70.3% having estrogen receptor positive tumors. The mean quality-of-care score was higher in the Latin region compared to the German region (86.0% vs. 83.2%, p < 0.0005). Similarly, 5- and 10-year overall survival rates were higher in the Latin compared to the German region (92.3% vs. 90.2%, p = 0.0593, and 84.3% vs. 81.5%, p = 0.0025, respectively). There was no difference in survival according to the score. In the univariate analysis, women in the Latin region had a 28% lower mortality risk compared to women in the German region (hazard ratio 0.72; 95% CI 0.59−0.89). In the multivariable analysis, only stage, differentiation, tumor subtype and treatment period remained independently associated with survival. Conclusions: We identified geographic disparities in the treatment and outcome of YWBC in Switzerland. National guidelines for YWBC should be implemented to standardize treatment. Awareness should be raised among YW and clinicians that BC does not discriminate by age.

Breast cancer in the oldest old (≥ 89 years): Tumor characteristics, treatment choices, clinical outcomes and literature review.

INTRODUCTION: Risk of breast cancer increases with age and very few data are available in patients older than 89. METHODS: A retrospective analysis on patients aged 89 and older treated between 2008 and 2019 at our certified breast center. The aim was to analyze clinical characteristics, decision-making, treatment, outcomes and open questions regarding this subpopulation for which there is a lack of guidelines. RESULTS: 58 patients included. Tumor characteristics were analyzed, 85% patients underwent surgery of which 44% had a mastectomy. The median follow-up and overall survival were 20 and 76 months, respectively.The median survival of metastatic and non-metastatic patients were 14 and 50 months, respectively. Most patients did not receive any adjuvant treatment and among these 14% had a relapse. CONCLUSIONS: Elderly patients should not be under or over-treated because of their age; they represent a large heterogeneous group deserving a sub-stratification for a better tailored treatment.

A Breast Cancer Smartphone App to Navigate the Breast Cancer Journey: Mixed Methods Study.

BACKGROUND: Several mobile apps have been designed for patients with a diagnosis of cancer. Unfortunately, despite the promising potential and impressive spread, their effectiveness often remains unclear. Most mobile apps are developed without any medical professional involvement and quality evidence-based assessment. Furthermore, they are often implemented in clinical care before any research is performed to confirm usability, appreciation, and clinical benefits for patients. OBJECTIVE: We aimed to develop a new smartphone app (Centro di Senologia della Svizzera Italiana [CSSI]) specifically designed by breast care specialists and patients together to help breast cancer patients better understand and organize their journey through the diagnosis and treatment of cancer. We describe the development of the app and present assessments to evaluate its feasibility, usefulness, and capability to improve patient empowerment. METHODS: A mixed method study with brief longitudinal quantitative data collection and subsequent qualitative semistructured interviews was designed. Twenty breast cancer patients participated in the study (mean age 51 years, SD 10 years). The usability of the app, the user experience, and empowerment were measured after 1 month. The semistructured interviews measured the utility of the app and the necessary improvements. RESULTS: The app received good responses from the patients in terms of positive perception of the purpose of the app (7/20, 35%), organizing the cure path and being aware of the steps in cancer management (5/20, 25%), facilitating doctor-patient communication (4/20, 20%), and having detailed information about the resources offered by the hospital (2/20, 10%). Correlation and regression analyses showed that user experience increased the level of empowerment of patients (B=0.31, 95% CI 0.22-0.69; P=.009). The interviews suggested the need to constantly keep the app updated and to synchronize it with the hospital's electronic agenda, and carefully selecting the best time to offer the tool to final users was considered crucial. CONCLUSIONS: Despite the very small number of participants in this study, the findings demonstrate the potential of the app and support a fully powered trial to evaluate the empowering effect of the mobile health app. More data will be gathered with an improved version of the app in the second phase involving a larger study sample.

Ovarian reserve of women with and without BRCA pathogenic variants: A systematic review and meta-analysis.

INTRODUCTION: Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations (BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type). MATERIAL AND METHODS: Systematic searches of PubMed, Medline, Scopus, Embase, Science Direct and the Cochrane Library from inception until July 2020 were conducted. All studies comparing AMH level in fertile age women, with and without BRCA pathogenic variants were considered. Sub-analyses were performed according to age, presence of breast cancer, and type of mutation. RESULTS: Among 64 studies, 10 series were included. For the entire cohort, a trend of reduced AMH level were found between BRCAm carriers and women without pathogenic variants. BRCAm carriers aged 41-years or younger had lower AMH levels compared to 41-years or younger wild type women (OR: 0.73 [95%CI-1.12;-0.35]; p = 0.0002). This finding was confirmed for BRCA1m carriers (OR: 1 [95%CI-1.96;-0.05]; p = 0.004) whereas no difference was observed between BRCA2m carriers and wild type women. The same analysis on breast cancer patients with and without BRCAm achieved the same results. CONCLUSION: Young BRCA1m carriers seem to have lower AMH level compared with wild type women and therefore a potential decreased ovarian reserve.

Fibrin Sealants and Axillary Lymphatic Morbidity: A Systematic Review and Meta-Analysis of 23 Clinical Randomized Trials.

BACKGROUND: use of fibrin sealants following pelvic, paraaortic, and inguinal lymphadenectomy may reduce lymphatic morbidity. The aim of this meta-analysis is to evaluate if this finding applies to the axillary lymphadenectomy. METHODS: randomized trials evaluating the efficacy of fibrin sealants in reducing axillary lymphatic complications were included. Lymphocele, drainage output, surgical-site complications, and hospital stay were considered as outcomes. RESULTS: twenty-three randomized studies, including patients undergoing axillary lymphadenectomy for breast cancer, melanoma, and Hodgkin's disease, were included. Fibrin sealants did not affect axillary lymphocele incidence nor the surgical site complications. Drainage output, days with drainage, and hospital stay were reduced when fibrin sealants were applied (p < 0.0001, p < 0.005, p = 0.008). CONCLUSION: fibrin sealants after axillary dissection reduce the total axillary drainage output, the duration of drainage, and the hospital stay. No effects on the incidence of postoperative lymphocele and surgical site complications rate are found.

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients.

BACKGROUND: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. PATIENTS AND METHODS: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). RESULTS: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75-0.80). After external validation the accuracy of the nomogram was confirmed. CONCLUSION: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.