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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.

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.

Growing numbers of asymptomatic women who become aware of carrying a breast cancer gene mutation (BRCA) mutation are choosing to undergo risk-reducing bilateral mastectomies with immediate breast reconstruction. We reviewed the literature with the aim of assessing the oncological safety of nipple-sparing mastectomy (NSM) as a risk-reduction procedure in BRCA-mutated patients. Nine studies reporting on the incidence of primary breast cancer post NSM in asymptomatic BRCA mutated patients undergoing risk-reducing bilateral procedures met the inclusion criteria. NSM appears to be a safe option for BRCA mutation carriers from an oncological point of view, with low reported rates of new breast cancers, low rates of postoperative complications, and high levels of satisfaction and postoperative quality of life. However, larger multi-institutional studies with longer follow-up are needed to establish this procedure as the best surgical option in this setting.

International audience; Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Background: Neoadjuvant chemotherapy (NAC) is increasingly used to treat node-positive (N+) breast cancer. Predictors of nodal pathological complete response (pCR) in Asian women are poorly described and there is variety in the management of the axilla after NAC. We evaluated predictors of nodal pCR and axillary management in a cohort of Asian N+ patients. Methods: Consecutive biopsy-proven N+ breast cancer patients treated with NAC were identified from the Shanghai Ruijin Hospital in China. Axillary lymph node dissection was performed on all patients, irrespective of the nodal response to NAC. Results: A total of 323 patients were included. Nodal pCR was achieved in 105 patients (33%), 15% of HR+/HER2– tumors, 38% of HR+/HER2+ tumors, 49% of HR–/HER2+ tumors, and 42% of HR–/HER2–tumors (p < 0.001). Factors associated with nodal pCR were (1) receptor status (HR+/HER2– [referent]: OR 3.42, 95% CI 1.43–8.16, p = 0.006 for HR+/HER2+; OR 4.19, 95% CI 1.85–9.50, p = 0.001 for HR–/HER2+; and OR 2.94, 95% CI 1.11–7.74, p = 0.029 for HR–/HER2–), (2) breast pCR (no pCR [referent]: OR 15.22, 95% CI 6.29–36.79, p < 0.001), and (3) absence of lymphovascular invasion (LVI [referent]: OR 9.04, 95% CI 2.09–39.18, p = 0.003). Conclusion: This study confirmed expected predictors of nodal pCR in Asian women and the benefit of NAC in downstaging the axilla independently of ethnicity.

Background Epidemiological and self-reported data suggest that Black women may be at increased risk of developing breast cancer related lymphedema (BCRL) after axillary lymph node dissection (ALND), however prospective clinical data is lacking. BCRL risk for other racial minorities has not been well studied. We sought to evaluate the impact of race and ethnicity on BCRL incidence and severity in a prospective cohort of patients treated with ALND using defined measurement protocols. Methods Patients undergoing ALND were enrolled in a prospective BCRL screening study with arm volume (perometer) measurements and body mass index (BMI) evaluated at baseline, post-operatively, and at 6-month intervals. BCRL was defined as a relative volume change (RVC) ≥ 10% from baseline. Groups were compared using Wilcoxon rank-sum and Fischer’s exact tests. Univariate (UVA) and multivariable analysis (MVA) were used to calculate the odds ratio (OR) of developing BCRL and to compare severity of BCRL. Results From 11/2016-03/2020, 304 patients were enrolled; 268 had at least one longitudinal measurement after baseline and are included in the study. Sixty-two percent of patients were Caucasian, 21% were Black, 11% were Asian and 6% were Hispanic. Black women were older (p = 0.007), had higher baseline BMI (p < 0.001), and were more likely to be clinically node-positive (p = 0.016) compared to Caucasian, Asian and Hispanic women. Both Black and Hispanic women were more likely to undergo breast-conserving surgery (p = 0.037) and receive nodal RT (p = 0.02) (Table). At a median follow-up of 1.62 years, 50 women developed BCRL. The 18-month BCRL rate for the entire cohort was 15.9% (95%CI, 11.5% - 21.8%). Black and Hispanic women had a higher incidence of BCRL compared to Asian and Caucasian women (18-month-rate: 30.9 % [Black]; 20.2% [Hispanic] vs 10.6% [Asian]; 11.8% [Caucasian], p = 0.004). On MVA, Black race was the strongest predictor of BCRL development (Caucasian [referent]): OR 4.41, 95%CI 2.42-8.10; p < 0.001); Asian race and Hispanic ethnicity were not associated with BCRL. Other factors, including receipt of NAC (upfront surgery [referent]): OR 1.89, 95%CI 1.02-3.63; p = 0.043), older age (1.04, 95%CI 1.01-1.06; per 1-year increase), increasing number of lymph nodes removed (OR 1.05, 95%CI 1.01-1.09 per 1 additional lymph node; p = 0.007) and a longer follow-up interval (OR 1.60, 95%CI 1.31-1.96 per 6-month increase; p < 0.001) were also independently associated with BCRL development. When assessing BCRL severity, Black women were 3.85 times more likely to have a higher relative volume change compared to Caucasian women (p = 0.007), with no difference in BCRL severity identified in Hispanic and Asian women (p = NS). Conclusions In this prospective screening study, Black and Hispanic women had a higher incidence of BCRL development compared to Caucasian women, with Black race being the strongest predictor of BCRL development and of severe BCRL. Further work should address the biologic mechanisms behind racial disparities in the risk of BCRL and possible preventive strategies. Table: Clinical Characteristics of study cohort stratified by race/ethnicityOverall#(n = 268)Caucasian(n = 161)Black (n = 54)Asian(n = 29)Hispanic (n = 16)P-valueAge (years)48. (40,57)49. (40,59)50. (42,55)44. (35,52)44. (33,49)0.007Baseline BMI (kg/m2)26.2. (22.5,31.1)25.2. (22.4,30.4)29.9. (25.9,34.0)22.1. (20.6,29.1)28.1. (23.5, 32.9)< 0.001cT. 1/2. 3/4180 (67%). 88 (33%)103 (64%). 58 (36%)36 (67%). 18 (33%)25 (86%). 4 (14%)12 (75%). 4 (25%)0.5cN. 0. 1. 2/372 (27%). 173 (65%). 23 (9%)46 (29%). 102 (63%). 13 (8%)8 (15%). 45 (83%). 1 (2%)12 (41%). 14 (48%). 3 (11%)3 (19%). 9 (56%). 4 (25%)0.016Histology. Ductal. Lobular or mixed. Other220 (82%). 36 (13%). 12(4.5%)128 (80%). 25 (16%). 8 (5.0%)47 (87%). 5 (9.3%). 2 (3.7%)25 (86%). 2 (6.9%). 2 (6.9%)12 (75%). 4 (25%). 0 (0%)0.5Subtype. HR+/HER2-. HER2+. HR-/HER2-181 (68%). 51 (19%). 36 (13%)111 (69%). 34 (21%). 16 (10%)31 (57%). 9 (17%). 14 (26%)23 (79%). 4 (14%). 2 (7%)10 (62%). 4 (25%). 2 (12%)0.1Chemotherapy. Neoadjuvant. Adjuvant190 (71%). 78(29%)111 (69%). 50 (31%)42(78%). 12(22%)17(59%). 12(41%)14(88%). 2(12%)0.12Type of Surgery. BCS. Mastectomy67 (25%). 201 (75%)36 (22%). 125 (78%)19 (35%). 35 (65%)3(10%). 26 (90%)6(38%). 10 (62%)0.037Type of Reconstruction†. None. Autologous/flap. TE/implant55 (27%). 23 (11%). 123 (61%)36 (29%). 11(9%). 78 (63%)9 (26%). 8 (23%). 18 (51%)8 (31%). 2(7%). 16 (62%)1(10%). 1 (10%). 8 (80%)0.083Total number of lymph nodes removed18 (14,23)19 (14,24)17 (13,22)15 (12,23)22 (18,24)0.059Total number of positive nodes2 (1, 5)3 (1, 6)2 (1, 3)2 (1, 4)2 (1, 3)0.073Radiation therapy††252 (94%)149 (93%)54 (100%)26 (90%)16 (100%)0.070Nodal RT244 (91%)145 (90%)53 (98%)23 (79%)16 (100%)0.020BCS, breast conserving surgery; TE, tissue expander Frequency (column percent) reported for categorical variables and median (IQR) reported for continuous variables #Race/ethnicity was unknown in 8 cases †Applies to mastectomy only ††Includes any type of radiation Citation Format: Andrea V. Barrio, Giacomo Montagna, Varadan Sevilimedu, Ethan A. Gomez, Babak Mehrara, Monica Morrow. Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: Results of a prospective screening study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-01.

Background Opioid-induced immunomodulation may be of particular importance in triple-negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and oncological outcomes and explored patterns of opioid receptor expression in TNBC. Methods Consecutive patients with stage I–III primary TNBC were identified from a prospectively maintained database. Opioid receptor expression patterns in the tumour microenvironment were analysed using publicly available bulk and single-cell RNA-seq data. Results A total of 1143 TNBC cases were retrospectively analysed. In multivariable analysis, higher intraoperative opioid dose was associated with favourable recurrence-free survival, hazard ratio 0.93 (95% confidence interval 0.88–0.99) per 10 oral morphine milligram equivalents increase (P=0.028), but was not significantly associated with overall survival, hazard ratio 0.96 (95% confidence interval 0.89–1.02) per 10 morphine milligram equivalents increase (P=0.2). Bulk RNA-seq analysis of opioid receptors showed that OPRM1 was nearly non-expressed. Compared with normal breast tissue OGFR, OPRK1, and OPRD1 were upregulated, while TLR4 was downregulated. At a single-cell level, OPRM1 and OPRD1 were not detectable; OPRK1 was expressed mainly on tumour cells, whereas OGFR and TLR4 were more highly expressed on immune cells. Conclusions We found a protective effect of intraoperative opioids on recurrence-free survival in TNBC. Opioid receptor expression was consistent with a net protective effect of opioid agonism, with protumour receptors either not expressed or downregulated, and antitumour receptors upregulated. In this era of personalised medicine, efforts to differentiate the effects of opioids across breast cancer subtypes (and ultimately individual patients) should continue.

Neoadjuvant endocrine therapy (NET) is effective in downstaging large hormone receptor-positive (HR+) breast cancers and increasing rates of breast-conserving surgery (BCS), but data regarding nodal pathologic complete response (pCR) are sparse. We reported nodal and breast downstaging rates with NET, and compared axillary response rates following NET and neoadjuvant chemotherapy (NAC). Consecutive stage I–III breast cancer patients treated with NET and surgery from January 2009 to December 2019 were identified from a prospectively maintained database. Nodal pCR rates were compared between biopsy-proven node-positive patients treated with NET, and HR+/HER2- patients treated with NAC from November 2013 to July 2019. 127 cancers treated with NET and 338 with NAC were included. NET recipients were older, more likely to have lobular and lower-grade tumors, and higher HR expression. With NET, the nodal pCR rate was 11% (4/38) of biopsy-proven cases, and the breast pCR rate was 1.6% (2/126). Nodal-dowstaging rates with NET and NAC were not significantly different (11% vs 18%; P = 0.37). Patients achieving nodal pCR with NET versus NAC were older (median age 70 vs 50, P = 0.004) and had greater progesterone receptor (PR) expression (85% vs 13%, P = 0.031), respectively. Of patients not candidates for BCS due to a large tumor relative to breast size, 36/47 (77%) became BCS-eligible with NET (median PR expression 55% vs 5% in those remaining ineligible, P

The aims of the Oncoplastic Breast Consortium initiative were to identify important knowledge gaps in the field of oncoplastic breast-conserving surgery and nipple-sparing or skin-sparing mastectomy with immediate breast reconstruction, and to recommend appropriate research strategies to address these gaps. A total of 212 surgeons and 26 patient advocates from 55 countries prioritised the 15 most important knowledge gaps from a list of 38 in two electronic Delphi rounds. An interdisciplinary panel of the Oncoplastic Breast Consortium consisting of 63 stakeholders from 20 countries obtained consensus during an in-person meeting to select seven of these 15 knowledge gaps as research priorities. Three key recommendations emerged from the meeting. First, the effect of oncoplastic breast-conserving surgery on quality of life and the optimal type and timing of reconstruction after nipple-sparing or skin-sparing mastectomy with planned radiotherapy should be addressed by prospective cohort studies at an international level. Second, the role of adjunctive mesh and the positioning of implants during implant-based breast reconstruction should ideally be investigated by randomised controlled trials of pragmatic design. Finally, the BREAST-Q questionnaire is a suitable tool to assess primary outcomes in these studies, but other metrics to measure patient-reported outcomes should be systematically evaluated and quality indicators of surgical morbidity should be further assessed.

E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as—(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC). This manuscript was supported by the Italian Ministry of Health (Project Code GR-2016-02361655) and was partially supported by the Ricerca Corrente and 5 × 1000 funds.

Background: The aim of this study was to compare the risk of complications and recurrence between oncoplastic and conventional breast surgery. Methods: This is a retrospective analysis of a consecutive series of 436 patients with stage I–III breast cancer who underwent surgery at the University Hospital of Basel between 2011 and 2018. Results: The nipple/skin-sparing mastectomy (NSM/SSM) group showed significantly more delayed wound healing (32.7 vs. 5.8%, p < 0.001) and skin necrosis (13.9 vs. 1.9%, p = 0.020) compared to conventional mastectomy (CM), which corresponded to significantly higher odds of short-term complications (OR 2.34, 95% CI 1.02–5.35, p = 0.044). The incidence rate of long-term morbidity in oncoplastic breast-conserving surgery (OBCS) was significantly higher compared to conventional breast-conserving surgery (CBCS; 25.5 vs. 11.3 per 100 patient years [PY], p < 0.001), in particular concerning chronic pain (13.3 vs. 6.6, p = 0.011) and lymphedema (4.1 vs. 0.4, p = 0.003). Seroma as a long-term morbidity occurred more often in the CM group compared to the NSM/SSM group (5.8 vs. 0.5 per 100 PY, p = 0.004). Patients received adjuvant treatment earlier after CM compared to NSM/SSM (HR 1.83, 95% CI 1.05–3.19, p = 0.034). There were no significant differences in the incidence of positive margins nor in the odds of recurrence after OBCS versus CBCS and after NSM/SSM versus CM. Conclusions: Even though the present study confirmed expected differences in complications and morbidity, it suggested that oncoplastic surgery is oncologically safe. Patients undergoing NSM/SSM should be followed closely to allow early detection and treatment of frequently associated complications and ensure timely start of adjuvant therapy.

Neoadjuvant chemotherapy (NAC) has been proven to increase breast-conserving surgery (BCS) rates, but data are limited on conversion rates from BCS-ineligible (BCSi) to BCS-eligible (BCSe), specifically, in patients with large tumors. Consecutive patients with stage I–III breast cancer treated with NAC from November 2013 to March 2019 were identified. BCS eligibility before and after NAC was prospectively determined. Patients deemed BCSi before NAC due to large tumor size were studied. Statistical analyses were conducted using Student’s t-test, Wilcoxon rank sum test, Chi-square test, Fisher’s test, and logistic regression. In this study, 600 of 1353 cancers were BCSi with large tumors; 69% were non-BCS candidates, 31% were borderline-BCS (bBCS) candidates. Of non-BCS candidates, 69% became BCSe after NAC; 66% chose BCS, and 90% were successful. Among bBCS candidates, 87% were BCSe after NAC, 73% chose BCS, and 96% were successful. On univariate analysis, bBCS candidacy, lower cT stage, cN0 status, absence of calcifications, human epidermal growth factor receptor 2 positive (HER2+)/triple negative (TN) receptor status, poor differentiation, ductal histology, and breast pCR were associated with conversion to BCS eligibility. On multivariable analysis, receptor status (hormone receptor positive [HR+]/HER2– ref; odds ratio [OR] HER2+ 1.63, P = 0.047; HR–/HER2– OR, 2.26, P = 0.003) and breast pCR (OR 2.62, P

Background: We challenge the concept of metastatic breast cancer (MBC) as a chronic disease. Methods: We analyzed an unselected cohort of 367 patients who were diagnosed with MBC over a 22-year period (1990–2011). Results: In order to create a “chronic disease subgroup”, we separated those patients from the entire cohort in whom systemic therapy was not applied after the diagnosis of MBC (n = 53; 14.4%). Three hundred fourteen patients (85.6%) comprised the “chronic disease subgroup”. The vast majority of those patients (89.8%) died of progressive disease after a median metastatic disease survival (MDS) of 25 months. Twenty patients (6.4%) died of non-MBC-related causes (MDS 38.5 months). Approximately 1 in 4 patients (26.8%) died within the first year after the MBC diagnosis. The 3- and 5-year MDS rates were 35.4 and 16.2%, respectively. Only 12 patients (3.8%) were exceptional survivors (MDS >10 years). Conclusion: The term “chronic disease” might be appropriate in selected MBC cases, bringing MBC into alignment with “classical” chronic diseases such as diabetes and hypertension. However, most cases display fundamental differences with regard to temporal progression and above all the case fatality rate. More than 90% of patients in the “chronic disease subgroup” died of the disease with a MDS of 2–3 years (even those who underwent systemic palliative therapies). Doctors and patients might understand the term “chronic disease” differently. The term must be used sparingly and explained carefully in order to create a common level of communication based on a shared understanding which avoids awakening false hopes and fostering misleading expectations.

Since its introduction nearly 30 years ago, sentinel lymph node biopsy (SLNB) has become the standard technique to stage the axilla for the great majority of patients with early breast cancer. While the accuracy of SLNB in clinically node-negative patients who undergo neoadjuvant chemotherapy (NAC) is similar to the upfront surgery setting, modifications of the technique to improve the false negative rate are necessary in node-positive patients at presentation. Currently, patients who present with matted nodes, cN1 patients who fail to downstage to cN0 with NAC and those with pathological residual disease have an indication to undergo axillary lymph node dissection. Ongoing trials will confirm if extensive nodal irradiation can replace surgery in patients with residual nodal disease after NAC and if nodal radiotherapy can be omitted in patients who achieve nodal pathological complete response. The aim of this review was to focus on the open questions on the management of the axilla after NAC.

The Breast Surgery theoretical and practical knowledge curriculum comprehensively describes the knowledge and skills expected of a fully trained breast surgeon practicing in the European Union and European Economic Area (EEA). It forms part of a range of factors that contribute to the delivery of high quality cancer care. It has been developed by a panel of experts from across Europe and has been validated by professional breast surgery societies in Europe. The curriculum maps closely to the syllabus of the Union of European Medical Specialists (UEMS) Breast Surgery Exam, the UK FRCS (breast specialist interest) curriculum and other professional standards across Europe and globally (USA Society of Surgical Oncology, SSO). It is envisioned that this will serve as the basis for breast surgery training, examination and accreditation across Europe to harmonise and raise standards as breast surgery develops as a separate discipline from its parent specialties (general surgery, gynaecology, surgical oncology and plastic surgery). The curriculum is not static but will be revised and updated by the curriculum development group of the European Breast Surgical Oncology Certification group (BRESO) every 2 years.

Background: Four prospective multi-institutional trials have demonstrated that clinically node-positive patients (cN1) who receive neoadjuvant therapy (NAC) and convert to cN0 can be reliably staged with sentinel lymph node biopsy (SLNB) with false-negative rates (FNRs) of < 10%, when ≥ 3 SLNs are retrieved. Since study patients all had axillary lymph node dissection (ALND), the rate of axillary recurrence after SLNB alone is unknown. Of concern is the possibility that residual chemotherapy-resistant axillary disease could lead to higher recurrence rates than seen in the primary surgery setting for cN0 patients where SLN FNRs of 5-10% result in axillary recurrence in < 1% of cases. Here we report regional recurrence rates in a prospectively defined cohort of cN1 patients receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. Methods: From 06/2014 to 02/2019, patients with cT1-3 biopsy-proven cN1 breast cancer who received NAC and converted to cN0 by physical exam were prospectively managed with SLNB with dual tracer mapping and omission of ALND if ≥ 3 SLNs were pathologically negative. Nodes were not routinely clipped, and retrieval of clipped metastatic nodes was not required. Pathologically negative SLNs were defined as the absence of any metastases including isolated tumor cells. Results: Of 610 cN1 patients treated with NAC, 555 (91%) converted to cN0 and had SLNB; 234 (42%) had ≥ 3 negative SLNs and were treated with SLNB alone. Median patient age was 49 years and median tumor size at presentation was 3 cm; 61% were HER2+ and 18% triple negative. Most (91%) received doxorubicin-based NAC and 88% received adjuvant radiotherapy (RT), with 80% (n = 164) of RT patients receiving nodal RT (Table). At a median follow-up of 35 months, there was only 1 (0.4%) axillary recurrence for the entire cohort, synchronous with a breast recurrence, in a patient who refused RT. Among patients who received RT (n = 205), there were no axillary recurrences. The 4-year rate of distant recurrence for all patients was 6.1% (95% CI, 3.4-10.7%) and 4-year overall survival was 93.9% (95% CI, 87.6-97.1%). Conclusion: In cN1 patients treated with NAC, rates of axillary recurrence in patients with ≥ 3 pathologically negative SLNs treated with SLNB alone were low, without routine nodal clipping. Although further follow-up is needed, multiple studies have shown that nodal recurrence is an early event, particularly in HER2+ and triple negative patients, who comprised the majority of the population. Our findings support omitting ALND in cN1 patients after NAC when the SLNs are negative using an optimal SLNB technique. Table. Patient PopulationOverall cohort (n = 234)Age, years (median, IQR)49 (40, 58)Tumor size at presentation, cm (median, IQR)3.0 (2.2, 5.0)Number SLNs retrieved (median, IQR)4 (3, 5)Palpable nodes at presentation (n, %)179 (76%)HistologyDuctal211 (90%)Lobular and mixed7 (3%)Micropapillary and mixed10 (4%)Other3 (1%)Occult3 (1%)DifferentiationWell1 (0.5%)Moderate36 (15%)Poor196 (84%)Unknown1 (0.5%)Receptor StatusHR+/HER2-47 (20%)HR+/HER2+80 (34%)HR-/HER2+64 (27%)HR-/HER2-43 (18%)Breast SurgeryBCS118 (50%)Mastectomy116 (50%)Breast pCR¥Yes161 (70%)No70 (30%)NAC regimenAC-T197 (84%)AC-T + carbo15 (6.4%)TC8 (3.4%)Other14 (6%)Neoadjuvant anti-HER2 treatmentHP (dual-therapy)144 (100%)Adjuvant RTYes205 (88%)No*29 (12%)¥3 patients had occult primary breast cancer and were not included in breast pCR calculation; *6/29 patients who did not receive RT enrolled in NSABP B-51 Citation Format: Andrea V Barrio, Giacomo Montagna, Anita Mamtani, Varadan Sevilimedu, Hiram S Cody, III, Mahmoud El-Tamer, Mary L Gemignani, Alexandra S Heerdt, Tracy-Ann Moo, Melissa Pilewskie, George Plitas, Lisa Sclafani, Kimberly J Van Zee, Monica Morrow. Axillary recurrence is a rare event in node-positive patients. treated with sentinel node biopsy alone after neoadjuvant chemotherapy: Results of a prospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-05.

Introduction Delay between clinical presentation and treatment of breast cancer (BC) can significantly impact mortality. We aimed at drawing a picture of women with locally advanced breast cancer (LABC) treated at our Breast Unit and at investigating factors associated with treatment delay. Material and methods A retrospective descriptive analysis, using a specific 28-item semi-structured questionnaire, was conducted in 67 patients diagnosed with T4 BC. Results Nearly a third of our patients had at least one known predisposing factor for LABC. 42% of patients did not perform routine medical breast checks, 49% reported indifference as the first feeling and 47% waited at least 3 months before seeking medical attention. The reasons for diagnostic delay were different in the various age groups. Doctor's delay in making the right diagnosis occurred in 60% of younger patients (≤40 years, n = 5), whereas among women aged 41–69years (n = 34) 50% suffered from psychiatric comorbidities. In patients ≥70 years (n = 28) social factors such as isolation, being widowed and living in a retirement home were present in most of the cases. Delay in seeking medical care was also associated with increasing age. Across all age groups, coping factors such as denial and indifference were also associated with an increase in the odds of delayed presentation, as opposed to fear. Conclusions Factors possibly explaining late medical consultation seem to differ according to age. Psychological factors are crucial in patients' delay whereas age and social factors are relevant in doctors' and system's delay.

Background: Previous data showed that distant metastatic breast cancer (MBC) might be curable in up to 3% of the cases in selected patients, mostly young, with good performance status and with low-volume metastatic disease, mainly by an aggressive multidisciplinary approach including aggressive combination chemotherapy regimens. These long-lasting responses question the belief that MBC is wholly incurable. This study evaluates the rate of long-term survivors and potentially cured patients in an unselected cohort of MBC patients. Methods: We analyzed the data from 342 patients in whom distant MBC was diagnosed from 1990 to 2011. For this study, we defined a metastatic disease survival (MDS) of 9 years as inclusion criterion for long-term survivorship. Results: Eighteen patients (5.3%) were long-term survivors (MDS: 126 months; range, 108–300 months). The rate of long-term survivors was equally distributed over time (1990–1999: 4.3% vs. 2000–2011: 5.9%, p = 0.63). Compared to patients who had a lower MDS, long-term survivors had significantly more often primary MBC (p = 0.005) and hormone receptor-positive carcinomas (p = 0.015). Age at MBC diagnosis, presence of visceral metastases, and limited number of metastatic sites at the time of MBC diagnosis appeared to have no significant impact on long-term survival. Long-term survival was not associated with the use of chemotherapy (50.0% vs. 65.7% in the control group, p = 0.21). Eight patients (2.3%) developed a complete remission and presented with no evidence of disease at the time of last follow-up (MDS: 234.5 months). Conclusion: Since long-term survivors in MBC comprise a relatively heterogeneous group, the factors that lead to the quite rare and felicitous case of long-term survival or even cure can hardly be evaluated systematically. Some patients may be considered cured of their disease. This fraction may be small, but the chance of survival, and even of cure, truly exists. Perhaps we must accept that the factors contributing to long-term survival remain an enigma. It appears, however, that aggressive chemotherapy is not the only key factor to long-term remission.

OBJECTIVE To show that the expression of urokinase plasminogen activator (uPA) in the leucocytes of patients with benign and malignant breast lesions correlates with its expression in the lesions, and to explore the role of uPA as a tumour marker in breast cancer. METHODS Using real time reverse transcriptase - polymerase chain reaction (RT-PCR), we examined the expression of uPA in leukocytes and tissues of three groups of women: a) with breast cancer (BC), b) with benign breast lesions and c) a control group of healthy women. An arbitrary value of 1 was assigned to the level of uPA expressed in the leucocytes of the healthy controls; all other measurements were expressed as a function of this value. RESULTS The expression of uPA was significantly higher in BC samples compared to benign breast lesion (5.7 versus 3.8 times; p < 0.001). The leukocyte uPA of healthy volunteers was significantly lower than the leukocyte uPA from patients with breast lesions (p < 0.001). Leukocyte uPA level of patients with BC was higher compared to leukocyte uPA of women with benign lesions (p < 0.01). The expression of tissue uPA was the highest in triple-negative breast cancer. Methylation status was similar across tissue and leukocyte samples. CONCLUSIONS Leukocyte uPA can be considered a surrogate of the tissue uPA expressed in BC samples. These results further support the use of leukocyte uPA as a biochemical marker of breast cancer.

Ductal carcinoma in situ (DCIS) is a heterogenous disease. The mainstay of its management is surgery, and lumpectomy with or without radiation therapy (RT) or mastectomy are standard options. Endocrine therapy may be given to maximize risk reduction. With standard treatment, the longterm breast cancer-specific survival is excellent and exceeds 95%. Currently, management strategies are based on standard clinicopathological features. Genomic tools to predict local recurrence have been developed, and prospective studies to evaluate their impact on RT recommendations and outcomes are ongoing. Because of concerns regarding overtreatment of DCIS, there has been much enthusiasm for de-escalating locoregional therapy. RT halves the risk of local recurrence but does not affect survival, and its omission can be considered in low-risk groups. Active surveillance for lowrisk DCIS is being evaluated in 4 prospective trials. The concern regarding these trials is whether the selected "low-risk" cases are truly at low risk, and what threshold of recurrence is considered acceptable. Additionally, it is unclear whether patients will be willing to trade short outpatient procedures for more biopsies, more imaging, and possibly increased concern about recurrence. The clinical relevance and the safety of this approach are yet to be determined.

542 Background: Opioid-induced immunomodulation may be of particular importance in triple negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and outcomes in a large TNBC cohort. Methods: Consecutive patients with stage I-III primary TNBC treated between 03/2010 and 12/2016 were identified from our prospectively maintained database. Total intraoperative opioid dose was extracted from anesthetic records and converted to oral morphine milligram equivalents (MME) (10 MME = 50 mcg fentanyl IV). Univariable and multivariable (MVA) Cox proportional hazards analysis (adjusting for relevant clinicopathological features, (neo)adjuvant therapy, anesthesia technique and morbidity score), were performed to quantify the association between opioid exposure and recurrence-free survival (RFS) and overall survival (OS). Results: 1143 patients were included. Median age was 54 years (IQR 45, 64). 911 (80%) had ductal histology, 359 (31%) had nodal metastases, and 1070 (94%) were poorly differentiated. 781 (68%) received adjuvant chemotherapy and 313 (27%) received neoadjuvant chemotherapy. 525 (46%) received total intravenous anesthesia and 618 (54%) had general anesthesia. Median intraoperative opioid dose was 30 MME (IQR 20, 60). 5-year RFS was 81% (95% CI 79%-84%), 5-year OS was 86% (95% CI 84%-88%). In MVA, higher opioid administration was associated with favorable RFS but did not significantly affect OS (Table). Conclusions: Our study is the first to directly evaluate intraoperative opioid administration in TNBC and suggests a protective effect on RFS. Future work will focus on elucidating the underlying mechanism for this effect, including possible modulation of endogenous opioid signaling pathways and immunologic correlates. [Table: see text]

Granular cell tumors are rare soft tissue tumors; they are almost never malignant, but can mimic a carcinoma clinically, radiologically and microscopically. The finding of a suspicious lump often entails subsequent diagnostic procedures that can pose significant anxiety on patients before reaching a challenging differential diagnosis. The physical and psychological burden is even more significant when such findings occur during the follow up of a previous oncologic condition. Sometimes the fear for a potential local or distant recurrence can be responsible for a misdiagnosis and lead to patient overtreatment.

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. Electronic supplementary material The online version of this article (10.1007/s10549-018-4937-1) contains supplementary material, which is available to authorized users.

Background:The total testosterone (T) cutoffs clinically adopted to define late-onset hypogonadism (LOH) do not consider the differences that exist between different analytical platforms, nor do they consider the body mass index (BMI) or age of the patient. We aimed at providing method, age and BMI-specific normal values for total T in European healthy men.Methods:A total of 351 eugonadal healthy men were recruited, and total T was measured with four automated immunometric assays (IMAs): ARCHITECT i1000SR (Abbott), UniCel DxI800 (Beckman Coulter), Cobas e601 (Roche), IMMULITE 2000 (Siemens) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Reference ranges (RRs) were calculated for each method.Results:Passing and Bablok regression analysis and Bland-Altman plot showed an acceptable agreement between Abbott and LC-MS/MS, but a poor one between LC-MS/MS and the other IMAs. Age-specific T concentrations in non-obese (BMI 2) men were greater than in all men. The total T normal range, in non-obese men aged 18–39 years, measured with LC-MS/MS was 9.038–41.310 nmol/L. RRs calculated with LC-MS/MS statistically differed from the ones calculated with all individual IMAs, except Abbott and among all IMAs. Statistically significant differences for both upper and lower reference limits between our RRs and the ones provided by the manufacturers were also noticed.Conclusions:We calculated normal ranges in a non-obese cohort of European men, aged 18–39 years, with four commercially available IMAs and LC-MS/MS and found statistically significant differences according to the analytical method used. Method-specific reference values can increase the accuracy of LOH diagnosis and should be standardly used.

Hashimoto's encephalopathy (HE) is a rare not well understood, progressive and relapsing multiform disease, characterized by seizures, movement disorders, subacute cognitive dysfunction, psychiatric symptoms and responsiveness to steroid therapy. The disorder is generally associated with thyroid diseases and the most common feature is the presence of anti-thyroperoxidase antibodies (TPOAb). Patients are usually euthyroid or mildly hypothyroid at presentation. All age groups can be affected. The pathophysiology is still unclear, especially the link between elevated serum TPOAb and the encephalopathy. Most reported cases occurred in women and girls. Unspecific symptoms, non-pathognomonic laboratory neurophysiology and neuroimaging features make its diagnosis a real challenge for clinicians. The case of a 16 year old boy, with a clinical picture of HE associated with hypothyroidism, demonstrating an excellent response to high dose steroids is presented together with a systematic review of the literature.