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This study aims to compare patient-reported outcomes (PROs) after different types of oncoplastic surgery (OPS) procedures and correlate the results with previously published normative data from women with no prior history of breast cancer (BC) and breast surgery.Cross-sectional study of patients with stage I-II BC undergoing a specific selection of OPS procedures from 04/2012 to 12/2018 by three breast surgeons at a single tertiary referral hospital in Switzerland. PROs were evaluated using the postoperative BREAST-Q questionnaire.One hundred twenty-seven patients met the inclusion criteria and were surveyed. All OPS techniques achieved comparably elevated scores in satisfaction with breasts, psychosocial, and sexual well-being. Compared to normative data of healthy women, all OPS groups postoperatively achieved significantly better satisfaction with breasts, psychosocial, and sexual well-being.This study shows high PROs across all types of OPS, which were superior to normative data from healthy women. Our findings confirm that OPS is associated with high quality of life and patient satisfaction.

RxPONDER showed no benefit of adjuvant chemotherapy in postmenopausal women with estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer and limited nodal burden (pN1) with a recurrence score ≤ 25, suggesting that axillary staging could be omitted in cN0 patients if significant numbers of such women do not have pN2-3 disease. Here we evaluate the pN2-3 disease rate in a large cohort of postmenopausal women presenting with cN0 breast cancer.Consecutive postmenopausal patients presenting with T1-2N0 breast cancer who underwent axillary surgery from February 2006 to December 2011 were identified. Clinicopathologic characteristics associated with pN2-3 disease were examined using chi-square or Fisher's exact tests.Of 3363 postmenopausal women with cT1-2N0 breast cancer (median age 58 years, IQR 48-67 years), median tumor size was 1.3 cm (IQR 0.90-1.90cm). Post-axillary staging, 2600 (77.3%) were pN0, 643 (19.1%) were pN1, and 120 (3.6%) were pN2-3. The pN2-3 disease rate did not differ across subtypes (4.4% HER2In postmenopausal women with cN0 disease, pN2-3 nodal burden is uncommon; omitting axillary staging would not miss a significant number of patients who might benefit from adjuvant chemotherapy. Information available preoperatively indicating a higher risk of nodal disease such as younger age and large, multifocal tumors should be considered in the multidisciplinary management of the axilla.

IMPORTANCE: Risk factors for breast cancer–related lymphedema (BCRL) after axillary lymph node dissection (ALND) are poorly understood. OBJECTIVE: To evaluate rates of and risk factors associated with BCRL in a prospective cohort of women treated with ALND. DESIGN, SETTING, AND PARTICIPANTS: This prospective BCRL screening study performed at a tertiary cancer center enrolled women with breast cancer 18 years and older undergoing breast surgery and unilateral ALND in the primary setting or after sentinel lymph node biopsy. EXPOSURES: Risk of BCRL during the first 2 years after ALND and radiotherapy. MAIN OUTCOMES AND MEASURES: Patients were prospectively evaluated with arm volume (perometer) measurements, and BCRL was defined as a relative volume change of 10% or greater from baseline. Cumulative incidence of BCRL was assessed using competing risk analysis. Risk factors for BCRL were assessed on univariate and multivariable analyses. RESULTS: From November 2016 to March 2020, 304 patients were enrolled; 276 had at least 1 longitudinal measurement. Median (IQR) age was 48 (40-57) years; median (IQR) body mass index, calculated as weight in kilograms divided by height in meters squared, was 26.4 (22.5-31.2). Of the 276 patients included in the analysis, 29 (11%) self-identified as Asian, 55 (20%) as Black, 16 (6%) as Hispanic, 166 (60%) as White, and 10 (3%) as unknown race and ethnicity; 70% received neoadjuvant chemotherapy (NAC); 93% received nodal irradiation. The 24-month BCRL rate was 23.8% (95% CI, 17.9%-29.8%), with significant variation by race and ethnicity (24-month rate: 37.2% [Black], 27.7% [Hispanic], 22.5% [Asian], and 19.8% [White]; P = .004). The BCRL rates were also higher among patients receiving NAC vs up-front surgery (24-month rate: 29.3% vs 11.1%; P = .01). On multivariable analysis, Black race and Hispanic ethnicity (compared with White race) (odds ratio [OR], 3.88; 95% CI, 2.14-7.08 and OR, 3.01; 95% CI, 1.10-7.62, respectively; P

Background and objectives The oncological benefit of axillary surgery (AS), with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND), in elderly women affected by breast cancer (BC) is controversial. We evaluated AS trends over a 10-year follow-up period as well as locoregional and survival outcomes in this subset of patients. Methods Patients aged 70 years or older, treated between 1994 and 2008, were selected and divided in two groups, depending on whether or not AS was performed. A (1:1) matched analysis for all relevant clinicopathological features was performed. Outcomes were analyzed using the Kaplan–Meier method and univariate Cox-proportional hazard ratio analysis. Results A total of 1.748 patients were identified and stratified by age (70–74, 75–79, 80–84). A matched analysis was performed for 252 patients: 122 who underwent AS and 122 who did not. At 10-year follow-up, ipsilateral breast tumor recurrence, distant metastasis and contralateral BC were similar, p = 0.83, p = 0.42 and p = 0.28, respectively. In the no-AS group, a significant increased risk of axillary lymph-node recurrence was identified at 5- and confirmed at 10-years (p = 0.038), without impact on overall survival at 5- and 10-years (p = 0.52). In the non-AS group, higher rate of axillary recurrence at 10-years was observed in patients with poorly differentiated (24.1%, 95% CI 7.2–46.2), highly proliferative (Ki67 ≥ 20%: 17.1%, 95% CI 0.6–33.3) and luminal B tumors (16.8%, 95% CI 5.9–35.5). Conclusions Axillary staging in elderly women does not impact long-term survival. Tailoring surgery according to tumor biology and age may improve locoregional outcome.

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.

Radiotherapy (RT) after breast-conserving surgery (BCS) halves the risk of local recurrence, and it is considered the standard of care for the vast majority of patients with early invasive breast cancer. However, the majority of patients treated with BCS will not recur locally, even in the absence of RT. Over the past several decades, the improved and widespread use of systemic therapy has significantly decreased the rate of local recurrence. This has stimulated interest in identifying favorable patient subsets not requiring RT. Randomized controlled trials have shown in women aged ≥ 70 years with stage I estrogen receptor-positive (ER+) tumors, RT can be safely omitted. To better identify patients with favorable prognosis, ongoing trials have incorporated biological markers and genomic assays. Despite great research efforts to de-escalate locoregional treatment, real-world data indicate that omission of RT in low-risk patients is inconsistent. Better decision-making is warranted to reduce overtreatment and financial toxicity.

Purpose Some studies have indicated age-specific differences in quality of life (QoL) among breast cancer (BC) patients. The aim of this study was to compare patient-reported outcomes after conventional and oncoplastic breast surgery in two distinct age groups. Methods Patients who underwent oncoplastic and conventional breast surgery for stage I-III BC, between 6/2011–3/2019, were identified from a prospectively maintained database. QoL was prospectively evaluated using the Breast-Q questionnaire. Comparisons were made between women Results One hundred thirty-three patients were included. Seventy-three of them were ≥ 60 years old. 15 (20.5%) of them received a round-block technique (RB) / oncoplastic breast-conserving surgeries (OBCS), 10 (13.7%) underwent nipple-sparing mastectomies (NSM) with deep inferior epigastric perforator flap (DIEP) reconstruction, 23 (31.5%) underwent conventional breast-conserving surgeries (CBCS), and 25 (34.2%) received total mastectomy (TM). Sixty patients were younger than 60 years, 15 (25%) thereof received RB/OBCS, 22 (36.7%) NSM/DIEP, 17 (28.3%) CBCS, and 6 (10%) TM. Physical well-being chest and psychosocial well-being scores were significantly higher in older women compared to younger patients (88.05 vs 75.10; p p = 0.002, respectively). In multivariate linear regression, longer time intervals had a significantly positive effect on the scales Physical Well-being Chest (p = 0.014) and Satisfaction with Breasts (p = 0.004). No significant results were found concerning different types of surgery. Conclusion Our findings indicate that age does have a relevant impact on postoperative QoL. Patient counseling should include age-related considerations, however, age itself cannot be regarded as a contraindication for oncoplastic surgery.

Introduction The rapid spread of COVID-19 across the globe is forcing surgical oncologists to change their daily practice. We sought to evaluate how breast surgeons are adapting their surgical activity to limit viral spread and spare hospital resources. Methods A panel of 12 breast surgeons from the most affected regions of the world convened a virtual meeting on April 7, 2020, to discuss the changes in their local surgical practice during the COVID-19 pandemic. Similarly, a Web-based poll based was created to evaluate changes in surgical practice among breast surgeons from several countries. Results The virtual meeting showed that distinct countries and regions were experiencing different phases of the pandemic. Surgical priority was given to patients with aggressive disease not candidate for primary systemic therapy, those with progressive disease under neoadjuvant systemic therapy, and patients who have finished neoadjuvant therapy. One hundred breast surgeons filled out the poll. The trend showed reductions in operating room schedules, indications for surgery, and consultations, with an increasingly restrictive approach to elective surgery with worsening of the pandemic. Conclusion The COVID-19 emergency should not compromise treatment of a potentially lethal disease such as breast cancer. Our results reveal that physicians are instinctively reluctant to abandon conventional standards of care when possible. However, as the situation deteriorates, alternative strategies of de-escalation are being adopted. Implications for Practice This study aimed to characterize how the COVID-19 pandemic is affecting breast cancer surgery and which strategies are being adopted to cope with the situation.

Introduction: The majority of cancer patients report malnutrition, with a significant impact on patient's outcome. This study aimed to compare how nutritional assessment is conducted across different surgical oncology sub-specialties.Methods: Survey modules were designed for breast, hepato-pancreato-biliary (HPB), upper-gastrointestinal (UGI), sarcoma, peritoneal and surface malignancies (PSM) and colorectal cancer (CRC) surgeries to describe 4 domains: participants' setting, evaluation of clinical factors, use of screening tools and clinical practice. Results were compared among sub-specialties and according to human development index (HDI) in the largest cohorts.Results: Out of 457 answers from 377 global participants (62% European), 35.0% were from breast and 28.9% were from CRC surgeons. Although MDTs management is consistently reported (64-88%), the presence of a nutritionist/dietician ranges from 14.1% to 44.2%. Breast surgeons seldom evaluate albumin (25.6%) and weight loss (30.6%), opposite to HPB, PSM and UGI groups (>70%, p 0.044). Overall, responders declared that the use of screening tools is largely neglected, that nutritional status is often assessed by the surgeons and that nutrition is not consistently modified according to risk factors (range among groups respectively: 1.9%-25.6%, 33.1%-51.4%, 33.1%-60.5%). Less than 20% of breast surgeons assess patients before/after surgery, comparing to >60% of PSM surgeons. However, no statistical differences were documented comparing groups for the majority of the items of the 4 domains. Nutritional evaluation is more often conducted by breast surgeons in medium/low HDI countries comparing very high/high HDI (p 0.04).Conclusions: Nutritional assessment is largely neglected. These results identify target-issues for the implementation of clinical practice. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Axillary lymph node dissection (ALND) can be avoided in node-positive patients who receive neoadjuvant chemotherapy (NAC) if three or more negative sentinel lymph nodes (SLNs) are retrieved. We evaluate how often node-positive patients avoid ALND with NAC, and identify predictors of identification of three or more SLNs and of nodal pathological complete response (pCR). From November 2013 to July 2019, all patients with cT1-3, biopsy-proven N1 tumors who converted to cN0 after NAC received SLN biopsy (SLNB) with dual mapping and were identified from a prospectively maintained database. 630 consecutive N1 patients were eligible for axillary downstaging with NAC; 573 (91%) converted to cN0 and had SLNB, and 531 patients (93%) had three or more SLNs identified. Lymphovascular invasion (LVI; odds ratio [OR] 0.46, 95% confidence interval [CI] 0.24–0.87; p = 0.02) and increasing body mass index (BMI; OR 0.77, 95% CI 0.62–0.96 per 5-unit increase; p = 0.02) were significantly associated with failure to identify three or more SLNs. 255/573 (46%) patients achieved nodal pCR; 237 (41%) had adequate mapping. Factors associated with ALND avoidance included high grade (OR 2.51, 95% CI 1.6–3.94, p = 0.001) and receptor status (HR+/HER2− [referent]: OR 1.99, 95% CI 1.15–3.46 [p = 0.01] for HR−/HER2−, OR 3.93, 95% CI 2.40–6.44 [p

E-cadherin protein (CDH1 gene) integrity is fundamental to the process of epithelial polarization and differentiation. Deregulation of the E-cadherin function plays a crucial role in breast cancer metastases, with worse prognosis and shorter overall survival. In this narrative review, we describe the inactivating mechanisms underlying CDH1 gene activity and its possible translation to clinical practice as a prognostic biomarker and as a potential targeted therapy. This manuscript was supported by a grant from the Italy Ministry of Health (Project Code GR-2016-02361655), in part by the Ricerca Corrente and 5x1000 funds, and in part by the Fondazione IEO-CCM.

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

In cN1 patients rendered cN0 with neoadjuvant chemotherapy, the false-negative rate of sentinel lymph node biopsy (SLNB) is 10% when ≥ 3 sentinel lymph nodes (SLNs) are removed. The added value of nodal clipping in this scenario is unknown. Here we determine how often the clipped node is a sentinel node when ≥ 3 SLNs are retrieved.We identified cT1-3N1 patients treated between 02/2018 and 10/2021 with a clipped lymph node at presentation. SLNB was performed with a standardized approach of dual-tracer mapping and retrieval of ≥ 3 SLNs. Clipped nodes were not localized; SLNs were X-rayed intraoperatively to determine clip location. Axillary lymph node dissection (ALND) was performed for any residual disease or retrieval of 3 SLNs.Of 269 patients, 251 (93%) had ≥ 3 SLNs. Median age was 51 years; the majority (92%) had ductal histology; 46% were HR+/HER2-. The median number of SLNs removed was 4 (IQR 3,5). The clipped node was an SLN in 88% (220/251) of cases. Of the 31 where the clipped node was not, 13 had a positive SLN mandating ALND, and the clip was identified in the ALND specimen. In the remaining 18, where ≥ 3 negative SLNs were retrieved and an ALND was not performed, the clip was not retrieved, with no axillary failures in this group (median follow-up: 55 months).When the SLNB procedure is optimized with dual tracer and retrieval of ≥ 3 SLNs, the clipped node is an SLN in the majority of cases, suggesting that failure to retrieve the clipped node should not be an indication for ALND.

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 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.

Oncoplastic techniques allow resection of larger tumors, permitting breast conservation in cases otherwise requiring mastectomy. We sought to prospectively compare quality of life (QoL) in patients undergoing oncoplastic surgery as compared to conventional breast conservation (CBC) or mastectomy is lacking.Patients diagnosed with BIRADS IV-VI lesion were eligible if resection of ≥10% of the breast volume was planned. Patients were allowed to decide whether they wanted to undergo CBC or oncoplastic breast conservation (OBC). Patients who underwent mastectomy and immediate breast reconstruction (IBR) were also included for comparison. The primary endpoint was breast self-esteem using the Breast Image Scale (BIS) at 12 months, secondary endpoints were perioperative morbidity and QoL using the BREAST-Q questionnaire.From 2011 to 2016, 205 patients were included in the study. 116 patients (56.6%) received CBC, 46 (22.4%) OBC and 43 (21%) MIBR. Women in the OBC group were more likely to have tumors ≥ 2 cm than those in the CBC group (34.7% vs. 17.5%, respectively). Women who underwent MIBR were more likely to have tumors5 cm than those in the CBC and OBC groups (23% vs 1% and 10%, respectively). The BIS and BREAST-Q improved in each group after 12 months but did not differ significantly between groups at any time point. Surgical complications (seroma, bleeding, infection, necrosis) were numerically more likely in the OBC and MIBR groups.OBC and the MIBR allow for resection of larger tumors with a similar quality of life as CBC.

Importance Prospective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically node-positive breast cancer rendered clinically node-negative with neoadjuvant chemotherapy (NAC). However, rates of nodal recurrence in such patients treated with SLN biopsy (SLNB) alone are unknown because axillary lymph node dissection (ALND) was performed in all patients, limiting adoption of this approach. Objective To evaluate nodal recurrence rates in a consecutive cohort of patients with clinically node-positive (cN1) breast cancer receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. Design, Setting, and Participants From November 2013 to February 2019, a cohort of consecutively identified patients with cT1 to cT3 biopsy-proven N1 breast cancer rendered cN0 by NAC underwent SLNB with dual tracer mapping and omission of ALND if 3 or more SLNs were identified and all were pathologically negative. Metastatic nodes were not routinely clipped, and localization of clipped nodes was not performed. The study was performed in a single tertiary cancer center. Intervention Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative. Main Outcome and Measures The primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC. Results Of 610 patients with cN1 breast cancer treated with NAC (median [IQR] age, 49 [40-58] years), 555 (91%) converted to cN0 and underwent SLNB; 234 (42%) had 3 or more negative SLNs and had SLNB alone. Median age was 49 years. Median tumor size was 3 cm; 144 (62%) wereERBB2(formerlyHER2)-positive, and 43 (18%) were triple negative. Most (212 [91%]) received doxorubicin-based NAC, 205 (88%) received adjuvant radiotherapy (RT), and 164 (70%) also received nodal RT. At a median follow-up of 40 months, there was 1 axillary nodal recurrence synchronous with local recurrence in a patient who refused RT. Among patients who received RT (n = 205), there were no nodal recurrences. Conclusions and Relevance This cohort study found that in patients with cN1 disease rendered cN0 with NAC, with 3 or more negative SLNs with SLNB alone, nodal recurrence rates were low, without routine nodal clipping. These findings potentially support omitting ALND in such patients.

INTRODUCTION: The contralateral prophylactic mastectomy (CPM) rate in the U.S. has been steadily increasing. This is of particular concern because many women who undergo this procedure are candidates for breast-conserving surgery. AREAS COVERED: CPM’s medical benefit is related to the risk of contralateral cancer development and whether CPM provides a survival benefit. Contralateral cancer rates have decreased, and CPM does not provide a survival benefit. Other potential benefits of the procedure may be improved quality of life; these data are reviewed. Research efforts have been undertaken to better understand the decision-making process of patients who consider, and ultimately undergo, this procedure. EXPERT OPINION: Decisional traits, personal values, the desire for peace of mind, and the desire to obtain breast symmetry are important factors that drive a woman’s decision to undergo CPM. Additionally, many patients lack knowledge on how different types of breast surgery impact outcomes. To improve the shared decision-making process, a stepwise approach to address possible misconceptions, and clarify the real risks/benefits of this procedure should be utilized. A clear recommendation (for/against) should be made for every patient with newly diagnosed breast cancer who considers CPM. Communication tools to assist patients and surgeons in this process are sorely needed.

Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5–43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0–108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4–10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9–30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.

One in five women will experience depression over her lifetime, and one out of eight will develop breast cancer. We evaluated the effect of depression on adherence to mammography in Switzerland, where opportunistic and organized screening programs coexist. We analyzed data from 3206 women aged 50-69 who participated in the Swiss Health Survey 2012. We compared mammographic rates among women with no to mild versus moderate to severe depressive symptoms. The effect of the type of screening on the odds of undertaking a mammography was calculated using multivariable logistic regression analysis. Women with moderate to severe major depressive symptoms were more likely to have had a mammography in the previous 2 years than their nondepressed or less-depressed counterparts (51 vs. 39.2%, respectively, P = 0.005). In the multivariable analysis, women with no to mild major depression living in cantons with an organized screening program had an adjusted odds ratio of 2.7 (95% confidence interval: 2.30-3.17, P 0.001) of having had a mammography within the past 24 months compared with those living in the regions with an opportunistic screening. The adjusted odds ratio for women with moderate to severe major depression was 4.21 (95% confidence interval: 2.13-8.33, P 0.001). In Switzerland. adherence to mammographic screening among women with moderate to severe major depression is higher than among women with no or minimal major depressive symptoms. This increased adherence is even more pronounced in regions with organized screening.

The goal of our study was to provide a general overview of noncompliance with palliative systemic therapy in distant metastatic breast cancer (MBC). We analyzed an unselected cohort of 339 patients who were diagnosed with MBC over a 22-year period (1990–2011, age restriction: ≥ 85 years old). Forty patients (11.8%) rejected the offered or recommended systemic therapy (age distribution of this noncompliance subgroup: ≤60 years at MBC diagnosis: 7.9%; 60–70 years: 13.2%; > 70 years: 15.6%). The rate of noncompliance was equally distributed over time (1990–1999: 12.2% vs. 2000–2011: 11.5%, p = 0.87). Compared to patients who had received palliative antineoplastic systemic therapy, those who remained untreated were significantly older (70 vs. 61 years, p = 0.015), had shorter metastatic disease survival (2 vs. 27 months, p

Postoperative complications after breast cancer surgery may be associated with decreased quality of life. It remains unclear whether oncoplastic breast-conserving surgery or mastectomy with reconstruction lead to more postoperative complications than conventional breast surgery (CBS). As delayed wound healing (DWH) is one of the most frequent minor complications, we sought to investigate the significance of DWH for patient-reported outcomes after oncoplastic, reconstructive, and CBS.Our study is a retrospective cohort study of consecutive patients with stage I-II breast cancer who underwent oncoplastic or CBS performed by three breast surgeons at a single tertiary referral hospital from June 2011 until May 2019. Patient-reported outcomes were evaluated postoperatively using the BREAST-Q questionnaire. Comparisons were made between patients with and without DWH.A total of 229 patients who met the inclusion criteria and 28 (12%) of them developed DWH, 27/158 (17%) in the oncoplastic breast-conserving surgery and reconstruction group and 1/71 (1%) in the CBS group. The mean time from surgery to BREAST-Q assessment was comparable in both groups (29 months in the DWH vs. 33 months in the normal wound healing group). No statistically significant difference for any BREAST-Q scale was detected between patients with and without DWH. This includes physical (p = 0.183), psychosocial (p = 0.489), sexual well-being (p = 0.895), and satisfaction with breasts (p = 0.068).Our study confirms that oncoplastic breast-conserving surgery and mastectomy with reconstruction lead to significantly more DWH than CBS. However, neither quality of life nor patient-reported outcomes following state-of-the-art reconstructive or oncoplastic breast-conserving surgery at a specialized center seem to be compromised.

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.

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.

Breast cancer (BC) is the most frequent cancer in women and the leading cause of cancer death in females worldwide. Rapid research advancements add to the complexity of treatment options for this disease. It is known that the quality of patients’ care is deeply affected by healthcare professionals following these advancements. There is a growing need for academic education to increase clinical knowledge and skills of physicians treating BC patients. The certificate of Competence in Breast Cancer Program (CCB) is a Certificate in Advanced Studies (CAS) organized by the European School of Oncology in cooperation with Ulm University (Germany), which focuses on both the clinical and scientific competence required for improving quality in the management of BC patients. This paper describes the experience of the second CCB cohort (CCB2), which brought together 24 physicians from four continents who shared the common will to improve their competence and skills in BC treatment.

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.

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

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.

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.

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.

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.

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.

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.