Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases.

BACKGROUND: Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS: We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS: Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy-only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy-only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS: The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).

Completion axillary lymph node dissection for the identification of pN2-3 status as an indication for adjuvant CDK4/6 inhibitor treatment: a post-hoc analysis of the randomised, phase 3 SENOMAC trial.

BACKGROUND: In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1-2, grade 1-2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2-3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial. METHODS: In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1-T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1-2, histological grade 1-2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing. FINDINGS: Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52-71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6-59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery. INTERPRETATION: As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose. FUNDING: Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.

Timing and type of breast reconstruction in SweBRO 3: long-term outcomes.

BACKGROUND: Breast reconstruction after mastectomy helps women with breast cancer feel better about their bodies and lives. There is debate about the best time and type of reconstruction (immediate versus delayed, and using own tissue versus implants). Long-term studies are rare. AIM: This study looked at long-term results of different breast reconstruction methods and timings in Swedish women who had mastectomies in 2000, 2005 or 2010. It focused on how satisfied the women were with their surgeries and their quality of life. METHOD: The study included 5853 women from the Swedish National Breast Cancer Registry who had mastectomies in 2000, 2005 or 2010. Of these, 2904 women answered the survey, and 895 had breast reconstruction. Satisfaction and quality of life were measured using two surveys: EORTC QLQ-BRECON23 and BREAST-Q. RESULTS: Of the women who answered the survey, 895 (31%) had breast reconstruction. Of these, 176 (20%) had immediate reconstruction, and 719 (80%) had delayed reconstruction; 58% had implant-based reconstructions, 31% had reconstructions using their own tissue, 2% had both types and 9% did not report the type of reconstruction. There were no major differences in satisfaction between immediate and delayed reconstruction. Women who used their own tissue were more satisfied with their results and breast appearance than those with implants. CONCLUSION: Autologous reconstruction leads to better satisfaction and outcomes than implants. The timing of reconstruction (immediate versus delayed) was less of an influence on quality of life.

'Balancing Challenges and Personal Resources': A Qualitative Study of Women's Experiences of Arm Impairment After Axillary Surgery for Breast Cancer.

AIM: To explore how women previously treated for breast cancer experience living with arm impairment after axillary surgery. DESIGN: Descriptive qualitative study. The inductive starting point for the analysis was followed by a deductive approach as the categories were related to the components of the sense of coherence framework. METHODS: Twenty-eight relapse-free Swedish-speaking females participated in six focus group discussions conducted between September and December 2022. All participants had undergone sentinel lymph node biopsy with or without completion axillary dissection 4 years earlier. Data were analysed using qualitative content analysis. RESULTS: Three categories and an overall theme were identified. The categories 'Sense-making', 'Daily life' and 'Driving force' reflect actions to understand and prevent arm symptoms, adaptations made in daily life and the empowering resources adopted to meet challenges. The overall theme, 'Balancing challenges and personal resources', comprised a process that began at diagnosis and remained ongoing for some participants. Most participants considered their new life situations manageable. However, those with more pronounced arm impairment reported that they did not always receive adequate aid, and that their daily lives were negatively affected. CONCLUSION: Returning to everyday life after axillary surgery for breast cancer is associated with varying degrees of challenges. Individuals with persistent arm impairment find returning to normal life more challenging. Therefore, further improvements in person-centred care are of utmost importance. PATIENT AND PUBLIC CONTRIBUTION: Members of the Swedish Breast Cancer Association were involved in the creation of the interview guide. IMPACT: This study emphasises the requirement for providing further individualised support to those living with more severe arm impairment after axillary surgery. REPORTING METHOD: This study was reported in accordance with the Standards for Reporting Qualitative Research.

Applicability of magnetic seeds for target lymph node biopsy after neoadjuvant chemotherapy in initially node-positive breast cancer patients: data from the AXSANA study.

PURPOSE: Currently, various techniques are available to mark and selectively remove initially suspicious axillary lymph nodes (target lymph nodes, TLNs) in breast cancer patients receiving neoadjuvant chemotherapy (NACT). To date, limited data are available on whether the use of magnetic seeds (MS) is suitable for localizing TLNs. This study aimed to investigate the feasibility of MS in patients undergoing target lymph node biopsy (TLNB) or targeted axillary dissection (TAD) after NACT. METHODS: Prospective data from the ongoing multicentric AXSANA study were extracted from selected patients in whom the TLN had been marked with an MS before NACT and who were enrolled from June 2020 to June 2023. The endpoints of the analysis were the detection rate, the rate of lost markers, and the potential impairment on magnetic resonance imaging (MRI) assessment. RESULTS: In 187 patients from 27 study sites in seven countries, MS were placed into the TLN before NACT. In 151 of these, post-NACT surgery had been completed at the time of analysis. In 146 patients (96.0%), a TLN could successfully be detected. In three patients, the seed was removed but no lymphoid tissue was detected on histopathology. The rate of lost markers was 1.2% (2 out of 164 MS). In 15 out of 151 patients (9.9%), MRI assessment was reported to be compromised by MS placement. CONCLUSION: MS show excellent applicability for TLNB/TAD when inserted before NACT with a high DR and a low rate of lost markers. Axillary MS can impair MRI assessment of the breast. TRIAL REGISTRATION NUMBER: NCT04373655 (date of registration May 4, 2020).

Medical and surgical postoperative complications after breast conservation versus mastectomy in older women with breast cancer: Swedish population-based register study of 34 139 women.

BACKGROUND: Mastectomy rates in breast cancer are higher in older patients. The aim was to compare postoperative complication rates after breast-conserving surgery (BCS) to mastectomy in women aged 70-79 and older than 80 years versus those aged 50-69 years, and to evaluate survival effects. METHODS: This population-based cohort included women aged 50 years and older with invasive breast cancer T1-3 N0-3 M0 operated on in Sweden 2008-2017. Major surgical and medical 30-day postoperative complications were assessed in adjusted logistic regression models. Overall survival was assessed in Cox models adjusted for clinical confounders, socio-economics, and comorbidity. RESULTS: Of 34 139 women, 8372 (24.5 per cent) were aged 70-79 years, 3928 (11.5 per cent) were 80 years of age or older, and 21 839 (64.0 per cent) were aged 50-69 years. Major surgical postoperative complications did not differ between age groups receiving equivalent surgery (BCS: 2.1 per cent and 2.0 per cent versus 2.1 per cent (P = 0.90); mastectomy: 4.6 per cent and 5.1 per cent versus 4.6 per cent (P = 0.49)). Major medical postoperative complications were higher in women aged >70 years than in women aged 50-69 years (BCS: 1.0 per cent and 2.3 per cent versus 0.4 per cent (P < 0.001); mastectomy: 3.1 per cent and 6.2 per cent versus 1.1 per cent (P < 0.001)), which persisted after adjustments. In women treated by mastectomy, major medical and surgical postoperative complications were associated with worse overall survival in all but the middle age group. CONCLUSION: Mastectomy has higher medical and surgical postoperative complication rates than BCS. Major medical postoperative complications increase significantly with age. Major postoperative complications are associated with worse survival after mastectomy, which should be used with caution in older women.

In breast cancer, either a bit of the breast or the whole breast is removed. Older women more often have their whole breast removed. Such larger surgery may have a higher risk of complications. Complications after surgery can lower the chances of survival. The aim of this project was to find out whether older age comes with more complications after breast surgery. The authors also wanted to know whether this has an effect on survival. This work used information on women aged 50 years and older operated on for breast cancer in Sweden from 2008 to 2017. Major surgical and medical complications after breast surgery were compared in three different age groups. In addition, death of any cause was analysed. Of 34 139 women, 8372 were 70­79 years old and 3928 were aged 80 years or older. These older women were compared to 21 839 women who were 50­69 years old. Major surgical complications did not increase with age. However, medical complications were more common in older women. Removing the whole breast gave more complications than removing only part of the breast. In women aged 80 years or older who had their whole breast removed, complications after surgery increased the risk of death. This was true even when considering how severe the cancer was, how it was treated, and also what kind of socio-economic background and afflictions other than breast cancer the women had. Therefore, removal of the whole breast should be done with caution in older women.

Current trends in diagnostic and therapeutic management of the axilla in breast cancer patients receiving neoadjuvant therapy: results of the German-wide NOGGO MONITOR 24 survey.

PURPOSE: In the last 2 decades, the optimal management of the axilla in breast cancer patients receiving neoadjuvant chemotherapy (NACT) has been one of the most frequently discussed topics. Little is known about the attitudes of surgeons/radiologists towards new developments such as targeted axillary dissection. Therefore, the NOGGO conducted a survey to evaluate the current approach to axillary management. METHODS: A standardized digital questionnaire was sent out to > 200 departments in Germany between 7/2021 and 5/2022. The survey was supported by EUBREAST. RESULTS: In total, 116 physicians completed the survey. In cN0 patients scheduled to receive NACT, 89% of respondents recommended sentinel lymph node biopsy (SLNB) after NACT. In case of ypN1mi(sn), 44% advised no further therapy, while 31% proposed ALND and 25% axillary irradiation. 64% of respondents recommended a minimally invasive axillary biopsy to cN + patients. TAD was used at the departments of 82% of respondents and was offered to all cN + patients converting to ycN0 by 57% and only to selected patients, usually based on the number of suspicious nodes at time of presentation, by 43%. The most common marking technique was a clip/coil. 67% estimated that the detection rate of their marker was very good or good. CONCLUSION: This survey shows a heterogenous approach towards axillary management in the neoadjuvant setting in Germany. Most respondents follow current guidelines. Since only two-thirds of respondents experienced the detection rate of the marker used at their department as (very) good, future studies should focus on the comparative evaluation of different marking techniques.

False-negative rate in the extended prospective TATTOO trial evaluating targeted axillary dissection by carbon tattooing in clinically node-positive breast cancer patients receiving neoadjuvant systemic therapy.

PURPOSE: In clinically node-positive breast cancer patients receiving neoadjuvant systemic therapy (NST), nodal metastases can be initially marked and then removed during surgical axillary staging. Marking methods vary significantly in terms of feasibility and cost. The purpose of the extended TATTOO trial was to report on the false-negative rate (FNR) of the low-cost method carbon tattooing. METHODS: The international prospective single-arm TATTOO trial included clinically node-positive breast cancer patients planned for NST from November 2017 to January 2021. For the present analysis, patients who received both the targeted procedure with or without an additional sentinel lymph node (SLN) biopsy and a completion axillary lymph node dissection (ALND) were selected. Primary endpoint was the FNR. RESULTS: Out of 172 included patients, 149 had undergone a completion ALND. The detection rate for the tattooed node was 94.6% (141 out of 149). SLN biopsy was attempted in 132 out of 149 patients with a detection rate of 91.7% (121 out of 132). SLN and tattooed node were identical in 58 out of 121 individuals (47.9%). The combined procedure, i.e. targeted axillary dissection (TAD) was successful in 147 of 149 cases (98.7%). Four out of 65 patients with a clinically node-negative status after NST had a negative TAD but metastases on ALND, corresponding to a FNR of 6.2%. All false-negative TAD procedures were performed in the first 2 years of the trial (2018-2019, p = 0.022). CONCLUSION: Carbon tattooing is a feasible marking method for TAD with a high detection rate and an acceptably low FNR. The TATTOO trial was preregistered as prospective trial before initiation at the University of Rostock, Germany (DRKS00013169).

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

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

Major surgical postoperative complications and survival in breast cancer: Swedish population-based register study in 57 152 women.

BACKGROUND: Postoperative complications may activate prometastatic systemic pathways through tissue damage, wound healing, infection, and inflammation. Postoperative complications are associated with inferior survival in several types of cancer. The aim was to determine the association between postoperative complications and survival in breast cancer. METHODS: This population-based cohort included women operated for T1-3 N0-3 M0 invasive breast cancer in Sweden from 2008 to 2017. Only major surgical postoperative complications leading to readmission and/or reoperation within 30 days were considered. Main outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Prospectively collected nationwide register data were used. Multivariable Cox models were adjusted for clinical and socioeconomic confounders and co-morbidity. RESULTS: Among 57 152 women, major surgical postoperative complications were registered for 1854 patients. Median follow-up was 6.22 (0.09-11.70) years. Overall, 9163 patients died, and 3472 died from breast cancer. Major surgical postoperative complications were more common after mastectomy with or without immediate reconstruction (7.3 and 4.3 per cent respectively) than after breast-conserving surgery (2.3 per cent). Unadjusted 5-year OS and BCSS rates were 82.6 (95 per cent c.i. 80.8 to 84.5) and 92.1 (90.8 to 93.5) per cent respectively for women with a major surgical postoperative complication, and 88.8 (88.6 to 89.1) and 95.0 (94.8 to 95.2) per cent for those without a complication (P < 0.001). After adjustment, all-cause and breast cancer mortality rates remained higher after a major surgical postoperative complication (OS: HR 1.32, 95 per cent c.i. 1.15 to 1.51; BCSS: HR 1.31, 1.04 to 1.65). After stratification for type of breast surgery, this association remained significant only for women who had mastectomy without reconstruction (OS: HR 1.41, 1.20 to 1.66; BCSS: HR 1.36, 1.03 to 1.79). CONCLUSION: Major surgical postoperative complications are associated with inferior survival, especially after mastectomy. These results underline the importance of surgical de-escalation.

Long-term outcomes of implant-based immediate breast reconstruction with and without radiotherapy: a population-based study.

BACKGROUND: Radiotherapy (RT) is a risk factor for impaired outcomes after implant-based immediate breast reconstruction (IBR). Large studies including long-term follow-up are relatively scarce. The purpose of this analysis was to assess long-term effects of RT in implant-based IBR, distinguishing between implant removal because of postoperative complications versus patient preference. METHODS: This population-based cohort study included all patients with breast cancer who underwent implant-based IBR in Stockholm between 2005 and 2015. Data were collected through national registers and medical charts. The main endpoint was implant removal owing to postoperative complications (wound breakdown, infection, bleeding) or patient preference (dissatisfaction, pain, capsular contracture), with or without conversion to autologous reconstruction. RESULTS: Some 1749 implant-based IBRs in 1687 women were included. Median follow-up was 72 (range 1-198) months. Reconstructions were divided according to receipt of RT: No RT (n = 856, 48.9 per cent), adjuvant RT (n = 749, 42.8 per cent), and previous RT (n = 144, 8.2 per cent). Implant removal occurred after 266 reconstructions (15.2 per cent); 68 (7.9 per cent) in the no RT, 158 (21.1 per cent) in the adjuvant RT, and 40 (27.8 per cent) in the previous RT group. Implant removal was because of postoperative complications in 152 instances (57.1 per cent) and was most common in the first 3 years. This was especially observed in the previous RT group, where 15 of 23 implant removals occurred during the first 6 months. Implant removal owing to patient preference (114 of 266, 42.9 per cent) became more common with increasing follow-up. CONCLUSION: Implant removal after implant-based IBR is significantly associated with RT. The reason for implant removal shifts over time from postoperative complications to patient preference.

Irradiation of the chest wall after breast removal and implant placement (reconstruction) increases the risk of complications. These may lead to removal of the implant. Some women then choose a new breast reconstruction without an implant. The aim of this project was to find out how much irradiation affects complications after breast reconstruction using implants. This work used information on women who had a breast reconstruction with implants in Stockholm, Sweden, from 2005 to 2015. The main focus was on removal of the implant. This could be due to complications or patient preference. Implant removal could be with or without a new breast reconstruction. Of 1749 reconstructed breasts in 1687 women, 266 implants were removed. This was most often because of a complication, especially in the first years after surgery, but nearly as often due to patient wish. Implant removal owing to patient wish occurred later. Irradiation was a major factor increasing the risk of implant removal, together with, for example, smoking and obesity.

Axillary surgery after neoadjuvant therapy in initially node-positive breast cancer: international EUBREAST survey.

BACKGROUND: There is no consensus on axillary management after neoadjuvant therapy (NAT) in patients with clinically node-positive (cN+) breast cancer. To investigate current clinical practice, an international survey was conducted among breast surgeons and radiation oncologists. The aim of the first part of the survey was to provide a snapshot of international discrepancies regarding axillary surgery in this context. METHODS: The European Breast Cancer Research Association of Surgical Trialists (EUBREAST) developed a web-based survey containing 39 questions describing clinical scenarios in the setting of axillary management in patients with cN1 disease converting to ycN0 after NAT. The survey was then distributed to breast surgeons and radiation oncologists via 14 breast cancer societies between April and October 2021. RESULTS: Responses from 349 physicians in 45 countries were recorded. The most common post-NAT axillary surgery in patients with cN1 disease converting to ycN0 was targeted axillary dissection (54.2 per cent), followed by sentinel lymph node biopsy (SLNB) alone (20.9 per cent), level 1-2 axillary lymph node dissection (ALND) (18.4 per cent), level 1-3 ALND (4 per cent), and targeted lymph node biopsy (2.5 per cent). For SLNB alone, dual tracers were most commonly used (62.3 per cent). Management varied widely in patients with ambiguous axillary status before initiation of treatment or a residual metastatic burden in the axilla after NAT. In patients with ycN+ tumours, ALND was the preferred surgical approach for 66.8 per cent of respondents. CONCLUSION: These results highlight the wide heterogeneity in surgical approaches to the axilla after NAT. To standardize the guidelines, further data from clinical research are urgently needed, which underlines the importance of the ongoing AXSANA (EUBREAST-3) study.

Effect of radiotherapy on expanders and permanent implants in immediate breast reconstruction: long-term surgical and patient-reported outcomes in a large multicentre cohort.

BACKGROUND: Current evidence for the effects of radiotherapy (RT) on implant-based immediate breast reconstruction (IBR) is limited by short follow-up and lack of patient-reported outcomes (PROs). It is central to integrate long-term comprehensive outcome data into the preoperative decision-making process. The aim of the present study was to determine long-term surgical outcomes and PROs in relation to RT after implant-based IBR. METHODS: This was a longitudinal cohort study of PRO data obtained in surveys conducted in 2012 and 2020 using the BREAST-Q questionnaire. All women undergoing therapeutic mastectomy and implant-based IBR between 1 January 2007 and 31 December 2011 at four breast centres in Stockholm, Sweden, were identified. The endpoint was implant removal owing to surgical complications or patient preference. RESULTS: Median follow-up was 120 (range 1-171) months. After 754 IBRs in 729 women, implant removal occurred in 128 (17 per cent): 34 of 386 (8.8 per cent) in the no-RT group, 20 of 64 (31.3 per cent) in the group with previous RT, and 74 of 304 (24.3 per cent) in the postoperative RT group (P < 0.001). Implant removal was because of surgical complications in 60 instances (7.9 per cent), and patient preference in 68 (9.0 per cent). The BREAST-Q response rate was 72.2 per cent. Women with previous RT scored lower than those without RT on all scales, apart from psychosocial well-being. Women with postoperative RT scored lower only on physical well-being. No scores in the two RT groups had deteriorated between the survey time points, whereas satisfaction with breasts and overall outcome had decreased in the no-RT group. CONCLUSION: Although RT was significantly associated with higher implant removal rates, PROs remained stable over 8 years despite irradiation.

Current evidence for the effects of radiotherapy (RT) on implant-based immediate breast reconstruction (IBR) is limited by short follow-up. The aim was to determine surgical outcomes and patient-reported outcomes (PROs) in relation to RT up to 13 years after implant-based IBR. After 754 implant-based breast reconstructions in 729 women in Stockholm, Sweden, implant removal was more common in irradiated than non-irradiated patients (P < 0.001). The response rate to the BREAST-Q questionnaire was 72.2 per cent. Women with previous RT scored lower than those without RT on all scales apart from psychosocial well-being. Women who had postoperative RT scored lower only on physical well-being. Although RT was significantly associated with higher implant removal rates, PROs remained stable despite irradiation.

The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer.

PURPOSE: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). METHODS: In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1-T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. RESULTS: Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. CONCLUSIONS: This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. TRIAL REGISTRATION: NCT02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015.

Breast and axillary surgery in malignant breast disease: a review focused on literature of 2018 and 2019.

PURPOSE OF REVIEW: There have been fundamental changes in the surgical approach to breast cancer management over the last decades. The primary objective of achieving locoregional control, however, remains unchanged. RECENT FINDINGS: In addition to strategies optimizing systemic treatment and radiotherapy, current discussions focus on improving the surgical approach to breast cancer. Especially in view of the increasingly pivotal role of neoadjuvant chemotherapy NAT/NAC (NACT), gauging the extent of tissue removal in the breast and the width of resection margins in breast-conserving surgery is highly important, as is the extent of axillary surgery. Although sentinel lymph node (SLN)-positive patients always underwent axillary lymph node dissection in the past, this paradigm has been challenged in recent years. Targeted axillary dissection (TAD) has emerged as a new staging option in biopsy-proven node-positive patients who convert to clinical node negativity (cN0) after NACT. TAD combines the removal of the SLN and of the target lymph node marked prior to NACT. The accuracy of axillary staging both before and after NACT plays an important role for prognostication and multidisciplinary treatment plans, while its extent has significant effects on patients' arm morbidity and quality of life. SUMMARY: The current review focuses on recent evidence regarding surgical management of the breast and axilla in patients with primary breast cancer based on a PubMed and EMBASE literature search for publication years 2018 and 2019.

Re-testing of predictive biomarkers on surgical breast cancer specimens is clinically relevant.

PURPOSE: The accuracy of predictive and prognostic biomarker assessment in breast cancer is paramount since these guide therapy decisions. The aim was to investigate the concordance of biomarkers and immunohistochemical (IHC)-based surrogate tumor subtypes between core needle biopsies (CNB) and consecutive paired breast cancer surgical resections. METHODS: This retrospective study comprised two cohorts of patients with primary breast cancer diagnosed between 2016 and 2017: one treated with primary surgery (n = 526) and one with neoadjuvant chemotherapy (NAC) (n = 216). The agreement between preoperative CNB and paired tumor specimens regarding the assessment of biomarkers and surrogate tumor subtypes was evaluated in both cohorts. RESULTS: In the primary surgery cohort, the concordance rates and kappa values for estrogen receptor (ER), progesterone receptor (PR) and Ki67 were 98.6% (κ = 0.917), 89.3% (κ = 0.725) and 78.8% (κ = 0.529), respectively. Importantly, human epidermal growth factor receptor 2 (HER2) IHC assessment showed only moderate agreement (κ = 0.462). HER2 status combining IHC and in situ hybridization was discordant in 3.6% of cases, potentially impacting on indications for HER2-targeted therapy. The concordance rate for IHC-based surrogate tumor subtypes was only 73.2-78.3%. Generally lower concordance rates for ER, PR and HER2 were observed in the NAC cohort. Here, HER2 status was discordant in 7.4%. CONCLUSIONS: The agreement of HER2 and Ki67 between CNB and paired surgical specimen in primary breast cancer is insufficient. Limited agreement of surrogate tumor subtypes indicates a significant clinical value of biomarker re-testing on surgical specimens.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

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

Swedish prospective multicenter trial on the accuracy and clinical relevance of sentinel lymph node biopsy before neoadjuvant systemic therapy in breast cancer.

PURPOSE: The timing of sentinel lymph node biopsy (SLNB) in the context of neoadjuvant systemic therapy (NAST) in breast cancer is still controversial. SLNB before NAST has been evaluated in few single-institution studies in which axillary lymph node dissection (ALND), however, was commonly not performed in case of a negative SLNB. We investigated the potential clinical relevance of SLNB before NAST by performing ALND in all patients after NAST. METHODS: This national multicenter trial prospectively enrolled clinically node-negative breast cancer patients planned for NAST at 13 recruiting Swedish hospitals between October 2010 and December 2015. SLNB before NAST was followed by ALND after NAST in all individuals. Repeat SLNB after NAST was encouraged but not mandatory. RESULTS: SLNB before NAST was performed in 224 patients. The identification rate was 100% (224/224). The proportion of patients with a negative SLNB before NAST but positive axillary lymph nodes after NAST was 7.4% (nine of 121 patients, 95% CI 4.0-13.5). Among those with a positive SLNB before NAST, 23.2% (86/112) had further positive lymph nodes after NAST. CONCLUSIONS: In clinically node-negative patients, SLNB before NAST is highly reliable. With this sequence, ALND and regional radiotherapy can be safely omitted in patients with a negative SLNB provided good clinical response to NAST. Additionally, SLNB-positive patients upfront will receive correct nodal staging unaffected by NAST and be consequently offered adjuvant locoregional treatment according to current guidelines pending the results of ongoing randomized trials.

Swedish prospective multicenter trial evaluating sentinel lymph node biopsy after neoadjuvant systemic therapy in clinically node-positive breast cancer.

PURPOSE: Patients with clinically node-positive breast cancer planned for neoadjuvant systemic therapy (NAST) may draw advantages from the nodal downstaging effect and reduce the extent of axillary surgery with sentinel lymph node biopsy (SLNB) performed after NAST. Since there are concerns about lower sentinel lymph node (SLN) detection and higher false-negative rates (FNR) in this setting, our aim was to define the accuracy of SLNB after NAST. METHODS: This Swedish national multicenter trial prospectively recruited 195 breast cancer patients from ten hospitals with T1-T4d biopsy-proven node-positive disease planned for NAST between October 1, 2010 and December 31, 2015. Clinically node-negative axillary status after NAST was not mandatory. SLNB was always attempted and followed by a completion axillary lymph node dissection (ALND). RESULTS: The SLN identification rate was 77.9% (152/195) but improved to 80.7% (138/171) with dual mapping. The median number of SLNs was two (range 1-5). A positive SLNB was found in 52% (79/152), almost 66% (52/79) of whom had additional positive non-sentinel lymph nodes. The overall pathologic nodal response rate was 33.3% (66/195). The overall FNR was 14.1% (13/92) but decreased to 4% (2/50) when only patients with two or more sentinel nodes were analyzed. CONCLUSIONS: In biopsy-proven node-positive breast cancer, SLNB after NAST is feasible even though the identification rate is lower than in clinically node-negative patients. Since the overall FNR is unacceptably high, the omission of ALND should only be considered if two or more SLNs are identified.

Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial.

BACKGROUND: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference. METHODS: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1:1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years. DISCUSSION: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors. TRIAL REGISTRATION: NCT 02240472 , retrospective registration date September 14, 2015 after trial initiation on January 31, 2015.