Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

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

Uncertainties and controversies in axillary management of patients with breast cancer.

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy.

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.

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.

Low Overall Survival in Women With De Novo Metastatic Breast Cancer: Does This Reflect Tumor Biology or a Lack of Access to Health Care?

PURPOSE: As a result of its epidemiologic and therapeutic aspects, metastatic breast cancer (MBC) is a highly relevant clinical condition. This study aimed to estimate overall survival (OS) in women with de novo MBC in a Brazilian population. PATIENTS AND METHODS: Patients were identified in the Goiânia population-based cancer registry between 1995 and 2011. All women with metastatic disease at diagnosis were included in the study. OS was analyzed at 5 and 10 years of follow-up. We used the Kaplan-Meier estimator and Cox regression for statistical analysis. RESULTS: Over the 16-year period covered by the study, 5,289 women were diagnosed with breast cancer in Goiânia. Of these, 277 women (5.2%) had MBC. OS rates at 5 and 10 years were 19.9% and 7.3%, respectively. The mean OS time of women treated in the public health system was 7.5 months shorter than in women who had private health care (19.7 v 27.2 months, respectively). In the univariable analysis, the following factors were statistically significant for OS: T3/4 staging, histologic grade 3, progesterone receptor status, tumor phenotype, breast surgery, CNS metastasis at initial presentation, and surgery for resection of metastasis. In multivariable analysis, initial CNS metastasis (hazard ratio, 3.09; 95% CI, 1.16 to 8.19) and breast surgery (hazard ratio, 0.45; 95% CI, 0.25 to 0.78) remained independent prognostic factors. CONCLUSION: OS was lower than rates found in specialist centers in Brazil and in developed countries. Several intrinsic and extrinsic factors were significant in predicting OS. Despite the difference in the 5-year survival rate, the type of access to health care was not significant in the multivariable analysis of the entire period.

The accuracy of the SONOBREAST statistical model in comparison to BI-RADS for the prediction of malignancy in solid breast nodules detected at ultrasonography.

OBJECTIVE: The objective of the present study was to compare the accuracy of SONOBREAST for the prediction of malignancy in solid breast nodules detected at ultrasonography with that of the BI-RADS system and to assess the agreement between these two methods. STUDY DESIGN: This prospective study included 274 women and evaluated 500 breast nodules detected at ultrasonography. The probability of malignancy was calculated based on the SONOBREAST model, available at www.sonobreast.com.br, and on the BI-RADS system, with results being compared with the anatomopathology report. RESULTS: The lesions were considered suspect in 171 cases (34.20%), according to both SONOBREAST and BI-RADS. Agreement between the methods was perfect, as shown by a Kappa coefficient of 1 (p<0.001). SONOBREAST and BI-RADS proved identical insofar as sensitivity (95.40%), specificity (78.69%), positive predictive value (48.54%), negative predictive value (98.78%) and accuracy (81.60%) are concerned. With respect to the categorical variables (BI-RADS categories 3, 4 and 5), the area under the receiver operating characteristic (ROC) curve was 94.41 for SONOBREAST (range 92.20-96.62) and 89.99 for BI-RADS (range 86.60-93.37). CONCLUSIONS: The accuracy of the SONOBREAST model is identical to that found with BI-RADS when the same parameters are used with respect to the cut-off point at which malignancy is suspected. Regarding the continuous probability of malignancy with BI-RADS categories 3, 4 and 5, SONOBREAST permits a more precise and individualized evaluation.

Effect of tamoxifen and raloxifene on the proliferative activity of the breast epithelium in premenopausal women.

OBJECTIVES: To compare the effects of tamoxifen and raloxifene on the proliferative activity of normal breast tissue in premenopausal women as measured by Ki-67/MIB-1 expression. STUDY DESIGN: A total of 48 women with benign breast nodules and a recommendation for surgical removal of the lesion took part in this study. They were randomized to use tamoxifen or raloxifene for 22 days, after which they were submitted to surgery. During the surgical procedure, a 1-cm fragment of normal breast tissue was removed to study Ki-67 expression. RESULTS: The mean percentage ratios between immunolabeled and non-labeled cells were 2.02 ± 1.09 and 3.13 ± 3.23 for the tamoxifen and raloxifene groups, respectively. There was no statistically significant difference between the tamoxifen (n = 16) and raloxifene (n = 14) groups in relation to the immunohistochemical analysis of Ki-67 (P = 0.205). CONCLUSION: The results of this study showed no difference between tamoxifen and raloxifene with respect to the potential of these drugs to reduce the proliferative activity of the normal breast epithelium in premenopausal women.

Incidence and risk factors for winged scapula after surgical treatment for breast cancer.

AIMS AND OBJECTIVES: To evaluate the incidence of winged scapula following surgical breast cancer treatment, determine its evolution over time and correlate factors that might influence this incidence. BACKGROUND: Winged scapula is a complication that may occur as a result of exposing the long thoracic nerve during axillary lymphadenectomy for the treatment for breast cancer. There is no consensus in the literature about the incidence of this complication after surgical treatment for breast cancer, and complication rates range from 1·5-74%. DESIGN: This is a prospective cohort study. METHODS: A prospective cohort study was conducted including 57 patients with breast cancer who underwent surgical treatment. Each patient was assessed before and after the surgery, by means of Hoppenfeld manoeuvre. The incidence rate of winged scapula was calculated at four different times. RESULTS: At the preoperative assessment, none of the patients presented with winged scapula, while 16 patients (28·1%) were shown to have this complication after the procedure. The incidence of winged scapula decreased over time. Factors associated with winged scapula were as follows: patients younger than 50 years, clinical stage I and II and no neoadjuvant chemotherapy. Other factors that were evaluated, such as type of surgery, number of lymph nodes compromised and removed, as well as body mass index, were not associated with the risk of winged scapula. CONCLUSIONS: This study demonstrated that the incidence of winged scapula is low and decreased over time. Furthermore, a greater incidence of winged scapula was noted in young women at an initial stage of the disease who had not been treated with neoadjuvant chemotherapy. RELEVANCE TO CLINICAL PRACTICE: The result of this work may have great impact, for demonstrating what risk factors are significantly associated with winged scapula after surgical treatment for breast cancer.

Avaliaçäo da resposta do câncer de mama localmente avançado em pacientes submetidas à quimioterapia neoadjuvante / Evaluation of te response of locally advanced breast cancer in patients submitted to neoadjuvant chemotherapy

Este trabalho tem como objetivo avaliar a resposta do câncer de mama, estádio III, em pacientes submetidas à quimioterapia neoadjuvante, estudar os fatores relacionados à resposta e verificar a acurácia do exame físico como método de avaliaçäo da resposta do tumor à quimioterapia. Em um período de 6 anos, 71 pacientes com carcinoma de mama, E III, foram submetidas à quimioterapia neoadjuvante com o esquema FACV (ciclofosfamida 400 mg/m2, 5-fluorouracil 400 mg/m, doxorrubicina 10 mg/m2 e vincristina 1 mg/m2). Foram realizados 6 ciclos semanais antes da cirurgia e 11 ciclos quinzenais, após o tratamento cirúrgico. Na avaliaçäo clínica após o 6§ ciclo, houve reduçao completa do tumor em 9 por cento dos casos; reduçäo maior que 50 por cento em 59 por cento das pacientes e, em 32 por cento dos casos houve reduçäo menor que 50 por cento ou progressäo. Apenas o tamanho do tumor inicial esteve significativamente associado à resposta tumoral, sendo que tumores maiores mostraram-se mais responsivos. Dentre os 57 casos apontados como tendo tumor residual ao exame físico, 52 foram confirmados histologicamente. Dos 6 casos sem tumor ao exame físico, dois foram confirmados histologicamente. A acurácia total do exame clínico foi de 86 por cento, a sensibilidade de 93 por cento, a especificidade de 29 por cento, o valor preditivo positivo de 91 por cento e o valor preditivo negativo de 33 por cento. Concluiu-se que a quimioterapia neoadjuvante proporcionou boa reduçäo dos tumores, sendo que os maiores apresentaram uma melhor resposta. O exame físico apresenta baixa acurácia no estudo da resposta tumoral e, isoladamente, näo é um bom método de avaliaçäo.