PROMRIINE (PRe-operatory Magnetic Resonance Imaging is INEffective) Study: A Systematic Review and Meta-analysis of the Impact of Magnetic Resonance Imaging on Surgical Decisions and Clinical Outcomes in Women with Breast Cancer.

BACKGROUND: The purpose of this study was to review and summarize the association between preoperative magnetic resonance imaging (MRI) and surgical outcomes in women with newly diagnosed invasive breast cancer from published randomized controlled trials (RCT). MATERIALS AND METHODS: Two independent researchers conducted a systematic review through a comprehensive search of electronic databases, including PubMed, Medline, Embase, Ovid, Cochrane Library, and Web of Science. If there was disagreement between the two reviewers, a third reviewer assessed the manuscript to determine whether it should be included for data extraction. The quality of the papers was assessed using the risk of bias tool, and the evidence was analyzed using GRADE. Meta-analyses using a fixed-effects model were used to estimate the pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS: Initially, 21 studies were identified, 15 of which were observational comparative studies. A total of five RCTs were included, and they suggested that preoperative MRI significantly reduced the rate of immediate breast-conserving surgery and increased the risk for mastectomy. CONCLUSIONS: From the RCT perspective, preoperative MRI for newly diagnosed invasive breast cancer did not improve surgical outcomes and may increase the risk of mastectomy.

The Attitudes of Brazilian Breast Surgeons on Axillary Management in Early Breast Cancer-10 Years after the ACOSOG Z0011 Trial First Publication.

PURPOSE: To evaluate the impact of the ACOSOG Z0011 trial on axillary breast cancer surgery management in Brazil following publication of that study (2010) and again in 2020. PATIENTS AND METHODS: A survey of members of the Brazilian Society of Mastology. RESULTS: Of 1627 breast surgeons, 799 (49.1%) completed and returned the questionnaire. For patients with the Z11 inclusion criteria, following detection of a positive sentinel lymph node (SLN), axillary dissection (AD) was recommended by 99.2% of respondents before publication of the study, 47.5% in 2010 and 18.5% in 2020 (p < 0.001). In breast-conserving surgery, if there were micro-metastases, 2.6% would perform AD, 30.3% axillary radiotherapy, and 67.1% no additional axillary treatment, while with macro-metastases, these proportions were 21.3%, 52.2%, and 26.5%, respectively. In cases of mastectomy and of nodal extracapsular extension, 43.4% and 36% of surgeons, respectively, recommended AD. For clinically negative axilla and suspicious findings at ultrasonography, 69% of the surgeons would apply the Z11 approach. Most applied the Z11 criteria in cases of younger patients (83.6%) and triple-negative and/or HER2 positive tumors (74%). AD was significantly more likely to be recommended by surgeons who did not work in academic institutes, who worked in locations other than capital cities, who were not board-certified, and who were ≥ 50 years old. CONCLUSIONS: This survey revealed substantial changes in axillary surgery management in cN0/pathologically positive SLN, particularly following publication of the updated Z11 results and other similar studies. A better education environment and long-term follow-up were factors associated with the incorporation of Z11-related changes in practice.

Management of early-stage triple-negative breast cancer: recommendations of a panel of experts from the Brazilian Society of Mastology.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogenous subtype involving different patterns of behavior and clinical course, demanding a complex, individualized sequence of treatment. The knowledge and attitudes of the affiliated members of the Brazilian Society of Mastology regarding TNBC were evaluated and a consensus regarding management and treatment was reached. METHODS: Affiliates completed a survey involving 44 objective questions. In addition, a specialist meeting was held with 27 experts and 3 ad hoc consultants. The panelists completed the survey before and after brainstorming. Answers achieving 70% of agreement were considered consensual. The chi-square test was used to compare answers between panelists and affiliates and the Kappa coefficient to calculate agreement. RESULTS: Consensus among the panelists increased from 26 (59.1%) to 32 questions (72.7%) following brainstorming (p = 0.17), including 7/10 questions on systemic treatment. Among the affiliates, consensus was achieved for 24 questions (54.5%), resulting in moderate agreement (κ = 0.445). Neoadjuvant chemotherapy should be indicated for almost all cases (except cT1a-b N0) and should include platinum agents. When indicated, immunotherapy is part of the standard of care. The panel reaffirmed the concept of no ink on tumor as indicative of adequate margins and the possibility of sentinel lymph node biopsy for cN1 patients who become cN0 following neoadjuvant therapy. Controversies remain on combining immunotherapy with capecitabine/olaparib in pertinent cases. CONCLUSION: Expert consensus was achieved for > 70% of the questions, with moderate agreement between panelists and affiliates. Educational interventions on systemic breast cancer treatment affected decision-making in 60% of the questions.

Management of early breast cancer during the COVID-19 pandemic in Brazil.

PURPOSE: The COVID-19 pandemic has impacted early breast cancer (EBC) treatment worldwide. This study analyzed how Brazilian breast specialists are managing EBC. METHODS: An electronic survey was conducted with members of the Brazilian Society of Breast Cancer Specialists (SBM) between April 30 and May 11, 2020. Bivariate analysis was used to describe changes in how specialists managed EBC at the beginning and during the pandemic, according to breast cancer subtype and oncoplastic surgery. RESULTS: The response rate was 34.4% (503/1462 specialists). Most of the respondents (324; 64.4%) lived in a state capital city, were board-certified as breast specialists (395; 78.5%) and either worked in an academic institute or one associated with breast cancer treatment (390; 77.5%). The best response rate was from the southeast of the country (240; 47.7%) followed by the northeast (128; 25.4%). At the beginning of the pandemic, 43% changed their management approach. As the outbreak progressed, this proportion increased to 69.8% (p < 0.001). The southeast of the country (p = 0.005) and the state capital cities (p < 0.001) were associated with changes at the beginning of the pandemic, while being female (p = 0.001) was associated with changes during the pandemic. For hormone receptor-positive tumors with the best prognosis (Ki-67 < 20%), 47.9% and 17.7% of specialists would recommend neoadjuvant endocrine therapy for postmenopausal and premenopausal women, respectively. For tumors with poorer prognosis (Ki-67 > 30%), 34% and 10.9% would recommend it for postmenopausal and premenopausal women, respectively. Menopausal status significantly affected whether the specialists changed their approach (p < 0.00001). For tumors ≥ 1.0 cm, 42.9% of respondents would recommend neoadjuvant systemic therapy for triple-negative tumors and 39.6% for HER2 + tumors. Overall, 63.4% would recommend immediate total breast reconstruction, while only 3.4% would recommend autologous reconstruction. In breast-conserving surgery, 75% would recommend partial breast reconstruction; however, 54.1% would contraindicate mammoplasty. Furthermore, 84.9% of respondents would not recommend prophylactic mastectomy in cases of BRCA mutation. CONCLUSIONS: Important changes occurred in EBC treatment, particularly for hormone receptor-positive tumors, as the outbreak progressed in each region. Systematic monitoring could assure appropriate breast cancer treatment, mitigating the impact of the pandemic.

Effect of intraoperative radiotherapy for early breast cancer on 10-year recurrence rates and overall survival.

The aim of this study was to evaluate 10-year local control and overall survival of IORT for early breast cancer treatment. We analyzed 68 patients submitted to breast conservative surgery and IORT, in the accelerator room of the Radiotherapy Service in South Brazil. In the long-term follow-up, we had 17.6% of patients with ipsilateral breast cancer recurrence, 2.9% with regional recurrence, 2.9% with contralateral breast recurrence, and 5.9% with distant metastasis. The 10-year overall survival was 82.8%. Our data show high local recurrence rates, however, good overall survival in early breast cancer patients treated with breast-conserving surgery and intraoperative radiotherapy with electron beams in the long-term follow-up.

The use of blue dye alone for sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with initially node-positive breast cancer.

INTRODUCTION: False-negative sentinel lymph node biopsy (SLNB) rates following neoadjuvant chemotherapy (NACT) in initially node-positive (cN1/2) breast cancer patients are high, but decrease when lymph nodes are clipped, ≥3 sentinel lymph nodes (SLN) are removed or dual-tracer localization (radioisotope and blue dye) is used. Radiotracer, however, is often unavailable and outcomes with blue dye alone are unknown. MATERIALS AND METHODS: Initially cT1-4, cN1/2 patients treated with NACT in 2013-2023 who underwent SLNB using blue dye alone were evaluated regarding SLN identification, axillary recurrence, disease-free and overall survival rates. RESULTS: Of 119 patients included, 19 remained cN1/2 after NACT. SLNB was performed using blue dye alone in 100 ycN0 cases (84%), with an identification rate of 96%. The SLN was negative in 70/119 cases (i.e. 59% avoided axillary dissection). The number of SLN detected was ≥3 in 55/70 cases (78%) (median 3.1; 1-6). Median age was 49 years (25-84). Most were T2 (n = 40, 57.1%), N1 (n = 64, 91.4%). Predominant subtypes were ERBB2 (52.9%) and triple-negative (20%). No axillary recurrence occurred over a median 36-month period. Five-year disease-free and overall survival were, respectively, 85.9% (95%CI: 74-99.8) and 96.3% (95%CI: 89.4-100). The ERBB2 subtype (1.99, 95%CI: 1.02-3.85, p = 0.04) and N1 lymph node status (2.58, 95%CI: 1.54-9.10, p = 0.03) were associated with a greater likelihood of undergoing SLNB alone without axillary dissection. CONCLUSIONS: SLNB with blue dye alone following NACT in initially cN1/2 patients avoided axillary dissection in almost 60% of cases, with no recurrences during the period evaluated. Longer follow-up studies are necessary.

Sentinel lymph node biopsy following neoadjuvant chemotherapy: an evidence-based review and recommendations for current practice.

Sentinel lymph node biopsy (SLNB) at upfront surgery is the gold-standard surgical method for axillary lymph node staging in early stage breast cancer: the technique provides adequate information regarding axillary status, with similar oncological safety and lower morbidity compared to axillary dissection, despite the false negative rates. Neoadjuvant chemotherapy (NACT), traditionally used for locally advanced breast cancer, plays an important role in the treatment of early stage breast cancer, making downstaging possible in axillary lymph node and breast cancer, thus minimizing the impact of surgery and reducing morbidity, as well as enabling patients with residual disease to be selected for adjuvant treatment. In this respect, the role of SLNB has proved controversial, particularly in view of the lack of data from randomized clinical trials on this subject. Currently, the de-escalation of axillary surgery after NACT is mainly based on retrospectives studies and false negative rates. This paper reviews current evidence on the management of axillary surgery following NACT under different circumstances, with suggested recommendations in each scenario: clinically negative nodes at diagnosis and SLNB after NACT, clinically positive nodes at diagnosis and SLNB after NACT, positive SLNB following NACT and finally the possibility of omitting axillary surgery in good responders.

Inframammary versus Periareolar Incision: A Comparison of Early Complications in Nipple-sparing Mastectomy.

Background: Nipple-sparing mastectomy (NSM), either used therapeutically or prophylactically, may yield more complications than conventional mastectomy. The incision may affect aesthetic outcome and complication rates, with periareolar incisions being associated with nipple-areolar complex (NAC) necrosis. Methods: Early complications were compared between NSM performed in 2015-2022 using inframammary fold (IMF) or periareolar incisions. Results: Overall, 180 procedures in 152 patients (bilateral NSM = 28) were included (IMF = 104; periareolar = 76). Mean age (47 versus 43.9 years; P < 0.038), mastectomy weight (312.7 versus 246.8 grams; P < 0.001), implant volume (447.5 versus 409.0 mL; P = 0.002), and use of tissue expanders (68.4% versus 50.0%; P = 0.013) were all greater with periareolar incisions. Prepectoral reconstruction was more common with IMF (18.3% versus 3.9%; P = 0.004). Forty-three complications (23.9%) were recorded (periareolar n = 27, 35%; IMF n = 16, 15.3%; P = 0.0002). NAC necrosis accounted for 17 complications (22.4%) in the periareolar group versus nine (8.5%) in the IMF group (P = 0.002). Necrosis was predominantly moderate (n = 6, 8.3% versus n = 1, 1.0%, respectively) (P = 0.014). Unadjusted odds ratios (OR) for complications [3.05; 95% confidence interval (CI): 1.27-7.26] and necrosis (3.04; 95% CI: 1.27-7.27) were higher in the periareolar group. In the multivariate analysis, necrosis was associated with periareolar incisions [adjusted odds ratio (aOR): 2.92; 95% CI: 1.14-7.44]. Prepectoral reconstruction was associated with IMF incisions (aOR: 25.51; 95% CI: 3.53-184.23; P = 0.001) and with body mass index of more than 25-30 (aOR: 37.09; 95% CI: 5.95-231.10; P < 0.001). Therapeutic mastectomies (aOR: 68.56; 95% CI: 2.50-188.36; P = 0.012) and tissue expanders (aOR: 18.36; 95% CI: 1.89-178.44; P = 0.026) were associated with seromas. Conclusions: Both incisions are viable options; however, the risk of NAC necrosis increased with the periareolar approach. Further research is required.

Impact of the COVID-19 Pandemic on Cancer Staging: An Analysis of Patients With Breast Cancer From a Community Practice in Brazil.

PURPOSE: A nationwide lockdown was enforced in Brazil starting in March 2020 because of the COVID-19 pandemic when cancer screening activities were reduced. In this study, we evaluated the impact of the COVID-19 pandemic on breast cancer (BC) diagnosis. METHODS: We extracted data from the medical records of patients age older than 18 years who were diagnosed with BC and started treatment or follow-up in private oncology institutions in Brazil between 2018 and 2021. The primary objective was to compare the stage distribution during the COVID-19 pandemic (2020-2021) with a historical prepandemic control cohort (2018-2019). Early BC was defined as stage I-II and advanced disease as stage IV. RESULTS: We collected data for 11,753 patients with an initial diagnosis of BC, with 6,493 patients in the pandemic (2020-2021) and 5,260 patients in the prepandemic period (2018-2019). We observed a lower prevalence of early-stage BC (63.6% v 68.4%) and a higher prevalence of advanced-stage BC (16.9 v 12.7%), after the onset of the pandemic (both P < .01). This pattern was similar for both estrogen receptor-positive/human epidermal growth factor receptor 2-negative and human epidermal growth factor receptor 2-positive tumors: significantly decreased in the early stage from 69% to 67% and 68% to 58%, respectively, and a considerable increase in advanced-stage disease from 13% to 15% and 13% to 20%, respectively. For triple-negative BC, there was a significantly higher percentage of patients with advanced-stage disease during the pandemic (17% v 11%). Overall, age 50 years or older and postmenopausal status were associated with a greater risk of advanced stage at diagnosis during the pandemic period. CONCLUSION: We observed a substantial increase in the number of cases of advanced-stage BC in Brazil during the COVID-19 pandemic.

Management of the positive sentinel lymph node following neoadjuvant chemotherapy: results of a survey conducted with breast surgeons.

Introduction: Despite the lack of randomised evidence, there is a current trend towards omitting axillary surgery in cases of positive sentinel lymph node (SLN) following neoadjuvant chemotherapy (NACT). This study evaluated practice patterns of Brazilian breast surgeons when managing positive SLN following NACT. Methods: This was a nationwide electronic survey of breast surgeons affiliated with the Brazilian Society of Mastology. Management approaches for positive SLN after NACT (axillary dissection (AD), regional nodal irradiation (RNI) or no additional treatment) were evaluated as a function of residual disease volume in the SLN (macro-metastasis, micro-metastasis or isolated tumour cells (ITC)). Results: Survey response rate was 49%, with 799/1,627 questionnaires returned. Most respondents were <50 years old (61%), lived in south-eastern Brazil (50%), in a major city (67%), worked in an academic institute (80%) and were board-certified (80%). AD recommendation rate decreased according to residual nodal disease volume: 91% of respondents recommended AD for cases of macro-metastasis, 64% for micro-metastasis and 38% for ITC (p < 0.00001). Furthermore, 35% would recommend no additional surgery for micro-metastasis, while 27% would recommend no treatment at all for ITC (p < 0.00001). Not working in an academic institute was associated with RNI for micro-metastasis (p = 0.02), but not for macro-metastasis or ITC. Being board-certified did not affect axillary management. Conclusion: Most respondents would recommend AD and/or RNI in residual nodal disease following NACT irrespective of disease volume. Nevertheless, a trend towards surgical de-escalation was found with low-volume disease (micro-metastasis and ITC). Ongoing randomised trials will clarify the impact of this trend.

Progress in Local Treatment of Breast Cancer: A Narrative Review.

The present paper reports on the local treatment of breast cancer from a historical perspective. A search for articles written in English was made in the Medline and EMBASE databases, and 40 papers were selected. Over the past 10 years, various randomized, controlled clinical trials on the local treatment of breast cancer indicated that patients with the same molecular subtype may receive different individualized surgical treatments aimed at optimizing systemic adjuvant therapy. With a view to retaining the gains made in disease-free and overall survival, surgical techniques have advanced from radical surgery to conservative mastectomies, thus reducing sequelae, while adjuvant and neoadjuvant therapies have contributed toward controlling the disease, both distant metastases and local recurrence. Current studies evaluate whether future breast cancer therapy may even succeed in eliminating surgery to the breast and axilla altogether.

Este artigo discute o tratamento local do câncer de mama a partir de uma perspectiva histórica. Uma busca de artigos publicados em inglês foi realizada nas bases de dados Medline e EMBASE, sendo selecionados 40 artigos. Nos últimos 10 anos, vários ensaios clínicos controlados e randomizados sobre o tratamento local do câncer de mama indicaram que pacientes com o mesmo subtipo molecular podem receber diferentes tratamentos cirúrgicos individualizados com o objetivo de otimizar a terapia adjuvante sistêmica. Pretendendo reter os ganhos obtidos na sobrevida livre de doença e na sobrevida global, as técnicas cirúrgicas avançaram progressivamente da cirurgia radical para mastectomias conservadoras, reduzindo sequelas, enquanto as terapias adjuvantes e neoadjuvantes contribuíram para o controle da doença, tanto em relação às metástases distantes quanto à recorrência local. Estudos atuais avaliam se a terapia futura contra o câncer de mama poderá até mesmo eliminar a cirurgia da mama e da axila por completo.

HspBP1 levels are elevated in breast tumor tissue and inversely related to tumor aggressiveness.

HspBP1 is a co-chaperone that binds to and regulates the chaperone Hsp70 (Hsp70 is used to refer to HSPA1A and HSPA1B). Hsp70 is known to be elevated in breast tumor tissue, therefore the purpose of these studies was to quantify the expression of HspBP1 in primary breast tumors and in serum of these patients with a follow-up analysis after 6 to 7 years. Levels of HspBP1, Hsp70, and anti-HspBP1 antibodies in sera of breast cancer patients and healthy individuals were measured by enzyme-linked immunosorbent assay. Expression of HspBP1 was quantified from biopsies of tumor and normal breast tissue by Western blot analysis. The data obtained were analyzed for association with tumor aggressiveness markers and with patient outcome. The levels of HspBP1 and Hsp70 were significantly higher in sera of patients compared to sera of healthy individuals. HspBP1 antibodies did not differ significantly between groups. HspBP1 levels were significantly higher in tumor (14.46 ng/microg protein, n = 51) compared to normal adjacent tissue (3.17 ng/microg protein, n = 41, p < 0.001). Expression of HspBP1 was significantly lower in patients with lymph node metastasis and positive for estrogen receptors. HspBP1 levels were also significantly lower in patients with a higher incidence of metastasis and death following a 6 to 7-year follow-up. The HspBP1/Hsp70 molar ratio was not associated with the prognostic markers analyzed. Our results indicate that low HspBP1 expression could be a candidate tumor aggressiveness marker.

Inducible heat shock protein 70 expression as a potential predictive marker of metastasis in breast tumors.

Heat shock protein (Hsp)-peptide complexes purified from tumors can prime the immune system against tumor antigens, but how they contribute to the generation of immune responses against naturally occurring tumors is unknown. Murine tumors expressing high amounts of Hsp70 are preferentially rejected by the immune system, suggesting that low Hsp70 expression is advantageous for tumor growth in the host. To determine whether Hsp70 was differentially expressed in human tumors, inducible Hsp70 expression was quantitatively (by Western blot) and qualitatively (by immunohistology) analyzed in 53 biopsies of tumor and normal breast tissue. The mean expression of inducible Hsp70 was significantly higher in tumor compared with normal tissue (U = 899.0; P = 0.0033). However, a significant negative association of the amount of Hsp70 expressed by tumor tissue was found with metastasis (r = -0.309; P = 0.05). After 3 years, follow-up analysis determined that 7 of the 53 patients relapsed, and 5 died. Hsp70 expression in tumor (but not normal) cells was significantly lower in relapse patients and patients with metastatic disease than in patients with no relapse or metastasis. Together, these observations support the hypothesis that Hsp70 plays a role in tumor expansion in vivo, and tumors that downregulate it may be able to evade immunosurveillance and grow.

Bilateral giant juvenile fibroadenomas of the breasts-a rare indication for bilateral skin reducing mastectomy.

Fibroadenoma is the most common benign tumor of the breast but giant juvenile fibroadenoma represent only 0.5% of all fibroadenomas and when bilateral are much more rare. We describe the case of a 25 years old girl that presented with bilateral giant juvenile fibroadenomas and was treated by bilateral skin reducing mastectomy using the inferior dermal flap, implant, and free nipple graft.