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Pembrolizumab plus weekly paclitaxel in platinum-resistant recurrent ovarian cancer (ENGOT-ov65/KEYNOTE-B96): a multicentre, randomised, double-blind, phase 3 study
(2026) Colombo, Nicoletta N.; Zsiros, Emese; Parma, Gabriella Maria; Rulli, Eliana; Sebastianelli, Alexandra; Bidziński, Mariusz; Gallardo Garrido, Carlos Andrés; Matanes, Emad; Kosei, Hasegawa; Köse, Fatih; Freitas Junior, Ruffo de
Background Epithelial ovarian cancer frequently recurs and becomes resistant to platinum chemotherapy. We investigated whether adding pembrolizumab to weekly paclitaxel, with or without bevacizumab, improves progression-free survival and overall survival compared with weekly paclitaxel, with or without bevacizumab, in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens. Methods ENGOT-ov65/KEYNOTE-B96 is a randomised, double-blind, phase 3 study conducted at 187 gynaecologic oncology centres in 25 countries in the Americas, Asia, Europe, and Oceania. Adults (≥18 years) with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who received one to two previous systemic therapies including at least one platinum regimen and who progressed 6 months or less after the last platinum regimen, were eligible. Participants were randomly assigned 1:1 to intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle or intravenous placebo (saline solution) every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle; intravenous bevacizumab 10 mg/kg every 2 weeks was permitted per investigator. Randomisation was stratified by planned bevacizumab use, region, and PD-L1 combined positive score (CPS). The primary endpoint was investigator-assessed progression-free survival per RECIST version 1.1; the key secondary endpoint was overall survival. Results from two interim analyses and the final analysis are included in this Article. This study is registered with ClinicalTrials.gov, NCT05116189, and is now completed. Findings Between Dec 13, 2021, and July 3, 2023, 643 female participants were randomly assigned; 322 to pembrolizumab plus paclitaxel and 321 to placebo plus paclitaxel. At the first interim analysis, pembrolizumab plus paclitaxel significantly improved progression-free survival versus placebo plus paclitaxel in both the PD-L1 CPS 1 or higher (median 8·3 months vs 7·2 months; hazard ratio [HR] 0·72; 95% CI 0·58–0·89; p=0·0014 α=0·012]) and overall populations (median 8·3 months vs 6·4 months; HR 0·70, 95% CI 0·58–0·84; p<0·0001, [α=0·0023]), meeting the prespecified criteria for confirmatory efficacy. At the second interim analysis, overall survival was significantly improved in the PD-L1 CPS 1 or higher population (median 18·2 months vs 14·0 months; HR 0·76, 95% CI 0·61–0·94; p=0·0053, [α=0·0083]). At the final analysis, overall survival was significantly improved in the overall population (median 17·7 months vs 14·0 months; HR 0·82, 95% CI 0·69–0·97; p=0·011 [α=0·024]). Grade 3 or worse treatment-related adverse events occurred in 217 (68%) of 320 participants in the pembrolizumab plus paclitaxel group versus 176 (55%) of 318 participants in the placebo plus paclitaxel group. The most common treatment-related adverse events (any grade) included anaemia, peripheral neuropathy, alopecia, fatigue, and nausea. Treatment-related adverse events resulted in death in four participants (1%) in the pembrolizumab plus paclitaxel group (colitis, interstitial lung disease, acute myeloid leukaemia, and intestinal perforation) and in five participants (2%) in the placebo plus paclitaxel group (cardiac failure, intestinal perforation [in two participants], and large-intestine perforation [in two participants]). Interpretation Pembrolizumab plus weekly paclitaxel, with or without bevacizumab, significantly improved progression-free survival and overall survival in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens, supporting this regimen as a new treatment option for this population. Funding
Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial
(2026) Dent , Rebecca Alexandra; Shao, Zhimin; Schmid, Peter; Cortes Castán, Javier; Cescon, David W.; Saj, Shigehira; Jung, Kyung Hae; Bachelot , Thomas; Wang, Shouman; Murillo Ramirez, Emilio; Freitas Junior, Ruffo de
Background Prognosis is poor and treatment options are limited for patients with previously untreated, advanced triple-negative breast cancer (TNBC), especially for those who are not candidates for immunotherapy. Patients and methods In the randomised, open-label, phase III TROPION-Breast02 trial, patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option were randomised 1:1 to datopotamab deruxtecan (Dato-DXd; 6 mg/kg intravenously every 3 weeks) or investigator’s choice of chemotherapy. Randomisation was stratified by geographic location, disease-free interval and programmed cell death ligand-1 status. Dual primary endpoints were progression-free survival (PFS; blinded independent central review per Response Evaluation Criteria in Solid Tumors, version 1.1) and overall survival (OS). Efficacy analyses were performed in the intention-to-treat population. Safety analyses included all patients who received ≥1 dose of study treatment. Results Between 16 May 2022 and 11 June 2024, 644 patients were randomised to Dato-DXd (n = 323) or chemotherapy (n = 321). Median PFS was 10.8 months (95% confidence interval [CI] 8.6–13.0) with Dato-DXd and 5.6 months (95% CI 5.0–7.0) with chemotherapy (hazard ratio 0.57 [99% CI 0.44–0.73]; P < 0.0001). Median OS was 23·7 months (95% CI 19.8–25.6) and 18.7 months (95% CI 16.0–21.8) with Dato-DXd and chemotherapy, respectively (hazard ratio 0.79 [95.01% CI 0.64–0.98]; P = 0.029). Treatment-related adverse events (TRAEs) of grade ≥3 were reported in 105 (33%) and 89 (29%) patients who received Dato-DXd and chemotherapy, respectively, and TRAEs led to treatment discontinuation in 14 (4%) and 23 (7%) patients. There were no treatment-related deaths in either arm. Conclusions Dato-DXd demonstrated significantly improved PFS and OS versus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. Safety was consistent with the known profile for Dato-DXd.
Determinants of delayed postoperative radiation therapy in breast cancer patients undergoing neoadjuvant chemotherapy: A subanalysis of the AMAZONA III prospective cohort
(2026) Prestes, Júlio César; Arruda, Gustavo Viani; Gouveia, André Guimarães; Silva, Maurício Fraga da; Moraes, Fabio Ynoe de; Rosa, Daniela Dornelles; Barrios, Carlos Henrique Escosteguy; Werutsky, Gustavo; Bines, Jose; Silva, Eduardo Henrique Cronemberger Costa e; Freitas Junior, Ruffo de
Background Delays in starting postoperative radiation therapy (PORT) in breast cancer patients may be associated with poorer clinical outcomes. This analysis aimed to identify factors contributing to delayed PORT in patients with breast cancer who underwent neoadjuvant chemotherapy followed by surgery and PORT in a Brazilian cohort. Methods Participants were categorized based on the interval from surgery to the initiation of PORT into two groups: ≤ 8 weeks and > 8 weeks. Socioeconomic and clinicopathological factors were analyzed for associations with delayed PORT. Univariable and multivariable regressions were performed. Results Factors significantly associated with delayed PORT included low educational level (RR: 1.50; 95 % CI: 1.05–2.14; p = 0.0276), public health insurance (RR: 3.29; 95 % CI: 1.76–6.12; p = 0.0002) and having a Luminal A or Luminal B-HER2-negative subtype (RR: 1.92; 95 % CI: 1.14–3.23; p = 0.0153) compared to the Triple Negative subtype. The absence of adjuvant endocrine therapy was associated with a lower risk of delayed PORT (RR: 0.67; 95 % CI: 0.46–0.99; p = 0.0338). In the multivariate analysis, public health insurance remained the sole independent predictor of delayed PORT (RR: 2.98; 95 % CI: 1.60–5.55; p = 0.0006). Conclusion In this cohort, reliance on public health insurance emerged as the primary independent predictor of delayed initiation of PORT in breast cancer patients who received neoadjuvant chemotherapy. Lower educational levels and household income also contributed to delays, highlighting disparities within the healthcare system. Addressing these barriers is essential for improving timely access to PORT and potentially enhancing clinical outcomes in this population.
Compliance with Brazilian Law 12.732: assessing breast cancer treatment delays across different therapeutic modalities (2017-2022)
(2025) Antonini, Marcelo; Freitas, Sofia Naiara Barboza; Mattar, Andre; Pinheiro, Denise Joffily Pereira da Costa; Campos, Rodrigo Caires; Felix, Leticia Xavier; Ferraro, Odair; Cavalcante, Francisco Pimentel; Zerwes, Felipe Pereira; Brenelli, Fabricio Palermo; Freitas Junior, Ruffo de
Introduction: Breast cancer (BC) is the most common cancer among women in Brazil and worldwide, followed by non-melanoma skin cancer. Law No. 12,732, of November 22, 2012, stipulates that cancer treatment should begin within 60 days of the anatomopathological diagnosis. However, the time to start treatment is still variable in Brazil. Methods: A cross-sectional observational ecological study was conducted using data on breast cancer in Brazil between 2017 and 2022, obtained from the DATASUS-SISCAN database. Patients with a diagnosis of breast cancer (ICD C50), the federative unit (UF) of residence, and the treatment modality were considered. Five-time intervals were defined for the start of treatment. The χ² and Z tests of two proportions were used, considering a 95% confidence interval (p<0.05). Results: Of the 243,277 evaluated cases, the highest frequency of patients was in the interval of more than 120 days to start treatment (25.5%). Surgery as a modality had a predominance of treatment initiation within 30 days in Brazil and in all regions, with the Northeast and South presenting 63.3% and 66.9% of patients starting treatment within 30 days, respectively. The chemotherapy modality had a greater distribution of patients in the interval of 31 to 60 days in the Northeast (26.1%) and in the South (26.3%), with the remaining regions predominantly showing intervals of more than 120 days. For radiation therapy, the predominance of treatment was after 120 days from diagnosis in all segments. Conclusion: Most patients waited more than 120 days to start breast cancer treatment. Surgical treatment had the shortest waiting time, while radiation therapy showed the longest intervals. For chemotherapy, the time until initiation was variable. In the trend analysis, a decrease in the time to start treatment was evident.
Prevalence of actionable pharmacogenomic variants in Brazilian patients with cancer
(2026) Schuch, Jaqueline Bohrer; Botton, Mariana Rodrigues; Baumont, Angélica Cerveira de; Curzel, Giovana Dallaio; Cadore, Nathan Araujo; Bordignon, Cláudia; Rosa, Mahira de Oliveira Lopes da; Vasconcellos, Vitor Fiorin de; Barros, Lilian Arruda do Rêgo; Souza, Cristiano de Pádua; Barra, Williams Fernandes; Freitas Junior, Ruffo de
Introduction: Pharmacogenomic (PGx) variants can influence drug efficacy and safety, yet their prevalence in Latin American populations with cancer is underexplored. Our aim is to characterize the frequency and phenotypic distribution of actionable pharmacogenes in Brazilian patients with metastatic prostate cancer (MPC) and Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer (BC).Methods: This analysis included 452 patients (259 BC, 193 MPC) from a multicenter study across 19 Brazilian sites. Exome sequencing was performed, and PGx variants were analyzed using the Pharmacogenomics Clinical Annotation Tool (PharmCAT) following the Clinical Pharmacogenetics Implementation Consortium (CPIC®) guidelines. Genotypes, star alleles, and predicted phenotypes were reported for 15 clinically relevant pharmacogenes.Results: Actionable PGx phenotypes were detected in 99.33% of participants. The decreased-function ABCG2 rs2231142 T allele occurred at 8.96%, and the VKORC1 rs9923231 T allele at 32.63%. In SLCO1B1, normal function predominated (63.11%), with 21.11% exhibiting decreased function. Normal metabolizer phenotypes were most frequent in CYP2C19 (45.35%), CYP2C9 (70.51%), and CYP3A4 (94.62%), whereas CYP2B6 was dominated by intermediate metabolizers (43.02%) and CYP3A5 by poor/intermediate metabolizers (93.79%). Normal diplotypes predominated in thiopurine-related genes (NUDT15: 92.92%; TPMT: 88.72%), although nonfunctional alleles were observed. In UGT1A1, decreased-function alleles accounted for approximately 37% of participants. Clinically relevant DPYD and RYR1 variants were rare (<2.0%).Conclusion: Nearly all Brazilian patients with cancer carried at least one actionable PGx variant, highlighting the potential impact of PGx-guided therapy in oncology. These results underscore the value of integrating pharmacogenomic strategies into clinical practice in Brazil.
Is axillary surgery still justified in DCIS diagnosed via vacuum-assisted biopsy?
(2025) Ramos, Marcellus do Nascimento Moreira; Mattar, André; Zerwes, Felipe Pereira; Cavagna, Felipe Andreotta; Cavagna, Felipe Andreotta; Cavalcante, Francisco Pimentel; Millen, Eduardo Camargo; Brenelli, Fabricio Palermo; Frasson, Antonio Luiz; Madeira, Marcelo; Freitas Junior, Ruffo de; Antonin, Marcelo
Background The role of axillary surgery in ductal carcinoma in situ (DCIS) remains controversial, particularly for cases diagnosed via vacuum-assisted biopsy (VAB), which may reduce “upstage” to invasive disease. This study evaluates the incidence of axillary metastasis and pathologic upstaging in DCIS to identify subgroups where axillary staging can be safely omitted. Methods A retrospective cohort of 494 patients with pure DCIS diagnosed by VAB (2011–2019) was analyzed. Patients were stratified by age, nuclear grade, comedonecrosis, and surgical approach (breast-conserving surgery [BCS] vs. mastectomy). Axillary management included sentinel node biopsy (SNB), axillary dissection (AD), or omission. Multivariate logistic regression identified predictors of axillary surgery and upstaging to invasive carcinoma. Results Most patients underwent BCS (72.7%), with axillary evaluation performed in 35.1% of BCS cases versus 91.9% of mastectomies (p < 0.001). Only 3.8% (19/494) were upstaged to invasive carcinoma, and nodal involvement occurred in 1.2% (3/250) of axillary procedures—all in patients with invasive foci on final pathology. No pure DCIS cases had nodal metastasis. Younger age (< 40 years, p = 0.039), high nuclear grade (grade 3, p = 0.006), and mastectomy (p < 0.001) independently predicted axillary surgery. Comedonecrosis and palpable lesions were associated with higher SNB rates but not nodal positivity. Conclusions Routine axillary surgery is unnecessary in VAB-diagnosed DCIS. Omission of SNB appears safe for patients undergoing BCS without high-risk features (palpability, high grade). Axillary staging may be reserved for mastectomy candidates or those with suspicions imaging of invasive disease.
Pathologic complete response and breast cancer survival post-neoadjuvant chemotherapy: a systematic review and meta-analysis of real-world data
(2025) Antonini, Marcelo; Mattar, André; Pereira, Thais Melo; Oliveira, Ludmilla Lemos; Teixeira, Marina Diógenes; Amorim, Andressa Gonçalves; Ferraro, Odair; Oliveira, Larissa Chrispim de; Ramos, Marcellus do Nascimento Moreira; Cavalcante, Francisco Pimentel; Freitas Junior, Ruffo de
Breast cancer is a leading cause of cancer-related mortality worldwide, and neoadjuvant chemotherapy (NAC) plays a pivotal role in its management by reducing tumor size, enabling breast-conserving surgery, and improving survival outcomes. Achieving pathologic complete response (pCR) is strongly associated with better overall survival (OS) and disease-free survival (DFS), particularly in aggressive subtypes such as triple-negative (TNBC) and HER2-positive breast cancers. This systematic review and meta-analysis evaluated the correlation between pCR, OS, and DFS in breast cancer patients treated with NAC, focusing exclusively on real-world data (RWD). A comprehensive search with PRISMA guidelines of major databases from 1999 to 2024 identified 22 retrospective studies comprising 12,115 patients. Hazard ratios (HRs) and confidence intervals (CIs) were pooled using random-effects models, and heterogeneity was assessed using the I statistic. pCR was achieved in 20.9 % of patients, with higher rates in HER2-positive (44.4 %) and TNBC (31.3 %) subtypes. Achieving pCR was associated with a 30 % improvement in OS (HR: 1.30; 95 % CI: 1.28–1.33) and a 29 % improvement in DFS (HR: 1.29; 95 % CI: 1.24–1.32). Among TNBC patients, pCR correlated with a 51 % increase in DFS (HR: 1.51; 95 % CI: 1.19–1.93). Significant heterogeneity (I
National survey on attitudes of brazilian breast surgeons regarding oncoplastic surgery: success of a training model
(2025) Cavalcante, Francisco Pimentel; Oliveira, Vilmar Marques de; Ziegelmann, Patrícia Klarmann; Brenelli, Fabrício Palermo; Paulinelli, Régis Resende; Garcia, Guilherme Novita; Hassan, Augusto Tufi; Millen, Eduardo Camargo; Zerwes, Felipe Pereira; Mattar, André; Freitas Junior, Ruffo de
Background Historically, breast reconstruction was performed by plastic surgeons. The Brazilian Society of Mastology (SBM) implemented initiatives to improve breast surgeons’ training in oncoplastic techniques; however, the current proportion of surgeons performing these techniques remained unknown. This study aimed to determine the proportion of Brazilian breast surgeons performing oncoplastic surgery, their previous training, the complexity of procedures performed, and factors influencing adoption of techniques. Methods In this survey, a structured questionnaire was sent to all SBM-affiliated breast surgeons between July and December 2023. Outcome proportions were estimated using binomial distribution. Adjusted proportion ratios (aPR) were calculated using robust Poisson regression. Results A 60.2% valid response rate was achieved (n = 1059/1759). Almost half of the respondents performed oncoplastic surgery, with most being young (< 40 years) (aPR: 1.66; 1.31–1.10; p < 0.001), male (aPR: 1.39; 1.22–1.59; p < 0.001), southern residents (aPR: 1.39; 1.18–1.63; p < 0.001), with a specialist degree in breast disease (aPR: 1.19; 1.00–1.42; p < 0.004), primarily trained in general surgery (aPR: 1.32; 1.16–1.51; p < 0.001) and secondarily in breast surgery (aPR: 1.41; 1.08–1.85; p = 0.01), and performing > 100 surgeries/year (aPR: 1.72; 1.49–1.99; p < 0.001). The techniques most commonly mastered were simple displacement (88.7%), therapeutic mammoplasty or contralateral symmetrization (96.4%), reconstruction with implants or tissue expanders (93.6%), extreme oncoplasty (81%), skin- and nipple-sparing (99%) or skin-reducing mastectomy (84.2%), and thoracoabdominal flaps (71.7%). Conclusions A high proportion of Brazilian mastologists perform oncoplastic surgery. These findings provide key insights to further enhance training and improve outcomes.
Sacituzumab govitecan plus pembrolizumab for advanced triple-negative breast cancer
(2026) Tolaney, Sara Michell; Azambuja, Evandro Lopes; Kalinsky, Kevin M.; Loi, Sherene; Kim, Sung-Bae; Yam, Clinton; Rapoport, Bernardo Leon; Im, Seol-ah; Pistilli, Barbara; Mchayleh, Wassim M.; Freitas Junior, Ruffo de
Background Triple-negative breast cancer is an aggressive breast cancer subtype, and there remains an unmet need to improve outcomes in patients with previously untreated, programmed death ligand 1 (PD-L1)–positive, locally advanced unresectable or metastatic triple-negative breast cancer. Methods In this phase 3, open-label, international trial, we randomly assigned patients in a 1:1 ratio to receive sacituzumab govitecan plus pembrolizumab or chemotherapy plus pembrolizumab. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included overall survival, objective response (complete or partial response) and duration of response as assessed by blinded independent central review, and safety. Research Summary Sacituzumab Govitecan plus Pembrolizumab for Breast Cancer Results A total of 443 patients were randomly assigned to receive sacituzumab govitecan plus pembrolizumab (221 patients) or chemotherapy plus pembrolizumab (222 patients). The median progression-free survival was 11.2 months (95% confidence interval [CI], 9.3 to 16.7) with sacituzumab govitecan plus pembrolizumab and 7.8 months (95% CI, 7.3 to 9.3) with chemotherapy plus pembrolizumab (hazard ratio for disease progression or death, 0.65; 95% CI, 0.51 to 0.84; two-sided P<0.001). Data for overall survival were immature. The percentage of patients with an objective response was 60% (95% CI, 53 to 66) with sacituzumab govitecan plus pembrolizumab and 53% (95% CI, 46 to 60) with chemotherapy plus pembrolizumab; among patients with a response, the median duration of response was 16.5 months (95% CI, 12.7 to 19.5) and 9.2 months (95% CI, 7.6 to 11.3), respectively. Adverse events of grade 3 or higher occurred in 71% of the patients receiving sacituzumab govitecan plus pembrolizumab and in 70% of those receiving chemotherapy plus pembrolizumab; the incidence of treatment discontinuation due to adverse events was 12% and 31%, respectively. Adverse events leading to death occurred in 3% of the patients in each group. Conclusions Sacituzumab govitecan plus pembrolizumab led to significantly longer progression-free survival than chemotherapy plus pembrolizumab among patients with previously untreated, PD-L1–positive, advanced triple-negative breast cancer. (Funded by Gilead Sciences; ASCENT-04/KEYNOTE-D19 ClinicalTrials.gov number, NCT05382286.)
Trends in mastectomy performance for early breast cancer in a public institution with limited access: a retrospective cohort
(2025) Cavalcante, Francisco Pimentel; Pinheiro, Tallita Moniele Gomes; Zerwes, Felipe Pereira; Millen, Eduardo Camargo; Mattar, Andre; Antonini, Marcelo; Brenelli, Fabricio Palermo; Novita, Guilherme Garcia; Frasson, Antônio Luiz; Freitas Junior, Ruffo de
Objective: To assess trends in breast surgery, Breast-conserving surgery (BCS) and mastectomy, in an institution with limited access to health resources. Methods: A retrospective cohort study was carried out in patients who underwent surgery for non-metastatic breast cancer between 2012 and 2019 at the Hospital Geral de Fortaleza (HGF), an institution that exclusively treats patients from the Brazilian public health system (SUS). The main objective of the study was to evaluate the rates of mastectomy in the period, with or without immediate reconstruction, as well as BCS rates. The χ2 test, with Bonferroni adjustment, was applied to the relative frequency of the procedures performed to test for statistical significance in the evolution of the frequencies of surgeries over the years. Results: A total of 805 patients underwent surgical treatment for non-metastatic breast cancer, with an average of 100 surgeries per year (range 85–118) during the study period. Mastectomy was performed in 552 cases (68.57%), while 253 patients underwent BCS (31.42%). Among the patients who underwent mastectomy, 181 (32.78%) had immediate reconstruction, with the highest proportion using implants (92.26%). No statistical difference was observed between mastectomies with or without reconstruction throughout the period (p=0.6635), with a statistically significant difference between BCS (p=0.04281) and mastectomies. Conclusion: There was no increase in the rates of mastectomies, with and without immediate reconstruction, over the years, but a trend towards an increase in BCS. Further studies are needed to better understand this trend in settings with limited access to health care.
Germline genetic testing in breast cancer: utilization and disparities in a middle-income country
(2025) Souza, Alessandra Borba Anton de; Barrios, Carlos Henrique Escosteguy; Jesus, Rafaela Gomes de; Reinert, Tomas; Giacomazzi, Juliana; Rosa, Daniela Dornelles; Silva, Eduardo Henrique Cronemberger Costa e; Freitas Junior, Ruffo de
PURPOSE Low rates of germline genetic testing (GGT) for breast cancer (BC) have been reported globally, with limited data from low- and middle-income countries (LMICs). In this study, we used real-world data to assess the GGT rate for BC in an LMIC and identified barriers to its use. METHODS We analyzed 2,974 newly diagnosed patients with BC from the AMAZONA III study, the largest Brazilian multicenter, prospective BC cohort. GGT rates were determined for the entire cohort and the high-risk hereditary BC group (HR), defined by the National Comprehensive Cancer Network criteria, between 2019 and 2020. Barriers to GGT performance associated with patient characteristics and health care systems were identified using multivariable Poisson regression model. Values of P < .05 were considered significant. RESULTS In the AMAZONA III cohort, 1,476 (49%) were classified as HR. Genetic counseling was recommended for 521 patients (35% of HR), and 282 (19%) underwent GGT. Notably, 97% of patients with HR treated within the public health care systems and 56% in the private system did not undergo GGT. Age, education, occupation, monthly income, availability of onsite genetic coun seling, and treatment at a teaching center were factors associated with GGT uptake (P < .05). Of those tested, 50 (17%) harbored a germline pathogenic or likely pathogenic variant. CONCLUSION Only 9% of this robust Brazilian BC cohort underwent GGT, highlighting a considerable gap from the current recommendation to test all patients with BC under age 65 years. GGT is underused by patients with HR in both public and private health care systems, with those in the public system being more af fected. The disparities and barriers identified emphasize the need for educa tional interventions and enhanced access to GGT. Prioritizing GGT is critical to improving BC outcomes in LMICs
Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1-positive advanced triple-negative breast cancer (TNBC): primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study
(2025) Tolaney, Sara Michell; Azambuja, Evandro Lopes; Kalinsky, Kevin M.; Loi, Sherene; Kim, Sung-Bae; Yam, Clinton; Rapoport, Bernardo Leon; Im, Seol-ah; Pistilli, Barbara; Cesco, David W.; Freitas Junior, Ruffo de; Mchayleh, Wassim M.
Background:AlthoughPD-1/PD-L1inhibitorspluschemohaveexpandedtreatmentoptionsfor previously untreated PD-L1–positive advanced TNBC, there still remains a critical unmet need to improve outcomes. SG previously demonstrated significant clinical benefit in pretreated metastatic TNBC (mTNBC). We report results from the ASCENT-04/KEYNOTE-D19 study in patients with previously untreated, PD-L1–positive (CPS $ 10; 22C3 assay) locally advanced unresectableormTNBC.Methods:Patientswererandomized1:1toSG(10mg/kgIV,day1&8)+ pembro (200 mg, day 1, max 35 cycles) in 21-day cycles or chemo (gemcitabine + carboplatin, paclitaxel, nab-paclitaxel) + pembro until disease progression or unacceptable toxicity. Ran domizationwasstratifiedbycurativetreatment-freeinterval,geography,andpriorexposureto anti–PD-(L)1 therapy in the curative setting. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). Key secondary endpoints include overall survival(OS);objectiveresponserate(ORR)anddurationofresponse(DOR)byBICR;andsafety. Results: 443 patients were randomized at a 1:1 ratio: 221 to SG + pembro and 222 to chemo + pembro. The median follow-up was 14 mo. SG +pembroshowedasignificant improvement in PFS by BICR compared with chemo + pembro (hazard ratio [HR], 0.65; 95% CI, 0.51-0.84; P = .0009;Table). MedianDORwas16.5moforSG+pembrovs9.2moforchemo+pembro(Table). AlthoughOSdatawereimmature,apositiveearlytrendinOSimprovementwasalsonoted.The mostfrequent($10%ofpatients)grade$3treatment-emergentadverseevents(TEAEs)with SG + pembro were neutropenia (43%) and diarrhea (10%); and with chemo + pembro were neutropenia (45%), anemia (16%), and thrombocytopenia (14%). Conclusions: SG + pembro led to a statistically significant and clinically meaningful improvement in PFS vs chemo + pembro with durable responses, no new safety concerns for SG or pembro, and a lower rate of treatmentdiscontinuationduetoTEAEsinpatientswithpreviouslyuntreated,PD-L1–positive advanced TNBC.ThesedatasupporttheuseofSG+pembroasapotentialnewstandardofcare treatment inthis patient population
Safety and efficacy of tiragolumab, atezolizumab and chemotherapy for early-stage or PD-L1-positive advanced triple-negative breast cancer: a phase Ib study
(2025) Kümmel, Sherko; Jung, Kyung Hae; Andrade, Livia Maria Querino da Silvo; Suzuki, Daniele Xavier Assad; Cruz Merino, Luis de la; Freitas Junior, Ruffo de; Hegg, Roberto; Huang, Chiun-Sheng; Martin, Hilary; Schneeweiss, Andreas
Background: Immune checkpoint inhibitors have transformed the management of triple-negative breast cancer (TNBC) but outcomes could be improved further. We explored combining the T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) inhibitor tiragolumab with atezolizumab-containing regimens for patients with early-stage or advanced TNBC. Patients and methods: This multinational open-label phase Ib study included two cohorts. In cohort A [programmed death-ligand 1 (PD-L1)-positive advanced TNBC], patients received first-line tiragolumab with atezolizumab and nabpaclitaxel. The primary endpoint was confirmed objective response rate. In cohort B (early-stage TNBC, irrespective of PD-L1 status), patients were randomised to receive tiragolumab, atezolizumab and sequential taxane- and anthracycline-based neoadjuvant therapy with (arm A) or without (arm B) carboplatin. The primary objective was to evaluate safety in arm A versus arm B. Results: Between September 2020 and October 2021, 83 patients were enrolled from 24 sites in eight countries. In cohort A (n = 41), the confirmed objective response rate was 54% [95% confidence interval (CI) 37% to 69%], median duration of response in 22 responding patients was 7.2 months (95% CI 4.9-13.1 months), median progression-free survival was 6.5 months (95% CI 5.4-9.0 months) and median overall survival was 24.6 months (95% CI 14.7 months-not estimable). Five patients (12%) discontinued tiragolumab for adverse events. In cohort B (n = 42), carboplatin was associated with more haematological effects but no increase in pathologic complete response rate [arm A: 46% (95% CI 24% to 68%); arm B: 55% (95% CI 32% to 77%)]. Adverse events led to treatment discontinuation in 23% and 20% of patients in arms A and B, respectively. Conclusions: The activity of tiragolumab-containing regimens appeared similar to that of atezolizumab plus chemotherapy in randomised phase III trials in early-stage and advanced TNBC. The safety profile of all three regimens was consistent with previous experience of similar regimens in other tumour types and with symptoms of the underlying disease. Clinical trial registration: ClinicalTrials.gov NCT04584112.
Hypofractionated whole and partial breast irradiation: Brazilian Society of Radiotherapy (SBRT) consensus
(2025) Freitas, Nilceana Maya Aires; Rosa, Arthur Accioly; Castilho, Marcus Simões; Hanna, Samir Abdallah; Carvalho, Heloisa de Andrade; Campos, Conceição Aparecida Machado de Souza; Gondim, Guilherme Rocha Melo; Zanuncio, Pedro Henrique da Rocha; Fernandez, Claudia Regina Scaramello Hadlich Willis; Almeida Júnior, Wilson José de; Freitas Junior, Ruffo de
Background: Breast cancer is the most common cancer in women worldwide, with 73,610 new cases expected annually in Brazil between 2023 and 2025. Post-operative radiation therapy (PORT) is a critical component of treatment, and recent advances have allowed for shorter treatment times that can help overcome shortages in low- and middle-income countries. The Brazilian Society of Radiotherapy (SBRT) updated its consensus on hypofractionated whole-breast radiotherapy and in cluded recommendations for partial breast irradiation. Materials and methods: The SBRT convened a national panel of experts to develop updated recommendations. Using a modified Delphi method, the panel reached a consensus through structured rounds of voting. Recommendations were categorized based on the strength of available evidence. Results: The consensus supports hypofractionation, which offers shorter, cost-effective treatment schedules, and partial breast irradiation (PBI), which targets high-risk areas while sparing healthy tissue. Despite high-quality evidence, adopting these techniques has been inconsistent. The panel’s recommendations provide evidence-based guidance to clinicians, tai lored to the Brazilian context, emphasizing safety and efficacy. Conclusion: The updated SBRT consensus presents hypofractionation and PBI as practical alternatives to conventional radia tion therapy, offering improved access and reduced costs. These recommendations aim to guide clinicians in adopting these approaches and help address barriers to access.
First-line lenvatinib plus pembrolizumab versus chemotherapy for advanced endometrial cancer: a randomized, open-label, phase III trial
(2025) Marth, Christian; Moore, Richard G.; Bidziński, Mariusz; Pignata, Sandro; Ayhan, Ali; Rubio Pérez, María Jesús; Beiner, Mario Emanuel; Hall, Marcia; Freitas Junior, Ruffo de; Vulsteke, Christof
PURPOSE Lenvatinib plus pembrolizumab (len 1 pembro) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in previously treated advanced or recurrent endometrial cancer (aEC) in the phase III Study 309/KEYNOTE-775. We report results from the phase III, randomized, open-label European Network of Gynaecological Oncological Trial-en9/LEAP-001 study (ClinicalTrials.gov identifier: NCT03884101) that evaluated len 1 pembro versus chemotherapy in first-line aEC. METHODS Patients with stage III to IV or recurrent, radiographically apparent EC and no previous chemotherapy or disease progression ≥6 months after neo/adjuvant platinum-based chemotherapy were randomly assigned 1:1 to lenvatinib 20 mg once daily plus pembrolizumab 200 mg once every 3 weeks or paclitaxel 175 mg/m2 plus carboplatin AUC 6 mg/mL/min once every 3 weeks. Primary end points were PFS and OS, evaluated in the mismatch repair-proficient (pMMR) and all-comers populations. Noninferiority was assessed for OS at final analysis (FA) for len 1 pembro versus chemotherapy (multiplicity-adjusted, one-sided nominal alpha, .0159; null hypothesis–tested hazard ratio [HR], 1.1). RESULTS Eight hundred forty-two patients were randomly assigned (len 1 pembro, n 5 420 [pMMR population, n 5 320]; chemotherapy, n 5 422 [pMMR population, n 5 322]). At FA (data cutoff, October 2, 2023), median PFS (95% CI) in the pMMR population was 9.6 (8.2 to 11.9) versus 10.2 (8.4 to 10.5) months with len 1 pembro versus chemotherapy (hazard ratio [HR], 0.99 [95% CI, 0.82 to 1.21]) and among all-comers was 12.5 (10.3 to 15.1) versus 10.2 (8.4 to 10.4)months (HR, 0.91 [95% CI, 0.76 to 1.09]; descriptive analyses). Median OS (95% CI) in the pMMR population was 30.9 (25.4 to 37.7) versus 29.4 (26.2 to 35.4) months with len 1 pembro versus chemotherapy (HR, 1.02 [95% CI, 0.83 to 1.26]; noninferiority P 5 .246, not statistically significant per multiplicity control strategy) and among all-comers was 37.7 (32.2 to 43.6) versus 32.1 (27.2 to 35.7) months (HR, 0.93 [95% CI, 0.77 to 1.12]). Grade ≥3 treatment-related adverse events occurred in 331/420 (79%) versus 274/411 (67%) treated patients. CONCLUSION First-line len 1 pembro did not meet prespecified statistical criteria for PFS or OS versus chemotherapy in pMMR aEC.
Vacuum-assisted excision: one-step approach to the diagnosis and percutaneous treatment of small early breast cancer (the VAE-BREAST 01 study protocol)
(2025) Couto, Henrique Lima; Coelho, Bertha Andrade; Ricardo, Bernardo Ferreira de Paula; Toppa, Paola Hartung; Soares, Aleida Nazareth; Silva, Bruna Torres Silvestre da; Pires, Douglas de Miranda; Oliveira, Tereza Cristina Ferreira de; Clarke, Paula; Freitas Junior, Ruffo de; Ferreira, Shirley das Graças
Introduction: Vacuum-assisted excision (VAE) of breast lesions is a technique used for diagnostic and therapeutic purposes and is performed on an outpatient basis, with local anesthesia and image guidance. Currently, VAE is used in themanagement of benign lesions and lesions of uncertain malignant potential (B3 lesions). More recently, there has been interest in VAE for the percutaneous treatment of small breast cancers, the aim of which was to reduce morbidity and aggressive surgical treatment. Due to how conventional VAE is performed, histopathological assessment of the resection margins is not possible. Obtaining free margins after a breast cancer resection is a primary objective in the surgical treatment of this disease. If VAE could ensure free margins and the absence of residual tumor in the surgical excision, it would represent a safe method for a minimally invasive treatment, providing an effective percutaneous treatment of small early breast cancers. Methods: The prospective VAE-BREAST 01 study explores the role of VAE associated with cavity margin sample shaving (CMSH) as a one-step approach in the diagnosis and complete excision of small breast tumors, ensuring the absence of residual disease in surgical pathology. Women with lesions smaller than 1.5 cm, ACR BI-RADS™ (American College of Radiology Breast Imaging Reporting and Data System) category 4 or 5, and identified by screening or clinical alteration are included. Multifocal, multicentric breast cancers and breast cancers associated with diffuse and extensive calcifications are excluded. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and the false-negative and false-positive rates of VAE+CMSH for the complete excision of breast cancers will be calculated. The collected data also will include patients’ demographics, image characteristics of the lesions, information regarding the VAE+CMSH and surgical procedure, biopsy and surgical pathology, and data on side effects, patient acceptance, cosmetic results, and patients’ experiences during VAE. Ethics and dissemination: Ethics approval was obtained from the Brazilian National Research Ethics Commission (CONEP). Participants will provide written informed consent, and researchers will follow institutional guidelines for data collection and management.
Clinical characteristics and prognostic impact of HER2 low expression in breast cancer subtypes from a Brazilian real-world cohort
(2026) Mattar, André; Antonin, Marcelo; Cavalcante, Francisco Pimentel; Zerwes, Felipe Pereira; Millen, Eduardo Camargo; Brenelli, Fabricio Palermo; Frasson, Antônio Luiz; Soares, Leonardo Ribeiro; Madeira, Marcelo; Teixeira, Marina Diógenes; Amorim, Andressa Gonçalves; Freitas Junior, Ruffo de
Breast cancer (BC) is the most prevalent cancer among Brazilian women, yet related data remain limited. The HER2-low classification has gained significance with the advent of targeted therapies. This study aimed to assess survival outcomes of HER2-low BC compared to other subtypes in a real-world Brazilian cohort. We analyzed data from 8,485 breast cancer patients treated at Pérola Byington Hospital between 2010 and 2019. Overall survival (OS) was the primary endpoint, stratified by cancer subtype. The t-test and chi-square test evaluated variable associations, while multivariate analysis calculated odds ratios and 95% confidence intervals. Cox regression assessed survival, and Kaplan–Meier curves illustrated OS differences. The patients with HER2-low breast cancers showed significantly better overall survival than those with the triple-negative subtype (p < 0.01). However, they had significantly poorer overall survival than those with the Luminal A-like subtype (p < 0.01). The patients with triple-negative HER2-low disease had a higher risk of mortality than those with HER2-0 (p < 0.01). Finally, patients who achieved pathological complete response experienced significantly better overall survival than those who did not (p < 0.01). Our findings highlight triple negative HER2- low BC as a distinct subtype identifiable via standard immunohistochemistry, beyond just biomarker status. The study underscores the prognostic diversity among BC subtypes and emphasizes the importance of personalized treatment strategies.
Breast cancer stage, molecular subtype and survival in patients with obesity: a real-world study
(2025) Mattar, André; Antonin, Marcelo; Cavalcante, Francisco Pimentel; Zerwes, Felipe Pereira; Millen, Eduardo Camargo; Brenelli, Fabricio Palermo; Frasson, Antônio Luiz; Soares, Leonardo Ribeiro; Madeira, Marcelo; Teixeira, Marina Diógenes; Amorim, Andressa Gonçalves; Freitas Junior, Ruffo de
Background: Breast cancer (BC) is a leading cause of cancer-related deaths worldwide. Obesity, an established risk factor for BC in postmenopausal women, may also affect prognosis. This study evaluated the impact of obesity on the survival of BC patients treated at a public reference center in Brazil. Methods: A retrospective cohort study was conducted with 7,424 BC patients treated at Hospital da Mulher (São Paulo, Brazil) from January 2011 to June 2021. Patients were categorized into four groups based on body mass index (BMI): underweight, healthy weight, overweight, and obese. Clinical, pathological, staging, and immunohistochemistry data were analyzed. Survival outcomes (overall and progression-free) were assessed using Kaplan-Meier estimates, with comparisons via logistic and Cox regression. Results: Among the patients, 67.81% were overweight or obese, and 64.82% were postmenopausal (assumed ≥50 years old). A total of 6,992 patients were included in the survival analysis, with 3.79% succumbing to BC. No statistically significant differences in overall or progression-free survival were observed across BMI categories. Conclusions: While obesity is highly prevalent among Brazilian women with BC, it did not significantly impact survival outcomes in this study. These findings underscore the need for prospective studies to explore potential confounding factors and long-term effects, as well as to inform tailored interventions in similar healthcare settings.
Cracking the code: pioneering early detection and management of breast cancer in the Brazilian public healthcare system
(2025) Santos, Arn Migowski Rocha dos; Freitas Junior, Ruffo de; Bines, José; Jansen, Angela Marie; Estevez Diz, Maria Del Pilar; Rico Restrepo, Mariana; Sanku, Gayatri; Mattar, André
Breast cancer (BC) remains a significant health concern in Brazil, particularly within its public healthcare system, the Unified Health System, known by its Portuguese acronym “SUS”, with early detection being one of the main challenges. A review of literature and policy documents was conducted to evaluate the performance and challenges of BC screening and early diagnosis in SUS. Brazilian experts in BC early detection attended a three-day meeting to discuss the challenges of SUS’s existing early detection program and provide recommendations for surmounting them. The study identified that Brazil’s current opportunistic BC screening model perpetuates issues with access to screening and regional disparities, while also generating low effectiveness and inefficiency. It also highlights several causes of delays in early diagnosis and treatment. The conclusions suggest an urgent need for an organized national BC screening program, in addition to the implementation of early diagnosis strategies, with multifaceted interventions, including urgent referral guidelines for suspected cases, training of key health professionals, patient navigation, and one-stop breast clinics. Implementing these changes could alleviate the economic strain on the healthcare system while improving patient outcomes.
Avaliação da distância côndilo-cápsula articular por ultrassonografia em pacientes saudáveis e com disfunção temporomandibular: uma revisão sistemática
(2025) Ferreira, Maria Geovania; Amaral, Waldemar Naves do
Introduction: The temporomandibular joint (TMJ) is frequently involved in disorders that affect masticatory function, jaw biomechanics, and patients' quality of life. The literature cites the measurement of the distance between the mandibular condyle and the joint capsule as a relevant parameter for detecting intra-articular changes, especially synovitis and joint effusion. Magnetic resonance imaging (MRI) is the most commonly used imaging test to evaluate the soft tissues of the TMJ, although ultrasound (US) is gaining prominence as an accessible, non-invasive, and low-cost method. Objective: To evaluate the capsule-condyle distance in healthy individuals and those with Temporomandibular Disorders. Methods: This is a systematic review that follows the PRISMA items. The search was conducted in PubMed and BVS databases using the terms: ("Temporomandibular disorder" OR "TMJ disorder" OR "DTM") AND ("Ultrasound" OR "Ultrasonography" OR "USG") AND ("Condyle" OR "Condylar distance" OR "Condyle-capsule distance" OR "Joint space"). Initially, 33 articles were identified, of which 11 were selected after applying eligibility criteria. Two independent reviewers performed title and abstract screening, followed by full-text reading for final selection. Results: The capsule-condyle distance in healthy individuals ranged from 1.65mm to 2.4mm, while in TMD patients values ranged from 1.04mm to 3.6mm, with values above 2.0-3.0mm being considered indicative of pathological changes. Conclusion: Individuals with TMD had larger joint space and smaller mouth opening range, indicating that ultrasonography may play a relevant role in the functional assessment of TMD, especially in dynamic approaches. Dysfunctional temporomandibular joints have greater separation between the mandibular condyle and the joint capsule than normal temporomandibular joints – although magnetic resonance imaging remains the gold standard for direct visualization of soft tissues (articular disc and synovial fluid). Ultrasound, in turn, has proven to be a valuable and non-invasive tool for indirectly measuring capsular distension, and helps in monitoring the clinical evolution of TMDs.

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