Assuntos
Antineoplásicos Hormonais , Biomarcadores Tumorais , Neoplasias da Mama , Antígeno Ki-67 , Terapia Neoadjuvante , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análise , Receptor ErbB-2/metabolismo , Prognóstico , Receptores de Estrogênio/metabolismo , Biomarcadores Tumorais/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Metanálise como AssuntoRESUMO
The results of the SOLAR-1 and CAPItello-291, highlight the benefit of the É-selective phosphoinositide 3-Kinase Pathway inhibitor (PI3Ki) alpelisib and the AKT inhibitor (AKTi) capivasertib in patients with hormone receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 (HER2)- negative metastatic breast cancer (mBC) that have PIK3CA/AKT1/PTEN tumour alterations. Although effective, these drugs are associated with significant toxicities, which often limit their use, particularly in frail patients. Following the recent incorporation of these agents into clinical practice, and with many others currently in development, significant challenges have emerged, particularly those regarding biomarkers for patient selection. This review will discuss biomarkers of response and their resistance to PI3K/AKT inhibitors (PI3K/AKTis) in HR+/HER- BC in early and advanced settings to ascertain which populations will most benefit from these drugs. Of the biomarkers that were analysed, such as PIK3CA, AKT, PTEN mutations, insulin levels, 18â¯F-FDG-PET/TC, only the PIK3CA-mutations (PIK3CA-mut) and the AKT pathway alterations seem to have a predictive value for treatments with alpelisib and capivasertib. However, due to the retrospective and exploratory nature of the study, the data did not provide conclusive results. In addition, the different methods used to detect PIK3CA/AKT1/PTEN alterations underline the fact that the optimal diagnostic companion has yet to be established. We have summarised the clinical data on the approved and discontinued agents targeting this pathway and have assessed the drugs development, successes, and failures. Finally, because of tumour heterogeneity, we emphasise the importance of reassessing the mutational status of PI3KCA in both metastatic tissue and blood at the time of disease progression to better tailor treatment for patients.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Receptor ErbB-2 , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
OPINION STATEMENT: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life.
Assuntos
Neoplasias da Mama , Qualidade de Vida , Feminino , Humanos , Ovário/patologia , Tamoxifeno/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Pré-Menopausa , Quimioterapia Adjuvante/efeitos adversos , Antineoplásicos Hormonais/uso terapêuticoRESUMO
INTRODUCTION: The CLEOPATRA trial (NCT00567190) established a dual anti-HER2 blockade in combination with docetaxel as the first-line standard of care for patients with metastatic HER2-positive breast cancer. While this treatment is overall associated with significant improvement in progression-free survival (PFS) and overall survival (OS), not all patients respond equally. We hypothesized that a radiological complete response (CR) at week 9 (i.e., first disease re-evaluation) is associated with prolonged OS and PFS compared to radiological partial response (PR) or stable disease (SD). METHODS: We performed an exploratory analysis of the CLEOPATRA study to address this question. RESULTS: Out of 362 patients treated with docetaxel, trastuzumab, and pertuzumab eligible for our analysis, 46 (12.7%) had radiological CR at week 9, 243 (67.1%) PR, and 73 (20.2%) SD per central RECIST v1.0. Radiological CR at first tumor re-evaluation was associated with a 60% risk reduction for death compared to SD (adjusted HR = 0.40 95% confidence interval (CI) 0.23-0.70), whereas no significant impact on survival was observed for PR (adjusted HR = 0.85 95% CI 0.60-1.20). The same was observed for PFS with adjusted HR = 0.30 (95% CI 0.18-0.48) for the CR subgroup and adjusted HR = 0.81 (95% CI 0.60-1.09) for the PR subgroup. In multivariate analysis, no variables were associated with radiological CR. CONCLUSIONS: Our findings suggest that radiological CR at first disease re-evaluation is associated with more prolonged survival; this might result from stronger dependence on HER2 pathway addiction, supporting the need for further translational research.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Docetaxel , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Docetaxel/uso terapêutico , Docetaxel/administração & dosagem , Trastuzumab/uso terapêutico , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Adulto , Idoso , Intervalo Livre de ProgressãoRESUMO
The results of several studies aiming to tailor early breast cancer treatment to individual risk were released in 2023. Axillary lymph node dissections and radiotherapy may be safely omitted in carefully selected patients. Sustained benefit from adjuvant CDK4/6 inhibitors was observed in high-risk hormone receptor-positive disease and the addition of immunotherapy to neoadjuvant chemotherapy improved pathological response. Continued benefit from perioperative pembrolizumab was reported in patients with triple negative breast cancer, while atezolizumab did not improve the risk of recurrence either pre- or postoperatively. The chance of pregnancy was higher in younger patients attempting to conceive after breast cancer.
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Excisão de Linfonodo , Neoplasias de Mama Triplo Negativas/patologia , Terapia NeoadjuvanteRESUMO
INTRODUCTION: Currently three antibody-drug-conjugates (ADC) are approved by the European Medicines Agency (EMA) for treatment of breast cancer (BC) patient: trastuzumab-emtansine, trastuzumab-deruxtecan and sacituzumab-govitecan. ADC are composed of a monoclonal antibody (mAb) targeting a specific antigen, a cytotoxic payload and a linker. Pharmacokinetics (PK) and pharmacodynamics (PD) distinguish ADC from conventional chemotherapy and must be understood by clinicians. AREAS COVERED: Our review delineates the PK/PD profiles of ADC approved for the treatment of BC with insight for future development. This is an expert opinion literature review based on the EMA's Assessment Reports, enriched by a comprehensive literature search performed on Medline in August 2023. EXPERT OPINION: All three ADC distributions are described by a two-compartment structure: tissue and serum. Payload concentration peak is immediate but remains at low concentration. The distribution varied for all ADC only with body weight. mAb will be metabolised firstly by the saturable complex formation of ADC/Tumour-Receptor and secondly by binding of FcgRs in immune cells. They are all excreted in the bile and faeces with minimal urine elimination. Dose adjustments, apart from weight, are not recommended. Novel ADC are composed of cleavable linkers with various targets/payloads with the same PK/PD properties, but novel structures of ADC are in development.
Assuntos
Antineoplásicos , Neoplasias da Mama , Imunoconjugados , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Trastuzumab , Ado-Trastuzumab Emtansina/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Imunoconjugados/farmacocinética , Imunoconjugados/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêuticoRESUMO
BACKGROUND: Neoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We aimed to assess the prognostic value of Ki-67 index after neoadjuvant endocrine therapy (NET). METHODS: We conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings up to 22nd August 2023 to identify studies reporting the association of Ki-67 index after NET with recurrence-free survival (RFS) and/or overall survival (OS) in women with ER-positive/HER2-negative early breast cancer. We combined RFS and OS hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Twelve studies including 7897 patients were analysed. Most studies were clinical trials (n = 7547) including only postmenopausal women (n = 3953) treated with aromatase inhibitor (n = 3359). Three studies evaluated Ki-67 in a preplanned core biopsy at 2-4 weeks of NET (n = 3348), while nine evaluated Ki-67 in the surgical specimen (n = 4549) after 2-24 weeks of NET. Median follow-up ranged between 37 and 95 months for RFS and 62-84 months for OS. High Ki-67 index after NET was significantly associated with worse RFS (HR 2.48, 95% CI 1.86-3.30) and OS (HR 2.66, 95% CI 1.65-4.28). A sensitivity analysis including three studies that measured Ki-67 in a preplanned core biopsy showed similar association with RFS (HR 2.41, 95% CI 1.77-3.30). CONCLUSIONS: High Ki-67 after NET is associated with worse survival outcomes, even after a short course of NET, emphasising the prognostic value of this biomarker in women with ER-positive/HER2-negative early breast cancer.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Antígeno Ki-67 , Prognóstico , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
PURPOSE OF REVIEW: This review aims to explore the role of circulating tumor DNA (ctDNA) as a biomarker for patient selection in breast cancer. We describe the current evidence and the main ongoing trials both in the early and metastatic setting. RECENT FINDINGS: In the metastatic setting, the analysis of ctDNA can identify specific genetic alterations amenable of molecularly targeted treatments. Several assays are now approved for the detection of genetic alterations in plasma cell-free DNA to guide treatment decision (e.g., PIK3CA mutations for PI3K inhibitors, and ESR1 mutations for the selective estrogen receptor degrader elacestrant). In the early setting, emerging evidence is demonstrating that ctDNA can identify a disease relapse with a lead-time of approximately 10âmonths before imaging. This could help select patients who may benefit from escalation treatment strategy, although this hypothesis needs to be first prospectively validated. SUMMARY: Liquid biopsy for ctDNA detection represents an exciting new field in rapid evolution. Several trials are ongoing to validate the clinical utility of ctDNA in daily practice in the early setting and to expand its current indications in the metastatic one.
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Neoplasias da Mama , DNA Tumoral Circulante , Humanos , Feminino , DNA Tumoral Circulante/genética , Neoplasias da Mama/tratamento farmacológico , Biomarcadores Tumorais/genética , Seleção de Pacientes , Fosfatidilinositol 3-Quinases , MutaçãoRESUMO
PURPOSE: Invasive lobular carcinoma (ILC) represents up to 15% of all breast carcinomas. While the proportion of women with overweight and obesity increases globally, the impact of body mass index (BMI) at primary diagnosis on clinicopathological features of ILC and the prognosis of the patients has not been investigated yet. PATIENTS AND METHODS: We performed a multicentric retrospective study including patients diagnosed with non-metastatic pure ILC. The association of BMI at diagnosis with clinicopathological variables was assessed using linear or multinomial logistic regression. Univariable and multivariable survival analyses were performed to evaluate the association of BMI with disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS). RESULTS: The data of 2856 patients with ILC and available BMI at diagnosis were collected, of which 2570/2856 (90.0%) had oestrogen receptor (ER)-positive and human epidermal growth factor receptor (HER2) not amplified/overexpressed (ER+/HER2-) ILC. Of these 2570 patients, 80 were underweight (3.1%), 1410 were lean (54.9%), 712 were overweight (27.7%), and 368 were obese (14.3%). Older age at diagnosis, a higher tumour grade, a larger tumour size, a nodal involvement, and multifocality were associated with a higher BMI. In univariable models, higher BMI was associated with worse outcomes for all end-points (DFS: hazard ratio (HR) 1.21, 95CI 1.12-1.31, p value<0.01; DRFS: HR 1.25, 95CI 1.12-1.40, p value<0.01; OS: HR 1.25, 95CI 1.13-1.37, p value<0.01). This association was not statistically significant in multivariable analyses (DFS: HR 1.09, 95CI 0.99-1.20, p value 0.08; DRFS: HR 1.03, 95CI 0.89-1.20, p value 0.67; OS: HR 1.11, 95CI 0.99-1.24, p value 0.08), whereas grade, tumour size, and nodal involvement were still prognostic for all end-points. CONCLUSION: Worse prognostic factors such as higher grade, larger tumour size, and nodal involvement are associated with higher BMI in ER+/HER2- ILC, while there was no statistical evidence for an independent prognostic role for BMI. Therefore, we hypothesise that the effect of BMI on survival could be mediated through its association with these clinicopathological variables.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Humanos , Feminino , Neoplasias da Mama/patologia , Índice de Massa Corporal , Carcinoma Lobular/patologia , Sobrepeso , Estudos Retrospectivos , Prognóstico , Obesidade/complicações , Receptores de Estrogênio/metabolismo , Carcinoma Ductal de Mama/patologiaRESUMO
Antibody-drug conjugates (ADCs) are a class of antineoplastic agents whose structure is composed of three main components: a monoclonal antibody (mAB) targeting a specific target antigen, a cytotoxic payload, and a linker binding the antibody to the payload. By combining the specificity of mABs with the high potency of the payloads, ADCs constitute a smart drug delivery system with improved therapeutic index. After recognition and binding of the mAB to its target surface antigen, ADCs are internalized by endocytosis by the tumor cell, releasing the payloads into the cytoplasm, where they exert their cytotoxic activity, eventually leading to cell death. The composition of some of the new ADCs confers additional functional properties that allow expanding their activity to neighboring cells not expressing the target antigen, constituting a valuable strategy to overcome tumor heterogeneity. Some of these 'off-target effects', such as the bystander effect, are possibly the mechanism underlying the antitumor activity demonstrated in patients with low expression of the target antigens, which represents an important paradigm shift in anticancer targeted therapy. Three ADCs are currently approved for the treatment of breast cancer (BC); two anti-HER2 (human epidermal growth factor receptor 2) ADCs (trastuzumab emtansine and trastuzumab deruxtecan); and one Trop-2-targeted ADC (sacituzumab govitecan). Based on the unprecedented efficacy data demonstrated by these agents, ADCs have been incorporated as part of standard regimens for all subtypes of advanced BC, as well as for high-risk early HER2-positive BC. Despite the remarkable advances, several hurdles still remain to overcome, including the development of reliable biomarkers for patient selection, prevention, and management of potentially severe toxicities, ADC resistance mechanisms, post-ADC resistance patterns, and optimal treatment sequencing and combinations. In this review, we will summarize the currently available evidence related to the use of these agents, as well as explore the current landscape of ADC development for BC treatment.
RESUMO
PURPOSE: This systematic review and meta-analysis aimed to evaluate the immune response to anti-SARS-CoV-2 prime-vaccination in patients with cancer. METHODS: We performed a systematic literature search using PubMed, Embase, and Cochrane Library until 28/09/2021, and conference proceedings from ASCO and ESMO 2021 annual meetings. We screened for observational or interventional studies including subjects ≥ 16 years old with cancer diagnosis who were vaccinated against SARS-CoV-2. Prime-vaccination was defined as one dose of Ad26.COV2-S vaccine or two doses of BNT162b2, mRNA-1273, ChAdOx1-S or inactivated SARS-CoV-2 vaccine. The outcomes were humoral and adaptive immune responses (proportion of subjects with positive titers of antibody anti-SARS-CoV-2 spike protein and anti-SARS-CoV-2 cellular responses, respectively). RESULTS: We included 89 records reporting data from 30,183 subjects. The overall seropositive rate within the first month after complete anti-SARS-CoV-2 prime-vaccination was 80% [95% confidence interval (CI), 72-86%], 60% (95%CI, 53-67%) in patients with hematological malignancies (HM) versus 94% (95%CI, 88-97%) in patients with solid malignancies (SM). The diagnosis of HM was significantly associated with a lower seropositive rate on multivariate meta-regression (odds ratio 0.35, 95% CI 0.18-0.69, HM versus both, p = 0.002). The overall humoral response was 49% (95% CI, 42-56%) after incomplete prime-vaccination and 79% (95% CI, 70-86%) at 2 months after complete prime-vaccination. These responses were also lower in patients with HM at these time points. The overall cellular response rate at any time after vaccination was 61% (95% CI, 44-76%). CONCLUSION: This meta-analysis provides compelling evidence of humoral and adaptive immune responses against SARS-CoV-2 in patients with cancer, which last for at least 2 months following complete prime-vaccination.
Assuntos
COVID-19 , Neoplasias Hematológicas , Neoplasias , Humanos , Adolescente , Vacinas contra COVID-19 , Vacina BNT162 , COVID-19/prevenção & controle , SARS-CoV-2 , Neoplasias/terapia , Vacinação , Imunidade , Anticorpos AntiviraisRESUMO
BACKGROUND: Cutaneous squamous-cell carcinoma (CSCC) is among the most frequent malignancies worldwide. For those not amenable to treatment with curative intent, immune checkpoint inhibition (ICI) with anti-programmed death receptor 1 (PD-1) antibodies has emerged as a novel therapeutic option. In this study, the authors sought to investigate the activity of the anti-PD-1 agent nivolumab in patients with advanced CSCC (aCSCC). METHODS: CA209-9JC was an open-label, single-arm, phase 2 study to evaluate the safety and/or efficacy of nivolumab in systemic treatment-naive patients with aCSCC. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or 12 months of treatment. The primary end point was the best objective response rate (BORR) as per RECIST 1.1 criteria. Secondary end points included safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-four patients with aCSCC were enrolled with a median age of 74 years (range, 48-93). Among the 24 patients evaluable for response, the BORR was 58.3% (14/24); there were no complete responses. With a median follow-up of 17.6 months, median duration of response has not been reached, and the estimated median PFS and OS were 12.7 and 20.7 months, respectively. Prior exposure to radiotherapy was associated with worse outcomes (p = .035, univariate analysis). Treatment-related adverse events of any grade and grade ≥ 3 occurred in 21 (87.5%) and six (25%) patients, respectively, and one patient discontinued nivolumab due to toxicities. CONCLUSIONS: Nivolumab resulted in robust antitumor activity, sustained responses, and good tolerability in systemic treatment-naive patients with aCSCC. These data provide further evidence to support the use of ICI as the standard treatment of aCSCC.
Assuntos
Carcinoma de Células Escamosas , Nivolumabe , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Nivolumabe/efeitos adversos , Carcinoma de Células Escamosas/induzido quimicamente , Intervalo Livre de Progressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Special histological types (SHT) of triple-negative breast cancer (TNBC) are a heterogeneous group of rare poorly understood diseases. We aimed to evaluate the clinical features, treatment, and outcomes of patients with SHT of TNBC. METHODS: We evaluated patients with a SHT of TNBC treated in a cancer center between 2009 and 2020. The endpoints were characterization of clinical and pathological features, pathologic complete response (PCR) rate after neoadjuvant chemotherapy, disease-free survival (DFS), progression-free survival, and overall survival (OS). RESULTS: The 132 patients included had the following histologies: metaplastic (n=71), medullary pattern (n=14), lobular (n=12), adenoid cystic (n=12), apocrine (n=10), and others (n=13). Metaplastic, lobular, and medullary pattern tumors had higher grade (66.6-85.7% grade 3); adenoid cystic and apocrine had mainly grade 1-2 (70-83.3%). Metaplastic and lobular carcinomas had higher disease stages (47.8% and 58.2% stages III-IV). PCR rates were 10.3% for metaplastic and 33.3% for lobular carcinomas, with 5-year DFS rates of 56% and 51.4%. Medullary pattern carcinomas had a great response to treatment, with PCR rate of 100%, and 5-year DFS rate of 92.8%. Apocrine carcinomas also had favorable prognosis, with no recurrence after early disease treatment, and 5-year DFS rate of 83.3%. Adenoid cystic carcinomas had intermediate prognosis, with 5-year DFS rate of 66.6%. CONCLUSION: SHT of TNBC encompasses heterogeneous malignancies with distinct behaviors. Lobular and metaplastic carcinomas showed high aggressiveness and poor treatment response, while medullary pattern and apocrine carcinomas had favorable outcomes. Treatment strategies focus on molecular features of each of these diseases are warranted.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/patologia , Carcinoma Lobular/patologia , Carcinoma Ductal de Mama/patologia , Neoplasias da Mama/patologia , Prognóstico , Terapia Neoadjuvante , MetaplasiaRESUMO
BACKGROUND: Patients with small node-negative HER2-positive breast cancer are commonly treated with paclitaxel and 1 year of adjuvant trastuzumab. We performed a sub-analysis of the ALTTO trial to explore the long-term outcomes of patients with small node-negative tumours. METHODS: The ALTTO trial randomised 8381 patients with early HER2-positive BC treated with adjuvant chemotherapy (anthracycline/taxane- or taxane/carboplatin-based), to trastuzumab (T), lapatinib (L), their sequence (T â L) or their combination (L + T). Patients with tumours ≤3 cm and node-negative were included in this sub-analysis. RESULTS: A total of 2821 patients were analysed (median follow-up of 7 years). The median age was 52 years, and most patients had tumours ≤2 cm (64.3%). The 7-year disease-free survival (DFS) was 88.1% (95% CI: 86.7-89.3%). DFS was similar for arms T, T + L and Tâ¶L and significantly lower for arm L (stratified log-rank P = 0.031). The 7-year overall survival rate was 95.9% (95% CI: [95.0-96.6%) and the 7-year time-to-distant recurrence was 93.4% (95% CI: 92.3-94.4%). CONCLUSION: With most patients treated with anthracycline-based regimens, ALTTO shows that patients with small tumours treated with trastuzumab and concomitant chemotherapy have excellent long-term outcomes, similar to those of the APT trial. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00490139.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Receptor ErbB-2 , Taxoides/uso terapêutico , TrastuzumabRESUMO
Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.
Breast cancer is the most common cancer among women worldwide. Breast cancer is not a unique disease, but rather a heterogeneous disease, with different subtypes. Lobular breast cancer is the second most common histologic subtype of breast cancer after ductal breast cancer. Lobular breast cancer has some peculiar characteristics that make it a distinct entity in the context of breast cancer. Nevertheless, few clinical studies so far have focused specifically on this subtype. ROSALINE is a clinical study aimed to test entrectinib, a new drug that showed promising activity in preliminary research studies, in combination with endocrine therapy in women with lobular breast cancer before surgery. Trial Registration Number: NCT04551495 (ClinicalTrials.gov).
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Caderinas , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/patologia , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Terapia Neoadjuvante , Proteínas Tirosina Quinases/uso terapêutico , Proteínas Proto-Oncogênicas , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismoRESUMO
INTRODUCTION: Triple negative breast cancer (TNBC) is an area of high unmet medical need in terms of new effective treatment strategies. Although breast cancer is traditionally considered a 'cold' tumor type, TNBC is the most appropriate subtype for immunotherapeutic strategies; this is due to the high level of tumor infiltrating lymphocytes, PD-L1 expression, and tumor mutational burden compared to other breast cancer subtypes. AREAS COVERED: This review examines the available evidence on the use of immunotherapeutic strategies in early and advanced TNBC, discusses the pitfalls and limitations often encountered in clinical research, and summarizes data on novel promising immunomodulatory approaches that have been explored in early-phase trials. EXPERT OPINION: PD-1-blockade is approved for stage II/III TNBC and for first-line treatment of PD-L1-positive TNBC patients with metastatic disease and should be considered standard of care. However, question marks and difficulties remain; these include the identification of predictive biomarkers to select patients who benefit from the addition of PD1-blockade and the balance between efficacy and long-term toxicity for an individual patient. Numerous treatment combinations and new immunotherapeutic strategies beyond PD1 blockade are being evaluated, thus reflecting a promising evolution towards a more personalized approach, and extended clinical benefit in TNBC.Abbreviations:Triple-negative breast cancer (TNBC); breast cancers (BCs); estrogen receptor (ER); progesterone receptor (PgR); human epidermal growth factor-2 (HER-2); basal-like 1 (BL1), basal-like 2 (BL2); mesenchymal (MES); mesenchymal stem-like (MSL); immunomodulatory (IM); luminal androgen receptor (LAR); basal-like immunosuppressed (BLIS); basal-like immune-activated (BLIA); tumor-infiltrating lymphocytes (TILs); tumor mutational burden (TMB); immune cells (ICs); immunohistochemistry (IHC); overall response rate (ORR); overall survival (OS); progression-free survival (PFS); intention-to-treat (ITT); hazard ratio (HR); confidence interval (CI); Food and Drug Administration (FDA); European Medicines Agency (EMA); immune checkpoint inhibitors (ICI); Combined Positive Score (CPS); disease control rate (DCR); neoadjuvant chemotherapy (NACT); pathological complete response (pCR); event-free survival (EFS); disease-free survival (DFS); residual cancer burden (RCB); San Antonio Breast Cancer Symposium (SABCS); antibody-drug conjugates (ADCs); PARP inhibitors (PARPi); clinical benefit rate (CBR); Histone deacetylase inhibitors (HDACi); Dendritic cell (DC); talimogene laherparepvec (TVEC); granulocyte-macrophage colony-stimulating factor (GM-CSF); mismatch repair deficiency (dMMR).
Assuntos
Melanoma , Terapia Viral Oncolítica , Neoplasias de Mama Triplo Negativas , Antígeno B7-H1 , Biomarcadores Tumorais , Humanos , Imunoterapia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: This study aimed to validate the Brazilian version of EORTC CAT Core and compare the Brazilian results with those from the original European EORTC CAT Core validation study. METHODS: After validated translation, 168 cancer patients from Brazil receiving radiation therapy with or without chemotherapy was assessed. Translated EORTC CAT Core and all QLQ-C30 items were administered to patients using CHES (Computer-Based Health Evaluation System) before (T0) and after (T1) treatment initiation. The association between QLQ-C30 and CAT scores and ceiling/floor effects were estimated. Based on estimates of relative validity (cross-sectional, known-group differences and changes over time), relative sample-size requirements for CAT compared to QLQ-C30 were estimated. RESULTS: Correlation coefficients between CAT and QLQ-C30 domains ranged from 0.63 to 0.93; except for dyspnoea, all coefficients were >0.82 (corresponding figures were 0.81-0.93 in the European study). On average across domains, floor/ceiling was reduced by 10% using CAT (9% in the European study) corresponding to a relative reduction of 32% (37% in the European study). Analyses of known-group validity and responsiveness indicated that, on average across domains, the sample-size requirements may be reduced by 17% using CAT rather than QLQ-C30, without loss of power (28% in the European study). The Brazilian sample had less symptom/quality of life impairment than the European sample, which likely explains the lower sample-size reduction using CAT when comparing with the European sample. CONCLUSIONS: The results in the Brazilian cohort were generally similar to those from the European sample and confirm the validity and usefulness of the EORTC CAT Core.
Assuntos
Neoplasias , Qualidade de Vida , Brasil , Estudos Transversais , Humanos , Neoplasias/terapia , Psicometria , Inquéritos e QuestionáriosRESUMO
PURPOSE: Patients with cancer are at increased risk for unfavorable outcomes from COVID-19. Knowledge about the outcome determinants of severe acute respiratory syndrome coronavirus 2 infection in this population is essential for risk stratification and definition of appropriate management. Our objective was to evaluate prognostic factors for all-cause mortality in patients diagnosed with both cancer and COVID-19. METHODS: All consecutive patients with cancer hospitalized at our institution with COVID-19 were included. Electronic medical records were reviewed for clinical and laboratory characteristics potentially associated with outcomes. RESULTS: Five hundred seventy-six consecutive patients with cancer and COVID-19 were included in the present study. An overall in-hospital mortality rate of 49.3% was demonstrated. Clinical factors associated with increased risk of death because of COVID-19 were age over 65 years, Eastern Cooperative Oncology Group performance status > 0 zero, best supportive care, primary lung cancer, and the presence of lung metastases. Laboratory findings associated with a higher risk of unfavorable outcomes were neutrophilia, lymphopenia, and elevated levels of D-dimer, creatinine, C-reactive protein, or AST. CONCLUSION: A high mortality rate in patients with cancer who were diagnosed with COVID-19 was demonstrated in the present study, emphasizing the need for close surveillance in this group of patients, especially in those with unfavorable prognostic characteristics.
Assuntos
COVID-19 , Neoplasias , Idoso , Hospitalização , Humanos , Neoplasias/terapia , Prognóstico , SARS-CoV-2RESUMO
PURPOSE: A substantial increase in melanoma incidence has been consistently observed worldwide over the past decades. However, melanoma mortality rates have remained stable or declined over the past years in most regions. Given the paucity of melanoma mortality data for different Brazilian regions, we sought to describe melanoma mortality trends in southeastern Brazil and their relationship with demographic variables. MATERIALS AND METHODS: A cross-sectional registry-based analysis was conducted to describe melanoma mortality trends in the state of São Paulo, Brazil, from 1996 to 2016. Demographic information from melanoma-related death records, including sex and age, was collected from the Fundação Sistema Estadual de Análise de Dados database. The annual percentage change (APC) was calculated to identify mortality trends over the period. RESULTS: An increasing melanoma mortality trend was detected among males, regardless of age (APC, 1.72%; P < .001), and was more pronounced for men ≥ 60 years old (APC, 2.63%; P < .001). Melanoma mortality rates have also increased for patients ≥ 60 years old, regardless of sex (APC, 1.11%; P < .001). A non-statistically significant increase in the overall melanoma mortality rate was observed over the 20-year period analyzed (APC, 0.36%; P = .4). CONCLUSION: Our data suggest a stable melanoma mortality over the past two decades for the overall population studied; however, a significant increase in melanoma mortality rates has been demonstrated among males and in the population ≥ 60 years old, emphasizing the need to implement prevention strategies and expand access to effective therapies for this population.