Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 357
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 185(10): 1694-1708.e19, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35447074

RESUMO

Immunotherapy is a promising treatment for triple-negative breast cancer (TNBC), but patients relapse, highlighting the need to understand the mechanisms of resistance. We discovered that in primary breast cancer, tumor cells that resist T cell attack are quiescent. Quiescent cancer cells (QCCs) form clusters with reduced immune infiltration. They also display superior tumorigenic capacity and higher expression of chemotherapy resistance and stemness genes. We adapted single-cell RNA-sequencing with precise spatial resolution to profile infiltrating cells inside and outside the QCC niche. This transcriptomic analysis revealed hypoxia-induced programs and identified more exhausted T cells, tumor-protective fibroblasts, and dysfunctional dendritic cells inside clusters of QCCs. This uncovered differential phenotypes in infiltrating cells based on their intra-tumor location. Thus, QCCs constitute immunotherapy-resistant reservoirs by orchestrating a local hypoxic immune-suppressive milieu that blocks T cell function. Eliminating QCCs holds the promise to counteract immunotherapy resistance and prevent disease recurrence in TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Imunossupressores/uso terapêutico , Imunoterapia , Recidiva Local de Neoplasia , Linfócitos T/patologia , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral
2.
Mol Cell ; 71(4): 606-620.e7, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30118680

RESUMO

Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin's role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1). Furthermore, we discover that AMP-activated protein kinase (AMPK) activated by metformin directly phosphorylates S195 of PD-L1. S195 phosphorylation induces abnormal PD-L1 glycosylation, resulting in its ER accumulation and ER-associated protein degradation (ERAD). Consistently, tumor tissues from metformin-treated breast cancer patients exhibit reduced PD-L1 levels with AMPK activation. Blocking the inhibitory signal of PD-L1 by metformin enhances CTL activity against cancer cells. Our findings identify a new regulatory mechanism of PD-L1 expression through the ERAD pathway and suggest that the metformin-CTLA4 blockade combination has the potential to increase the efficacy of immunotherapy.


Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/genética , Antígeno CTLA-4/genética , Regulação Neoplásica da Expressão Gênica , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/imunologia , Animais , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Linhagem Celular Tumoral , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Degradação Associada com o Retículo Endoplasmático , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Feminino , Glicosilação , Humanos , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/efeitos dos fármacos , Glândulas Mamárias Humanas/imunologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/genética , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos NOD , Fosforilação , Serina/metabolismo , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
3.
Breast Cancer Res ; 26(1): 20, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297352

RESUMO

BACKGROUND: Patients with inflammatory breast cancer (IBC) have overall poor clinical outcomes, with triple-negative IBC (TN-IBC) being associated with the worst survival, warranting the investigation of novel therapies. Preclinical studies implied that ruxolitinib (RUX), a JAK1/2 inhibitor, may be an effective therapy for TN-IBC. METHODS: We conducted a randomized phase II study with nested window-of-opportunity in TN-IBC. Treatment-naïve patients received a 7-day run-in of RUX alone or RUX plus paclitaxel (PAC). After the run-in, those who received RUX alone proceeded to neoadjuvant therapy with either RUX + PAC or PAC alone for 12 weeks; those who had received RUX + PAC continued treatment for 12 weeks. All patients subsequently received 4 cycles of doxorubicin plus cyclophosphamide prior to surgery. Research tumor biopsies were performed at baseline (pre-run-in) and after run-in therapy. Tumors were evaluated for phosphorylated STAT3 (pSTAT3) by immunostaining, and a subset was also analyzed by RNA-seq. The primary endpoint was the percent of pSTAT3-positive pre-run-in tumors that became pSTAT3-negative. Secondary endpoints included pathologic complete response (pCR). RESULTS: Overall, 23 patients were enrolled, of whom 21 completed preoperative therapy. Two patients achieved pCR (8.7%). pSTAT3 and IL-6/JAK/STAT3 signaling decreased in post-run-in biopsies of RUX-treated samples, while sustained treatment with RUX + PAC upregulated IL-6/JAK/STAT3 signaling compared to RUX alone. Both treatments decreased GZMB+ T cells implying immune suppression. RUX alone effectively inhibited JAK/STAT3 signaling but its combination with PAC led to incomplete inhibition. The immune suppressive effects of RUX alone and in combination may negate its growth inhibitory effects on cancer cells. CONCLUSION: In summary, the use of RUX in TN-IBC was associated with a decrease in pSTAT3 levels despite lack of clinical benefit. Cancer cell-specific-targeting of JAK2/STAT3 or combinations with immunotherapy may be required for further evaluation of JAK2/STAT3 signaling as a cancer therapeutic target. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , NCT02876302. Registered 23 August 2016.


Assuntos
Neoplasias Inflamatórias Mamárias , Nitrilas , Paclitaxel , Pirazóis , Pirimidinas , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Neoplasias Inflamatórias Mamárias/patologia , Interleucina-6 , Terapia Neoadjuvante , Nitrilas/uso terapêutico , Paclitaxel/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
4.
Cancer ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39211977

RESUMO

BACKGROUND: This study evaluated the accuracy, clinical concordance, and readability of the chatbot interface generative pretrained transformer (ChatGPT) 3.5 as a source of breast cancer information for patients. METHODS: Twenty questions that patients are likely to ask ChatGPT were identified by breast cancer advocates. These were posed to ChatGPT 3.5 in July 2023 and were repeated three times. Responses were graded in two domains: accuracy (4-point Likert scale, 4 = worst) and clinical concordance (information is clinically similar to physician response; 5-point Likert scale, 5 = not similar at all). The concordance of responses with repetition was estimated using intraclass correlation coefficient (ICC) of word counts. Response readability was calculated using the Flesch Kincaid readability scale. References were requested and verified. RESULTS: The overall average accuracy was 1.88 (range 1.0-3.0; 95% confidence interval [CI], 1.42-1.94), and clinical concordance was 2.79 (range 1.0-5.0; 95% CI, 1.94-3.64). The average word count was 310 words per response (range, 146-441 words per response) with high concordance (ICC, 0.75; 95% CI, 0.59-0.91; p < .001). The average readability was poor at 37.9 (range, 18.0-60.5) with high concordance (ICC, 0.73; 95% CI, 0.57-0.90; p < .001). There was a weak correlation between ease of readability and better clinical concordance (-0.15; p = .025). Accuracy did not correlate with readability (0.05; p = .079). The average number of references was 1.97 (range, 1-4; total, 119). ChatGPT cited peer-reviewed articles only once and often referenced nonexistent websites (41%). CONCLUSIONS: Because ChatGPT 3.5 responses were incorrect 24% of the time and did not provide real references 41% of the time, patients should be cautioned about using ChatGPT for medical information.

5.
Ann Surg ; 279(2): 231-239, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37916404

RESUMO

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.


Assuntos
Pesquisa Biomédica , Cirurgiões , Humanos , Estados Unidos , Mentores , Docentes , Centros Médicos Acadêmicos , Mobilidade Ocupacional , National Institutes of Health (U.S.)
6.
Breast Cancer Res Treat ; 206(1): 185-193, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38649618

RESUMO

PURPOSE: Breast cancer mortality is higher in Black women than other racial groups. This difference has been partially attributed to a higher proportion of triple-negative breast cancer (TNBC). However, it is uncertain if survival disparities exist in racially diverse TNBC patients receiving similar treatments. Here, we examine racial differences in disease-related outcomes in TNBC patients treated on the E5103 clinical trial. METHODS: From 2007 to 2011, 4,994 patients with stage I-III HER2-negative breast cancer were randomized to adjuvant chemotherapy with or without bevacizumab. This analysis was limited to the subset of 1,742 TNBC patients with known self-reported race. Unadjusted Kaplan-Meier curves and adjusted Cox-Proportional Hazards models were used to determine breast cancer events and survival outcomes. RESULTS: Of the analysis population, 51 (2.9%) were Asian, 269 (15.4%) Black, and 1422 (81.6%) White. Median age was 51 years. Patient characteristics, treatment arm, and local therapies were similar across racial groups. White women were more commonly node-negative (56% vs. 49% and 44% in Asian and Black women, respectively; p < 0.01). At a median follow-up of 46 months, unadjusted Kaplan-Meier locoregional and distant recurrence, and disease-free and overall survival, did not differ significantly by race. In Cox models adjusted for patient and tumor characteristics and treatment arm, race was not associated with any disease event. Larger tumor size and nodal involvement were consistently associated with breast cancer events. CONCLUSION: This clinical trial population of similarly treated TNBC patients showed no racial differences in breast cancer outcomes. Disease extent, rather than race, was associated with disease events.


Assuntos
Estadiamento de Neoplasias , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/etnologia , Feminino , Pessoa de Meia-Idade , Quimioterapia Adjuvante/métodos , Adulto , Resultado do Tratamento , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Disparidades em Assistência à Saúde , Estimativa de Kaplan-Meier
7.
Ann Surg Oncol ; 31(7): 4470-4476, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38734863

RESUMO

With new investigations and clinical trials in breast oncology reported every year, it is critical that surgeons be aware of advances and insights into the evolving care paradigms and treatments available to their patients. This article highlights five publications found to be particularly impactful this past year. These articles report on efforts to select the minimal effective dose of tamoxifen for prevention, to challenge the existing age-based screening guidelines as they relate to race and ethnicity, to refine axillary management treatment standards, to optimize systemic therapy in multidisciplinary care settings, and to reduce the burden of breast cancer-related lymphedema after treatment. Taken together, these efforts have an impact on all facets of the continuum of care from prevention and screening through treatment and survivorship.


Assuntos
Neoplasias da Mama , Continuidade da Assistência ao Paciente , Humanos , Neoplasias da Mama/terapia , Feminino , Continuidade da Assistência ao Paciente/normas , Linfedema/terapia , Linfedema/etiologia , Linfedema/prevenção & controle , Tamoxifeno/uso terapêutico
8.
Ann Surg Oncol ; 31(2): 920-930, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37851196

RESUMO

BACKGROUND: In women ≥ 70 years of age with T1N0 hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, breast surgery type and omission of axillary surgery or radiation therapy (RT) do not impact overall survival. Although frailty and life expectancy ideally factor into therapy decisions, their impact on therapy receipt is unclear. We sought to identify trends in and factors associated with locoregional therapy type by frailty and life expectancy. METHODS: Women ≥ 70 years of age with T1N0 HR+/HER2- breast cancer diagnosed in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 2010 and 2015 were stratified by validated claims-based frailty and life expectancy measures. Therapy trends over time by regimen intensity ('high intensity': lumpectomy + axillary surgery + RT, or mastectomy + axillary surgery; 'moderate intensity': lumpectomy + RT, lumpectomy + axillary surgery, or mastectomy only; or 'low intensity': lumpectomy only) were analyzed. Factors associated with therapy type were identified using generalized linear mixed models. RESULTS: Of 16,188 women, 21.8% were frail, 22.2% had a life expectancy < 5 years, and only 12.3% fulfilled both criteria. In frail women with a life expectancy < 5 years, high-intensity regimens decreased significantly (48.8-31.2%; p < 0.001) over the study period, although in 2015, 30% still received a high-intensity regimen. In adjusted analyses, frailty and life expectancy < 5 years were not associated with breast surgery type but were associated with a lower likelihood of axillary surgery (frailty: odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76-0.96; life expectancy < 5 years: OR 0.22, 95% CI 0.20-0.25). Life expectancy < 5 years was also associated with a lower likelihood of RT receipt in breast-conserving surgery patients (OR 0.30, 95% CI 0.27-0.34). CONCLUSIONS: Rates of high-intensity therapy are decreasing but overtreatment persists in this population. Continued efforts aimed at appropriate de-escalation of locoregional therapy are needed.


Assuntos
Neoplasias da Mama , Fragilidade , Feminino , Humanos , Idoso , Estados Unidos/epidemiologia , Neoplasias da Mama/patologia , Mastectomia/métodos , Medicare , Mastectomia Segmentar , Estadiamento de Neoplasias
9.
Ann Surg Oncol ; 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39031264

RESUMO

INTRODUCTION: As the benefits of intensive locoregional therapy for ductal carcinoma in situ (DCIS) are realized over time in older adults, life expectancy may help to guide treatment decisions. We examined whether life expectancy was associated with extent of locoregional therapy in this population. PATIENTS AND METHODS: Women ≥ 70 years old with < 5 cm of DCIS diagnosed 2010-2015 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset and categorized by a life expectancy ≤ 5 or > 5 years, defined by a validated claims-based measure. Differences in locoregional therapy (mastectomy + axillary surgery, mastectomy-only, lumpectomy + radiation therapy (RT) + axillary surgery, lumpectomy + RT, lumpectomy-only, and no treatment) by life expectancy were assessed using Pearson chi-squared tests. Generalized linear mixed models were used to identify factors associated with receipt of lumpectomy-only. RESULTS: Of 5346 women (median age of 75 years, range 70-97 years), 927 (17.3%) had a life expectancy ≤ 5 years. Of the 4041 patients who underwent lumpectomy, 710 (13.3%) underwent axillary surgery. More patients with life expectancy ≤ 5 years underwent lumpectomy-only (39.4% versus 27%), mastectomy-only (8.1% versus 5.3%), or no treatment (5.8% versus 3.2%; p < 0.001). On multivariable analysis, women with life expectancy ≤ 5 years had a significantly greater likelihood of undergoing lumpectomy-only [OR 1.90, 95% CI (1.63-2.22)]. CONCLUSIONS: Life expectancy is associated with lower-intensity locoregional therapy for older women with DCIS, yet a large proportion of patients with a life expectancy ≤ 5 years received RT and axillary surgery, highlighting potential overtreatment and opportunities to de-escalate locoregional therapy in older adults.

10.
Ann Surg Oncol ; 31(3): 1623-1633, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38071708

RESUMO

BACKGROUND: Understanding long-term arm symptoms in breast cancer survivors is critical given excellent survival in the modern era. METHODS: This cross-sectional study included patients treated for stage 0-III breast cancer at our institution from 2002 to 2012. Patient-reported arm symptoms were collected from the EORTC QLQ-BR23 questionnaire. We used linear regression to evaluate adjusted associations between locoregional treatments and the continuous Arm Symptom (AS) score (0-100; higher score reflects more symptoms). RESULTS: A total of 1126 patients expressed interest in participating and 882 (78.3%) completed the questionnaire. Mean time since surgery was 10.5 years. There was a broad distribution of locoregional treatments, including axillary lymph node dissection (ALND) in 37.1% of patients, mastectomy with reconstruction in 36.5% of patients, and post-mastectomy radiation in 38.2% of patients. Overall, 64.3% (95% confidence interval [CI] 61.1-67.4%) of patients reported no arm symptoms, 17.0% (95% CI 14.7-19.6%) had one mild symptom, 9.4% (95% CI 7.7-11.5%) had two or more mild symptoms, and 9.3% (95% CI 7.6-11.4%) reported one or more severe symptoms. Adjusted AS scores were significantly higher with ALND versus sentinel node biopsy (ß 3.5, p = 0.01), and with autologous reconstruction versus all other breast/reconstructive surgery types (ß 4.5-5.5, all p < 0.05). There was a significant interaction between axillary and breast/reconstructive surgery, with the greatest effect of ALND in those with mastectomy with implant (ß 9.7) or autologous (ß 5.7) reconstruction. CONCLUSIONS: One in three patients reported arm symptoms at a mean of 10 years from treatment for breast cancer, although rates of severe symptoms were low (<10%). Attention is warranted to the arm morbidity related to both axillary and breast surgery during treatment counseling and survivorship.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Linfedema , Humanos , Feminino , Neoplasias da Mama/cirurgia , Mastectomia , Braço/patologia , Estudos Transversais , Biópsia de Linfonodo Sentinela/efeitos adversos , Excisão de Linfonodo/efeitos adversos , Axila/patologia , Medidas de Resultados Relatados pelo Paciente , Linfedema/etiologia
11.
Ann Surg Oncol ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048900

RESUMO

BACKGROUND: Patient-reported outcomes (PROs) are a critical component of value-based care. Limited data exist describing long-term PROs in patients undergoing breast-conserving surgery (BCS). PATIENTS AND METHODS: Patients undergoing surgery for stage 0-III breast cancer at our institution from 2002 to 2012 who agreed to be contacted were invited to participate in a cross-sectional PRO study. Health-related quality of life outcomes using BREAST-Q, EORTC QLQ-C30, and EORTC QLQ-BR45 were collected. Patients reporting chemotherapy within 6 months of receiving the survey were excluded. For this work, we focused on patients who underwent BCS. Multivariable linear regression was performed to identify factors associated with PRO scores, adjusting for age, time since surgery, anatomic stage, molecular subtype, receipt of systemic and/or radiation therapy (RT), locoregional recurrence, or contralateral breast cancer. RESULTS: Among 562 interested and eligible patients, 437 (78%) responded; median time from surgery to survey completion was 10.4 years (interquartile range: 8.0-13.5). Median age at surgery was 53 years (standard deviation 9.8 years), ≥ 90% were white, had upfront surgery for early-stage disease, and completed adjuvant RT. Physical and psychological well-being scores were generally high, with more variation seen for sexual well-being and satisfaction with breasts. CONCLUSION: This study provides long-term PRO data for patients treated with BCS, demonstrating the ongoing association of breast cancer surgery with quality of life in the survivorship period and highlighting the importance of examining PROs beyond the perioperative period. These data also provide important reference values for the interpretation of PROs among women treated with BCS as we move towards value-based care.

12.
Ann Surg Oncol ; 31(9): 5888-5895, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38862840

RESUMO

BACKGROUND: The technical aspects of cancer surgery have a significant impact on patient outcomes. To monitor surgical quality, in 2020, the Commission on Cancer (CoC) revised its accreditation standards for cancer surgery and introduced the synoptic operative reports (SORs). The standardization of SORs holds promise, but successful implementation requires strategies to address key implementation barriers. This study aimed to identify the barriers and facilitators to implementing breast SOR within diverse CoC-accredited programs. METHODS: In-depth semi-structured interviews were conducted with 31 health care professionals across diverse CoC-accredited sites. The study used two comprehensive implementation frameworks to guide data collection and analysis. RESULTS: Successful SOR implementation was impeded by disrupted workflows, surgeon resistance to change, low prioritization of resources, and poor flow of information despite CoC's positive reputation. Participants often lacked understanding of the requirements and timeline for breast SOR and were heavily influenced by prior experiences with templates and SOR champion relationships. The perceived lack of monetary benefits (to obtaining CoC accreditation) together with the significant information technology (IT) resource requirements tempered some of the enthusiasm. Additionally, resource constraints and the redirection of personnel during the COVID-19 pandemic were noted as hurdles. CONCLUSIONS: Surgeon behavior and workflow change, IT and personnel resources, and communication and networking strategies influenced SOR implementation. During early implementation and the implementation planning phase, the primary focus was on achieving buy-in and initiating successful roll-out rather than effective use or sustainment. These findings have implications for enhancing standardization of surgical cancer care and guidance of future strategies to optimize implementation of CoC accreditation standards.


Assuntos
Acreditação , Neoplasias da Mama , Humanos , Neoplasias da Mama/cirurgia , Feminino , COVID-19/epidemiologia , Fluxo de Trabalho , Oncologia Cirúrgica/normas , SARS-CoV-2 , Cirurgiões/normas
13.
Ann Surg Oncol ; 31(4): 2244-2252, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38161200

RESUMO

BACKGROUND: We sought to better define estrogen receptor-low-positive (ER-low+) breast cancer biology and determine the utility of the Oncotype DX Breast Recurrence Score® (RS) assay in this population. METHODS: Patients with information regarding percentage ER positivity and PAM50 subtype were identified in The Cancer Genome Atlas (TCGA) and subtype distribution was determined. Next, patients with ER-low+ (ER 1-10%), HER2- breast cancer undergoing upfront surgery with known RS result were identified in the National Cancer Database (NCDB) and our institutional Dana-Farber Brigham Cancer Center (DF/BCC) database; RS distribution was examined. Finally, patients with ER-low+, HER2- breast cancer treated at DF/BCC from 2011 to 2020 without prior RS results and in whom tissue was available to perform the assay were identified. RS results, treatment, recurrence and breast cancer-specific survival (BCSS) were determined. RESULTS: Of 1033 patients in TCGA, ER percentage and PAM50 subtype were available for 342 (33.1%) patients. Forty-six (13.5%) had ER-low+/HER2- tumors, among whom 82.6% were basal and 4.3% were luminal A. Among 3423 patients with ER-low+/HER2- disease in the NCDB, RS results were available for 689 (20.1%) patients; 67% had an RS ≥26. In our institutional database, only two patients with ER-low+/HER2- disease and an RS were identified, both with RS ≥26. Among 37 patients in our institutional cohort without prior RS, 35 (97.4%) had an RS ≥26, determined with testing. After a median follow-up of 40 months (range 3-106), three patients, all treated with chemotherapy, recurred. Three-year BCSS was 97.0% (95% confidence interval 96.9-97.1%). CONCLUSIONS: Most ER-low+/HER2- breast cancers are basal-like, with RS ≥26 suggesting these tumors are similar to triple-negative disease.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Receptor ErbB-2/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Receptores de Estrogênio/genética
14.
Ann Surg Oncol ; 31(9): 5919-5928, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38916700

RESUMO

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Mastectomia Segmentar , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Pessoa de Meia-Idade , Radioterapia Adjuvante , Prognóstico , Estudos Prospectivos , Idoso , Seguimentos , Recidiva Local de Neoplasia/patologia , Tomada de Decisão Clínica , Adulto , Tomada de Decisões , Biomarcadores Tumorais
15.
CA Cancer J Clin ; 67(4): 290-303, 2017 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-28294295

RESUMO

Answer questions and earn CME/CNE The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system. AJCC levels of evidence and guidelines for all tumor types were followed as much as possible. The panel felt that, to maintain worldwide value, the tumor staging system should remain based on TNM anatomic factors. However, the recognition of the prognostic influence of grade, hormone receptor expression, and HER2 amplification mandated their inclusion into the staging system. The value of commercially available, gene-based assays was acknowledged and prognostic input added. Tumor biomarkers and low Oncotype DX recurrence scores can alter prognosis and stage. These updates are expected to provide additional precision and flexibility to the staging system and were based on the extent of published information and analysis of large, as yet unpublished databases. The eighth edition of the AJCC TNM staging system, thus, provides a flexible platform for prognostic classification based on traditional anatomic factors, which can be modified and enhanced using patient biomarkers and multifactorial prognostic panel data. The eighth edition remains the worldwide basis for breast cancer staging and will incorporate future online updates to remain timely and relevant. CA Cancer J Clin 2017;67:290-303. © 2017 American Cancer Society.


Assuntos
Neoplasias da Mama/patologia , Estadiamento de Neoplasias/métodos , Biomarcadores Tumorais , Neoplasias da Mama/classificação , Feminino , Humanos , Metástase Linfática , Metástase Neoplásica , Guias de Prática Clínica como Assunto , Prognóstico , Estados Unidos
16.
Cancer ; 129(12): 1836-1845, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36951169

RESUMO

BACKGROUND: The optimal treatment strategy for patients with small human epidermal growth factor receptor 2 (HER2)-positive tumors is based on nodal status. The authors' objective was to evaluate pathologic nodal disease (pathologic lymph node-positive [pN-positive] and pathologic lymph node-positive after preoperative systemic therapy [ypN-positive]) rates in patients who had clinical T1-T2 (cT1-cT2)N0M0, HER2-positive breast cancer treated with upfront surgery or neoadjuvant chemotherapy (NAC). METHODS: Two databases were queried for patients who had cT1-cT2N0M0, HER2-positive breast cancer: (1) the Dana-Farber Brigham Cancer Center (DF/BCC) from February 2015 to October 2020 and (2) the Hospital Clinic of Barcelona and the Hospital Clinico of Valencia (HCB/HCV) from January 2012 to September 2021. The pN-positive/ypN-positive and axillary lymph node dissection (ALND) rates were compared between patients who underwent upfront surgery versus those who received NAC. RESULTS: Among 579 patients from the DF/BCC database, 368 underwent upfront surgery, and 211 received NAC; the rates of nodal positivity were 19.8% and 12.8%, respectively (p = .021). The pN-positive rates increased by tumor size (p < .001), reaching 25% for those with cT1c tumors. The ypN-positive rates did not correlate with tumor size. NAC was associated with decreased nodal positivity (odds ratio, 0.411; 95% confidence interval, 0.202-0.838), but the ALND rates were similar (22 of 368 patients [6.0%] who underwent upfront surgery vs. 18 of 211 patients [8.5%] who received NAC; p = .173). Among 292 patients from the HCB/HCV database, 119 underwent upfront surgery, and 173 received NAC; the rates of nodal positivity were 21% and 10.4%, respectively (p = .012). The pN-positive rates increased with tumor size (p = .011). The ALND rates were equivalent by treatment strategy (23 of 119 patients [19.3%] who underwent upfront surgery vs. 24 of 173 patients [13.9%] who received NAC; p = .213). CONCLUSIONS: Among patients who had cT1-cT2N0M0, HER2-positive breast cancer, approximately 20% who underwent upfront surgery were pN-positive, and the rate reached 25% for those with cT1c tumors. Given the opportunity for tailored therapy among lymph node-positive, HER2-positive patients, these data provide rationale for future analyses investigating the utility of routine axillary imaging in patients with HER2-positive breast cancer.


Assuntos
Neoplasias da Mama , Hepatite C , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Excisão de Linfonodo , Terapia Neoadjuvante/métodos , Quimioterapia Adjuvante , Hepatite C/tratamento farmacológico , Axila/patologia , Biópsia de Linfonodo Sentinela , Linfonodos/patologia
17.
Breast Cancer Res Treat ; 199(3): 457-469, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37061619

RESUMO

PURPOSE: Neoadjuvant anti-PD-(L)1 therapy improves the pathological complete response (pCR) rate in unselected triple-negative breast cancer (TNBC). Given the potential for long-term morbidity from immune-related adverse events (irAEs), optimizing the risk-benefit ratio for these agents in the curative neoadjuvant setting is important. Suboptimal clinical response to initial neoadjuvant therapy (NAT) is associated with low rates of pCR (2-5%) and may define a patient selection strategy for neoadjuvant immune checkpoint blockade. We conducted a single-arm phase II study of atezolizumab and nab-paclitaxel as the second phase of NAT in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02530489). METHODS: Patients with stage I-III, AC-resistant TNBC, defined as disease progression or a < 80% reduction in tumor volume after 4 cycles of AC, were eligible. Patients received atezolizumab (1200 mg IV, Q3weeks × 4) and nab-paclitaxel (100 mg/m2 IV,Q1 week × 12) as the second phase of NAT before undergoing surgery followed by adjuvant atezolizumab (1200 mg IV, Q3 weeks, × 4). A two-stage Gehan-type design was employed to detect an improvement in pCR/residual cancer burden class I (RCB-I) rate from 5 to 20%. RESULTS: From 2/15/2016 through 1/29/2021, 37 patients with AC-resistant TNBC were enrolled. The pCR/RCB-I rate was 46%. No new safety signals were observed. Seven patients (19%) discontinued atezolizumab due to irAEs. CONCLUSION: This study met its primary endpoint, demonstrating a promising signal of activity in this high-risk population (pCR/RCB-I = 46% vs 5% in historical controls), suggesting that a response-adapted approach to the utilization of neoadjuvant immunotherapy should be considered for further evaluation in a randomized clinical trial.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Antraciclinas/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
18.
Ann Surg Oncol ; 30(10): 5978-5987, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37436607

RESUMO

BACKGROUND: Randomized trials have established the safety of observation or axillary radiation (AxRT) as an alternative to axillary lymph node dissection (ALND) in patients with limited nodal disease who undergo upfront surgery. Variability remains in axillary management strategies in cN0 patients undergoing mastectomy found to have one to two positive sentinel lymph nodes (SLNs). We examined the impact of intraoperative pathology assessment in axillary management in a national cohort of AMAROS-eligible mastectomy patients. METHODS: The National Cancer Database was used to identify AMAROS-eligible cT1-2N0 breast cancer patients undergoing upfront mastectomy and SLN biopsy (SLNB) and found to have one to two positive SLNs, from 2018 to 2019. We constructed a variable defining intraoperative pathology as 'not performed/not acted on' if ALND was either not performed or performed at a later date than SLNB, or 'performed/acted on' if SLNB and ALND were completed on the same day. Adjusted multivariable analysis examined predictors of treatment with both ALND and AxRT. RESULTS: Overall, 8222 patients with cT1-2N0 disease underwent upfront mastectomy and had one to two positive SLNs. Intraoperative pathology was performed/acted on in 3057 (37.2%) patients. These patients were significantly more likely to have both ALND and AxRT than those without intraoperative pathology (41.0% vs. 4.9%; p < 0.001). On multivariate analysis, the strongest predictor of receiving both ALND and AxRT was use of intraoperative pathology (odds ratio 8.99, 95% confidence interval 7.70-10.5; p < 0.001). CONCLUSIONS: We advocate that consideration should be made for omission of routine intraoperative pathology in mastectomy patients likely to be recommended postmastectomy radiation to minimize axillary overtreatment with both ALND and AxRT in appropriate patients.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mastectomia , Biópsia de Linfonodo Sentinela , Axila/patologia , Metástase Linfática/patologia , Excisão de Linfonodo , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia
19.
Ann Surg Oncol ; 30(1): 100-106, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35941343

RESUMO

BACKGROUND: Adding pembrolizumab to preoperative chemotherapy improves event-free survival in patients with early-stage triple-negative breast cancer (TNBC). However, owing to potential toxicities, the risk-benefit ratio of pembrolizumab must be considered. There is consensus that the addition of immunotherapy should be recommended in node-positive patients. This study is undertaken to determine nodal positivity rates in patients with TNBC presenting with cT1-2N0 disease undergoing upfront surgery and to evaluate the utility of axillary ultrasound and biopsy in the setting of a negative clinical examination. PATIENTS AND METHODS: Patients with cT1-2N0 TNBC undergoing upfront surgery were identified from our institutional database (January 2016-February 2021; n = 343) and from the National Cancer Database (NCDB) (n = 46,015). Pathologic nodal status was determined. A second cohort of patients with cT1-T2 TNBC with a negative clinical examination was defined in our institutional database (n = 499), and utilization of axillary ultrasound was examined. RESULTS: For patients undergoing upfront surgery, pathologically positive nodes were found in 14.6% patients of our institutional cohort: 9.4% cT1a/b, 14.9% cT1c, and 20.8% cT2 tumors. In the NCDB cohort, 13.7% patients were node positive: 4.9% cT1a/b, 11.4% cT1c, and 19.7% cT2 tumors. For patients with a normal clinical examination undergoing axillary ultrasound, 7.5% of cT1c and 8.7% of cT2 had suspicious nodes biopsied and confirmed positive for metastasis. CONCLUSIONS: Pathologic node-positive disease is found in > 10 and 20% patients with cT1cN0 and cT2N0 TNBC, respectively. Axillary ultrasound can be used to identify patients presenting with a normal clinical examination for whom preoperative pembrolizumab should be considered.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/terapia
20.
Ann Surg Oncol ; 30(13): 8404-8411, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37777685

RESUMO

BACKGROUND: Racial and ethnic disparities in outcomes after treatment for ductal carcinoma in situ (DCIS) are largely unknown. The objective of this study was to examine breast cancer outcomes by race and ethnicity in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 clinical trial. PATIENTS AND METHODS: The NSABP B-35 trial randomized postmenopausal women with hormone receptor-positive DCIS treated with breast-conserving therapy to 5 years of tamoxifen or anastrozole. In total, 3104 women were enrolled between 2003 and 2006. For this analysis, patients without complete self-reported race and ethnicity or with immediate trial dropout were excluded. Kaplan-Meier curves and adjusted Cox-proportional hazards models were used for analyses. RESULTS: Of the 3061 women included, 2614 (85.4%) were non-Hispanic white (NHW), 255 (8.3%) were non-Hispanic Black (NHB), 95 (3.1%) were Hispanic, and 96 (3.1%) were Asian or Pacific Islander (API). Endocrine therapy assignment and duration were well balanced between racial and ethnic groups. Median follow-up was 9 years; unadjusted Kaplan-Meier curves did not show any racial differences in disease events. Adjusted Cox-proportional hazards models found API (versus NHW) race to be associated with higher local recurrence [hazard ratio (HzR) 2.45, p = 0.035] and NHB race to be associated with higher distant recurrence (HzR 5.03, p = 0.020) and breast cancer mortality (HzR 3.83, p = 0.046). CONCLUSIONS: Despite similar locoregional treatments and standard endocrine therapy in a clinical trial population, racial and ethnic disparities exist in long-term outcomes for hormone-receptor-positive DCIS. These findings suggest that factors outside of access and treatment may impact DCIS outcomes by race and ethnicity.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Feminino , Humanos , Carcinoma Intraductal não Infiltrante/cirurgia , Neoplasias da Mama/cirurgia , Tamoxifeno/uso terapêutico , Anastrozol/uso terapêutico , Etnicidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA