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1.
Breast Cancer Res Treat ; 204(1): 49-59, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38060077

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective. METHODS: We conducted a randomized phase IIB adaptive sequential selection trial of cryotherapy vs. compression therapy vs. placebo ("loose" gloves/socks) during taxane chemotherapy. Participants were randomized in triplets. Garments were worn for 90-120 min, beginning 15 min prior and continuing for 15 min following the infusion. The primary goal was to select the best intervention based on a Levin-Robbins-Leu sequential selection procedure. The primary endpoint was a < 5-point decrease in the Functional Assessment of Cancer Therapy Neurotoxicity (FACT-NTX) at 12 weeks. An arm was eliminated if it had four or more fewer successes than the currently leading arm. Secondary endpoints included intervention adherence and patient-reported comfort/satisfaction. RESULTS: Between April 2019 and April 2021, 63 patients were randomized (cryotherapy (20); compression (22); placebo (21)). Most patients (60.3%) were treated with docetaxel. The stopping criterion was met after the 17th triplet (n = 51) was evaluated; success at 12 weeks occurred in 11 (64.7%) on compression therapy, 7 (41.1%) on cryotherapy, and 7 (41.1%) on placebo. Adherence to the intervention was lowest with cryotherapy (35.0%) compared to compression (72.7%) and placebo (76.2%). CONCLUSION: Compression therapy was the most effective intervention in this phase IIB selection trial to prevent CIPN and was well tolerated. Compression therapy for the prevention of CIPN should be evaluated in a phase III study. CLINICAL TRIAL REGISTRATION: ClinicaTrials.gov Identifier: NCT03873272.


Assuntos
Neoplasias da Mama , Doenças do Sistema Nervoso Periférico , Feminino , Humanos , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes , Crioterapia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Taxoides/efeitos adversos
2.
Breast Cancer Res Treat ; 194(1): 35-47, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35575954

RESUMO

PURPOSE: We evaluated whether a novel, fully automated convolutional neural network (CNN)-based mammographic evaluation can predict breast cancer relapse among women with operable hormone receptor (HR)-positive breast cancer. METHODS: We conducted a retrospective cohort study among women with stage I-III, HR-positive unilateral breast cancer diagnosed at Columbia University Medical Center from 2007 to 2017, who received adjuvant endocrine therapy and had at least two mammograms (baseline, annual follow-up) of the contralateral unaffected breast for CNN analysis. We extracted demographics, clinicopathologic characteristics, breast cancer treatments, and relapse status from the electronic health record. Our primary endpoint was change in CNN risk score (range, 0-1). We used two-sample t-tests to assess for difference in mean CNN scores between patients who relapsed vs. remained in remission, and conducted Cox regression analyses to assess for association between change in CNN score and breast cancer-free interval (BCFI), adjusting for known prognostic factors. RESULTS: Among 848 women followed for a median of 59 months, there were 67 (7.9%) breast cancer relapses (36 distant, 25 local, 6 new primaries). There was a significant difference in mean absolute change in CNN risk score from baseline to 1-year follow-up between those who relapsed vs. remained in remission (0.001 vs. - 0.022, p = 0.030). After adjustment for prognostic factors, a 0.01 absolute increase in CNN score at 1-year was significantly associated with BCFI, hazard ratio = 1.05 (95% Confidence Interval 1.01-1.09, p = 0.011). CONCLUSION: Short-term change in the CNN-based breast cancer risk model on adjuvant endocrine therapy predicts breast cancer relapse, and warrants further evaluation in prospective studies.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Redes Neurais de Computação , Estudos Prospectivos , Estudos Retrospectivos
3.
BMC Med Inform Decis Mak ; 22(1): 208, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927732

RESUMO

BACKGROUND: Chemoprevention with anti-estrogens, such as tamoxifen, raloxifene or aromatase inhibitors, have been shown to reduce breast cancer risk in randomized controlled trials; however, uptake among women at high-risk for developing breast cancer remains low. The aim of this study is to identify provider-related barriers to shared decision-making (SDM) for chemoprevention in the primary care setting. METHODS: Primary care providers (PCPs) and high-risk women eligible for chemoprevention were enrolled in a pilot study and a randomized clinical trial of web-based decision support tools to increase chemoprevention uptake. PCPs included internists, family practitioners, and gynecologists, whereas patients were high-risk women, age 35-75 years, who had a 5-year invasive breast cancer risk ≥ 1.67%, according to the Gail model. Seven clinical encounters of high-risk women and their PCPs who were given access to these decision support tools were included in this study. Audio-recordings of the clinical encounters were transcribed verbatim and analyzed using grounded theory methodology. RESULTS: Six primary care providers, of which four were males (mean age 36 [SD 6.5]) and two were females (mean age 39, [SD 11.5]) and seven racially/ethnically diverse high-risk female patients participated in this study. Qualitative analysis revealed three themes: (1) Competing demands during clinical encounters; (2) lack of knowledge among providers about chemoprevention; and (3) limited risk communication during clinical encounters. CONCLUSIONS: Critical barriers to SDM about chemoprevention were identified among PCPs. Providers need education and resources through decision support tools to engage in risk communication and SDM with their high-risk patients, and to gain confidence in prescribing chemoprevention in the primary care setting.


Assuntos
Neoplasias da Mama , Quimioprevenção , Tomada de Decisão Compartilhada , Adulto , Idoso , Neoplasias da Mama/prevenção & controle , Técnicas de Apoio para a Decisão , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Médicos de Atenção Primária , Projetos Piloto , Atenção Primária à Saúde , Medição de Risco
4.
Breast Cancer Res ; 23(1): 16, 2021 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-33517909

RESUMO

BACKGROUND: The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR). METHODS: In this retrospective evaluation of 105 patients with stage II-III breast cancer, oxy-hemoglobin (ctO2Hb) from the contralateral non-tumor-bearing breast was collected and analyzed at different time points during NAC. The earliest monitoring imaging time point was after 2-3 weeks receiving taxane. Longitudinal data were analyzed using linear mixed-effects modeling to evaluate the contralateral breast ctO2Hb changes across chemotherapy when corrected for pCR status, age, and BMI. RESULTS: Patients who achieved pCR to NAC had an overall decrease of 3.88 µM for ctO2Hb (95% CI, 1.39 to 6.37 µM), p = .004, after 2-3 weeks. On the other hand, non-pCR subjects had a non-significant mean reduction of 0.14 µM (95% CI, - 1.30 to 1.58 µM), p > .05. Mixed-effect model results indicated a statistically significant negative relationship of ctO2Hb levels with BMI and age. CONCLUSIONS: This study demonstrates that the contralateral normal breast tissue assessed by DOTBIS is modifiable after NAC, with changes associated with pCR after only 2-3 weeks of chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Tomografia Óptica , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Gerenciamento Clínico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Terapia Neoadjuvante , Tomografia Óptica/métodos , Tomografia Óptica/normas , Resultado do Tratamento , Carga Tumoral
5.
Breast Cancer Res Treat ; 189(1): 297-304, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34213660

RESUMO

PURPOSE: Diffuse optical tomography breast imaging system (DOTBIS) non-invasively measures tissue concentration of hemoglobin, which is a potential biomarker of short-term response to neoadjuvant chemotherapy. We evaluated whether DOTBIS-derived measurements are modifiable with targeted therapies, including AKT inhibition and endocrine therapy. METHODS: We conducted a proof of principle study in seven postmenopausal women with stage I-III breast cancer who were enrolled in pre-surgical studies of the AKT inhibitor MK-2206 (n = 4) or the aromatase inhibitors exemestane (n = 2) and letrozole (n = 1). We performed DOTBIS at baseline (before initiation of therapy) and post-therapy in the affected breast (tumor volume) and contralateral, unaffected breast, and measured tissue concentrations (in µM) of total hemoglobin (ctTHb), oxyhemoglobin (ctO2Hb), and deoxyhemoglobin (ctHHb), as well as water fraction (%). RESULTS: We found consistent decreases in DOTBIS-measured hemoglobin concentrations in tumor volume, with median percent changes for ctTHb, ctHHb, ctO2Hb, and water fraction for the entire cohort of - 27.1% (interquartile range [IQR] 37.5%), - 49.8% (IQR 29.3%), - 33.5% (IQR 47.4%), and - 3.6% (IQR 10.6%), respectively. In the contralateral breast, median percent changes for ctTHb, ctHHb, ctO2Hb, and water fraction were + 1.8% (IQR 26.7%), - 8.6% (IQR 29.3%), + 6.2% (IQR 29.5%), and + 1.9% (IQR 30.7%), respectively. CONCLUSION: We demonstrated that DOTBIS-derived measurements are modifiable with pre-surgical AKT inhibition and endocrine therapy, supporting further investigation of DOTBIS as a potential imaging assessment of response to neoadjuvant targeted therapies in early stage breast cancer.


Assuntos
Neoplasias da Mama , Tomografia Óptica , Inibidores da Aromatase , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Letrozol , Terapia Neoadjuvante
6.
Cancer ; 126(7): 1541-1549, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31913500

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death among patients with early-stage breast cancer (BC), but adherence to cardiovascular disease risk factor (CVD-RF) medications is reported to be poor in BC survivors. The objective of the current study was to determine the association between nonadherence to CVD-RF medications and cardiovascular events in BC survivors. METHODS: The authors included patients with stages I to III BC from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database who had Medicare part D coverage and who were taking at least 1 CVD-RF medication prior to their BC diagnosis (2008-2013). Logistic regression was performed to define factors associated with nonadherence. Cox regression was used to calculate the association between nonadherence and new cardiac events after treatment. RESULTS: Among 15,576 patients included in the current analysis, 4797 (30.8%) were nonadherent to at least 1 category after the initial BC treatment period. Black race, greater comorbidity burden, more advanced cancer stage, hormone receptor-negative status, and receipt of chemotherapy were found to be associated with nonadherence. Nonadherence after treatment demonstrated a trend toward an increased risk of a subsequent cardiac event (hazard ratio [HR], 1.15; 95% CI 1.00-1.33 [P = .06]). This effect size increased with nonadherence to a greater number of medications (P < .01). There was an increased risk of experiencing a cardiac event noted with becoming nonadherent to hypertension medications (HR, 1.33; 95% CI, 1.18-1.51 [P < .0001]), hyperlipidemia medications (HR, 1.21; 95% CI, 1.05-1.40 [P = .009]), and diabetes medications (HR, 1.31; 95% CI, 1.10-1.56 [P = .003]). CONCLUSIONS: Nonadherence to CVD-RF medications after treatment of BC is associated with an increased risk of a cardiac event. Improving outcomes and reducing morbidity after a diagnosis of BC requires attention to non-BC conditions.


Assuntos
Neoplasias da Mama/complicações , Doenças Cardiovasculares/prevenção & controle , Adesão à Medicação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Sobreviventes de Câncer/estatística & dados numéricos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Incidência , Fatores de Risco , Programa de SEER
7.
Breast J ; 23(5): 519-524, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28323373

RESUMO

We evaluated whether mental illness is a barrier to genetic counseling for hereditary breast and ovarian cancer (HBOC) in multiethnic breast cancer patients. We conducted a retrospective analysis of 308 women with newly diagnosed breast cancer and eligible for HBOC genetic testing seen in the breast clinic of an academic, urban medical center from 2007 to 2015. Uptake of genetic services and history of mental health disorder (MHD), defined as a psychiatric diagnosis or treatment with an antidepressant, mood stabilizer, anxiolytic, or antipsychotic medication, were ascertained by medical chart review. The mean age at breast cancer diagnosis was 56 years, with 44% non-Hispanic whites, 37% Hispanics, and 15% non-Hispanic blacks. Ninety-nine (32%) women met study criteria for MHD, 73% had a genetics referral, 57% had genetic counseling, and 54% completed BRCA testing. Uptake of genetic counseling services did not differ by race/ethnicity or presence of MHD. In multivariable analysis, younger age at diagnosis, Ashkenazi Jewish heritage, and family history of breast cancer were associated with HBOC genetic counseling. A relatively high proportion of breast cancer patients eligible for HBOC genetic testing were referred to a genetic counselor and referral status did not vary by MHD or race/ethnicity.


Assuntos
Neoplasias da Mama/psicologia , Predisposição Genética para Doença , Transtornos Mentais/epidemiologia , Neoplasias Ovarianas/psicologia , Idoso , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Estudos de Coortes , Etnicidade , Feminino , Aconselhamento Genético , Humanos , Transtornos Mentais/etnologia , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/genética , Inquéritos e Questionários
8.
Breast J ; 23(3): 333-337, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27900810

RESUMO

Given the high prevalence (1 in 40) of BRCA1 and BRCA2 mutations among Ashkenazi Jews, population-based BRCA genetic testing in this ethnic subgroup may detect more mutation carriers. We conducted a cross-sectional survey among Orthodox Jewish women in New York City to assess breast cancer risk, genetic testing knowledge, self-efficacy, perceived breast cancer risk and worry, religious and cultural factors affecting medical decision-making. We used descriptive statistics and multivariable logistic regression models to identify predictors of genetic testing intention/uptake. Among evaluable respondents (n = 243, 53% response rate), median age was 25 and nearly half (43%) had a family history of breast cancer. Only 49% of the women had adequate genetic testing knowledge and 46% had accurate breast cancer risk perceptions. Five percent had already undergone BRCA genetic testing, 20% stated that they probably/definitely will get tested, 28% stated that they probably/definitely will not get tested, and 46% had not thought about it. High decision self-efficacy, adequate genetic testing knowledge, higher breast cancer risk, and overestimation of risk were associated with genetic testing intention/uptake. Decision support tools that improve knowledge and self-efficacy about genetic testing may facilitate population-based BRCA testing among Orthodox Jews.


Assuntos
Predisposição Genética para Doença/psicologia , Testes Genéticos , Judeus , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Estudos Transversais , Feminino , Humanos , Judeus/genética , Judeus/psicologia , Modelos Logísticos , Pessoa de Meia-Idade , Mutação , New York , Neoplasias Ovarianas/genética , Inquéritos e Questionários , Adulto Jovem
9.
Breast Cancer Res Treat ; 156(3): 453-464, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27013473

RESUMO

To investigate the effect of electro-acupuncture (EA) as a non-pharmacological intervention to prevent or reduce chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients undergoing chemotherapy of taxane. Women with stage I-III breast cancer scheduled to receive taxane therapy were randomized to receive a standardized protocol of 12 true or sham EA (SEA) weekly treatments concurrent with taxane treatment. Subjects completed the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Taxane neurotoxicity subscale (FACT-NTX), and other assessments at baseline and weeks 6, 12, and 16. A total of 180 subjects were screened, 63 enrolled and 48 completed week 16 assessments. Mean age was 50 with 25 % white, 25 % black, and 43 % Hispanic; 52 % had no prior chemotherapy. At week 12, both groups reported an increase in mean BPI-SF worst pain score, but no mean differences were found between groups (SEA 2.8 vs. EA 2.6, P = .86). By week 16, the SEA group returned to baseline, while the EA group continued to worsen (SEA 1.7 vs. EA 3.4, P = .03). The increase in BPI-SF worst pain score was 1.62 points higher in the EA group than in the SEA group at week 16 (P = .04). In a randomized, sham-controlled trial of EA for prevention of taxane-induced CIPN, there were no differences in pain or neuropathy between groups at week 12. Of concern, subjects on EA had a slower recovery than SEA subjects. Future studies should focus on EA for treatment as opposed to prevention of CIPN.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Eletroacupuntura/métodos , Doenças do Sistema Nervoso Periférico/prevenção & controle , Taxoides/efeitos adversos , Adulto , Idoso , Neoplasias da Mama/etnologia , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Projetos Piloto , Taxoides/uso terapêutico , Resultado do Tratamento
11.
Clin Adv Hematol Oncol ; 13(12): 858-68, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27058852

RESUMO

Programmed death 1 (PD-1) is an immune checkpoint that provides inhibitory signals to the immune system in order to modulate the activity of T cells in peripheral tissues and maintain self-tolerance in the setting of infection and inflammation. In cancer, the immune checkpoints are exploited so that the tumor cells are able to evade the immune system. Immune checkpoint inhibitors are a type of cancer immunotherapy that targets pathways such as PD-1 in order to reinvigorate and enhance the immune response against tumor cells. The US Food and Drug Administration (FDA) has approved 2 PD-1 inhibitors, nivolumab and pembrolizumab, and several others are under investigation. Although PD-1 inhibitors have demonstrated activity in many different types of malignancies, FDA approval has been granted only in melanoma and in non-small cell lung cancer (NSCLC). Identifying biomarkers that can predict response to PD-1 inhibitors is critical to maximizing the benefit of these agents. Future directions for PD-1 inhibitors include investigation of combination therapies, use in malignancies other than melanoma and NSCLC, and refinement of biomarkers.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Pontos de Checagem do Ciclo Celular , Proteínas de Neoplasias , Neoplasias , Receptor de Morte Celular Programada 1 , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/imunologia , Humanos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/metabolismo , Nivolumabe , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo
12.
Public Health Genomics ; 27(1): 57-67, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38402864

RESUMO

INTRODUCTION: Although the prevalence of a pathogenic variant in the BRCA1 and BRCA2 genes is about 1:400 (0.25%) in the general population, the prevalence is as high as 1:40 (2.5%) among the Ashkenazi Jewish population. Despite cost-effective preventive measures for mutation carriers, Orthodox Jews constitute a cultural and religious group that requires different approaches to BRCA1 and BRCA2 genetic testing relative to other groups. This study analyzed a dialog of key stakeholders and community members to explore factors that influence decision-making about BRCA1 and BRCA2 genetic testing in the New York Orthodox Jewish community. METHODS: Qualitative research methods, based on Grounded Theory and Narrative Research, were utilized to analyze the narrative data collected from 49 key stakeholders and community members. A content analysis was conducted to identify themes; inter-rater reliability was 71%. RESULTS: Facilitators of genetic testing were a desire for preventive interventions and education, while barriers to genetic testing included negative emotions, feared impact on family/romantic relationships, cost, and stigma. Views differed on the role of religious leaders and healthcare professionals in medical decision-making. Education, health, and community were discussed as influential factors, and concerns were expressed about disclosure, implementation, and information needs. CONCLUSION: This study elicited the opinions of Orthodox Jewish women (decision-makers) and key stakeholders (influencers) who play critical roles in the medical decision-making process. The findings have broad implications for engaging community stakeholders within faith-based or culturally distinct groups to ensure better utilization of healthcare services for cancer screening and prevention designed to improve population health.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Testes Genéticos , Judeus , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/etnologia , Neoplasias da Mama/psicologia , Tomada de Decisão Clínica/métodos , Predisposição Genética para Doença/psicologia , Testes Genéticos/métodos , Judeus/genética , Judeus/psicologia , New York , Pesquisa Qualitativa
13.
Fam Cancer ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609522

RESUMO

INTRODUCTION: Orthodox Jewish women face unique social, cultural, and religious factors that may influence uptake of BRCA1/2 genetic testing. We examined the impact of a web-based decision aid (DA) on BRCA1/2 genetic testing intention/completion among Orthodox Jewish women. We conducted a single-arm pilot study among 50 Orthodox Jewish women who were given access to a web-based DA entitled RealRisks and administered serial surveys at baseline and 1 and 6 months after exposure to the DA. Descriptive statistics were conducted for baseline characteristics and study measures. Comparisons were made to assess changes in study measures over time. Fifty Orthodox Jewish women enrolled in the study with a mean age of 43.9 years (standard deviation [SD] 14.6), 70% Modern Orthodox, 2% with personal history of breast cancer, and 68% and 16% with a family history of breast or ovarian cancer, respectively. At baseline, 27 (54%) participants intended to complete genetic testing. Forty-three participants (86%) completed RealRisks and the 1-month survey and 38 (76%) completed the 6-month survey. There was a significant improvement in BRCA1/2 genetic testing knowledge and decrease in decisional conflict after exposure to the DA. At 1 month, only 20 (46.5%) completed or intended to complete genetic testing (p = 0.473 compared to baseline). While the DA improved genetic testing knowledge and reduced decisional conflict, genetic testing intention/completion did not increase over time. Future interventions should directly address barriers to BRCA1/2 genetic testing uptake and include input from leaders in the Orthodox Jewish community. GOV ID: NCT03624088 (8/7/18).

14.
Nat Cancer ; 4(2): 257-275, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36585452

RESUMO

Inhibiting individual histone deacetylase (HDAC) is emerging as well-tolerated anticancer strategy compared with pan-HDAC inhibitors. Through preclinical studies, we demonstrated that the sensitivity to the leading HDAC6 inhibitor (HDAC6i) ricolinstat can be predicted by a computational network-based algorithm (HDAC6 score). Analysis of ~3,000 human breast cancers (BCs) showed that ~30% of them could benefice from HDAC6i therapy. Thus, we designed a phase 1b dose-escalation clinical trial to evaluate the activity of ricolinostat plus nab-paclitaxel in patients with metastatic BC (MBC) (NCT02632071). Study results showed that the two agents can be safely combined, that clinical activity is identified in patients with HR+/HER2- disease and that the HDAC6 score has potential as predictive biomarker. Analysis of other tumor types also identified multiple cohorts with predicted sensitivity to HDAC6i's. Mechanistically, we have linked the anticancer activity of HDAC6i's to their ability to induce c-Myc hyperacetylation (ac-K148) promoting its proteasome-mediated degradation in sensitive cancer cells.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Desacetilase 6 de Histona/metabolismo , Neoplasias da Mama/tratamento farmacológico , Histona Desacetilases/metabolismo , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico
15.
J Clin Oncol ; 41(24): 4004-4013, 2023 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-37207300

RESUMO

PURPOSE: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) improves progression-free survival (PFS) and overall survival (OS) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Although preclinical and clinical data demonstrate a benefit in changing ET and continuing a CDK4/6i at progression, no randomized prospective trials have evaluated this approach. METHODS: In this investigator-initiated, phase II, double-blind placebo-controlled trial in patients with HR+/HER2- MBC whose cancer progressed during ET and CDK4/6i, participants switched ET (fulvestrant or exemestane) from ET used pre-random assignment and randomly assigned 1:1 to the CDK4/6i ribociclib versus placebo. PFS was the primary end point, defined as time from random assignment to disease progression or death. Assuming a median PFS of 3.8 months with placebo, we had 80% power to detect a hazard ratio (HR) of 0.58 (corresponding to a median PFS of at least 6.5 months with ribociclib) with 120 patients randomly assigned using a one-sided log-rank test and significance level set at 2.5%. RESULTS: Of the 119 randomly assigned participants, 103 (86.5%) previously received palbociclib and 14 participants received ribociclib (11.7%). There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo. CONCLUSION: In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2- MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Quinase 4 Dependente de Ciclina , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Método Duplo-Cego , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quinase 6 Dependente de Ciclina
16.
JAMA Netw Open ; 5(7): e2222092, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35849397

RESUMO

Importance: To promote the identification of women carrying BRCA1/2 variants, the US Preventive Services Task Force recommends that primary care clinicians screen asymptomatic women for an increased risk of carrying a BRCA1/2 variant risk. Objective: To examine the effects of patient and clinician decision support about BRCA1/2 genetic testing compared with standard education alone. Design, Setting, and Participants: This clustered randomized clinical trial was conducted at an academic medical center including 67 clinicians (unit of randomization) and 187 patients. Patient eligibility criteria included women aged 21 to 75 years with no history of breast or ovarian cancer, no prior genetic counseling or testing for hereditary breast and ovarian cancer syndrome (HBOC), and meeting family history criteria for BRCA1/2 genetic testing. Interventions: RealRisks decision aid for patients and the Breast Cancer Risk Navigation Tool decision support for clinicians. Patients scheduled a visit with their clinician within 6 months of enrollment. Main Outcomes and Measures: The primary end point was genetic counseling uptake at 6 months. Secondary outcomes were genetic testing uptake at 6 and 24 months, decision-making measures (perceived breast cancer risk, breast cancer worry, genetic testing knowledge, decision conflict) based upon patient surveys administered at baseline, 1 month, postclinic visit, and 6 months. Results: From December 2018 to February 2020, 187 evaluable patients (101 in the intervention group, 86 in the control group) were enrolled (mean [SD] age: 40.7 [13.2] years; 88 Hispanic patients [46.6%]; 15 non-Hispanic Black patients [8.1%]; 72 non-Hispanic White patients [38.9%]; 35 patients [18.9%] with high school education or less) and 164 (87.8%) completed the trial. There was no significant difference in genetic counseling uptake at 6 months between the intervention group (20 patients [19.8%]) and control group (10 patients [11.6%]; difference, 8.2 percentage points; OR, 1.88 [95% CI, 0.82-4.30]; P = .14). Genetic testing uptake within 6 months was also statistically nonsignificant (13 patients [12.9%] in the intervention group vs 7 patients [8.1%] in the control group; P = .31). At 24 months, genetic testing uptake was 31 patients (30.7%) in intervention vs 18 patients (20.9%) in control (P = .14). Comparing decision-making measures between groups at baseline to 6 months, there were significant decreases in perceived breast cancer risk and in breast cancer worry (standard mean differences = -0.48 and -0.40, respectively). Conclusions and Relevance: This randomized clinical trial did not find a significant increase in genetic counseling uptake among patients who received patient and clinician decision support vs those who received standard education, although more than one-third of the ethnically diverse women enrolled in the intervention underwent genetic counseling. These findings suggest that the main advantage for these high-risk women is the ability to opt for screening and preventive services to decrease their cancer risk. Trial Registration: ClinicalTrials.gov Identifier: NCT03470402.


Assuntos
Neoplasias da Mama , Síndrome Hereditária de Câncer de Mama e Ovário , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Feminino , Aconselhamento Genético , Testes Genéticos , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Atenção Primária à Saúde
17.
JCO Oncol Pract ; 18(4): e472-e483, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34705516

RESUMO

PURPOSE: Increasing usage of multigene panel testing has identified more patients with pathogenic or likely pathogenic (P or LP) variants in low-moderate penetrance genes or variants of uncertain significance (VUS). Our study evaluates the association between genetic test results and contralateral prophylactic mastectomy (CPM) among patients with breast cancer. METHODS: We conducted a retrospective cohort study among women diagnosed with unilateral stage 0-III breast cancer between 2013 and 2020 who underwent genetic testing. We examined whether genetic test results were associated with CPM using multivariable logistic regression models. RESULTS: Among 707 racially or ethnically diverse women, most had benign or likely benign (B or LB) variants, whereas 12.5% had P or LP and 17.9% had VUS. Racial or ethnic minorities were twice as likely to receive VUS. Patients with P or LP variants had higher CPM rates than VUS or B or LB (64.8% v 25.8% v 25.9%), and highest among women with P or LP variants in high-penetrance genes (74.6%). On multivariable analysis, P or LP compared with B or LB variants were significantly associated with CPM (odds ratio = 4.24; 95% CI, 2.48 to 7.26). CONCLUSION: Women with P or LP variants on genetic testing were over four times more likely to undergo CPM than B or LB. Those with VUS had similar CPM rates as B or LB. Our findings suggest appropriate genetic counseling and communication of cancer risk to multiethnic breast cancer survivors.


Assuntos
Neoplasias da Mama , Mastectomia Profilática , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Feminino , Testes Genéticos , Humanos , Mastectomia , Estudos Retrospectivos
18.
Cancer Prev Res (Phila) ; 15(11): 721-726, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36001346

RESUMO

Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO with the goal of collecting valuable data on the biologic effects of denosumab on gynecologic tissue. The study was terminated early due to the inability to accrue participants. Challenges which impacted the conduct of this study included a study design with highly selective eligibility criteria and requirements and the COVID-19 pandemic. It is critical to reflect on these issues to enhance the successful completion of future prevention studies in individuals with hereditary cancer syndromes.


Assuntos
Neoplasias da Mama , COVID-19 , Neoplasias Ovarianas , Feminino , Humanos , Salpingo-Ooforectomia , Denosumab/uso terapêutico , Projetos Piloto , Pandemias , Mutação , Proteína BRCA1/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/epidemiologia , Ovariectomia
19.
Clin Breast Cancer ; 22(4): e457-e462, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34920954

RESUMO

INTRODUCTION: Diagnosis of LM is limited by low sensitivity of cerebrospinal fluid (CSF) cytopathology. Detecting tumor cells in CSF (CSF-TCs) might be more sensitive. We evaluated if CNSide (CNSide), a novel assay for tumor cell detection in CSF, can detect CSF-TCs better than conventional CSF cytology. METHODS: We enrolled adults with metastatic breast cancer and clinical suspicion for LM to undergo lumbar puncture (LP) for CSF cytopathology and CNSide. CNSide captured CSF-TCs using a primary 10-antibody mixture, streptavidin-coated microfluidic channel, and biotinylated secondary antibodies. CSF-TCs were assessed for estrogen receptor (ER) expression by fluorescent antibody and HER2 amplification by fluorescent in situ hybridization (FISH). CSF cell-free DNA (cfDNA) was extracted for next-generation sequencing (NGS). Leptomeningeal disease was defined as positive CSF cytology and/or unequivocal MRI findings. We calculated sensitivity and specificity of CSF cytology and CNSide for the diagnosis of LM. RESULTS: Ten patients, median age 51 years (range, 37-64), underwent diagnostic LP with CSF evaluation by cytology and CNSide. CNSide had sensitivity of 100% (95% Confidence Interval [CI], 40%-100%) and specificity of 83% (95% CI, 36%-100%) for LM. Among these patients, concordance of ER and HER2 status between CSF-TCs and metastatic biopsy were 60% and 75%, respectively. NGS of CSF cfDNA identified somatic mutations in three patients, including one with PIK3CA p.H1047L in blood and CSF. CONCLUSIONS: CNSide may be a viable platform to detect CSF-TCs, with potential use as a diagnostic tool for LM in patients with metastatic breast cancer. Additional, larger studies are warranted.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , Carcinomatose Meníngea , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Carcinomatose Meníngea/secundário
20.
Clin Cancer Res ; 27(7): 1949-1957, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33451976

RESUMO

PURPOSE: This study's primary objective was to evaluate the changes in optically derived parameters acquired with a diffuse optical tomography breast imaging system (DOTBIS) in the tumor volume of patients with breast carcinoma receiving neoadjuvant chemotherapy (NAC). EXPERIMENTAL DESIGN: In this analysis of 105 patients with stage II-III breast cancer, normalized mean values of total hemoglobin ([Formula: see text]), oxyhemoglobin ([Formula: see text]), deoxy-hemoglobin concentration ([Formula: see text]), water, and oxygen saturation ([Formula: see text]) percentages were collected at different timepoints during NAC and compared with baseline measurements. This report compared changes in these optical biomarkers measured in patients who did not achieve a pathologic complete response (non-pCR) and those with a pCR. Differences regarding molecular subtypes were included for hormone receptor-positive and HER2-negative, HER2-positive, and triple-negative breast cancer. RESULTS: At baseline, [Formula: see text] was higher for pCR tumors (3.97 ± 2.29) compared with non-pCR tumors (3.00 ± 1.72; P = 0.031). At the earliest imaging point after starting therapy, the mean change of [Formula: see text] compared with baseline ([Formula: see text]) was statistically significantly higher in non-pCR (1.23 ± 0.67) than in those with a pCR (0.87 ± 0.61; P < 0.0005), and significantly correlated to residual cancer burden classification (r = 0.448; P < 0.0005). [Formula: see text] combined with HER2 status was proposed as a two-predictor logistic model, with AUC = 0.891; P < 0.0005; and 95% confidence interval, 0.812-0.969. CONCLUSIONS: This study demonstrates that DOTBIS measured features change over time according to tumor pCR status and may predict early in the NAC treatment course whether a patient is responding to NAC.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Tomografia Óptica/métodos , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Receptor ErbB-2/análise
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