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The combination of the phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single-agent therapy. This phase 1 study (NCT02914938) included a dose-finding stage in patients with relapsed/refractory (R/R) B-cell malignancies (n = 20) and disease-specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1-7 plus zanubrutinib 80 mg twice daily continuously in 28-day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3-4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression-free survival (PFS) were not reached in either group. The estimated 1-year PFS was 72.3% (95% confidence interval [CI], 51.9-85.1) for FL and 56.3% (95% CI, 28.9-76.7) for MCL (median follow-up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular , Linfoma de Células del Manto , Pirazoles , Pirimidinas , Humanos , Linfoma de Células del Manto/tratamiento farmacológico , Femenino , Masculino , Anciano , Persona de Mediana Edad , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/mortalidad , Pirimidinas/efectos adversos , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Adulto , Tiazoles/efectos adversos , Tiazoles/administración & dosificación , Tiazoles/uso terapéutico , Anciano de 80 o más Años , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Resultado del Tratamiento , PiperidinasRESUMEN
Tumor mutational burden (TMB) in circulating tumor DNA (ctDNA) has shown promise in predicting benefit from PD-L1/PD-1 inhibitors in retrospective studies. Aiming to assess blood TMB (bTMB) prospectively, we conducted B-F1RST ( NCT02848651 ), an open-label, phase 2 trial that evaluated bTMB as a predictive biomarker for first-line atezolizumab monotherapy in locally advanced or metastatic stage IIIB-IVB non-small cell lung cancer (n = 152). The co-primary endpoints were investigator-assessed objective response rate (ORR) per RECIST version 1.1 and investigator-assessed progression-free survival (PFS) between high and low bTMB subgroups at the pre-defined bTMB ≥ 16 (14.5 mutations per megabase) cutoff. Secondary endpoints included investigator-assessed PFS, overall survival (OS) and duration of response at various bTMB cutoffs, as well as safety. Investigator-assessed PFS in the bTMB ≥ 16 versus bTMB < 16 groups was not statistically significant. However, bTMB ≥ 16 was associated with higher ORR, and ORR improved as bTMB cutoffs increased. No new safety signals were seen. In exploratory analyses, patients with maximum somatic allele frequency (MSAF) < 1% had higher ORR than patients with MSAF ≥ 1%. However, further analysis showed that this effect was driven by better baseline prognostics rather than by MSAF itself. At 36.5-month follow-up, an exploratory analysis of OS found that bTMB ≥ 16 was associated with longer OS than bTMB < 16. Further study and assay optimization will be required to develop bTMB as a predictive, standalone biomarker of immunotherapy or for use in conjunction with other biomarkers.
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Carcinoma de Pulmón de Células no Pequeñas , ADN Tumoral Circulante , Neoplasias Pulmonares , Anticuerpos Monoclonales Humanizados , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , ADN Tumoral Circulante/genética , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación/genética , Estudios RetrospectivosRESUMEN
OBJECTIVE: College of American Pathologists and the American Society of Clinical Oncology guidelines provide straightforward criteria for HER2 interpretation in breast carcinomas; however, a subset of cases present unusual diagnostic dilemmas. MATERIALS AND METHODS: Ten challenging HER2 fluorescence in situ hybridization (FISH) cases were selected for analysis. The study included a variety of problematic cases such as those with discordant immunohistochemistry (IHC) and FISH results, cases with high intratumoral variability in HER2 copy number, a case with a highly amplified clone in 5% to 10% of the tumor sample, and a case with tumor cells containing tightly clumped HER2 signals. Six high volume HER2 FISH laboratories performed and interpreted HER2 FISH (adding HER2 IHC if necessary). Interpretation strategies were discussed. RESULTS: There was 100% concordance between laboratories in 4/10 cases. Tumors with increased intratumoral variability (tumors with high variability in HER2 copy number per cell but which otherwise do not fulfill College of American Pathologists and the American Society of Clinical Oncology criteria for heterogeneity) exhibited 100% concordance in 3/4 cases, but 1 case had only 50% agreement. Low positive HER2 cases (group 1 cases with <6 average HER2 copies/cell) had 1 laboratory disagreeing with the majority in 4/4 cases, and this was the only category with discordance between IHC and FISH methodologies. All laboratories identified the case with heterogeneity and interpreted it as positive. Five of the 6 laboratories interpreted the case with tightly clustered HER2 signals as positive. CONCLUSIONS: This study offers specific observations and interpretation strategies that laboratories can use when confronted with difficult HER 2 cases. It then highlights communication strategies a laboratory may use to discuss these unusual HER2 results with the clinical team.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama , Hibridación Fluorescente in Situ , Receptor ErbB-2/biosíntesis , Adulto , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVES: The response to HER2-targeted neoadjuvant chemotherapy (NAC) in HER2-positive (+) breast cancer can be quantified using residual cancer burden (RCB) pathologic evaluation to predict relapse free/overall survival. However, more information is needed to characterize the relationship between patterns of HER2 testing results and response to NAC. We evaluated clinicopathologic characteristics associated with RCB categories in HER2+ patients who underwent HER2-directed NAC. METHODS: A retrospective chart review was conducted with Stage I-III HER2+ breast cancer cases following NAC and surgical resection. HER2 immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH), histologic/clinical characteristics, hormone receptor status, and RCB scores (RCB-0, RCB-I, RCB-II, and RCB-III) were evaluated. RESULTS: 64/151 (42.4%) patients with HER2+ disease had pathologic complete response (pCR). Tumors with suboptimal response (RCB-II and RCB-III) were more likely to demonstrate less than 100% HER2 IHC 3+ staining (p < 0.0001), lower HER2 FISH copies (p < 0.0001), and lower HER2/CEP17 ratios (p = 0.0015) compared to RCB-I and RCB-II responses. Estrogen receptor classification using ≥10% versus ≥1% staining showed greater association with higher RCB categories. CONCLUSIONS: HER2+ characteristics show differing response to therapy despite all being categorized as positive; tumors with less than 100% IHC 3+ staining, lower HER2 FISH copies, and lower HER2/CEP17 ratios resulted in higher RCB scores.
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PURPOSE: As monotherapies, eribulin (chemotherapy) and pembrolizumab (immunotherapy) have shown promise for patients with metastatic triple-negative breast cancer (mTNBC). This phase Ib/II study examined eribulin plus pembrolizumab as a potential mTNBC treatment in first-line and later-line settings. PATIENTS AND METHODS: In this open-label, single-arm, phase Ib/II study, eligible patients had mTNBC, measurable disease, and ≤2 prior systemic anticancer therapies in the metastatic setting. Patients were enrolled by number of prior systemic anticancer therapies (stratum 1: 0 vs stratum 2: 1-2) in the metastatic setting and further analyzed by tumor programmed death-ligand 1 (PD-L1) expression status. All patients received intravenous eribulin 1.4 mg/m2 on day 1 and day 8, plus intravenous pembrolizumab 200 mg on day 1, of 21-day cycles. The primary objectives were the safety, tolerability, and objective response rate (ORR) of this combination. RESULTS: The study included 167 patients (phase Ib, n = 7; phase II, n = 160). The most common treatment-emergent adverse events were fatigue (66%), nausea (58%), peripheral sensory neuropathy (41%), alopecia (40%), and constipation (37%). ORRs were 25.8% [95% confidence interval (CI): 15.8-38.0] for stratum 1 (n = 66) and 21.8% (95% CI: 14.2-31.1) for stratum 2 (n = 101). Patients with PD-L1-positive tumors (combined positive score ≥1) had numerically higher ORR than those with PD-L1-negative tumors, particularly in stratum 1 [stratum 1: 34.5% (95% CI: 17.9-54.3) vs 16.1% (95% CI: 5.5-33.7); stratum 2, 24.4% (95% CI: 12.9-39.5) vs 18.2% (95% CI: 8.2-32.7)]. CONCLUSIONS: Eribulin plus pembrolizumab was generally well tolerated and showed promising antitumor activity in mTNBC. Efficacy outcomes appeared influenced by line of therapy and PD-L1 status.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Furanos/administración & dosificación , Cetonas/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Expresión Génica , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Seguridad , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
BACKGROUND: Although breast cancer (BC) is uncommon in women age ≤ 35 years, women in this age group may have more aggressive cancer subtypes and high-risk pathogenic variants (HRPVs). Higher recurrence and mortality rates in young patients may be related to differences in tumor biology, pathologic mutation status, or treatment. The purpose of this study was to evaluate germline mutation status and other factors that affect recurrence-free survival (RFS) and overall survival (OS) in young women with BC. MATERIALS AND METHODS: This was a retrospective study of women diagnosed with BC at age ≤ 35 years at Allina Health System from 2000 through 2017 (n = 306). Information was collected on germline mutation status, tumor characteristics (grade, hormone receptor, and human epidermal growth factor receptor 2), molecular subtype, pregnancy-associated cancers, and treatment. Survival analyses using Kaplan-Meier curves were conducted for RFS and OS. RESULTS: With mean follow-up of 6.5 years, OS was 87.0% for invasive cancers, RFS was 84.7%; 69% obtained genetic testing, and 26.9% had HRPVs. There were no differences in RFS or OS between patients with HRPV versus unknown/low/moderate risk variants. Recurrence analysis showed increased recurrence rates in luminal B-like cancers followed by triple negative and human epidermal growth factor receptor 2-positive cancers (P = .041). Pregnancy-associated BC diagnoses, angiolymphatic invasion, and tumor stage were associated with reduced OS. In spite of young age at diagnosis, nearly one-third of patients did not receive germline genetic testing. CONCLUSIONS: Similar survival patterns were found between women with HRPV versus no known mutations. Luminal B-like subtype, pregnancy-associated BC, angiolymphatic invasion, and cancer stage were associated with reduced OS.
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Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Supervivencia sin Enfermedad , Mutación de Línea Germinal , Adulto , Neoplasias de la Mama/genética , Femenino , Humanos , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: The Polo-like kinase 1 (PLK1) is a master regulator of mitosis and overexpressed in acute myeloid leukemia (AML). We conducted a phase Ib study of the PLK1 inhibitor, onvansertib, in combination with either low-dose cytarabine (LDAC) or decitabine in patients with relapsed or refractory (R/R) AML. PATIENTS AND METHODS: Onvansertib was administered orally, in escalating doses, on days 1-5 in combination with either LDAC (20 mg/m2; days 1-10) or decitabine (20 mg/m2; days 1-5) in a 28-day cycle. The primary endpoint was to evaluate first-cycle dose-limiting toxicities and the MTD. Secondary and exploratory endpoints included safety, pharmacokinetics, antileukemic activity, and response biomarkers. RESULTS: Forty patients were treated with onvansertib (12-90 mg/m2) in combination with LDAC (n = 17) or decitabine (n = 23). Onvansertib was well tolerated with most grades 3 and 4 adverse events related to myelosuppression. In the decitabine arm, the MTD was established at 60 mg/m2, and 5 (24%) of the 21 evaluable patients achieved complete remission with or without hematologic count recovery. Decrease in mutant circulating tumor DNA (ctDNA) during the first cycle of therapy was associated with clinical response. Engagement of the PLK1 target, TCTP, was measured in circulating blasts and was associated with greater decrease in bone marrow blasts. CONCLUSIONS: The onvansertib and decitabine combination was well tolerated and had antileukemic activity particularly in patients with target engagement and decreased mutant ctDNA following treatment. This combination will be further investigated in the ongoing phase II trial.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Adulto , Anciano , Anciano de 80 o más Años , Citarabina/administración & dosificación , Decitabina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Piperazinas/administración & dosificación , Pronóstico , Pirazoles/administración & dosificación , Quinazolinas/administración & dosificaciónRESUMEN
Molecular testing for genomic variants is recommended in advanced non-small cell lung cancer (NSCLC). Standard tissue biopsy is sometimes infeasible, procedurally risky, or insufficient in tumor tissue quantity. We present the analytical validation and concordance study of EGFR variants using a new 17-gene liquid biopsy assay (NCT02762877). Of 144 patients enrolled with newly diagnosed or progressive stage IV nonsquamous NSCLC, 140 (97%) had liquid assay results, and 117 (81%) had both EGFR blood and tissue results. Alterations were detected in 58% of liquid samples. Overall tissue-liquid concordance for EGFR alterations was 94.0% (95% CI 88.1%, 97.6%) with positive percent agreement of 76.7% (57.7%, 90.1%) and negative percent agreement of 100% (95.8%, 100%). Concordance for ALK structural variants was 95.7% (90.1%, 98.6%). This assay detected alterations in other therapeutically relevant genes at a rate similar to tissue analysis. These results demonstrate the analytical and clinical validity of this 17-gene assay.
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Clinical management of microinvasive breast cancer (Tmic) remains controversial. Although metastases are infrequent in Tmic carcinoma patients, surgical treatment typically includes lymph node sampling. The objective of this study was to determine the rate and predictors of lymph node metastases, recurrence, and survival in a large series of Tmic breast carcinomas. Consecutive cases of Tmic were identified within our health care system from 2001 to 2015. We reviewed results of lymph node sampling and other pathologic factors including hormone receptor/HER2 status, associated in situ tumor size/grade, margin status, number of invasive foci, surgical/adjuvant therapies, and recurrence/survival outcomes. In this cohort, 294 Tmic cases were identified with mean follow-up of 4.6 years. Of 260 patients who underwent axillary staging, lymph node metastases were identified in 1.5% (all of which were ductal type). All Tmic cases with positive lymph node metastases had associated DCIS with size > 5 cm (5.3-8.5 cm) compared to a median DCIS tumor size of 2.5 cm (0.2-19.0 cm) for the entire cohort. No lymph node metastases were seen with microinvasive lobular carcinoma. During the follow-up period, there were no regional/distant recurrences or breast cancer-associated deaths in a mean follow-up period of 4.6 years. Two patients developed subsequent ipsilateral breast cancer (DCIS) in a different quadrant than the original Tmic. Clinical behavior of microinvasive breast cancer in this series is similar to DCIS. Lymph node metastases are uncommon and were only seen with ductal type microinvasive carcinoma. Our data suggest limited benefit for routine node sampling and support management of Tmic similar to DCIS, particularly for patients with DCIS < 5 cm in size.
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Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Lobular/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Intraductal no Infiltrante/terapia , Carcinoma Lobular/terapia , Terapia Combinada , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Retrospectivos , Biopsia del Ganglio Linfático CentinelaRESUMEN
Family history information comprises an important tool in identifying and referring patients at risk for hereditary breast and ovarian cancer (HBOC) to cancer genetic counseling. Despite recommendations and support provided by numerous professional organizations, cancer genetic counseling services are underutilized by atrisk patients. This study aimed to: (1) determine the rate of genetic counseling utilization following a referral letter, (2) characterize factors (barriers and supports) which influenced uptake of services, and (3) identify potential strategies for increasing utilization. This study evaluated the uptake of cancer genetic counseling among 603 screening mammography patients identified as having an increased risk for HBOC based on National Comprehensive Cancer Network (NCCN) guidelines. At risk individuals and their primary care providers were mailed a referral letter recommending genetic counseling. Three focus groups (N = 24) were conducted to identify responses to receiving a letter recommending genetic counseling, barriers to seeking genetic counseling, and facilitating factors to utilizing these services. Participant responses were qualitatively analyzed using thematic and cross case analysis. Within one year, 50/603 (8 %) of the identified at-risk women completed a genetic counseling appointment. Participant-perceived barriers which influenced their decision not to seek genetic counseling included lack of relevance and utility, limited knowledge about genetic counseling, concerns about the genetic counseling process, and concerns about cost and insurance coverage. Participant-perceived facilitating factors which would support a decision to seek genetic counseling included greater awareness and education about genetic counseling services when receiving a referral, and improved follow up and guidance from their provider. Findings from this study support the need for patient and primary care provider education, and improved provider-patient communication to increase uptake of genetic counseling services.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Asesoramiento Genético/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Accesibilidad a los Servicios de Salud , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Derivación y Consulta/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Management recommendations for lobular neoplasia (LN) including lobular carcinoma-in-situ (LCIS) and atypical lobular hyperplasia (ALH) diagnosed in core biopsies (CB) are controversial. Our aim was to prospectively identify a subset of patients who do not require subsequent surgical excision (SE). PATIENTS AND METHODS: All patients diagnosed with LN on CB were enrolled and referred for SE. Cases with coexistent ductal carcinoma-in-situ or invasive carcinoma were excluded. Cases with coexistent ductal atypia (LN-DA) and LCIS variants (LN-V) were separated from pure classic LN (LN-C). Dedicated breast pathologists and radiologists reviewed cases with careful imaging/pathology correlation. RESULTS: Of 13,772 total percutaneous breast CB procedures, 302 of 370 patients diagnosed with LN underwent SE. Upgrade to carcinoma was present in 3.5% (8/228) LN-C, 26.7% LN-V (4/15), and 28.3% LN-DA (15/53). Calcifications were the imaging target for 180 (79%) of 228 LN-C cases; 7 were associated with upgrade (3.9%). Upgrades were rare for mass lesions (1/32) and magnetic resonance imaging-targeted lesions (0/14). Upgrades were similar for ALH and LCIS (3.4% vs. 4.5%). During postsurgical follow-up (mean, 34.5 months), 6.5% LN-C patients developed carcinoma in either breast. CONCLUSION: Although LN with nonclassic morphology or with associated ductal atypia requires SE, this can be avoided in LN-C diagnosed on CB targeting calcifications when careful imaging/pathology correlation is applied. Until larger numbers are studied, excising LN-C diagnosed as masses or magnetic resonance imaging-detected lesions may be prudent. Regardless of their selection for surgical management, LN patients need close surveillance in view of their long-term risk of breast cancer.
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Carcinoma de Mama in situ/patología , Carcinoma de Mama in situ/cirugía , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Mama/patología , Carcinoma Lobular/patología , Carcinoma Lobular/cirugía , Lesiones Precancerosas/patología , Lesiones Precancerosas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Gruesa , Carcinoma de Mama in situ/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Carcinoma Lobular/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Hiperplasia/diagnóstico por imagen , Hiperplasia/cirugía , Imagen por Resonancia Magnética , Mamografía , Persona de Mediana Edad , Lesiones Precancerosas/diagnóstico por imagen , Estudios Prospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION/BACKGROUND: Oncotype DX (Genomic Health, Redwood City, CA) uses reverse transcriptase polymerase chain reaction analysis to measure tumor gene expression for determining recurrence risk (RR) and guiding chemotherapy decisions for breast cancer patients. Invasive lobular carcinoma (ILC) is a histologic subtype that has not been the focus of prior studies validating Oncotype DX. The study purpose was to develop a model using histologic tumor characteristics to predict uniformly low Oncotype DX Recurrence Scores (RS) in ILC. PATIENTS AND METHODS: ILC cases in our pathology database with Oncotype DX testing were identified. Histologic tumor characteristics, immunohistochemical (IHC) of estrogen receptor (ER)/progesterone receptor (PgR) percent, HER2, E-cadherin expression, and Ki-67 levels were obtained for cases. Discriminant analysis was used to test the hypothesis that tumors classified as lower/higher risk based on Oncotype DX RS would differ significantly on a linear combination of variables. RESULTS: From 2006 - 2014, 158 cases of ILC having Oncotype DX testing were identified; 90 low risk (RS < 18), 66 intermediate risk (RS 18 - 30) and 2 high risk (RS > 30). Discriminant analysis showed that PgR% followed by Ki-67 provided the greatest contribution to discern low versus elevated RS. A subset of 57 cases (â¼36%) with predicted probabilities > 86% for either low or high RS yielded 96.5% correct classification, 92.3% sensitivity, and 97.7% specificity. CONCLUSION: Our analytical model may be useful in predicting lower RR in patients with ILC. If validated, this provides a faster and less expensive alternative to Oncotype DX testing in certain patients with ILC.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Carcinoma Lobular/patología , Perfilación de la Expresión Génica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Neoplasias de la Mama/genética , Carcinoma Lobular/genética , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Curva ROC , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo/métodos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To analyze serum markers of bone turnover, angiogenesis, endocrine function, and inflammation in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) who discontinued long-term intravenous bisphosphonate (BP) therapy. PATIENTS AND METHODS: Serum samples were obtained from 25 BRONJ patients who had discontinued long-term intravenous BP therapy for an average of 11.4 ± 8.7 months and 48 non-BRONJ controls who continued receiving intravenous BP therapy. Samples were analyzed for total alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin, C-telopeptide, vascular endothelial growth factor, triiodothyronine, thyroxine, thyroid-stimulating hormone, 25-hydroxyvitamin D, and C-reactive protein. RESULTS: The mean number of BP infusions was significantly higher in BRONJ patients compared with controls (38.4 ± 26.3 infusions vs 18.8 ± 7.2 infusions, P < .0001); however, the duration of BP therapy was not significantly different between the groups (P = .23). Overall, there were no significant differences in any of the markers between BRONJ patients and controls (all P values ≥ .16). In a subgroup analysis that matched BRONJ patients and controls according to mean age and number of BP infusions (10 BRONJ patients and 48 controls), log10 vascular endothelial growth factor (2.9 ± 0.4 pg/mL vs 2.4 ± 0.4 pg/mL, P < .001) and C-reactive protein (34 ± 26 mg/L vs 13 ± 8 mg/L, P < .01) levels were significantly higher in BRONJ patients compared with controls. Within BRONJ patients, none of the serum markers were correlated with duration of BP discontinuation. CONCLUSIONS: Levels of bone turnover and endocrine markers in BRONJ patients who discontinue long-term intravenous BP therapy are similar to those in non-BRONJ controls receiving intravenous BP therapy. However, levels of angiogenesis and inflammation markers are higher in BRONJ patients who discontinue long-term intravenous BP therapy. The prolonged skeletal half-life of BPs may suppress bone turnover markers in BRONJ patients for several years after discontinuation of intravenous BP therapy, suggesting an extended effect on bone homeostasis.
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Proteínas Angiogénicas/sangre , Biomarcadores/sangre , Osteonecrosis de los Maxilares Asociada a Difosfonatos/sangre , Conservadores de la Densidad Ósea/administración & dosificación , Huesos/metabolismo , Difosfonatos/administración & dosificación , Administración Intravenosa , Anciano , Fosfatasa Alcalina/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Colágeno Tipo I/sangre , Femenino , Humanos , Mediadores de Inflamación/sangre , Masculino , Persona de Mediana Edad , Osteocalcina/sangre , Péptidos/sangre , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
BACKGROUND: Previous case reports and animal studies suggest that periodontitis is associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). This case-control study is conducted to evaluate the association between clinical and radiographic measures of periodontal disease and BRONJ. METHODS: Twenty-five patients with BRONJ were matched with 48 controls. Trained examiners measured probing depth, clinical attachment level (CAL), and bleeding on probing on all teeth except third molars and gingival and plaque indices on six index teeth. Alveolar bone height was measured from orthopantomograms. Most patients with BRONJ were using antibiotics (48%) or a chlorhexidine mouthrinse (84%) at enrollment. Adjusted comparisons of patients with BRONJ versus controls used multiple linear regression. RESULTS: The average number of bisphosphonate (BP) infusions was significantly higher in patients with BRONJ compared with controls (38.4 versus 18.8, P = 0.0001). In unadjusted analyses, patients with BRONJ had more missing teeth (7.8 versus 3.1, P = 0.002) and higher average CAL (2.18 versus 1.56 mm, P = 0.047) and percentage of sites with CAL ≥3 mm (39.0 versus 23.3, P = 0.039) than controls. Also, patients with BRONJ had lower average bone height (as a fraction of tooth length, 0.59 versus 0.62, P = 0.004) and more teeth with bone height less than half of tooth length (20% versus 6%, P = 0.001). These differences remained significant after adjusting for age, sex, smoking, and number of BP infusions. CONCLUSIONS: BRONJ patients have fewer teeth, greater CAL, and less alveolar bone support compared with controls after adjusting for number of BP infusions. Group differences in antibiotics and chlorhexidine rinse usage may have masked differences in the other clinical measures.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos/complicaciones , Periodontitis/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Hueso Alveolar/clasificación , Pérdida de Hueso Alveolar/diagnóstico por imagen , Antibacterianos/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Osteonecrosis de los Maxilares Asociada a Difosfonatos/tratamiento farmacológico , Estudios de Casos y Controles , Clorhexidina/uso terapéutico , Índice de Placa Dental , Difosfonatos/administración & dosificación , Femenino , Hemorragia Gingival/clasificación , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Antisépticos Bucales/uso terapéutico , Pérdida de la Inserción Periodontal/clasificación , Índice Periodontal , Bolsa Periodontal/clasificación , Periodontitis/clasificación , Radiografía Panorámica , Factores de Riesgo , Pérdida de Diente/clasificaciónRESUMEN
BACKGROUND: Cancer treatments can lead to detriments in patients' health and declines in quality of life (QOL). Cancer rehabilitation programs may improve functional status, symptom control, and QOL. OBJECTIVE: The objective of this study was to determine if an outpatient, physical therapy-supervised Cancer Rehabilitation Strengthening and Conditioning (CRSC) program improved patients' conditioning level, functional status, QOL, and symptoms. METHODS: This was a prospective study of oncology patients participating in CRSC program. Measurements included conditioning level (6-minute walk test [SMWT], metabolic equivalent level, grip strength), functional status (Physical Component Summary of Short Form 36), QOL (Mental Component Summary of Short Form 36), and symptoms (M. D. Anderson Symptom Inventory). Paired t tests were conducted to determine significant changes between pre- and post-CRSC program measures, and regression methods identified predictors of change from baseline. RESULTS: One hundred fifteen patients with cancer were enrolled in the study; 75 patients completed pre- and post-CRSC program measures. Significant improvements were noted in SMWT by 186.4 ft, SMWT speed by 0.35 mph, treadmill time (3.5 minutes longer), metabolic equivalent level (by 0.87 units), QOL, symptom severity, symptom interference with daily life, fatigue, shortness of breath, and sadness. CONCLUSIONS: In a pretest-posttest design, significant improvements were noted in conditioning level, functional status, QOL, and symptoms. Greater improvements were noted in participants who were most deconditioned at baseline. IMPLICATIONS FOR PRACTICE: Further research should be conducted to provide additional support for CRSC programs. Cancer rehabilitation strengthening and condition programs may benefit patients across the continuum of care, including deconditioned patients.
Asunto(s)
Ejercicio Físico , Neoplasias/enfermería , Pacientes Ambulatorios , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/rehabilitación , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento , CaminataRESUMEN
PURPOSE/OBJECTIVES: To estimate and compare responsiveness of standardized self-reported measures of musculoskeletal symptoms (MSSs) and physical functioning (PF) during treatment with aromatase inhibitors (AIs). DESIGN: Prospective, longitudinal study. SETTING: Park Nicollet Institute and North Memorial Cancer Center, both in Minneapolis, MN. SAMPLE: 122 postmenopausal women with hormone receptor-positive breast cancer. METHODS: MSSs and PF were assessed before starting AIs and at one, three, and six months using six self-reported MSSs measures and two PF tests. MAIN RESEARCH VARIABLES: MSSs and PF changes from baseline to six months. FINDINGS: Using the Breast Cancer Prevention Trial-Musculoskeletal Symptom (BCPT-MS) subscale, 54% of participants reported MSSs by six months. Scores from the BCPT-MS subscale and the physical function subscales of the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) were most responsive to changes over six months. CONCLUSIONS: BCPT-MS, AUSCAN, and WOMAC were the most responsive instruments for measuring AI-associated MSSs. IMPLICATIONS FOR NURSING: Assessment and management of MSSs are important aspects of oncology care because MSSs can affect functional ability and AI adherence. KNOWLEDGE TRANSLATION: The three measures with the greatest sensitivity were the BCPT-MS, AUSCAN, and WOMAC questionnaires. These measures will be useful when conducting research on change in MSSs associated with AI treatment in women with breast cancer.
Asunto(s)
Antineoplásicos Hormonales/efectos adversos , Inhibidores de la Aromatasa/efectos adversos , Artralgia/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Estrógenos , Limitación de la Movilidad , Debilidad Muscular/inducido químicamente , Mialgia/inducido químicamente , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Actividades Cotidianas , Anciano , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/terapia , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Cumplimiento de la Medicación , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/terapia , Dimensión del Dolor , Posmenopausia , Estudios Prospectivos , Encuestas y Cuestionarios , Evaluación de Síntomas , Resultado del TratamientoRESUMEN
INTRODUCTION: Previous research has identified gaps in cancer survivors' knowledge of their diagnosis and treatment. This study assessed the effect of treatment summaries on survivors' accuracy in reporting details of diagnosis and treatment. METHODS: Written surveys were completed by 203 breast cancer survivors and 141 colorectal cancer survivors diagnosed between 1999 and 2008 at a cancer center in the Minneapolis, MN, area (78 % response rate). All completed the survey before and again 17 months after receiving a treatment summary, which was sent to them upon request. Accuracy of response at each assessment was compared to cancer registry and medical records. RESULTS: Both breast and colorectal cancer survivors showed significant improvement in accuracy on stage of disease, and breast cancer survivors showed significant improvement in accuracy on morphology, estrogen receptor status, progesterone receptor status, receipt of hormone therapy, and receipt of doxorubicin after receiving the treatment summary. Breast cancer survivors and older individuals were more likely than colorectal cancer survivors or younger individuals to indicate that they used the treatment summary in completing the second survey. Even for items on which accuracy improved significantly, however, patient knowledge remained incomplete. CONCLUSIONS: The provision of treatment summaries can improve cancer survivors' knowledge of details about their diagnosis and treatment. IMPLICATIONS FOR CANCER SURVIVORS: Treatment summaries can meet the specific goal of increasing patient knowledge. Their effectiveness might be greater if presented during a dedicated survivorship health care appointment.
Asunto(s)
Neoplasias de la Mama/terapia , Neoplasias Colorrectales/terapia , Conocimiento , Registros Médicos , Educación del Paciente como Asunto , Sobrevivientes/psicología , Acceso a la Información , Adulto , Cuidados Posteriores , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/psicología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/psicología , Comunicación , Recolección de Datos , Femenino , Humanos , Conducta en la Búsqueda de Información , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Aspects of a personal cancer history can have implications for future decisions regarding screening, diagnosis, and treatment. Clinicians must sometimes rely on patients' self-report of their medical history. This study assessed knowledge of details of cancer diagnosis and treatment among breast and colorectal cancer survivors. METHODS: Written surveys were completed by 480 breast cancer survivors and 366 colorectal cancer survivors diagnosed between 1999 and 2008 at a large cancer center in the Minneapolis, MN, area (81% response rate). Responses were compared with cancer registry and medical records. RESULTS: Forty percent of breast cancer survivors and 65% of colorectal cancer survivors were unable to identify their stage of disease. Seven percent of breast cancer survivors and 21% of colorectal cancer survivors in whom regional nodes were examined did not know whether they had positive nodes. Accuracy of knowledge of estrogen and progesterone status among breast cancer survivors was 58% and 39%, respectively. Of breast cancer survivors treated with doxorubicin, 43% correctly identified it as a drug they had received. Their accuracy of identification of receipt of tamoxifen or specific aromatase inhibitors was >90%. Of colorectal cancer survivors treated with oxaliplatin, 52% correctly identified it as a drug they had received. Accuracy on many items decreased with patient age. CONCLUSIONS: This study identifies several gaps in adult cancer survivors' knowledge of details of their diagnosis and treatment that have implications for follow-up care. IMPLICATIONS FOR CANCER SURVIVORS: Provision of written treatment summaries to cancer survivors could help them obtain appropriate patient-centered long-term follow-up care.