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PURPOSE: Approximately 15% of women who receive ovarian function suppression (OFS) as adjuvant treatment for high-risk, localized hormone receptor-positive (HR+) breast cancer may have inadequate estradiol suppression which can require therapeutic modification when used in combination with an aromatase inhibitor (AI). We previously reported that abemaciclib may interfere with the estradiol Abbott Alinity chemiluminescent microparticle immunoassay (CMIA) commonly used to monitor estradiol levels and suggested liquid chromatography-mass spectrometry (LC-MS/MS) is preferred in this setting. The aim of this study was to determine discrepancies in estradiol levels using CMIA compared to LC-MS/MS and subsequent treatment changes in a larger patient population. METHODS: We conducted a retrospective review of premenopausal women with early-stage HR+ breast cancer at our institution who received adjuvant OFS and abemaciclib with at least 1 CMIA estradiol level drawn during abemaciclib therapy from October 2021 to April 2023. RESULTS: Of the 22 women who met criteria for review, 20 (90.9%) had CMIA estradiol levels in the premenopausal range, of whom 9 also had estradiol measured by LC-MS/MS. All 9 women receiving OFS and abemaciclib with estradiol measurements by both methods had premenopausal range CMIA estradiol levels and postmenopausal range LC-MS/MS estradiol levels. Of the 20 patients with premenopausal estradiol levels by CMIA estradiol, treatment changes included increased OFS dosage or preparation (n = 7), change from AI to tamoxifen (n = 3), and surgical oophorectomy (n = 7). CONCLUSION: Our findings suggest the likely interference of abemaciclib with the Abbott Alinity immunoassay which may lead to unnecessary treatment changes. It is recommended that the LC-MS/MS assay be used when monitoring estradiol levels in patients receiving abemaciclib concurrently with OFS.
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Background: Perioperative use of immune checkpoint blockade (ICB) improves survival in patients with early-stage cancer. Treatment-related adverse events (AEs), frequently involve the endocrine system which may increase perioperative complications and affect quality of life. Objective: We conducted a meta-analysis to elucidate the impact of adding ICB to conventional neoadjuvant/adjuvant therapy on the incidence of endocrine AEs. Design: A systematic review and meta-analysis of randomize-controlled trials (RCTs). Data sources and methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed for RCTs comparing groups with and without the addition of ICB to conventional perioperative therapy in patients with cancer. Outcomes included all-grade and grade 3-5 thyroiditis, hyperthyroidism, hypothyroidism, adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, and hyperglycemia. The odds ratios (ORs) of all-grade and grade 3-5 endocrine were pooled using the random-effect model meta-analysis. Results: Twenty-four RCTs comprising 12,199 patients were identified for meta-analysis. The addition of ICB was associated with higher incidence of thyroiditis [all grade: OR = 3.53 (95% confidence interval (CI): 1.88-6.64)], hyperthyroidism [all-grade: 7.18 (4.30-12.01); grade 3-5: 3.93 (1.21-12.82)], hypothyroidism [all-grade: 5.39 (3.68-7.90); grade 3-5: 3.63 (1.18-11.11)], adrenal insufficiency [all-grade: 3.82 (1.88-7.79); grade 3-5: 5.91 (2.36-14.82)], hypophysitis [all-grade: 10.29 (4.97-21.3); grade 3-5: 5.80 (1.99-16.92)], and type 1 diabetes mellitus [all-grade: 2.24 (1.06-4.74); grade 3-5: 3.49 (1.21-10.08)]. The cumulative incidence of each grade 3-5 endocrine AE was low (<1.3%). No grade 5 AEs leading to death were observed. Conclusion: The addition of neoadjuvant/adjuvant ICB to conventional therapy was associated with an increased incidence of several endocrine AEs. Clinicians should be aware of the risk of endocrinopathy from the perioperative ICB use to facilitate risk-benefit discussion with patients with early-stage cancer. Trial registration: The protocol of this research was registered in PROSPERO (CRD42022332624).
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INTRODUCTION: The release of tumor-associated antigens with cytotoxic chemotherapy treatment may enhance the response to immune checkpoint blockade. Eribulin is a microtubule inhibitor with proven overall survival (OS) benefit in metastatic breast cancer (MBC), which may also enhance intratumoral vascular remodeling. Durvalumab, a humanized monoclonal antibody, targets the programmed cell death ligand-1 (PD-L1) receptor. This study sought to determine the maximum tolerated dose and recommended phase II dose (RP2D) of eribulin in combination with durvalumab, as well as the safety and preliminary antitumor activity of the combination in patients with previously treated HER2-negative (HER2-) MBC and recurrent ovarian cancer (ROC). METHODS: Cohorts of 3-6 patients with HER2- MBC and ROC were treated in a modified 3+3 design. Eligible patients received escalating doses of eribulin (1.1 mg/m2 or 1.4 mg/m2 IV on day 1 and day 8) with durvalumab (1.12 g IV on day 1) in 21-day cycles until dose-limiting toxicity (DLT), intolerable adverse events (AEs), disease progression, or other reasons for withdrawal. PRIMARY ENDPOINT: the rate of DLTs during cycles 1 and 2 of therapy. Secondary endpoints: AE rate, objective response rate (ORR), progression-free survival (PFS), and OS. RESULTS: Nine patients with a median of 4 prior therapies for advanced disease were treated: 5 patients with HER2- MBC (1 with triple-negative disease and 4 with hormone-positive disease) and 4 patients with ROC. The RP2D of eribulin was 1.4 mg/m2 in combination with durvalumab. There were no DLTs experienced during the first two cycles of therapy. The most common treatment-related AEs (>50%) were fatigue, neutropenia, decreased white blood cell count, anemia, AST and alkaline phosphatase elevation, hyperglycemia, and nausea; most were grade 1 or 2. There was one immune-related AE of grade 3 (hepatitis) after 5 cycles of treatment, for which patient came off study. Two other patients discontinued study drug related to toxicity (neutropenia [n = 1], hepatic toxicity [n = 1]). ORR was 55%, and 4 additional patients experienced stable disease. All MBC patients exhibited a response to therapy. Median PFS was 6.2 months. Median OS was 15.0 months. CONCLUSION: The combination of eribulin at a dose of 1.4 mg/m2 with standard dose durvalumab had a favorable AE profile in patients with previously treated HER2- MBC and ROC. The early antitumor activity observed in all MBC patients enrolled in the study suggests that further investigation of this combination is warranted.
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Neoplasias da Mama , Furanos , Cetonas , Neutropenia , Neoplasias Ovarianas , Policetídeos de Poliéter , Humanos , Feminino , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Anticorpos Monoclonais/efeitos adversos , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Abemaciclib is approved for use in the adjuvant setting in combination with endocrine therapy for patients with high-risk, hormone receptor-positive, HER2-negative early-stage breast cancer based on the monarchE trial. Options for endocrine therapy for premenopausal women include an aromatase inhibitor with ovarian function suppression or tamoxifen with or without ovarian suppression. We describe a unique case of a premenopausal woman with early-stage breast cancer receiving adjuvant abemaciclib and an aromatase inhibitor with elevated estradiol levels as measured by the Abbott Alinity chemiluminescent immunoassay despite chemical and surgical ovarian function suppression. Given low estradiol levels using liquid chromatography-mass spectrometry testing following a bilateral salpingo-oopherectomy, our case report suggests an interference of abemaciclib with the Abbott Alinity immunoassay. This possible interference has significant impacts on clinical care as false elevations in estradiol levels measured by immunoassays can lead to unnecessary treatment changes, including surgery.
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BACKGROUND: Optimism, coping, and resilience may be independent predictors of anxiety, distress, depression, or health-related quality of life (HRQOL) in women with breast cancer. METHODS: Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) searches of PubMed, PsycINFO, and Google Scholar databases from January 1, 1990, to April 30, 2018, for articles (i.e., studies) determining the impact of optimism, coping, or resilience on anxiety, distress, depression, or HRQOL in women with breast cancer. Articles included only those that measured optimism by the life orientation test (LOT) or LOT-revised (R), coping by the COPE, brief (B)-COPE, or religious (R)-COPE, and resilience by the CD-Resilience Scale (CD-RIS). RESULTS: Forty-one out of 52 (79%) studies showed that optimism is a statistically significant predictor of study-specific aspects of anxiety, distress, depression, or HRQOL. In a meta-analysis focused on depression, optimism was a statistically significant predictor of depression. Coping style is a statistically significant predictor for study-specific aspects of anxiety, distress, depression, or HRQOL in 41/43 (95%) studies. The coping studies were too heterogeneous in their outcome variables to perform meta-analyses. There were too few studies (n = 6) on resilience to draw any conclusions. CONCLUSIONS: Despite many limitations of this literature, including the heterogeneity of study designs, differing sample sizes, across different countries, cultures, ethnicities, and races, most studies support that optimism and coping are predictors of anxiety, distress, depression, or HRQOL. Awareness of these psychological constructs and their potential impact on anxiety, depression, and HRQOL are a high priority.
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Neoplasias da Mama , Qualidade de Vida , Adaptação Psicológica , Ansiedade/epidemiologia , Ansiedade/etiologia , Neoplasias da Mama/epidemiologia , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Avaliação de Resultados em Cuidados de Saúde , Estresse PsicológicoRESUMO
BACKGROUND: Cancer is prevalent in the rapidly growing Chinese American community, yet little is known about the symptom experience to guide comprehensive treatment planning. This study evaluated symptom prevalence and patient subgroups with symptom distress in a large sample of Chinese American cancer patients. METHODS: Patients were consecutively recruited from 4 oncology practices, and they completed a translated cancer symptom scale. Latent class cluster analysis was used to identify subgroups of patients with distinct symptom distress profiles. RESULTS: There were 1436 patients screened; 94.4% were non-English-speaking, and 45.1% were undergoing cancer therapy. The cancers included breast (32.6%), lung (14.8%), head and neck (12.5%), and hematologic cancer (10.1%). Overall, 1289 patients (89.8%) had 1 or more symptoms, and 1129 (78.6%) had 2 or more. The most prevalent symptoms were a lack of energy (57.0%), dry mouth (55.6%), feeling sad (49.3%), worrying (47.5%), and difficulty sleeping (46.8%). Symptoms causing "quite a bit" or "very much" distress included difficulty sleeping (37.9%), a lack of appetite (37.2%), feeling nervous (35.8%), pain (35.2%), and worrying (34.0%). Four patient subgroups were identified according to the probability of reporting moderate to high symptom distress: very low physical and psychological symptom distress (49.5%), low physical symptom distress and moderate psychological symptom distress (25.2%), moderate physical and psychological symptom distress (17.4%), and high physical and psychological symptom distress (7.8%). CONCLUSIONS: Symptom prevalence is high in community-dwelling Chinese American cancer patients, and nearly half experience severe distress (rated as "quite a bit" or "very much" distressing) from physical symptoms, psychological symptoms, or both. These data have important implications for the development of effective symptom control interventions.
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Neoplasias/complicações , Neoplasias/psicologia , Populações Vulneráveis/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asiático/estatística & dados numéricos , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Data regarding the clinical significance of HER2(+) and TN status in patients with small node-negative tumors are limited and conflicting. It remains unclear who, among those with small lesions, might benefit from more aggressive adjuvant therapy. PATIENTS AND METHODS: We identified all node-negative breast cancer patients with tumor size ≤ 1 cm diagnosed between January 1, 1995 and December 31, 2008 using our institutional breast service database. Patients were classified according to their receptor status into 3 groups: (1) hormone receptor (HR)-positive (estrogen receptor [ER]- or progesterone receptor [PR]-positive, HER2(-)); (2) HER2(+) (immunohistochemistry 3(+) or fluorescence in situ hybridization amplification ≥ 2); and (3) TN (ER(-), PR(-), and HER2(-)). RFS was calculated using Kaplan-Meier methods. RESULTS: Among 656 patients with tumors ≤ 1 cm, 494 (75%) of the patients were HR(+), 107 (16%) were HER2(+), and 55 (9%) were TN. Median age was 59 years (range, 27-92 years). Median follow-up was 3.5 years. The 5-year RFS rates were 98.2%, 97.1%, and 83.5% in patients with HR(+), HER2(+), and TN tumors, respectively (P < .001). In multivariate analysis, TN status was associated with worse RFS (hazard ratio, 6.70; 95% confidence interval [CI], 3.02-14.86), and HER2(+) was not (hazard ratio, 1.64; 95% CI, 0.73-3.69). CONCLUSION: TN, but not HER2(+) status, was associated with worse RFS in patients with T1abN0 tumors, and adjuvant chemotherapy might be considered in patients with TN breast cancer.
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Receptor ErbB-2/biossíntese , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Fatores de RiscoRESUMO
Previous studies have reported higher recurrence rates in T1a/b N0 breast cancers characterized by high-risk biology (HER2+ or triple-negative), but the benefits of adjuvant chemotherapy in these patients have not been established. This study was designed to determine whether recurrence risk is reduced with chemotherapy and to define a group of patients most appropriate for treatment based on retrospective data. We pooled cases from two multi-institutional databases spanning the period of 1996-2010. A propensity score model adjusted unbalanced confounders between the groups treated or untreated with adjuvant chemotherapy and, in case of HER2-positive disease, with trastuzumab. Competing risk analysis was utilized to study effects of chemotherapy on cancer recurrences in the matched populations. Among the 318 patients identified, 41 % received adjuvant chemotherapy and 54 % of HER2+ patients received it with trastuzumab. The cumulative risk of recurrence at 5 years was 7.3 %. Age less than 35 years and triple-negative status were the only significant prognostic factors. Overall, administration of chemotherapy was not associated with a significant decrease in the risk of recurrence (HR 0.93, p = 0.91). The rate of recurrence in HER2+ patients who received trastuzumab was lower but not statistically significant (HR 0.50, p = 0.63). Clinical characteristics are of limited prognostic value for stratifying risk of recurrence in very small, node-negative HER2+, or triple-negative cancers. While limited by the small number of events, our analysis does not support the increasingly prevalent practice of administering adjuvant chemotherapy in this population without more accurate prognostic and predictive factors.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Receptor ErbB-2/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Recidiva , Estudos Retrospectivos , TrastuzumabRESUMO
PURPOSE: Many women with hormone receptor-positive breast cancer discontinue effective aromatase inhibitor (AI) treatment due to joint symptoms. METHODS: We conducted a single-arm, open-label, phase II study evaluating glucosamine-sulfate (1,500 mg/day) + chondroitin-sulfate (1,200 mg/day) for 24 weeks to treat joint pain/stiffness in postmenopausal women with early stage breast cancer who developed moderate-to-severe joint pain after initiating AIs. The primary endpoint was improvement in pain/stiffness at week 24 assessed by the Outcome Measure in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Secondary endpoints assessed changes in pain, stiffness, and function using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index for hips/knees and the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) for hands/wrists. The Brief Pain Inventory (BPI) assessed pain interference, severity, and worst pain. RESULTS: Of 53 patients enrolled, 39 were evaluable at week 24. From baseline to week 24, 46 % of patients improved according to OMERACT-OARSI criteria. At week 24, there were improvements (all P < 0.05) in pain and function as assessed by WOMAC and M-SACRAH, and in pain interference, severity, and worst pain as assessed by BPI. Estradiol levels did not change from baseline. The most commonly reported side effects were headache (28 %), dyspepsia (15 %), and nausea (17 %). CONCLUSIONS: In this single-arm study, 24 weeks of glucosamine/chondroitin resulted in moderate improvements in AI-induced arthralgias, with minimal side effects, and no changes in estradiol levels. These results suggest a need to evaluate efficacy in a placebo-controlled trial.
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Inibidores da Aromatase/efeitos adversos , Artralgia/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Condroitina/uso terapêutico , Glucosamina/uso terapêutico , Adulto , Idoso , Artralgia/induzido quimicamente , Quimioterapia Combinada , Feminino , Articulação do Quadril , Humanos , Articulação do Joelho , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
In addition to its role in calcium homeostasis and bone health, vitamin D has also been reported to have anticancer activities against many cancer types, including breast cancer. The discovery that breast epithelial cells possess the same enzymatic system as the kidney, allowing local manufacture of active vitamin D from circulating precursors, makes the effect of vitamin D in breast cancer biologically plausible. Preclinical and ecologic studies have suggested a role for vitamin D in breast cancer prevention. Inverse associations have also been shown between serum 25-hydroxyvitamin D level (25(OH)D) and breast cancer development, risk for breast cancer recurrence, and mortality in women with early-stage breast cancer. Clinical trials of vitamin D supplementation, however, have yielded inconsistent results. Regardless of whether or not vitamin D helps prevent breast cancer or its recurrence, vitamin D deficiency in the U.S. population is very common, and the adverse impact on bone health, a particular concern for breast cancer survivors, makes it important to understand vitamin D physiology and to recognize and treat vitamin D deficiency. In this review, we discuss vitamin D metabolism and its mechanism of action. We summarize the current evidence of the relationship between vitamin D and breast cancer, highlight ongoing research in this area, and discuss optimal dosing of vitamin D for breast cancer prevention.
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Neoplasias da Mama/metabolismo , Neoplasias da Mama/prevenção & controle , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Animais , Feminino , HumanosRESUMO
Testosterone is important for the development of secondary sexual characteristics in female-to-male (FtM) transsexuals, but it may increase breast cancer risk. To date, only one breast cancer case has been reported in the literature in a FtM transsexual after 10 years of testosterone therapy. We describe 2 cases of breast cancers diagnosed in FtM transsexuals who have been treated with supraphysiological doses of testosterone. Our 2 cases demonstrate the unique issues that concern the management of FtM transsexuals with breast cancer and examine possible roles of testosterone in the development of breast cancer.
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Neoplasias da Mama/induzido quimicamente , Testosterona/administração & dosagem , Transexualidade , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Testosterona/efeitos adversosRESUMO
Despite the benefit of adjuvant hormonal therapy (HT) on mortality among women with breast cancer (BC), many women are non-adherent with its use. We investigated the effects of early discontinuation and non-adherence to HT on mortality in women enrolled in Kaiser Permanente of Northern California (KPNC). We identified women diagnosed with hormone-sensitive stage I-III BC, 1996-2007, and used automated pharmacy records to identify prescriptions and dates of refill. We categorized patients as having discontinued HT early if 180 days elapsed from the prior prescription. For those who continued, we categorized patients as adherent if the medication possession ratio was ≥80%. We used Cox proportional hazards models to estimate the association between discontinuation and non-adherence with all-cause mortality. Among 8,769 women who filled at least one prescription for HT, 2,761 (31%) discontinued therapy. Of those who continued HT, 1,684 (28%) were non-adherent. During a median follow-up of 4.4 years, 813 women died. Estimated survival at 10 years was 80.7% for women who continued HT versus 73.6% for those who discontinued (P < 0.001). Of those who continued, survival at 10 years was 81.7 and 77.8% in women who adhered and non-adhered, respectively (P < 0.001). Adjusting for clinical and demographic variables, both early discontinuation (HR 1.26, 95% CI 1.09-1.46) and non-adherence (HR 1.49, 95% CI 1.23-1.81), among those who continued, were independent predictors of mortality. Both early discontinuation and non-adherence to HT were common and associated with increased mortality. Interventions to improve continuation of and adherence to HT may be critical to improve BC survival.
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Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/mortalidade , Cooperação do Paciente , Tamoxifeno/uso terapêutico , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Carga TumoralRESUMO
PURPOSE: While studies have found that adjuvant hormonal therapy for hormone-sensitive breast cancer (BC) dramatically reduces recurrence and mortality, adherence to medications is suboptimal. We investigated the rates and predictors of early discontinuation and nonadherence to hormonal therapy in patients enrolled in Kaiser Permanente of Northern California health system. PATIENTS AND METHODS: We identified women diagnosed with hormone-sensitive stage I-III BC from 1996 to 2007 and used automated pharmacy records to identify hormonal therapy prescriptions and dates of refill. We used Cox proportional hazards regression models to analyze factors associated with early discontinuation and nonadherence (medication possession ratio < 80%) of hormonal therapy. RESULTS: We identified 8,769 patients with BC who met our eligibility criteria and who filled at least one prescription for tamoxifen (43%), aromatase inhibitors (26%), or both (30%) within 1 year of diagnosis. Younger or older age, lumpectomy (v mastectomy), and comorbidities were associated with earlier discontinuation, while Asian race, being married, earlier year at diagnosis, receipt of chemotherapy or radiotherapy, and longer prescription refill interval were associated with completion of 4.5 years of therapy. Of those who continued therapy, similar factors were associated with full adherence. Women age younger than 40 years had the highest risk of discontinuation (hazard ratio, 1.51; 95% CI, 1.23 to 1.85). By 4.5 years, 32% discontinued therapy, and of those who continued, 72% were fully adherent. CONCLUSION: Only 49% of patients with BC took adjuvant hormonal therapy for the full duration at the optimal schedule. Younger women are at high risk of nonadherence. Interventions to improve adherence and continuation of hormonal therapy are needed, especially for younger women.
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Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adesão à Medicação , Tamoxifeno/uso terapêutico , Fatores Etários , Idoso , Neoplasias da Mama/patologia , California , Quimioterapia Adjuvante , Estudos de Coortes , Prescrições de Medicamentos , Feminino , Sistemas Pré-Pagos de Saúde , Humanos , Seguro de Serviços Farmacêuticos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
CONTEXT: Adjuvant chemotherapy is associated with significant reductions in bone mineral density (BMD) in premenopausal women with breast cancer (BC) that is prevented with zoledronic acid (ZA) every 3 months for 1 yr. OBJECTIVE: The aim of the study was to examine the effect on BMD of discontinuing ZA during the subsequent year. DESIGN: We conducted a randomized, double-blind trial. PATIENTS: Premenopausal women (mean age, 42 yr) undergoing adjuvant chemotherapy for BC participated in the study. INTERVENTION: ZA (4 mg iv every 3 months) vs. placebo was administered for 12 months. OUTCOME MEASURES: We measured percentage change in BMD and bone turnover markers at 12 and 24 months (1 yr after last infusion). RESULTS: Of 101 women randomized, 85 completed 12-month and 62 completed 24-month evaluations. In the placebo group, serum C-telopeptide (CTX) increased progressively over the first 12 months, returned toward baseline but remained significantly above baseline by 24 months. Lumbar spine BMD decreased from baseline by 5.5% at 12 and 6.3% at 24 months. Similarly, by 24 months, total hip and femoral neck BMD declined by 2.6 and 2.4%, respectively. In ZA patients, BMD remained stable (P < 0.0001 compared to placebo). Serum CTX declined significantly by 6 months, but returned to baseline by 12 months, remaining there at 24 months. CONCLUSIONS: Premenopausal women receiving chemotherapy for BC sustained significant bone loss during the first year, without recovery during the second year. ZA effectively prevented bone loss during the first year of chemotherapy. BMD remained stable 1 yr after completion of ZA. Serum CTX increased significantly by 12 and 24 months. More frequent administration may be required to suppress bone resorption in this patient population.
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Conservadores da Densidade Óssea/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose/prevenção & controle , Adulto , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea , Quimioterapia Adjuvante , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Ácido ZoledrônicoRESUMO
BACKGROUND: Expansion of the health care workforce in Peru to combat tuberculosis (TB) includes both professional health care providers (HCPs) such as doctors and nurses, and non-professional HCPs such as community health workers (CHWs). We describe the knowledge and attitudes of these HCPs, and identify modifiable barriers to appropriate anti-tuberculosis treatment. METHODOLOGY: We surveyed HCPs practicing in 30 clinical settings (hospitals, community health centers, and health posts) in the San Juan de Lurigancho district of Eastern Lima, Peru. Multiple-choice questions were used to assess knowledge of TB. A five-item Likert scale was created to assess attitudes toward the community, patients, and clinics. Linear regression was used to identify predictors of mean knowledge score, and analysis of variance was used to test differences in HCP score. RESULTS: Of the 73 HCPs surveyed, 15% were professionals (doctors or nurses). The remaining 85% were health technicians, community health workers (CHWs) or students. The mean knowledge score was 10.0 +/- 1.9 (maximum 14) with professional HCPs scoring higher than other HCPs (11.7 +/- 1.1 vs. 9.7 +/- 1.9), p < .01). Knowledge gaps included identification of patients at high risk for TB, assessment of treatment outcomes, and consequences of treatment failure. The most commonly cited modifiable barriers were structural, including laboratory facilities and staffing of TB clinics, with 52.1% and 62.5% of HCPs, respectively, citing these as problematic. CONCLUSIONS: Efforts to improve knowledge of TB HCPs in Peru should focus on the specific gaps we have identified. Further research is needed to evaluate whether these knowledge gaps correlate with TB control.
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Conhecimentos, Atitudes e Prática em Saúde , Tuberculose Pulmonar/psicologia , Adulto , Atitude do Pessoal de Saúde , Competência Clínica , Feminino , Pessoal de Saúde/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Educação de Pacientes como Assunto , Peru , Inquéritos e Questionários , Tuberculose Pulmonar/terapiaRESUMO
Anthracyclines are among the most active agents for the treatment of breast cancer; their use in combination regimens improves both disease-free and overall survival in patients with breast cancer. Unfortunately, the clinical utility of anthracycline use is limited by a cumulative dose-dependent cardiac toxicity resulting in congestive heart failure. As methods for detecting and treating breast cancer improve, there has been a steady decline in breast cancer mortality over the past 15 years. With an increasing number of long-term breast cancer survivors, the number of patients experiencing anthracycline-induced cardiotoxicity may also continue to grow. Moreover, new agents used in the treatment of breast cancer can potentiate cardiac toxicity. Recently, studies of non-anthracycline-containing regimens have been found to be effective in preventing recurrence of breast cancer (as compared with anthracycline-containing regimens) in patients with early-stage breast cancer, with a reduced incidence of adverse cardiac outcomes. In this article, we summarize the incidence, presentation, and mechanism of anthracycline-associated cardiotoxicity. We also discuss risk factors for the development of anthracycline-induced cardiotoxicity and new therapies, such as trastuzumab, that may potentiate cardiac toxicity. Finally, we review monitoring and preventive practices that may reduce the long-term risk of anthracycline-related cardiotoxicity.
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Antraciclinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiopatias/induzido quimicamente , Feminino , Cardiopatias/prevenção & controle , HumanosRESUMO
OBJECTIVES: Cholecystectomy has been implicated as a possible risk factor for colorectal cancer. However, the clinical evidence and the underlying mechanism for this association are still inconclusive. We conducted a population-based study to further clarify this association. METHODS: We conducted a retrospective cohort study among all patients aged 40 yr or older in the General Practice Research Database from the United Kingdom. We excluded patients with <1 yr of colorectal cancer-free database follow-up as well as those patients who developed colorectal cancer within 1 yr after their cholecystectomies. Crude and adjusted incidence rate ratios (IRRs) were determined using Poisson regression. RESULTS: The incidence rate of colorectal cancer among cholecystectomy patients (n = 55,960) was 119 (95% CI: 106-133) per 100,000 person-years, compared to 86 (95% CI: 83-90) per 100,000 person-years among patients without a cholecystectomy (n = 574,668). Among the covariates examined, only sex and age were significant confounders and were included in the adjusted analyses. The adjusted IRR of colorectal cancer associated with cholecystectomy was 1.32 (95% CI: 1.16-1.48, p < 0.001). The positive association was present for colon cancer (adjusted IRR 1.51, 95% CI: 1.30-1.74, p < 0.001), but not for rectal cancer (adjusted IRR 1.00, 95% CI: 0.85-1.17, p= 0.99). The pattern of association was similar in men versus women. A similar association with colon cancer was observed for cholelithiasis. CONCLUSIONS: Cholecystectomy is associated with a modestly increased risk of colon cancer but not for rectal cancer. Lithogenic bile could be the underlying mechanism.