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BACKGROUND: Pre-treatment characteristics of women with early breast cancer that are associated with persistent fatigue or suboptimal health-related quality of life (HRQOL) post-chemotherapy need to be identified as potential targets for pre-habilitation. PATIENTS AND METHODS: Ancillary analysis of previously collected data from patients with newly diagnosed Stage I-III breast cancer scheduled to receive chemotherapy. The objective was to identify baseline (pre-chemotherapy) variables associated with meaningful deteriorations in fatigue and other measures of HRQOL from pre-treatment to 6 months after chemotherapy completion. Percentages are reported along with unadjusted and adjusted relative risks. RESULTS: In a sample of 249 women post-chemotherapy, 32% reported worsening fatigue (FACIT-F), 35% worsening Physical Well-Being (PWB), 16% worsening Functional Well-Being (FWB), 8% worsening Emotional Well-Being (EWB), and 30% worsening Social Well-Being (SWB). In multivariable (MV) analysis, variables that were significant in univariate analysis - Black race, high BMI, and baseline poorer EWB - remained significant for worsening post-chemotherapy fatigue (FACIT-F). In MV analysis that included race, education, falls, and baseline EWB, Black race and a positive falls history remained significant for worsening PWB. In MV analysis inclusive of race, Short Physical Performance Battery (SPPB) and FWB, lower SPPB and FWB remained significant predictors of worsening FWB. In MV analysis that included baseline Mental Health Index-Anxiety, EWB and SWB, a higher SWB and lower EWB remained significant for worsening SWB. CONCLUSION: Pre-chemotherapy characteristics in women with early-stage breast cancer that are associated with increased fatigue and reduced HRQOL post-treatment could be used to identify patients who may benefit from pre-habilitation interventions.
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Antineoplásicos , Neoplasias de la Mama , Fatiga , Calidad de Vida , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Fatiga/inducido químicamente , Fatiga/etiología , Fatiga/epidemiología , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , AncianoRESUMEN
BACKGROUND: To describe reasons for deviations from planned chemotherapy treatments in women with nonmetastatic breast cancer that contribute to less-than-planned receipt of chemotherapy. METHODS: Electronic medical records for patients receiving chemotherapy were reviewed for adverse events and treatment modifications. Log-binomial regression models were used to estimate relative risks (RRs) with 95% CIs to examine associations between chemotherapy modifications, patient characteristics, and treatment modalities. RESULTS: Delays in chemotherapy initiation (7%) were for surgical complications (58%), personal reasons (16%), and other (26%; port malfunction, infections, and obtaining extra imaging). Delays during chemotherapy (38%) were for infections (20%), neutropenia (13%), and personal reasons (13%). Dose reductions (38%) were for neuropathy (36%), unknown causes (9%), anemia (9%), and neutropenia (8%). Early treatment discontinuations (23%) were for neuropathy (29%). Patients receiving paclitaxel/nab-paclitaxel (RR 2.05; 95% CI, 1.47-2.87) and an anthracycline (RR 1.89; 95% CI, 1.39-2.57) reported more dose delays during chemotherapy. Black race (RR 1.46; 95% CI, 1.07-2.00), stage 3 (RR 1.79; 95% CI, 1.09-2.93), and paclitaxel/nab-paclitaxel receipt (RR 1.39; 95% CI, 1.02-1.90) increased the likelihood of dose reduction. Both Black race (RR 2.06; 95% CI, 1.35-3.15) and receipt of paclitaxel/nab-paclitaxel (RR 1.93; 95% CI, 1.19-3.13) increased the likelihood of early discontinuation. Patients receiving anthracyclines had higher rates of hospitalizations during chemotherapy (RR: 1.79; 95% CI, 1.11-2.89). CONCLUSION: Toxicities are the most common reason for treatment modifications and need close monitoring in high-risk groups for timely intervention. Dose reductions and early treatment discontinuations occurred more for Black patients and need further study.
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INTRODUCTION: Palbociclib is a widely used treatment for advanced breast cancer in older adults. However, the existing evidence regarding its safety and tolerability in this age group is inconsistent and limited to retrospective subgroup or pooled analyses. MATERIALS AND METHODS: We conducted a prospective single-arm multicenter phase 2 study to evaluate the safety and tolerability of palbociclib in participants aged 70 years or older with advanced hormone receptor-positive breast cancer. Participants were given palbociclib in combination with their physician's choice of endocrine therapy (letrozole or fulvestrant). The primary endpoint was the incidence of grade 3+ adverse events (AEs) by six months. Secondary endpoints included AE-related dose delays, dose reductions, early discontinuations, and hospitalizations. Additionally, we compared these endpoints by age groups (70-74 and ≥ 75 years). RESULTS: Of the 90 participants (median age 74 years [70-87]) enrolled, 75.6% (95% confidence interval [CI], 65.4-84.0) had grade 3+ AEs by six months. The most frequent grade 3+ AEs were neutropenia (61%), fatigue (4%), and nausea (3%). Febrile neutropenia was uncommon (1.1%). Due to AEs, 36% had dose delays, 34% had dose reductions, 10% had early discontinuations, and 10% had hospitalizations. Compared to those aged 70-74 years, participants aged ≥75 years had higher rates of early discontinuations (5.9% vs 15.9%, a difference of 9.5% [95% CI 3.5%-22.5%]). DISCUSSION: Palbociclib has an overall favorable safety profile in adults aged ≥70 with advanced breast cancer. However, adults ≥75 years had a trend toward higher rates of AE-related early discontinuations compared to those 70-74 years. Further research is needed to evaluate tolerability and improve the delivery of palbociclib in older adults. CLINICALTRIALS: gov:NCT03633331.
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Neoplasias de la Mama , Piperazinas , Piridinas , Humanos , Piridinas/efectos adversos , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Anciano , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Piperazinas/efectos adversos , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Anciano de 80 o más Años , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Fulvestrant/administración & dosificación , Fulvestrant/uso terapéutico , Letrozol/administración & dosificación , Letrozol/uso terapéutico , Factores de EdadRESUMEN
BACKGROUND: Medical mistrust, rooted in unethical research, is a barrier to cancer-related health care for Black/African American (AA) persons. Understanding trust, mistrust, and health care experiences is crucial, especially in multiple myeloma (MM), which disproportionately burdens Black/AA persons in incidence and survival. STUDY PURPOSE: This study qualitatively examines the experiences of Black/AA and White dyads (patient with MM and adult caregiver) to gain insights into these phenomena. METHODS: From November 2021 to April 2022, we recruited 21 dyads from the UNC Lineberger Comprehensive Cancer Center. Participants completed a sociodemographic survey and a 60-90 min semi-structured interview. We used ATLAS.ti v9 for project management and to facilitate data analysis using the Sort and Sift, Think and Shift approach (ResearchTalk Inc). RESULTS: We interviewed 21 racially concordant dyads (11 Black/AA, 10 White) with mean patient ages of 70 (Black/AA) and 72 (White) at enrollment. Both Black/AA and White caregivers had a mean enrollment age of 68. The mean duration from MM diagnosis to enrollment for all patients was 5.5 years. Four key themes emerged: (1) knowledge and trust, (2) heightened emotions and discomfort, (3) differing mental constructs of health care experiences, and (4) mitigating mistrust, which varied by self-identified race. Black/AA participants had greater knowledge of historical events like the U.S. Public Health Service Untreated Syphilis Study at Tuskegee and carried the emotional burden longer. They also emphasized self-learning and self-guided research about MM for informed medical decision-making. Both Black/AA and White dyads emphasized the pivotal role of patient-provider relationships and effective communication in fostering trust and addressing concerns. CONCLUSION: Our study offers contextual insights into the enduring challenges of medical mistrust, particularly within the Black/AA community, and its implications for patients and caregivers accessing and receiving MM-related care. Future studies should leverage these insights to guide the development of multilevel interventions addressing medical mistrust within the Black/AA community.
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Negro o Afroamericano , Cuidadores , Mieloma Múltiple , Confianza , Población Blanca , Humanos , Mieloma Múltiple/psicología , Mieloma Múltiple/terapia , Masculino , Femenino , Anciano , Cuidadores/psicología , Negro o Afroamericano/psicología , Persona de Mediana Edad , Población Blanca/psicología , Anciano de 80 o más Años , Investigación CualitativaRESUMEN
PURPOSE: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both. METHODS: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference). RESULTS: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001). CONCLUSION: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes. CLINICAL TRIAL: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study.
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Neoplasias de la Mama , Supervivientes de Cáncer , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Anciano , Estudios Prospectivos , Estudios de Casos y Controles , Anciano de 80 o más Años , Calidad de VidaRESUMEN
BACKGROUND: Delivery of cancer treatments, such as chemotherapy, requires a complex set of decisions that can change over time. Traditional measures of chemotherapy delivery, such as relative dose intensity, measure the amount of chemotherapy received by the end of treatment but mask the timing of dose reductions, delays, and discontinuation. These events may be important for delivering timely interventions to support adherence and lower the risk of recurrence. MATERIALS AND METHODS: We used an institutional database to identify women diagnosed with stage I-III breast cancer receiving adjuvant chemotherapy with a standard 4-cycle regimen of docetaxelâ +â cyclophosphamide (TC, every 21 days) from April 2014 to December 2019. LCD was calculated as the amount of a given chemotherapy agent delivered at a specified time, t, divided by the total planned standard chemotherapy dose at time t. We visualized LCD curves for each chemotherapy agent and reported the median LCD and interquartile range (IQR) at the end of the regimen, overall and by age group (<65 years vs. 65+ years). RESULTS: The study population included 80 women. At the end of treatment, overall median LCDs for both cyclophosphamide and docetaxel were 100% (IQR: 99.6%, 100%), suggesting that TC was well tolerated. However, the lower quartile LCD for cyclophosphamide was 98.7% in older women treated with TC compared with 99.7% in younger women. CONCLUSION: Within our cohort, adjuvant TC was well tolerated with LCD curves showing largely on-time and full-dose administration. Subgroup analyses showed only slight decreases in adjuvant TC LCD for patients aged 65+ versus <65 years.
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Neoplasias de la Mama , Humanos , Femenino , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Docetaxel/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/uso terapéutico , Quimioterapia Adyuvante/efectos adversosRESUMEN
BACKGROUND: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer. METHODS: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. RESULTS: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003). CONCLUSIONS: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.
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Neoplasias de la Mama , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Estudios Prospectivos , Quimioterapia Adyuvante/efectos adversos , Evaluación Geriátrica/métodos , HospitalizaciónRESUMEN
INTRODUCTION: Geriatric assessment (GA)-guided supportive care programs have been successful in improving treatment outcomes for older adults with solid-organ cancers. This study aimed to evaluate the feasibility of a GA-guided supportive care program among older adults treated for multiple myeloma (MM). MATERIALS AND METHODS: The study utilized an existing registry of adults with plasma cell disorders at the University of North Carolina. Patients with MM, aged 60 or older, and having a GA-identified deficit in one or more problem area were offered referrals to supportive care resources during routine visits. Problem areas included physical function deficits, polypharmacy, and anxiety or depression. Patients with physical function deficits were offered referral to physical therapy (PT), those with polypharmacy to an Oncology Clinical Pharmacist Practitioner (CPP), and those with mental health symptoms to the Comprehensive Cancer Support Program (CCSP). RESULTS: Of the 58 individuals identified as having at least one deficit on the GA, PT was the most commonly identified relevant resource (79%), followed by CPP visits (57%). Among individuals that were offered referral(s) to at least one new supportive care resource, the acceptance rate was 50%. Referral acceptance rates were highest among those recommended for a CPP visit (55% of those approached) and lowest for CCSP (0%). DISCUSSION: The study examined the feasibility and acceptability of a referral program for supportive care resources among older adults with MM who have deficits on GA. The most commonly identified deficit was physical functioning, followed by polypharmacy and mental health. The study found that physical interventions and referrals to CPPs were the most accepted interventions. However, the low proportion of patients who accepted physical therapy referrals indicates the need for tailored and more personalized approaches. Further research is needed to explore the feasibility and impact of supportive care referral programs for older adults with MM.
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Mieloma Múltiple , Neoplasias , Anciano , Humanos , Mieloma Múltiple/terapia , Evaluación Geriátrica , Estudios de Factibilidad , Neoplasias/terapia , Oncología Médica , Salud MentalRESUMEN
Importance: Black women in the United States have higher breast cancer (BC) mortality rates than White women. The combined role of multiple factors, including body mass index (BMI), age, and tumor subtype, remains unclear. Objective: To assess the association of race and ethnicity with survival among clinical trial participants with early-stage BC (eBC) according to tumor subtype, age, and BMI. Design, Setting, and Participants: This cohort study analyzed survival data, as of November 12, 2021, from participants enrolled between 1997 and 2010 in 4 randomized adjuvant chemotherapy trials: Cancer and Leukemia Group B (CALGB) 9741, 49907, and 40101 as well as North Central Cancer Treatment Group (NCCTG) N9831, legacy groups of the Alliance of Clinical Trials in Oncology. Median follow-up was 9.8 years. Exposures: Non-Hispanic Black and Hispanic participants were compared with non-Hispanic White participants within subgroups of subtype (hormone receptor positive [HR+]/ERBB2 [formerly HER2] negative [ERBB2-], ERBB2+, and HR-/ERBB2-), age (<50, 50 to <65, and ≥65 years), and BMI (<18.5, 18.5 to <25.0, 25.0 to <30.0, and ≥30.0). Main Outcomes and Measures: Recurrence-free survival (RFS) and overall survival (OS). Results: Of 9479 participants, 436 (4.4%) were Hispanic, 871 (8.8%) non-Hispanic Black, and 7889 (79.5%) non-Hispanic White. The median (range) age was 52 (19.0-89.7) years. Among participants with HR+/ERBB2- tumors, non-Hispanic Black individuals had worse RFS (hazard ratio [HR], 1.49; 95% CI, 1.04-2.12; 5-year RFS, 88.5% vs 93.2%) than non-Hispanic White individuals, although the global test for association of race and ethnicity with RFS was not significant within any tumor subtype. There were no OS differences by race and ethnicity in any subtype. Race and ethnicity were associated with OS in young participants (age <50 years; global P = .008); young non-Hispanic Black participants (HR, 1.34; 95% CI, 1.04-1.71; 5-year OS, 86.6% vs 92.0%) and Hispanic participants (HR, 1.62; 95% CI, 1.16-2.29; 5-year OS, 86.2% vs 92.0%) had worse OS than young non-Hispanic White participants. Race and ethnicity were associated with RFS in participants with BMIs of 25 to less than 30, with non-Hispanic Black participants having worse RFS (HR, 1.81; 95% CI, 1.23-2.68; 5-year RFS, 83.2% vs 87.3%) than non-Hispanic White participants. Conclusions and Relevance: In this cohort study, racial and ethnic survival disparities were identified in patients with eBC receiving standardized initial care, and potentially at-risk subgroups, for whom focused interventions may improve outcomes, were found.
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Neoplasias de la Mama , Humanos , Femenino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios de Cohortes , Mama , EtnicidadRESUMEN
BACKGROUND: The aim of this study is to gather detailed insights from breast cancer (BC) clinicians on how to have patient-centered conversations about weight and weight management with women diagnosed with early BC. A high body mass index (BMI) is a risk factor for female BC, and many women diagnosed with BC experience unhealthy weight gain after their primary treatment. The oncology team has the opportunity to discuss the importance of healthy weight for BC prognosis and survival. METHODS: The sample of community-based BC clinicians included the following: three Black clinicians, three White clinicians, and two clinicians who were neither Black nor White; six females and two males; and six MDs and two physician assistants or nurse practitioners. Semistructured telephone interviews were conducted with these clinicians regarding their experience with and insights into having healthy weight conversations during routine clinic visits. RESULTS: Clinicians noted that weight-related conversations should focus less on BMI and weight loss and more on "healthy behavior." Clinicians looked for cues from their patients as to when they were ready for "healthy weight" counseling, receptive to diet/nutrition counseling and referrals, and ready to attempt behavioral change. Clinicians noted that encouraging physical activity could be especially challenging with patients accustomed to a sedentary lifestyle. CONCLUSIONS: Clinic-based conversations about healthy weight are likely to be most productive for both patients and their treating oncologists during the post-primary treatment phase when patients are most receptive to behavioral change that enhances their prognosis and survival.
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Mantenimiento del Peso Corporal , Neoplasias de la Mama , Atención Dirigida al Paciente , Relaciones Médico-Paciente , Aumento de Peso , Neoplasias de la Mama/fisiopatología , Neoplasias de la Mama/terapia , Atención Dirigida al Paciente/métodos , Índice de Masa Corporal , Humanos , Masculino , Femenino , Entrevistas como Asunto , Señales (Psicología) , Dieta Saludable , Oncólogos , Enfermeras y EnfermerosRESUMEN
Background: Biological aging begins decades before the onset of age-related clinical conditions and is mediated by both cellular senescence and declining adaptive immune function. These processes are functionally related with the rate of senescent cell accumulation dependent upon a balance between induction and immune clearance. We previously showed that biomarkers in these domains can identify patients at-risk of surgery-related adverse events. Here, we describe evidence of clinical relevance in early aging and metabolic phenotypes in a general adult population. Methods: We enrolled a total of 482 participants (ages 25-90) into two prospective, cross-sectional healthy aging cohorts. Expression of biomarkers of adaptive immune function and cellular senescence (SapereX) was measured in CD3+ T cells isolated from peripheral blood. Findings: We established a network of biomarkers of adaptive immune function that correlate with cellular senescence and associate with early aging phenotypes. SapereX immune components associated with a decrease in CD4+ T cells, an increase in cytotoxic CD8+ T cells, and a loss of CD8+ naïve T cells (Pearson correlation 0.3-0.6). These components also associated with a metric of immune resilience, an ability to withstand antigen challenge and inflammation. In contrast, SapereX components were only weakly associated with GlycanAge (Pearson correlation 0.03-0.15) and commonly used DNA methylation clocks (Pearson correlation 0-0.25). Finally, SapereX biomarkers, in particular p16, were associated with chronic inflammation and metabolic dysregulation. Interpretation: Measurement of SapereX biomarkers may capture essential elements of the relationship between cellular senescence and dysregulated adaptive immune function and may provide a benchmark for clinically relevant health decisions.
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PURPOSE: Research studies have demonstrated that comprehensive geriatric assessment (CGA) improves outcomes in older adults with cancer treated with chemotherapy. We compared survival outcomes on older adults with advanced cancer before and after the initiation of a geriatric oncology service (GOS) in a single Japanese cancer center. METHODS: This was a comparative study of two groups of consecutive patients 70 years and older with advanced cancer who were referred to medical oncology for first-line chemotherapy before (controls; n = 151, September 2015-August 2018) and after (GOS; n = 191, September 2018-March 2021) implementation of the GOS. When the treating physician requested a consultation from the GOS, a geriatrician and an oncologist performed CGA and provided recommendations for cancer treatment and geriatric interventions. Time to treatment failure (TTF) and overall survival (OS) were compared between the two groups. RESULTS: The median age for all patients was 75 (range, 70-95) years, and 85% had GI cancers. In the GOS group, 82 patients received the CGA before a treatment decision and oncologic treatment plans were changed in 49 patients (60%). The overall implementation rate of the CGA-based geriatric interventions was 45%. Two hundred and eighty-two patients received chemotherapy (controls; n = 128 and GOS; n = 154), and 60 patients were treated with best supportive care only (controls; n = 23 and GOS; n = 37). Among patients receiving chemotherapy, TTF event rates for the GOS group compared with the control group were 5.7% versus 14% at 30 days (P = .02) and 13% versus 29% at 60 days (P = .001). The GOS group had longer OS than the control group with a hazard ratio of 0.64 (95% CI, 0.44 to 0.93; P = .02). CONCLUSION: In this study, older adults with advanced cancer managed after the implementation of a GOS had improved survival outcomes compared with a historical control of patients.
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Neoplasias , Humanos , Anciano , Anciano de 80 o más Años , Japón/epidemiología , Neoplasias/tratamiento farmacológico , Oncología Médica , Evaluación Geriátrica , Planificación de Atención al PacienteRESUMEN
Previous work from our group and others has shown that patients with breast cancer can generate a T cell response against specific human epidermal growth factor 2 (HER2) epitopes. In addition, preclinical work has shown that this T cell response can be augmented by Ag-directed mAb therapy. This study evaluated the activity and safety of a combination of dendritic cell (DC) vaccination given with mAb and cytotoxic therapy. We performed a phase I/II study using autologous DCs pulsed with two different HER2 peptides given with trastuzumab and vinorelbine to a study cohort of patients with HER2-overexpressing and a second with HER2 nonoverexpressing metastatic breast cancer. Seventeen patients with HER2-overexpressing and seven with nonoverexpressing disease were treated. Treatment was well tolerated, with one patient removed from therapy because of toxicity and no deaths. Forty-six percent of patients had stable disease after therapy, with 4% achieving a partial response and no complete responses. Immune responses were generated in the majority of patients but did not correlate with clinical response. However, in one patient, who has survived >14 y since treatment in the trial, a robust immune response was demonstrated, with 25% of her T cells specific to one of the peptides in the vaccine at the peak of her response. These data suggest that autologous DC vaccination when given with anti-HER2-directed mAb therapy and vinorelbine is safe and can induce immune responses, including significant T cell clonal expansion, in a subset of patients.
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Neoplasias de la Mama , Neoplasias Mamarias Animales , Humanos , Femenino , Animales , Epítopos/metabolismo , Vinorelbina/metabolismo , Vinorelbina/uso terapéutico , Receptor ErbB-2 , Neoplasias de la Mama/metabolismo , Inmunoterapia , Péptidos/metabolismo , Células Dendríticas , Trastuzumab/uso terapéutico , Trastuzumab/metabolismoRESUMEN
BACKGROUND: This study investigates whether high body mass index (BMI) in women diagnosed with early breast cancer (BC) is associated with patient-reported symptom severity during chemotherapy. METHODS: Women with Stage I-III BC completed toxicity reports for 17 side effects throughout regularly scheduled chemotherapy infusions. Toxicity reports were compared in women with obesity (BMI > = 30) versus no obesity (BMI < 30). Fisher's exact tests and 2-sample t-tests compared baseline patient characteristics. Risk ratios (RR) for women with obesity as compared to no obesity were estimated for individual symptoms that were patient-rated as moderate, severe or very severe (MSVS) severity, adjusting for marital status and race. RESULTS: In a sample of 286 patients, Black women comprised 23% of the sample. The obesity rate was 76% among Black patients and 31% among White patients (p < .0001). Women with obesity rated an average of 6.9 side effects (standard deviation, SD 4.2) as MSVS vs 5.5 side effects (SD 3.7) among women with no obesity (p = .003). In adjusted analysis, women with obesity had significantly greater risk for MSVS fatigue (RR 1.18, 95% CI 1.01-1.36), dyspnea (RR 1.71, 95% CI 1.09-2.69), arthralgia (RR 1.47, 95% CI 1.10-1.97), peripheral neuropathy (RR 1.45, 95% CI 1.01-2.08), edema of limbs (RR 1.84, 95% CI 1.18-2.88), and abdominal pain (RR 1.75, 95% CI 1.07-2.87). There were no inter-group differences in BC stage or phenotype, chemotherapy treatment modifications, or hospitalizations. CONCLUSIONS: Among women with early BC, patients with obesity reported higher chemotherapy toxicity as compared to patients without obesity; however, this did not result in differences in treatment completion.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias , Femenino , Humanos , Masculino , Índice de Masa Corporal , Calidad de Vida , Quimioterapia Adyuvante , Obesidad , Medición de Resultados Informados por el PacienteRESUMEN
BACKGROUND: Chemotoxicity risk scores were developed to predict grade 3-5 chemotherapy toxicity in older women with early breast cancer. However, whether these toxicity risk scores are associated with clinically meaningful decline in patient health remains unknown. METHODS: In a prospective study of women aged 65 years and older with stage I-III breast cancer treated with chemotherapy, we assessed chemotoxicity risk using the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score (categorized as low, intermediate, and high). We measured patient health status before (T1) and after (T2) chemotherapy using a clinical frailty index (Deficit Accumulation Index, categorized as robust, prefrail, and frail). The population of interest was robust women at T1. The primary outcome was decline in health status after chemotherapy, defined as a decline in Deficit Accumulation Index from robust at T1 to prefrail or frail at T2. Multivariable logistic regression was used to examine the association between T1 CARG-BC score and decline in health status, adjusted for sociodemographic and clinical characteristics. RESULTS: Of the 348 robust women at T1, 83 (24%) experienced declining health status after chemotherapy, of whom 63% had intermediate or high CARG-BC scores. After adjusting for sociodemographic and clinical characteristics, women with intermediate (odds ratio = 3.14, 95% confidence interval = 1.60 to 6.14, P < .001) or high (odds ratio = 3.80, 95% confidence interval = 1.35 to 10.67, P = .01) CARG-BC scores had greater odds of decline in health status compared with women with low scores. CONCLUSIONS: In this cohort of older women with early breast cancer, higher CARG-BC scores before chemotherapy were associated with decline in health status after chemotherapy independent of sociodemographic and clinical risk factors.
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Neoplasias de la Mama , Supervivientes de Cáncer , Humanos , Femenino , Anciano , Neoplasias de la Mama/epidemiología , Estudios Prospectivos , Factores de Riesgo , Quimioterapia Adyuvante/efectos adversosRESUMEN
INTRODUCTION: Older patients with cancer often require acute care treatment through emergency department (ED) visits and hospitalizations. This study investigates acute care utilization through ED visits and hospitalizations during treatment and in the two years following the completion of primary treatment for early stage breast cancer (EBC) in women aged 65 and older. MATERIALS AND METHODS: A retrospective analysis including descriptive statistics, univariate analysis, and relative risk analysis of 256 women with EBC was performed through medical record review of demographics, comorbidities, disease characteristics, treatment details, and causes of hospitalizations and ED visits. RESULTS: Both hospitalizations and ED visits were significantly more frequent for patients in the post-primary treatment period compared to during treatment (hospitalizations: 22% post-primary treatment vs 13% during treatment, 95% confidence interval [CI] of true difference = 2.5%-15.5; ED visits: 21% post-primary treatment vs 10% during treatment, 95% CI of true difference = 4.8%-17.2%). Both hospitalizations (79% versus 32%, 95% CI of true difference = 28.7%-65.3%) and ED visits (42% versus 12%, 95% CI of true difference = 9.1%-50.9%) were more often breast cancer related during primary treatment compared to following treatment. Following treatment, EBC related hospitalizations were most often for disease progression (42%) and EBC related ED visits were most often for post-systemic therapy complications (43%). Significant predictors for EBC related hospitalizations in the two years following treatment included stage III disease (relative risk [RR] = 8.77, 95% CI = 2.50-30.82), having underwent mastectomy (RR = 12.51, 95% CI = 2.91-53.78), and having received chemotherapy (RR = 3.95, 95% CI = 1.18-13.23). However, chemotherapy does not appear to be a significant predictor for hospitalization when controlling for stage III disease (RR = 2.22, 95% CI = 0.61-8.05), whereas stage III disease remains a significant risk factor when controlling for chemotherapy (RR = 6.09, 95% CI = 1.58-23.52). DISCUSSION: Our findings suggests that stage III disease, undergoing mastectomy, and chemotherapy treatment predict higher likelihood of EBC related hospitalization following primary treatment in older EBC patients, with stage III disease likely the strongest risk factor.
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Neoplasias de la Mama , Humanos , Femenino , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Estudios Retrospectivos , Mastectomía , Hospitalización , Servicio de Urgencia en HospitalRESUMEN
BACKGROUND: Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. METHODS: Patients with stage I-III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. RESULTS: Of 126 patients approached, 56 (44%) enrolled. Forty-five (80%) received ≥1 dose of memantine and completed pre-post assessments. Seventy-six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty-four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%-91% across objective cognitive domain composite measures. Sixty-six percent self-reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. CONCLUSIONS: Memantine was well-tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre- to post-assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT04033419.
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Neoplasias de la Mama , Disfunción Cognitiva , Humanos , Persona de Mediana Edad , Femenino , Memantina/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Factibilidad , CogniciónRESUMEN
PURPOSE: Older women with high-risk early breast cancer (EBC) benefit from adjuvant chemotherapy, but their treatment is frequently complicated by toxic side effects, resulting in dose reductions and delays. This makes it challenging for oncologists to maintain a relative dose intensity (RDI) ≥ 85%, as recommended for optimal curative-intent treatment. Understanding which women are at risk of receiving suboptimal RDI may inform treatment discussions and guide early, targeted supportive care or geriatric comanagement interventions. METHODS: This was a prespecified secondary analysis of the HOPE trial, which enrolled women age ≥ 65 years with EBC initiating neoadjuvant or adjuvant chemotherapy. RDI was calculated as the ratio of delivered to planned chemotherapy dose intensity. The primary outcome was low RDI, defined as RDI < 85%. Multivariable logistic regression with stepwise selection was used to evaluate the association between baseline variables (demographic, clinical, and geriatric assessment) and low RDI. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used to compare overall survival. RESULTS: Three hundred twenty-two patients (median age at diagnosis, 70 years; range, 65-86 years) were included. The median follow-up was 4 years. Sixty-six patients (21%) had a low RDI. Age ≥ 76 years (odds ratio [OR], 2.57; 95% CI, 1.12 to 5.91; P = .03), lower performance status (OR, 4.32; 95% CI, 1.98 to 9.42; P < .001), and use of anthracycline-based or cyclophosphamide, methotrexate, and fluorouracil regimens (OR, 3.47; 95% CI, 1.71 to 7.05; P < .001) were associated with low RDI. The 5-year overall survival probability was 0.80 versus 0.91 in patients with RDI < 85 versus ≥ 85%, respectively (log-rank P = .02). CONCLUSION: One in five older patients with EBC treated with standard chemotherapy received low RDI and had inferior survival outcomes. Older patients at risk for low RDI should be identified and targeted upfront before initiating chemotherapy.
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Neoplasias de la Mama , Humanos , Femenino , Anciano , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida , Quimioterapia Adyuvante/métodos , Estudios RetrospectivosRESUMEN
PURPOSE: Residents of communities facing social vulnerability (eg, poverty) have limited access to clinical trials, leaving them susceptible to experiencing poor health outcomes. We examined the association between North Carolina county-level social vulnerability and available multiple myeloma (MM) trials. METHODS: Using a novel data linkage between ClinicalTrials.gov, the 2019 American Community Survey, and the Centers for Disease Control and Prevention's Social Vulnerability Index, we investigated at the county level (1) availability of MM trial sites and (2) the relationship between Social Vulnerability Index and MM trial site availability using logistic regression. RESULTS: Between 2002 and 2021, 229 trials were registered across 462 nonunique trial sites in 34 counties. Nearly 50% of trial sites were in academic medical centers, 80% (n = 372) of all trials were industry-sponsored, 60% (n = 274) were early-phase, and 50% (n = 232) were for patients with relapsed or refractory MM. Counties with low as opposed to high poverty rates had six times greater odds of having ≥ 1 MM trial sites (odds ratio [OR], 5.60; 95% CI, 1.85 to 19.64; P = .004). Counties with the lowest percentage of Black Indigenous Persons of Color and non-native English speakers had 77% lower odds (OR, 0.23; 95% CI, 0.07 to 0.69; P = .011) of having ≥ 1 trial sites. The effect remained significant after accounting for the presence of five academic medical centers (n = 95; OR, 0.18; 95% CI, 0.05 to 0.6; P = .008) and adjustment for metropolitan, suburban, or rural status (OR, 0.25; 95% CI, 0.07 to 0.81; P = .025). CONCLUSION: Counties with the lowest poverty rates had more MM trial sites, whereas those with the lowest percentage of Black Indigenous Persons of Color populations had fewer MM trial sites. Multilevel efforts are needed to improve the availability and access to trials for socially vulnerable populations.
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Población Rural , Vulnerabilidad Social , Humanos , North Carolina/epidemiología , Estudios Transversales , Características de la ResidenciaRESUMEN
BACKGROUND: In this study, we explore recruitment, retention, and potential quality of life (QoL) and function benefits from a self-directed, home-based walking intervention in women during active treatment for metastatic breast cancer (MBC). METHODS: In this single-arm pilot study, women with stage IV BC wore an activity tracker (FitbitTM) to measure steps per week throughout the intervention study. Participants were asked to walk 150 min per week at a comfortable and safe pace. Patient-reported outcome measures (PRO) were collected at baseline and follow-up. RESULTS: Target recruitment of 60 patients was achieved. In 52 patients who completed all baseline measures, mean age was 55 (SD 11.1), 23% were pre-menopausal, and 19% non-White. Forty patients (77%) were retained at 3 months and 29 (56%) at 6 months. Baseline walking was the strongest predictor of retention at 3 months (P = .02). For 24 patients (46%) with analyzable Fitbit data at 3 months, mean steps/week rose from 19,175 to 31,306. Higher number of steps correlated with larger improvements FACT-G General well-being (FACT-G, rho = 0.55, P = .01), FACT-G Physical well-being (rho = 0.48, P = .03), and PROMIS Mental Health (rho = 0.55, P = .01). CONCLUSION: Recruitment into a walking intervention is feasible (a priory target of N = 60) in women during treatment for MBC, but retention at 3 months follow-up fell short (77% versus a priori 80%), yet there were potential benefits in general and physical well-being and mental health. CLINICALTRIALS.GOV IDENTIFIER: NCT02682836.