Skeletal muscle loss, commonly known as sarcopenia, is highly prevalent and prognostic of adverse outcomes in oncology. However, there is limited information on adults with early breast cancer and ...examination of other skeletal muscle indices, despite the potential prognostic importance. This study characterizes and examines age‐related changes in body composition of adults with early breast cancer and describes the creation of a novel integrated muscle measure. Female patients diagnosed with stage I‐III breast cancer with abdominal computerized tomography (CT) scans within 12 weeks from diagnosis were identified from local tumor registry (N = 241). Skeletal muscle index (muscle area per height cm2/m2), skeletal muscle density, and subcutaneous and visceral adipose tissue areas, were determined from CT L3 lumbar segments. We calculated a novel integrated skeletal measure, skeletal muscle gauge, which combines skeletal muscle index and density (SMI × SMD). 241 patients were identified with available CT imaging. Median age 52 years and range of 23‐87. Skeletal muscle index and density significantly decreased with age. Using literature based cut‐points, older adults (≥65 years) had significantly higher proportions of sarcopenia (63 vs 28%) and myosteatosis (90 vs 11%) compared to younger adults (<50 years). Body mass index was positively correlated with skeletal muscle index and negatively correlated with muscle density. Skeletal muscle gauge correlated better with increasing age (ρ = 0.52) than with either skeletal muscle index (ρ = 0.20) or density (ρ = 0.46). Wide variations and age‐related changes in body composition metrics were found using routinely obtained abdominal CT imaging. Skeletal muscle index and density provide independent, complementary information, and the product of the two metrics, skeletal muscle gauge, requires further research to explore its impact on outcomes in women with curable breast cancer.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Biomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)-positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ...ER-positive, lymph node-negative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole.
A prospective-retrospective, nested case-control design of 83 recurrences matched to 166 nonrecurrences from letrozole- and placebo-treated patients within MA.17 was conducted. Expression of H/I within primary tumors was determined by reverse-transcription polymerase chain reaction with a prespecified cutpoint. The predictive ability of H/I for ascertaining benefit from letrozole was determined using multivariable conditional logistic regression including standard clinicopathological factors as covariates. All statistical tests were two-sided.
High H/I was statistically significantly associated with a decrease in late recurrence in patients receiving extended letrozole therapy (odds ratio OR = 0.35; 95% confidence interval CI = 0.16 to 0.75; P = .007). In an adjusted model with standard clinicopathological factors, high H/I remained statistically significantly associated with patient benefit from letrozole (OR = 0.33; 95% CI = 0.15 to 0.73; P = .006). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with high H/I (P = .007). The interaction between H/I and letrozole treatment was statistically significant (P = .03).
In the absence of extended letrozole therapy, high H/I identifies a subgroup of ER-positive patients disease-free after 5 years of tamoxifen who are at risk for late recurrence. When extended endocrine therapy with letrozole is prescribed, high H/I predicts benefit from therapy and a decreased probability of late disease recurrence.
Background
Cellular senescence, measured by expression of the cell cycle kinase inhibitor p16INK4a, may contribute to accelerated aging in survivors of childhood, adolescent, and young adult cancer. ...The authors measured peripheral blood T‐lymphocyte p16INK4a expression among pediatric and young adult cancer survivors, hypothesizing that p16INK4a expression is higher after chemotherapy and among frail survivors.
Methods
A cross‐sectional cohort of young adult survivors and age‐matched, cancer‐free controls were assessed for p16INK4a expression and frailty. Newly diagnosed pediatric patients underwent prospective measurements of p16INK4a expression before and after cancer therapy. Frailty was measured with a modified Fried frailty phenotype evaluating sarcopenia, weakness, slowness, energy expenditure, and exhaustion.
Results
The cross‐sectional cohort enrolled 60 survivors and 29 age‐matched controls with a median age of 21 years (range, 17‐29 years). The prospective cohort enrolled 9 newly diagnosed patients (age range, 1‐18 years). Expression of p16INK4a was higher among survivors compared with controls (9.6 vs 8.9 log2 p16 units; 2‐sided P = .005, representing a 25‐year age acceleration in survivors) and increased among newly diagnosed patients from matched pretreatment to posttreatment samples (7.3‐8.9 log2 p16 units; 2‐sided P = .002). Nine survivors (16%) were frail and had higher p16INK4a expression compared with robust survivors (10.5 frail vs 9.5 robust log2 p16 units; 2‐sided P = .055), representing a 35‐year age acceleration among frail survivors.
Conclusions
Chemotherapy is associated with increased cellular senescence and molecular age in pediatric and young adult cancer survivors. Frail survivors, compared with robust survivors, exhibit higher levels of p16INK4a, suggesting that cellular senescence may be associated with early aging in survivors.
The expression of p16INK4a, a biomarker of cellular aging and senescence, increases among childhood, adolescent, and young adult cancer survivors after chemotherapy and is higher among frail survivors, indicating advanced cellular aging related to cancer treatment.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
This study explores the incidence of patient‐reported major toxicity—symptoms rated “moderate,” “severe,” or “very severe”—for chemotherapy regimens commonly used in early breast cancer.
...Patients and Methods
Female patients aged 21 years or older completed a validated Patient‐Reported Symptom Monitoring instrument and rated 17 symptoms throughout adjuvant or neoadjuvant chemotherapy. Fisher's exact tests compared differences in percentages in symptom ratings, and general linear regression was used to model the incidence of patient‐reported major toxicity.
Results
In 152 patients, the mean age was 54 years (range, 24–77), and 112 (74%) were white; 51% received an anthracycline‐based regimen. The proportion of patients rating fatigue, constipation, myalgia, diarrhea, nausea, peripheral neuropathy, and swelling of arms or legs as a major toxicity at any time during chemotherapy varied significantly among four chemotherapy regimens (p < .05). The mean (SD) number of symptoms rated major toxicities was 6.3 (3.6) for anthracycline‐based and 4.4 (3.5) for non‐anthracycline‐based regimens (p = .001; possible range, 0–17 symptoms). Baseline higher body mass index (p = .03), patient‐reported Karnofsky performance status ≤80 (p = .0003), and anthracycline‐based regimens (p = .0003) were associated with greater total number of symptoms rated major toxicities (alternative model: chemotherapy duration, p < .0001). Twenty‐six percent of dose reductions (26 of 40), 75% of hospitalizations (15 of 20), and 94% of treatment discontinuations (15 of 16) were in anthracycline‐based regimens.
Conclusion
Capturing multiple toxicity outcomes throughout chemotherapy enables oncologists and patients to understand the range of side effects as they discuss treatment efficacies. Continuous symptom monitoring may aid in the timely development of interventions that minimize toxicity and improve outcomes.
Implications for Practice
This study investigated patient‐reported toxicities for 17 symptoms recorded prospectively during adjuvant and neoadjuvant chemotherapy regimens for early breast cancer. An analysis of four commonly used chemotherapy regimens identified significant differences among regimens in both individual symptoms and total number of symptoms rated moderate, severe, or very severe. Longer chemotherapy regimens, such as anthracycline‐based regimens followed by paclitaxel, had higher proportions of symptoms rated major toxicities. The inclusion of patient perspectives on multiple toxicity outcomes at the same time at multiple time points during chemotherapy has the potential for improving patient‐provider communication regarding symptom management, patient satisfaction, and long‐term clinical outcomes.
摘要
背景。本研究探索了在常用于治疗早期乳腺癌的化疗方案中患者报告的主要毒性(即被评为“中度”、“重度”或“极重度”的症状)的发生率。
患者和方法。年满 21 岁或以上的女性患者填写一份经验证的患者报告的症状监测文件并对辅助或新辅助化疗期间的 17 个症状进行评级。Fisher's精确检验对症状评级百分比之间的差异进行比较，一般线性回归用于模拟患者报告的主要毒性的发生率。
结果。在 152 名患者中，平均年龄为 54 岁(范围介于 24–77 岁之间)，112 名患者 (74%) 为白种人；51% 的患者接受蒽环类方案治疗。在化疗期间的任何时间将疲劳、便秘、肌痛、腹泻、恶心、周围神经病变以及手臂或腿部肿胀评为主要毒性的患者的比例在 4 个化疗方案中显著不同 (p < 0.05)。在蒽环类方案和非蒽环类方案中，被评为主要毒性的症状的平均数 (SD) 分别为 6.3 (3.6) 和 4.4 (3.5)(p = 0.001；可能的范围，0–17 个症状)。基线较高的体质量指数 (p = 0.03)、患者报告的 Karnofsky 体力状态 ≤80 (p = 0.000 3) 以及蒽环类方案 (p = 0.000 3) 与被评为主要毒性的症状的总数较高相关(替代模式:化疗持续时间，p < 0.000 1)。在蒽环类方案中，剂量减少占 26%(40 名患者中的 26 名患者)，住院治疗占 75%(20 名患者中的 15 名患者)，治疗中断占 94%(16 名患者中的 15 名患者)。
结论。获取化疗过程中的多种毒性结果，可令肿瘤学家和患者在讨论治疗有效性时了解副作用的范围。持续的症状监测可能有助于及时地制定可以最大限度地减少毒性并改进预后的干预措施。
《肿瘤学家》
实践意义:本研究调查了患者报告的早期乳腺癌辅助和新辅助化疗方案中前瞻性记录的 17 个症状的毒性。针对 4 个常用化疗方案的分析在单项症状和被评为“中度”、“重度”或“极重度”的症状的总数方面确定了方案之间的显著差异。在较长的化疗方案中，如后续采用紫杉醇治疗的蒽环类方案，被评为主要毒性的症状占有较高的比例。同时，在化疗期间的多个时间点加入患者关于多种毒性结果的看法，这可能会改进患者和医疗服务提供者之间有关症状管理、患者满意度以及长期临床预后的沟通。
This article focuses on the incidence of patient‐reported major toxicity for chemotherapy regimens commonly used in breast cancer, especially considering the need for patient‐centered assessments of treatment tolerability as an important complement to the NCI's CTCAE.
Senescent cells, which express p16 (INK4a) , accumulate with aging and contribute to age-related pathology. To understand whether cytotoxic agents promote molecular aging, we measured expression of ...p16 (INK4a) and other senescence markers in breast cancer patients treated with adjuvant chemotherapy.
Blood and clinical information were prospectively obtained from 33 women with stage I to III breast cancer at four time points: before anthracycline-based chemotherapy, immediately after anthracycline-based chemotherapy, 3 months after anthracycline-based chemotherapy, and 12 months after anthracycline-based chemotherapy. Expression of senescence markers p16 (INK4a) and ARF mRNA was determined using TaqMan quantitative reverse-transcription polymerase chain reaction in CD3(+) T lymphocytes, telomere length was determined by Southern analysis, and senescence-associated cytokines were determined by enzyme-linked immunosorbent assay. Findings were independently assessed in a cross-sectional cohort of 176 breast cancer survivors enrolled a median of 3.4 years after treatment; 39% previously received chemotherapy. All statistical tests were two-sided.
In prospectively analyzed patients, expression of p16 (INK4a) and ARF increased immediately after chemotherapy and remained elevated 12 months after treatment. Median increase in log2 p16 (INK4a) was 0.81 (interquartile range = 0.28-1.62; Wilcoxon signed-rank P < .001), or a 75% absolute increase in expression, equivalent to the increase observed over 14.7 years of chronological aging. ARF expression was comparably increased (P < .001). Increased expression of p16 (INK4a) and ARF was associated with dose-dense therapy and hematological toxicity. Expression of two senescence-associated cytokines (VEGFA and MCP1) was durably increased by adjuvant chemotherapy. Telomere length was not affected by chemotherapy. In a cross-sectional cohort, prior chemotherapy exposure was independently associated with a log2-increase in p16 (INK4a) expression of 0.57 (repeated measures model, P < .001), comparable with 10.4 years of chronological aging.
Adjuvant chemotherapy for breast cancer is gerontogenic, inducing cellular senescence in vivo, thereby accelerating molecular aging of hematopoietic tissues.
Purpose.
Breast cancer (BC) is a disease of aging and the number of older BC patients in the U.S. is rising. Immunohistochemical data show that with increasing age, the incidence of hormone ...receptor‐positive tumors increases, whereas the incidence of triple‐negative tumors decreases. Few data exist on the frequency of molecular subtypes in older women. Here, we characterize the incidence and outcomes of BC patients by molecular subtypes and age.
Patients and Methods.
Data from 3,947 patients were pooled from publicly available clinical and gene expression microarray data sets. The PAM50 algorithm was used to classify tumors into five BC intrinsic subtypes: luminal A, luminal B, HER2‐enriched, basal‐like, and normal‐like. The association of age and subtype with recurrence‐free survival (RFS), overall survival, and disease‐specific survival (DSS) was assessed.
Results.
The incidence of luminal (A, B, and A+B) tumors increased with age (p < .01, p < .0001, and p < .0001, respectively), whereas the percentage of basal‐like tumors decreased (p < .0001). Among patients 70 years and older, luminal B, HER2‐enriched, and basal‐like tumors were found at a frequency of 32%, 11%, and 9%, respectively. In older women, luminal subtypes had better outcomes than basal‐like and HER2‐enriched subtypes. After controlling for subtype, treatment, tumor size, nodal status, and grade, increasing age had no impact on RFS or DSS.
Conclusion.
More favorable BC subtypes increase with age, but older patients still have a substantial percentage of high‐risk tumor subtypes. After accounting for tumor subtypes, age at diagnosis is not an independent prognostic factor for outcome.
The PAM50 algorithm was used to analyze data from publicly available clinical and gene expression microarray data sets. The association of age and tumor subtype with survival was assessed. More favorable breast cancer subtypes increase with age, but older patients still have a substantial percentage of high‐risk tumor subtypes. After controlling for subtype, treatment, tumor size, nodal status, and grade, increasing age had no impact on survival.
Background
Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and ...undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single‐item reports.
Materials and Methods
Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log‐binomial regression. Cohen's kappa was used to assess agreement between patient‐ and clinician‐reported symptoms.
Results
In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient‐provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk RR, 2.17; 95% confidence interval CI, 1.36–3.45) and anxiety (RR, 1.48; 95% CI, 1.05–2.09).
Conclusion
Oncologists frequently underestimate patients’ depression and anxiety and should consider incorporating patient‐reported outcomes to enhance monitoring of mental health symptoms.
Implications for Practice
In this sample of 256 patients with breast cancer, depression and anxiety, measured using single‐item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient‐reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients’ mental health symptoms. The use of patient‐reported, single‐item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients’ psychological health.
Depression and anxiety are underrecognized and undermanaged in oncology practice. This article describes the severity of depression and anxiety and associated factors in women with early breast cancer undergoing chemotherapy.
An objective measure is needed to identify frail older adults with cancer who are at increased risk for poor health outcomes. The primary objective of this study was to develop a frailty index from a ...cancer-specific geriatric assessment (GA) and evaluate its ability to predict all-cause mortality among older adults with cancer.
Using a unique and novel data set that brings together GA data with cancer-specific and long-term mortality data, we developed the Carolina Frailty Index (CFI) from a cancer-specific GA based on the principles of deficit accumulation. CFI scores (range, 0-1) were categorized as robust (0-0.2), pre-frail (0.2-0.35), and frail (>0.35). The primary outcome for evaluating predictive validity was all-cause mortality. The Kaplan-Meier method and log-rank tests were used to compare survival between frailty groups, and Cox proportional hazards regression models were used to evaluate associations.
In our sample of 546 older adults with cancer, the median age was 72 years, 72% were women, 85% were white, and 47% had a breast cancer diagnosis. Overall, 58% of patients were robust, 24% were pre-frail, and 18% were frail. The estimated 5-year survival rate was 72% in robust patients, 58% in pre-frail patients, and 34% in frail patients (log-rank test,
<.0001). Frail patients had more than a 2-fold increased risk of all-cause mortality compared with robust patients (adjusted hazard ratio, 2.36; 95% CI, 1.51-3.68).
The CFI was predictive of all-cause mortality in older adults with cancer, a finding that was independent of age, sex, cancer type and stage, and number of medical comorbidities. The CFI has the potential to become a tool that oncologists can use to objectively identify frailty in older adults with cancer.
To update the 1999 American Society of Clinical Oncology (ASCO) guideline on breast cancer follow-up and management in the adjuvant setting.
An ASCO Expert Panel reviewed pertinent information from ...the literature through March 2006. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design.
The evidence supports regular history, physical examination, and mammography as the cornerstone of appropriate breast cancer follow-up. All patients should have a careful history and physical examination performed by a physician experienced in the surveillance of cancer patients and in breast examination. Examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For those who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. Patients at high risk for familial breast cancer syndromes should be referred for genetic counseling. The use of CBCs, chemistry panels, bone scans, chest radiographs, liver ultrasounds, computed tomography scans, 18Ffluorodeoxyglucose-positron emission tomography scanning, magnetic resonance imaging, or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine breast cancer follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination.
Careful history taking, physical examination, and regular mammography are recommended for appropriate detection of breast cancer recurrence.
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