Kirsten A. Nyrop

Background: Age, race, body mass index (BMI), breast density, parity, smoking and alcohol use are associated with increased risk for breast cancer. These factors, as well as tumor characteristics, treatment regimens and comorbidities, are analyzed for associations with five-year event free survival (EFS) in a sample of women with Stage I-III breast cancer who received chemotherapy with curative intent. Methods: EFS was defined in terms of breast cancer recurrence, second primary, metastasis, and overall survival. Analyses were stratified by age (under age 65 vs. over age 65). EFS was estimated using the Kaplan–Meier method and compared using a Cox proportional hazard model. Results: In a sample of 821 women, mean age at diagnosis was 54 years, with 75% White and 22% Black. Younger women had higher proportions of Stage II and III tumors (p = 0.005), larger tumor size (p = 0.0004), and higher breast density (p = 0.003). Five-year EFS was 91% among younger vs. 82% among older women (p = 0.0005). In women aged < 65, there were 48 EFS events, and triple negative patients had significantly worse EFS compared to other subtypes (p = 0.003). Smokers also had worse EFS (p = 0.04). In women aged ≥ 65, there were 26 events, and both tumor size (p = 0.02) and mastectomy (p = 0.03) were significant for EFS. Conclusions: In our sample, triple negative subtype, smoking history, tumor size, and surgery type were significantly associated with shorter EFS. Race, BMI, alcohol use, parity, breast density, radiation treatment, and specific chemotherapy regimen were not significant for EFS in either age group.

Background: p16 ^INK4a ( p16 ), a robust marker of cell senescence, rises rapidly and dramatically after adjuvant chemotherapy for breast cancer. We measured p16 in peripheral blood T cells of 119 women with stage I–III breast cancer, 75 with previous adjuvant chemotherapy and 44 randomly selected women who had never received chemotherapy. p16 was measured at least 3 years (mean, 6 years) following diagnosis. Aims: This study aims to assess the expression of p16 after long‐term follow‐up and define the trajectory of the p16 increase in a subset of patients with baseline, 6‐month post‐chemotherapy, and long‐term follow‐up data. Methods and Results: All patients were treated in accordance with national guidelines, and 53% of the chemotherapy‐treated patients received anthracycline regimens. After a mean follow‐up of 6 years from the end of treatment, chemotherapy‐treated patients demonstrated p16 levels corresponding to approximate age‐equivalent increase of ∼14 years compared to 2.1 years in non‐chemotherapy‐treated patients. When compared to community‐dwelling adults, p16 expression increased markedly at 6 months post‐chemotherapy, particularly among anthracycline‐treated patients (corresponding to larger age‐equivalent deviation: median 21.5 years vs. median 15.4 years). At long‐term follow‐up, both anthracycline and non‐anthracycline‐treated patients showed elevated but converging p16 levels (age‐equivalent median of 18.1 years vs. median 17.2 years), indicating an improvement in p16 levels over time in anthracycline‐treated patients. Age‐equivalent values are reported as an interpretive aid derived from population‐level p16 –age relationship and are not intended to represent literal biological age or clock‐based aging. Conclusion: Early breast cancer patients treated with chemotherapy exhibited a marked increase in p16 expression shortly after treatment completion that persists for years after treatment. The long‐term impact of these changes remains uncertain but raises the possibility that chemotherapy‐related cellular senescence could contribute to an increased risk of age‐related comorbidities over time.

Background: Many patients with breast cancer report cognitive impairment for several years after treatment. The objective of this study was to describe associations between neurobehavioral symptoms experienced during chemotherapy for early‐stage breast cancer and patient‐reported cancer‐related cognitive impairment (CRCI) ≥ 3 years post‐chemotherapy. Methods: This study is a secondary analysis of women with stage I‐III breast cancer who had enrolled in clinical trials promoting self‐directed walking during chemotherapy and were re‐consented for a study focused on quality‐of‐life outcomes ≥ 3 years post‐chemotherapy. Patient‐reported CRCI was assessed using the FACT‐Cog PCI (cut point for impairment < 54). Multivariable log‐binomial regression models, adjusting for age, race, and education, examined associations between long‐term CRCI and baseline demographic characteristics, cancer diagnosis and treatment, and patient‐reported neurobehavioral symptoms during chemotherapy and at long‐term follow‐up. Results: Among 104 participants, 39% reported CRCI at long‐term follow‐up, on average 6 years post‐chemotherapy [range: 2.9–8.8]. CRCI was more common among those reporting moderate or worse depressive (RR 1.75, 95% CI 1.11–2.75, p = 0.02), anxiety (RR 1.95, 95% CI 1.22–3.11, p = 0.005), or fatigue (RR 1.92, 95% CI 1.09–3.36, p = 0.02) symptoms during chemotherapy. In sensitivity analyses limited to patients with none or mild symptoms prior to chemotherapy, depressive (RR 2.11, 95% CI 1.23–3.63, p = 0.007) and fatigue (RR 1.81, 95% CI 1.81, 95% CI 1.01–3.24, p = 0.05) symptoms emerging during chemotherapy were also associated with CRCI at follow‐up. Conclusions: Patient‐reported neurobehavioral symptoms experienced during chemotherapy, including depression, anxiety, and fatigue, were associated with patient‐reported CRCI years after primary treatment and should be monitored for timely intervention opportunities.

Background: The Institute of Medicine (IOM) recommends that essential aspects of a patient’s sociodemographic, psychological, and behavioral characteristics be documented in the electronic health record (EMR). Patients and Methods: For this study of women receiving chemotherapy for early breast cancer (Stages I-III), EMR clinician notes were queried with regard to documentation of the patient’s current (1) living situation, (2) caregiver responsibilities, and (3) accompaniment during chemotherapy. Descriptive statistics for patient sociodemographic and tumor characteristics, and clinician-reported social circumstances were reported for older and younger patients and compared between two age groups using Fisher’s exact tests for categorical variables and t-tests for continuous variables. Results: The sample includes 104 women aged 65 or older (range 65-83; 17% Black) and 250 under age 65 (range 23-64; 22% Black). Mean number of comorbidities was 3.7 (range 0-8) among older patients and 1.7 (range 0-9) among younger patients (P < .0001). There were no significant inter-group differences in breast cancer stage or phenotype. Clinician notes affirmatively documented that the patient was living with someone (70% older/85% younger; P = .002), the patient had caregiver responsibilities (12% older/44% younger; P < .0001) and was accompanied by someone during chemotherapy (79% older/89% younger; P = .02). Conclusion: Clinician notes pertaining to younger patients as compared to older patients more often provided affirmative and specific documentation that the patient was living with someone, a caregiver for someone, and accompanied by someone during the chemotherapy infusion visit. These three factors are important to document and monitor in patients of all ages as they can impact treatment experience and quality of life during and after chemotherapy.

Background As patient-reported symptoms are increasingly incorporated into routine clinical practice and captured in electronic medical records these data can be used to conduct health-related quality of life research studies. This study compares symptom reports from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and its precursor patient reported symptom monitoring (PRSM) (hereafter PRSM/PRO-CTCAE) with multi-item patient-reported outcome (PRO) scales for fatigue (Functional Assessment of Chronic Illness Therapy/FACIT-Fatigue) and depression and anxiety (Mental Health Index/MHI). Methods This is a secondary analysis of data collected from women with early breast cancer (Stage I-III) scheduled for chemotherapy who completed PRSM/PRO-CTCAE, FACIT-Fatigue, and MHI scales pre- and post-chemotherapy. Spearman correlation coefficients estimated the magnitude and direction of correlations between measures (convergent validity). For each symptom, patients were then categorized based on who improved, stayed the same, or worsened on the composite PRSM/PRO-CTCAE score, and changes in scores on the PRO scales were compared. Results In a sample of 374 women, mean age was 57 years (SD 12.6) with 76% White. PRSM/PRO-CTCAE fatigue measures were strongly correlated with FACIT-Fatigue total scale and had mixed moderate to strong correlation for individual items within the FACIT-Fatigue scale. PRSM/PRO-CTCAE Sad and Anxiety measures were strongly correlated with MHI-Depression and MHI-Anxiety total scales, respectively, and had mixed moderate to strong correlation with individual items within the MHI subscales. PRSM/PRO-CTCAE pre-post changes in symptom scores mirrored pre-post changes in FACIT-Fatigue and MHI subscales.

In a convenience sample of women scheduled for chemotherapy for early-stage breast cancer, we investigated associations of the Center for Disease Control and Prevention’s neighborhood-level social vulnerability index (SVI) with pretreatment demographics and patient-reported outcome (PRO) measures (health behavior, function and quality of life, treatment toxicities during chemotherapy). The SVI Overall score is comprised of 4 themes: socioeconomic, household composition, minority status/language, and household type/transportation, with scores ranging from 0 = lowest to 1 = highest vulnerability neighborhoods. Participant SVI scores were derived from zip codes listed in the patient’s address within the electronic medical record (EMR). Associations of study variables with SVI were evaluated using Spearman correlation for continuous variables and Kruskal–Wallis tests for categorical variables. In a sample of 309 women, the mean age was 56 years (range 23-83) and 75% White. Greater vulnerability SVI Overall score was associated with lower education (P =.02), nonmarriage (P ≤.0001), higher body mass index (P =.03), and prechemotherapy PRO measures such as fewer self-reported walking minutes/week (P ≤.001), history of smoking (P =.02) and alcohol use (P < .001), depression (P =.01), and lower emotional social support (P =.008). During chemotherapy, moderate, severe, or very severe symptoms were associated with greater vulnerability SVI Overall scores for hot flashes (P =.03), arthralgia (P =.02), myalgia (P =.02), peripheral neuropathy (P =.01), edema of limbs (P =.04), and nausea (P <.001). SVI scores derived from addresses in the patient’s EMR can be used to generate information that adds to the patient’s social history in ways that are informative for anticipating and monitoring chemotherapy-related toxicities.

Purpose We developed a self-directed Leg And Walking Self-exercise (LAWS) program informed by the Exercise is Medicine initiative and evaluated the feasibility and acceptability of this program in older adults with cancer. Methods Over a 1-year period, we prospectively enrolled 40 older adults who received a comprehensive geriatric assessment (CGA) at a geriatric oncology service and initiated a new line of systemic therapy for advanced cancer as inpatients. LAWS is a tailored, self-directed exercise program consisting of leg resistance training and walking. Exercise adherence was recorded using an exercise diary to assess feasibility. Patient perspectives on this program were evaluated using the Feasibility of Intervention Measure (FIM) and Acceptability of Intervention Measure (AIM), with a score range of 1–5, higher being better. Results Overall, 28% of patients were fit, 53% pre-frail, and 20% frail based on the CGA. During hospitalization (average 12 days), 63% of the patients adhered to exercises at lowest intensity during more than 50% of their inpatient stay: on average, 2.8 leg exercises, 23 repetitions a day, 5.6 days/week, and 19 min of walking a day, 4.9 days/week. Patients rated their perceived exertion at 3.0 for leg exercise and 3.0 for walking on a 1–10 Likert scale. During the period between discharge and their first outpatient appointment (average 11 days), 71% of patients adhered to the LAWS program. Mean scores of FIM and AIM were 4.2 (SD = 0.5) and 4.2 (SD = 0.7), respectively. Conclusions For older adults undergoing cancer treatment, LAWS is a feasible and acceptable self-directed exercise program.

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.