Second breast cancer: recurrence score results, clinicopathologic characteristics, adjuvant treatments, and outcomes-exploratory analysis of the Clalit registry.

Data on using the 21-gene Recurrence Score (RS) testing on second breast cancer (BC; second primary or local recurrence) are lacking. This cohort study examined patients with first and second BC, who underwent 21-gene testing both times. It included a 'study-cohort' (60 N0/N1mi/N1 ER + HER2‒ BC patients with ≥2 RS results >1 year apart) and a 'general 21-gene-tested BC-cohort' (2044 previously described N0/N1mi/N1 patients). The median time between the first and second BC was 5.2 (IQR, 3.1-7.1) years; the second BC was ipsilateral in 68%. Patient/tumor characteristics of the first- and second-BC in the 'study-cohort' were similar, except for the RS which was higher in the second BC (median [IQR]: 23 [17-30] vs 17 [14-22], p < 0.001). Overall, 56 patients had follow-up data, of whom 5 experienced distant recurrence (2 RS 11-25 patients and 3 RS 26-100 patients). Studies exploring the prognostic utility of the RS in this setting are warranted.

Body mass index and patient-reported function, quality of life and treatment toxicity in women receiving adjuvant chemotherapy for breast cancer.

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.

Alpelisib Efficacy in Hormone Receptor-Positive HER2-Negative PIK3CA-Mutant Advanced Breast Cancer Post-Everolimus Treatment.

This real-world cohort analysis assessed the efficacy of alpelisib and endocrine treatment (ET) combinations in a post-everolimus setting. Thirteen women who started alpelisib and ET at standard doses between 2018 and 2022 for advanced breast cancer (ABC), after undergoing CDK4/6i and everolimus treatment, were eligible for the study entry. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and clinical benefit rate (CBR), with different molecular profiling. The patients had previously received a median of four (range 3-8) systemic treatments, including CDK4/6i and everolimus. The median PFS on alpelisib was 5.5 months (range 0.5-10), and four women each had an ORR and three (23%) had a stable disease. The 6-month CBR was 46.1%, similar to the BYLeive study cohort C (47.8%). Notably, our cohort included patients with a long CBR under everolimus treatment (median 6 months, range 1-18); however, the responses to alpelisib and everolimus were not correlated (Pearson r = -0.23, p = 0.44). The PIK3CA, P53, ARID, GATA3, and ESR1 mutations were not associated with the 6-month CBR. Despite heavy pre-treatments, including everolimus, alpelisib was clinically relevant in our cohort, even among patients with an ESR1 mutation. The best treatment sequence for PIK3CA/mTOR inhibitors warrants examination in future trials on PIK3CA-mutant inpatients with luminal ABC.

The association between geriatric assessment, muscle measures, and treatment-related toxicity in older adults with cancer: An Israeli prospective study.

INTRODUCTION: We investigated the associations among frailty, as determined via the comprehensive geriatric assessment (CGA), muscle measures (i.e., sarcopenia), and treatment-related toxicity in older adults with cancer in Israel. MATERIALS AND METHODS: This prospective cohort study enrolled patients ≥65 years with newly-diagnosed stage IV lung, breast, or genitourinary cancer. Patients were enrolled and completed CGA before their first line of systemic therapy (chemotherapy, biologic therapy, immunologic therapy, or a combination thereof). CGA was used to classify patients as robust, pre-frail, or frail, and routine pre-treatment computed tomography (CT) images were used to quantify skeletal muscle index (SMI) and skeletal muscle density (SMD) at L3 cross-section. Two sarcopenia definitions were used: i. for women SMI <41 cm2/m2 regardless of body mass index (BMI), and for men SMI <43 cm2/m2 for those with BMI of <25 and < 53 cm2/m2 for those with BMI ≥25; and ii. SMI <38 cm2/m2 for women and < 41 cm2/m2 for men, regardless of BMI. The associations between frailty and muscle measures with the occurrence of at least one adverse event (AE) grade ≥ 2 were examined using the chi-square test, and logistic regression to determine odds ratio (OR) and 95% confidence interval (CI). RESULTS: In total, 51 patients were included in the analysis. The median (interquartile range) age was 72 (68-76) years, 30 (59%) were male, and 26 (51%) had lung cancer. CGA data were available for 48 patients: fifteen (31%), thirteen (27%), and twenty (42%) were defined as robust, pre-frail, and frail, respectively. Overall, 33 (65%) were sarcopenic by the first aforementioned definition, and sixteen (31%) by the second. No statistically significant associations were identified between frailty and having at least one AE grade ≥ 2, or between frailty and sarcopenia. Statistically significant associations were found between having sarcopenia (the second definition) and having at least one AE grade ≥ 2 (P = 0.0217). The corresponding odds ratio (95% CI) was 4.2 (1.2-15.0), P = 0.026. DISCUSSION: Our findings suggests that sarcopenia is significantly associated with treatment-related toxicity. Further studies with larger sample sizes are warranted.

Patient-reported symptom severity, interference with daily activities, and adverse events in older and younger women receiving chemotherapy for early breast cancer.

BACKGROUND: To the authors' knowledge, it is unknown whether patient-reported symptom severity and symptom interference with daily activities differ between younger (aged <65 years) and older (aged ≥65 years) women receiving similar chemotherapy regimens for early breast cancer (EBC). METHODS: Study participants rated 17 side effects of chemotherapy regimens currently in use in clinical practice (2014-2019). RESULTS: Of 284 women with EBC (stage I-III), approximately 57% were aged <65 years and 43% were aged ≥65 years. For anthracycline-based regimens, a higher percentage of younger women reported moderate, severe, or very severe (MSVS) hot flashes (49% vs 18%) (P < .001). For nonanthracycline regimens, a higher percentage of younger women reported MSVS hot flashes (38% vs 19%) (P = .009) and a lower percentage reported MSVS arthralgia (28% vs 49%) (P = .005). With regard to symptom interference with daily activities, a higher percentage of younger women being treated with anthracycline-based regimens reported MSVS hot flashes (32% vs 7%) (P = .001) and myalgia (38% vs 18%) (P = .02). For nonanthracycline chemotherapy, a higher percentage of younger women reported MSVS interference for hot flashes (26% vs 9%) (P = .006) and lower percentages reported abdominal pain (13% vs 28%) (P = .02). Overall, there were no significant differences noted among younger versus older patients with regard to hospitalizations (19% vs 12%; P = .19), dose reductions (34% vs 31%; P = .50), dose delays (22% vs 25%; P = .59), or early treatment discontinuation (16% vs 16%; P = .9546). CONCLUSIONS: Older and younger women with EBC who were treated with identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events. LAY SUMMARY: In this study, women receiving chemotherapy for early breast cancer rated the severity of 17 symptoms and symptom interference with their activities of daily living. Older (aged ≥65 years) and younger (aged <65 years) women who received identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events.

Obesity, comorbidities, and treatment selection in Black and White women with early breast cancer.

BACKGROUND: This study investigates obesity and comorbidity in Black and White women with early breast cancer (stages I-III) and their potential impact on treatment decisions for patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) tumors. METHODS: In this retrospective chart review, comparisons of frequencies for Black and White patients were calculated with the Fisher exact test. Log binomial regression was used to estimate prevalence ratios (PRs) with 95% confidence intervals for total and individual comorbidities, and multivariable modeling was used to estimate PRs adjusted for age and body mass index (BMI). RESULTS: In a sample of 548 patients, 26% were Black, and 74% were White. Sixty-two percent of Black patients and 32% of White patients were obese (BMI ≥ 30 kg/m2 ; P < .0001). Seventy-five percent of Black patients and 87% of White patients had HR+ tumors (P = .001). Significant intergroup differences were seen for 2 or more total comorbidities (62% of Blacks vs 47% of Whites; P = .001), 2 or more obesity-related comorbidities (33% vs 10%; P < .0001), hypertension (60% vs 32%; P < .0001), diabetes mellitus (23% vs 6%; P < .0001), hypercholesterolemia or hyperlipidemia (28% vs 18%; P = .02), and hypothyroidism (4% vs 11%; P = .012). In women with HR+/HER2- tumors, there were no intergroup differences in treatment decisions regarding the type of surgery, chemotherapy regimen, radiation, or endocrine treatment despite significant differences in the prevalence of obesity and comorbidities. CONCLUSIONS: This study documents significant disparities between Black and White women with early breast cancer with regard to high rates of obesity, overall comorbidities, and obesity-related comorbidities, and it highlights the prevalence of competing risks that may complicate outcomes in breast cancer.

Assessment of Sarcopenia Measures, Survival, and Disability in Older Adults Before and After Diagnosis With Cancer.

Importance: Progressive loss of muscle mass and strength, known as sarcopenia, is a well-known phenomenon of aging; however, little is known about the trajectory of sarcopenia measures before and after cancer diagnosis and its contribution to subsequent disability. Objective: To examine the rate of decline of sarcopenia measures (ie, appendicular lean mass [ALM], muscle strength, and physical performance) in older adults with cancer both before and after the cancer diagnosis compared with the trajectory of a population without cancer, and secondarily to assess the association of sarcopenia measures with overall survival and major disability in patients with cancer. Design, Setting, and Participants: This matched cohort study included participants from the Health, Aging, and Body Composition (Health ABC) study, which included 3075 community-dwelling older adults aged 70 to 79 years recruited from a random sample of white Medicare beneficiaries and all eligible black residents in and around Pittsburgh, Pennsylvania, and Memphis, Tennessee, beginning in January 1997 and observed for 17 years until December 2013. Data were analyzed from May 2018 to February 2020. Exposures: The development of an adjudicated cancer diagnosis confirmed with pathology or cytology reports during the first 7 years of follow-up. Main Outcomes and Measures: Annual assessments of ALM, hand grip strength, and gait speed were the primary outcome measures. Linear mixed-effect models were used to compare the change in ALM, hand grip strength, and gait speed between individuals who developed cancer and those who did not, adjusted for multiple comparisons (P < .01). Multivariable Cox regression was used to examine the association of sarcopenia measures with overall survival and major disability from date of cancer diagnosis. Results: Of the 3075 included patients, 1491 (48.5%) were male, 1281 (41.7%) were black, and the mean (SD) age was 74.1 (2.9) years. A total of 515 patients (16.7%) developed cancer within the first 7 years of the study. The most common cancers were prostate (117 [23.2%]), colorectal (63 [12.5%]), lung (61 [12.1%]), and breast (61 [12.1%]) cancer, and 165 patients (32.0%) were diagnosed as having metastatic disease. Compared with controls without cancer, patients with a cancer diagnosis had a steeper decline in gait speed (ß = -0.02; 95% CI, -0.03 to -0.01; P < .001) but not ALM (ß = -0.02; 95% CI, -0.07 to 0.04; P = .49) or hand grip strength (ß = -0.21; 95% CI, -0.43 to 0; P = .05) prior to cancer diagnosis. After cancer diagnosis, there was a decline in ALM (ß = -0.14; 95% CI, -0.23 to -0.05; P < .001) but not hand grip strength (ß = -0.02; 95% CI, -0.37 to 0.33; P = .92) or gait speed (ß = 0; 95% CI, -0.01 to 0.02; P = .51). Declines in ALM after a cancer diagnosis were most striking in patients with metastases (ß = -0.32; 95% CI, -0.53 to -0.10; P = .003). Slow gait speed was associated with a 44% increase in mortality (hazard ratio, 1.44; 95% CI, 1.05 to 1.98; P = .02) and a 70% increase in disability (hazard ratio, 1.70; 95% CI, 1.08 to 2.68; P = .02) but not low ALM or hand grip strength. Conclusions and Relevance: Accelerated losses in differing sarcopenia measures exist both prior to and after a cancer diagnosis and may present opportunities for targeted interventions to improve outcomes.

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer.

BACKGROUND: The National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, collected alongside the clinician-reported Common Terminology Criteria for Adverse Events, enables comparisons of patient and clinician reports on treatment toxicity. METHODS: In a multisite study of women receiving chemotherapy for early-stage breast cancer, symptom reports were collected on the same day from patients and their clinicians for 17 symptoms; their data were not shared with each other. The proportions of moderate, severe, or very severe patient-reported symptom severity were compared with the proportions of clinician-rated grade 2, 3, or 4 toxicity. Patient-clinician agreement was assessed via κ statistics. Chi-square tests investigated whether patient characteristics were associated with patient-clinician agreement. RESULTS: Among 267 women, the median age was 58 years (range, 24-83 years), and 26% were nonwhite. There was moderate scoring agreement (κ = 0.413-0.570) for 53% of symptoms, fair agreement for 41% (κ = 0.220-0.378), and slight agreement for 6% (κ = 0.188). For example, patient-reported and clinician-rated percentages were 22% and 8% for severe or very severe fatigue, 41% and 46% for moderate fatigue, 32% and 39% for mild fatigue, and 6% and 7% for none. Clinician severity scores were lower for nonwhite patients in comparison with white patients for peripheral neuropathy, nausea, arthralgia, and dyspnea. CONCLUSIONS: Although clinician reporting of symptoms is common practice in oncology, there is suboptimal agreement with the gold standard of patient self-reporting. These data provide further evidence supporting the integration of patient-reported outcomes into oncological clinical research and clinical practice to improve monitoring of symptoms as well as timely interventions for symptoms.

Bioelectrical Impedance Analysis for the Assessment of Sarcopenia in Patients with Cancer: A Systematic Review.

BACKGROUND: The loss of muscle mass, known as sarcopenia, is a natural process of aging that is associated with adverse health outcomes regardless of age. Because cancer is a disease of aging, interest in sarcopenia and its potential impact in multiple cancer populations has increased significantly. Bioelectrical impedance analysis (BIA) is a guideline-accepted method for sarcopenia detection. This systematic review assesses the literature pertaining to BIA use in the detection of sarcopenia in adults with cancer. MATERIALS AND METHODS: In this systematic review, a search of the literature for randomized controlled trials and observational studies was conducted using MEDLINE, Cochrane CENTRAL, and EMBASE, through July 15, 2019. The study is registered at Prospero (CRD 42019130707). For study inclusion, patients had to be aged 18 years or older and diagnosed with solid or hematological neoplasia, and BIA had to be used to detect sarcopenia. RESULTS: Through our search strategy, 5,045 articles were identified, of which 24 studies were selected for inclusion in the review (total number of 3,607 patients). In five studies, BIA was rated comparable to axial computed tomography (CT) scan, calf circumference, or grip strength for sarcopenia screening. In 14 studies, BIA-identified sarcopenia was associated with adverse clinical outcomes. CONCLUSION: BIA is an accurate method for detecting sarcopenia in adults with cancer prior to treatment and is a viable alternative to CT, dual-energy x-ray absorptiometry, and magnetic resonance imaging in oncology clinical practice. IMPLICATIONS FOR PRACTICE: Bioelectrical impedance analysis (BIA) is an attractive method for identifying sarcopenic patients in clinical practice because it provides an affordable, noninvasive test that can be completed within a few minutes during a clinic visit. BIA does not require highly skilled personnel, and results are immediately available. This systematic review summarizes the literature pertaining to BIA assessment of sarcopenia in adults with cancer, with a focus on its use in diverse cancer populations.

Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16INK4a.

BACKGROUND: Although chemotherapy saves lives, increasing evidence shows that chemotherapy accelerates aging. We previously demonstrated that mRNA expression of p16INK4a , a biomarker of senescence and molecular aging, increased early and dramatically after beginning adjuvant anthracycline-based regimens in early stage breast cancer patients. Here, we determined if changes in p16INK4a expression vary by chemotherapy regimen among early stage breast cancer patients. METHODS: We conducted a study of stage I-III breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. p16INK4a expression was analyzed prechemotherapy and postchemotherapy (median 6.2 months after the last chemotherapy) in peripheral blood T lymphocytes. Chemotherapy-induced change in p16INK4a expression was compared among regimens. All statistical tests were 2-sided. RESULTS: In 146 women, chemotherapy was associated with a statistically significant increase in p16INK4a expression (accelerated aging of 17 years; P < .001). Anthracycline-based regimens were associated with the largest increases (accelerated aging of 23 to 26 years; P ≤ .008). Nonanthracycline-based regimens demonstrated a much smaller increase (accelerated aging of 9 to 11 years; P ≤ .15). In addition to the type of chemotherapy regimen, baseline p16INK4a levels, but not chronologic age or race, were also associated with the magnitude of increases in p16INK4a . Patients with lower p16INK4a levels at baseline were more likely to experience larger increases. CONCLUSIONS: Our findings suggest that the aging effects of chemotherapy may be influenced by both chemotherapy type and the patient's baseline p16INK4a level. Measurement of p16INK4a expression is not currently available in the clinic, but nonanthracycline regimens offering similar efficacy as anthracycline regimens might be favored.

p16 a biomarker of aging and tolerance for cancer therapy.

There is great variability in life-expectancy, physical, cognitive, and functional domains in cancer patients of similar chronologic age. Nowhere is this more apparent than among middle-aged and older patients. However, even in younger patients of similar age, extensive exposure to environmental stressors can cause great variability in health status. A biomarker that would reflect biologic age and any and all health deficits in a cancer patient at a distinct point in time might help predict long term outcomes related to treatment, especially toxicity and overall survival. p16INK4a (hereafter referred to as p16) expression represents an ideal biomarker that reflects both cellular senescence and biologic aging. In murine models, p16 expression reflects biologic aging in almost all organs. Preliminary findings in patients with cancer support p16 measurement as a marker of physiologic aging and predictor of toxicity in patients treated with chemotherapy. This review describes the role of p16 in cell senescence, the methodology of p16 measurement in humans, preliminary studies of p16 in humans, and the potential clinical utility of p16 in guiding treatment for cancer patients.

Body Composition, Adherence to Anthracycline and Taxane-Based Chemotherapy, and Survival After Nonmetastatic Breast Cancer.

Importance: Although most chemotherapies are dosed on body surface area or weight, body composition (ie, the amount and distribution of muscle and adipose tissues) is thought to be associated with chemotherapy tolerance and adherence. Objectives: To evaluate whether body composition is associated with relative dose intensity (RDI) on anthracycline and taxane-based chemotherapy or hematologic toxic effects and whether lower RDI mediates the association of adiposity with mortality. Design, Setting, and Participants: An observational cohort study with prospectively collected electronic medical record data was conducted at Kaiser Permanente Northern California, a multicenter, community oncology setting within an integrated health care delivery system. Participants included 1395 patients with nonmetastatic breast cancer diagnosed between January 1, 2005, and December 31, 2013, and treated with anthracycline and taxane-based chemotherapy. Data analysis was performed between February 25 and September 4, 2019. Exposures: Intramuscular, visceral, and subcutaneous adiposity as well as skeletal muscle were evaluated from clinically acquired computed tomographic scans at diagnosis. Main Outcomes and Measures: The primary outcome was low RDI (<0.85), which is the ratio of delivered to planned chemotherapy dose, derived from infusion records; in addition, hematologic toxic effects were defined based on laboratory test values. To evaluate associations with overall and breast cancer-specific mortality, logistic regression models adjusted for age and body surface area were fit as well as Cox proportional hazards models adjusted for age, race/ethnicity, adiposity, Charlson comorbidity index score, and tumor stage and subtype. The mediation proportion was computed using the difference method. Results: The mean (SD) age at diagnosis of the 1395 women included in the study was 52.8 (10.2) years. Greater visceral (odds ratio [OR], 1.19; 95% CI, 1.02-1.39 per SD) and intramuscular (OR, 1.16; 95% CI, 1.01-1.34 per SD) adiposity were associated with increased odds of RDI less than 0.85. Greater muscle mass was associated with a decreased odds of hematologic toxic effects (OR, 0.84; 95% CI, 0.71-0.98 per SD). Relative dose intensity less than 0.85 was associated with a 30% increased risk of death (hazard ratio, 1.30; 95% CI, 1.02-1.65). Lower RDI partially explained the association of adiposity with breast cancer-specific mortality (mediation proportion, 0.20; 95% CI, 0.05-0.55). Conclusions and Relevance: Excess adiposity, presenting as larger visceral or intramuscular adiposity, was associated with lower RDI. Lower RDI partially mediated the association of adiposity with worse breast cancer-specific survival. Body composition may help to identify patients likely to experience toxic effects and subsequent dose delays or reductions, which could compromise chemotherapeutic efficacy.

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer.

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.).

Weight trajectories in women receiving systemic adjuvant therapy for breast cancer.

BACKGROUND: Weight gain after breast cancer (BC) diagnosis is a well-known phenomenon; however, it is not a universal phenomenon and identification of patients at highest risk for weight gain is needed. This study investigates weight trajectories in early BC patients at 2 years post-primary treatment, examining potential contributing factors such as age, race, and receipt of chemotherapy, anti-HER-2 therapy, and endocrine treatment (ET). METHODS: A single institution cohort of newly diagnosed women age 21 and older with early breast cancer patients (Stage 0-3) were identified by retrospective chart review (diagnosis year 1995 to 2016). Log-binomial regression models for net weight changes at 2 years post-primary treatment including patient demographic, clinical, and treatment characteristics. RESULTS: The final sample of 625 patients included 29% who were non-White and 37% who were pre-menopausal at diagnosis. Body mass index (BMI) at diagnosis was calculated and found to be normal in 33% (BMI 18 to < 25), overweight in 27% (BMI 25 to < 30), and obese in 40% (BMI 30 and higher). At 2 years, compared to weight at diagnosis, 31% had lost > 2 kg, 34% had stable weight ± 2 kg, and 35% had gained > 2 kg. Factors associated with > 2 kg weight gain were menopausal status (pre-menopausal HR 1.65, 95% CI 1.34-2.04, p < .0001), receiving any chemotherapy (HR 1.36, 95% CI 1.04-1.77), and anthracycline-based chemotherapy followed by ET (HR 1.60, CI 1.01-2.45). Anti-HER-2 therapy and transition from pre- to post-menopausal during the 2-year study period were not significant factors in weight gain. In multivariate analysis, menopausal status remained the only significant variable related to weight gain when adjusted for treatment. For all treatment combinations, pre-menopausal women had significantly more weight gain. CONCLUSIONS AND RELEVANCE: Weight gain, weight loss, and stable weight in women with early breast cancer vary greatly by treatment plan. However, pre-menopausal patients have the highest risk for weight gain.

Patient-reported and clinician-reported chemotherapy-induced peripheral neuropathy in patients with early breast cancer: Current clinical practice.

BACKGROUND: In the current study, the authors investigated the incidence of moderate to severe chemotherapy-induced peripheral neuropathy (CIPN) for chemotherapy regimens commonly used in current clinical practice for the treatment of patients with early breast cancer. Patient-reported and clinician-assessed CIPN severity scores were compared, and risk factors for CIPN severity were identified. METHODS: Patients completed a Patient-Reported Symptom Monitoring form and oncologists completed a Common Terminology Criteria for Adverse Events form. CIPN reports were collected prospectively during regularly scheduled infusion visits throughout the duration of chemotherapy. RESULTS: The sample included 184 women with a mean age of 55 years; approximately 73% were white. The 4 chemotherapy regimens used were doxorubicin and cyclophosphamide plus paclitaxel (60 patients); docetaxel and cyclophosphamide (50 patients); docetaxel, carboplatin, and anti-human epidermal growth factor receptor 2 (HER2) (24 patients); and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin (18 patients). All patients treated with doxorubicin and cyclophosphamide plus paclitaxel and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin received paclitaxel; all patients treated with docetaxel and cyclophosphamide and docetaxel, carboplatin, and anti-HER2 received docetaxel. The chemotherapy dose was reduced in 52 patients (28%); in 15 patients (29%), this reduction was due to CIPN. Chemotherapy was discontinued in 26 patients (14%), 8 because of CIPN. Agreement between patient-reported and clinician-assessed CIPN severity scores was minimal (weighted Cohen kappa, P = .34). Patient-reported moderate to severe CIPN was higher for paclitaxel (50%) compared with docetaxel (17.7%) (P < .001). Pretreatment arthritis and/or rheumatism (relative risk [RR], 1.58; 95% CI, 1.06-2.35 [P = .023]) and regimens containing paclitaxel (RR, 2.88; 95% CI, 1.72-4.83 [P < .0001]) were associated with higher CIPN severity. Being married (RR, 0.57; 95% CI, 0.37-0.887 [P = .01]) was found to be associated with lower CIPN severity. CONCLUSIONS: The discrepancy between patient-reported and clinician-assessed CIPN underscores the need for both patient and clinician perspectives regarding this common, dose-limiting, and potentially disabling side effect of chemotherapy.

Frailty and health-related quality of life in older women with breast cancer.

PURPOSE: In older women, breast cancer and its treatment can have profound impact on their physical, mental, and social health, especially in frail patients. This study evaluated the association between frailty and long-term health-related quality of life (HRQOL) in older women undergoing breast cancer treatment. METHODS: Using the Carolina Senior Registry (CSR), participants with breast cancer were contacted to complete a follow-up HRQOL questionnaire (median 4 years). Baseline Geriatric Assessment (GA) variables were used to calculate the Carolina Frailty Index (CFI) and categorize participants as robust, pre-frail, or frail. Outcomes included HRQOL domains of physical function, social roles, fatigue, depression, anxiety, pain, and sleep disturbance assessed using PROMIS® instruments. Regression modeling compared outcomes between frailty groups using adjusted mean differences (AMD). RESULTS: Of 190 eligible patients, 63 completed follow-up HRQOL survey. Mean age was 70 years (range 65-86) and 91% were white. Based on the CFI, 49 (78%) patients were robust, 11 (18%) pre-frail, and 3 (5%) frail. After controlling for age and cancer stage, patients identified as pre-frail/frail reported worse physical function (AMD - 9.2, p < 0.001) and social roles (AMD - 7.2, p = 0.002) and more fatigue (AMD 7.6, p = 0.008), depression (AMD 5.6, p = 0.004), and sleep disturbance (AMD 6.9, p = 0.008) compared to robust patients at follow-up. CONCLUSIONS: Frailty in older women with breast cancer was associated with worse long-term HRQOL outcomes. Further research is needed to develop interventions for frail patients at-risk for reduced HRQOL.

Patient-Reported Toxicities During Chemotherapy Regimens in Current Clinical Practice for Early Breast Cancer.

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.

Patient-Reported Outcomes with PD-1/PD-L1 Inhibitors for Advanced Cancer: A Meta-Analysis.

BACKGROUND: The aim of this meta-analysis was to compare patient-reported outcomes (PROs) between programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors and standard-of-care therapy in patients with advanced cancer. METHODS: We searched randomized controlled trials (RCTs) comparing single-agent PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, atezolizumab, avelumab, or durvalumab) with standard-of-care therapy in patients with advanced cancer reporting PROs with generic measures: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (QLQ-C30) and the EuroQol Five Dimensions Questionnaire. The summary outcomes were changes in PROs from baseline to follow-up within and between treatment groups and time to deterioration (TTD) in PROs based on clinically meaningful change. RESULTS: A total of 6,334 patients from 13 RCTs were included: six nivolumab, five pembrolizumab, and two atezolizumab trials. For the QLQ-C30 global health status/quality of life, the pooled difference in mean change between treatment groups was 5.1 (95% confidence interval [CI], 3.3-6.9; p < .001) favoring PD-1/PD-L1 inhibitors. The pooled mean change from baseline in PD-1/PD-L1 inhibitors and controls was 0.1 (95% CI, -2.2, 2.5) and - 6.1 (95% CI, -8.4, -3.8), respectively. The TTD was significantly longer with PD-1/PD-L1 inhibitors, with a hazard ratio of 0.72 (95% CI, 0.55-0.93; p = .011). Similarly, significantly better outcomes were noted with PD-1/PD-L1 inhibitors on most of the other PRO measures. CONCLUSION: PD1/PD-L1 inhibitors maintained health-related quality of life to a greater degree and had less worsening in symptoms than standard-of-care therapy even though patients on these immune modulators were on treatment longer. The better PRO profile further supports the clinical benefit of this treatment strategy for advanced cancer. IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare patient-reported outcomes (PROs) of programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors and standard-of-care therapy in patients with advanced cancer. PD-1/PD-L1 inhibitors were associated with consistently smaller PRO score deterioration from baseline to follow-up for different health-related quality-of-life and symptoms scales. In addition, the time to deterioration in multiple PRO domains was significantly longer with PD-1/PD-L1 inhibitors. Taken together, these findings indicate that the patients treated with PD-1/PD-L1 inhibitors maintained health-related quality of life to a greater degree and had less symptom burden compared with those treated with standard-of-care therapy.