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IntroductionPalbociclib 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 methodsWe 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).ResultsOf 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%]).DiscussionPalbociclib 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.Clinicaltrialsgov:NCT03633331.

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 docetaxel + 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. [ABSTRACT FROM AUTHOR]

Statins have the potential to reduce breast cancer incidence and recurrence as shown in both epidemiologic and laboratory studies. The purpose of this study was to evaluate the effect of a lipophilic statin, atorvastatin, on breast cancer biomarkers of risk [mammographic density (MD) and insulin growth factor 1 (IGF-1)] in high-risk premenopausal women.Premenopausal women at increased risk for breast cancer received either 40 mg of atorvastatin or placebo for 1 year. Biomarker assessment was performed prior to initiation and at completion of study medication. MD was determined using both Breast Imaging Reporting and Data System and the visual analogue scale. Serum IGF-1 was determined by ELISA assay at the end of the study.Sixty-three women were enrolled between December 2005 and May 2010. Sixteen (25%) women withdrew. The mean age of participants was 43 (range, 35-50), 100% were white, and the average body mass index (BMI) was 26.4. The statin group demonstrated a significant decrease in cholesterol and low-density lipoprotein (LDL), suggesting compliance with study medication. After accounting for BMI, there was no difference in change in MD between groups. There was a significant increase in serum IGF-1 in the statin group.In this multi-institutional randomized prospective clinical trial of premenopausal women at increased risk for breast cancer, we did not see an effect of atorvastatin on MD. Further investigation of statins may be warranted; however, design of prior trials and potential mechanism of action of the agent need to be considered in the design of future trials. Cancer Prev Res; 9(5); 379-84. ©2016 AACR.

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. In this study, nearly one in four older women with early breast cancer experienced toxicity‐related hospitalization during chemotherapy. Women who reported more than one fall in the 6 months leading up to chemotherapy had a greater than four times higher odds of experiencing toxicity‐related hospitalization during treatment than women who reported no falls. [ABSTRACT FROM AUTHOR]

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. Conversations about healthy weight will be most productive and well received by patients with breast cancer during the post–primary treatment phase of the cancer care continuum when patients are receptive to behavioral change that enhances their prognosis and survival. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Newer adjuvant treatment options for non-metastatic breast cancer have increased survival. There is a need to investigate whether demographic and clinical characteristics of women with hormone receptor-positive, human epidermal growth receptor 2-negative non-metastatic breast cancer (stages I-III) differentially influence treatment decisions in older (age 65 or older) versus younger patients (under age 65). In a retrospective electronic medical record review, prevalence ratio with 95% confidence interval for treatment decisions in older vs younger patients was calculated using log binomial regression adjusted for race, stage, and total number of comorbidities. In a sample of 537 patients, 66% were age < 65 and 34% age ≥ 65. Older patients included a higher proportion of White women (85% vs 75%, P =.02), higher number of comorbidities (P ≤0.0001), and lower stage tumors (P =.0004). In multivariable analysis, age ≥ 65 was independently associated with fewer mastectomies (95% CI 0.65–0.96, P =.02), more lumpectomies (95% CI 1.05–1.42, P =.01), and less receipt of radiation treatment (95% CI 0.78–0.97, P =.01) and/or chemotherapy (95% CI 0.73–0.95, P =.006). In multivariate analysis, stage was independently significant for all treatment modalities, except endocrine therapy, and race was not. This study suggests that age, in addition to breast cancer stage, is a predictor of treatment modality, independent of race and number of comorbidities. Treatment modality reflects a combination of patient preference and clinician assessment of fitness for current standard of care. [ABSTRACT FROM AUTHOR]

Background: Women with obesity are at higher risk for high-grade and/or advanced-stage breast cancer in comparison with women without obesity. Many women with a high body mass index (BMI) at breast cancer diagnosis experience further weight gain during and after treatment. This study investigated Black and White patient perspectives on conversations with their oncologists about weight and weight management.Methods: Focus groups using a virtual platform (Zoom) were conducted with women after primary treatment for stage I to III breast cancer who were 21 years or older and had a BMI ≥ 30 kg/m2 : 2 with Black women (n = 12) and 2 with White women (n = 14).Results: Participants asked that their oncologists be "transparent" about weight gain as a potential side effect of their cancer treatment and how excess weight might affect their prognosis and survival. They asked to be "seen as an individual" to facilitate both person-centered and culturally appropriate conversations about behavioral changes needed for weight management. Participants urged clinicians to take the lead in initiating conversations about weight to underscore its importance in cancer care and survivorship. They welcomed actionable recommendations about nutrition and exercise from either the oncology clinician or a specialist. Participants offered specific suggestions on how clinicians could initiate weight-related conversations, beginning with questions eliciting patients' perspectives on their weight and lifestyle.Conclusions: Many women with early-stage breast cancer and obesity have concerns about weight and weight gain and urge their oncologists to use an active and personalized approach in recommending and supporting efforts at weight management.Lay Summary: Focus group discussions with Black and White women with early-stage breast cancer and obesity have elicited patient perspectives on conversations with their oncologists about weight and weight management. Many patients have concerns about weight and weight gain and urge their oncologists to use an active and personalized approach in recommending and supporting efforts at weight management. [ABSTRACT FROM AUTHOR]

Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 – 60 minute mixed mode aerobic exercises, comprising 10 – 30 minutes aerobic and 30 minutes resistance training. At Base and Final, we took BCS blood samples before (PRE), immediately after (POST), and 1 hour after (1Hr) acute exercise to determine neutrophil counts, phenotype, bacterial killing, IL-6, and IL-8 levels. Eleven healthy, age- and physical activity levels-matched women (Control) completed the acute bout of exercise once as a healthy response reference. Resting Responses. BCS and Controls had similar Base PRE absolute neutrophil counts [mean (SD): 3.3 (1.9) v 3.1 (1.2) x 109/L, p=0.801], but BCS had lower bacterial phagocytosis [3991 (1233) v 4881 (417) MFI, p=0.035] and higher oxidative killing [6254 (1434) v 4709 (1220) MFI, p=0.005], lower CD16 [4159 (1785) v 7018 (1240) MFI, p<0.001], lower CXCR2 [4878 (1796) v 6330 (1299) MFI, p=0.032] and higher TLR2 [98 (32) v 72 (17) MFI, p=0.022] expression, while IL-6 [7.4 (5.4) v 4.0 (2.7) pg/mL, p=0.079] levels were marginally higher and IL-8 [6.0 (4.7) v 7.9 (5.0) pg/mL, p=0.316] levels similar. After 16 weeks of training, compared to Controls, BCS Final PRE phagocytosis [4510 (738) v 4881 (417) MFI, p=0.146] and TLR2 expression [114 (92) v 72 (17) MFI, p=0.148] were no longer different. Acute Exercise Responses. As compared to Controls, at Base, BCS phagocytic Pre-Post response was lower [mean difference, % (SD): 12% (26%), p=0.042], CD16 Pre-Post response was lower [12% (21%), p=0.016] while CD16 Pre-1Hr response was higher [13% (25%), p=0.022], TLR2 Pre-Post response was higher [15% (4%) p=0.002], while IL-8 Pre-Post response was higher [99% (48%), p=0.049]. As compared to Controls, following 16 weeks of training BCS phagocytic Pre-Post response [5% (5%), p=0.418], CD16 Pre-1Hr response [7% (7%), p=0.294], TLR2 Pre-Post response [6% (4%), p=0.092], and IL-8 Pre-Post response [1% (9%), p=0.087] were no longer different. Following cancer therapy, BCS may have impaired neutrophil functions in response to an acute bout of exercise that are partially restored by 16 weeks of exercise training. The improved phagocytosis of bacteria in BCS may represent an exercise-induced intrinsic improvement in neutrophil functions consistent with a reduced risk of infectious disease. Clinical Trial Registration: ClinicalTrials.gov , identifier NCT03760536. [ABSTRACT FROM AUTHOR]

Women over 70 years old who have advanced breast cancer may respond to chemotherapy as well as younger women. Many elderly women are excluded from chemotherapy trials or are given a lower dose because they are thought to have an increased risk of side effects. Of 161 women with advanced breast cancer selected from five different chemotherapy trials, 70 were over 70 years old and 91 were younger. There were no differences in response, progression of disease or survival between the older women and the younger women. The older women were more likely to develop neutropenia, which is a drop in the level of a type of white blood cell. Neutropenia was the cause of death in one elderly woman. Elderly women with advanced breast cancer could be given colony stimulating factors, which are naturally-occurring substances in the body that boost the production of white blood cells.

Caring for older patients with breast cancer presents unique clinical considerations because of preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision making for older patients is especially challenging and encourages us to refocus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the "new normal" for the approximately 30% of breast cancer patients aged 70 years and older who are diagnosed in the United States annually and for the thousands of older patients living with recurrent and/or metastatic disease. [ABSTRACT FROM AUTHOR]

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. In the current study, women receiving chemotherapy for early breast cancer rate 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. [ABSTRACT FROM AUTHOR]

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. This study documents significant disparities between Black and White women with early breast cancer with respect to high rates of obesity as well as overall comorbidities and obesity‐related comorbidities—many of which are independent of age and obesity itself—and it highlights the prevalence of competing risks that may complicate outcomes in breast cancer. Patients need to be counseled that their long‐term overall health and survival depend as much on the effective management of their comorbidities as they do on the successful completion of cancer treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Despite data demonstrating the safety of omitting axillary surgery in older women with early-stage breast cancer, the incidence of axillary surgery remains high. It was hypothesized that the prevalence of nodal positivity would decrease with advancing age.Methods: The National Cancer Data Base was used to construct a cohort of adult women with early-stage, clinically node-negative, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative breast cancer treated between 2013 and 2015. Multivariable logistic regression was used to assess the relationship between age and nodal positivity, and this was stratified by the axillary surgery category. Modified Poisson regression was used to estimate the proportion of women receiving adjuvant therapy according to age and nodal status.Results: The incidence of axillary surgery among women aged 70 and older (n = 51,917) remained high nationwide (86%). There was a significant decrease in nodal positivity with advancing age in women with early-stage, ER+, clinically node-negative breast cancer from the youngest cohort up to patients aged 70 to 89 years, and this was independent of histologic subtype (ductal vs lobular), race, comorbidities, and socioeconomic factors. Overall, less than 10% of women aged 70 or older who underwent surgery had node-positive disease, regardless of axillary surgery type, and almost 95% of node-positive patients aged 70 or older were at pathological stage N1mi or N1.Conclusions: Axillary surgery may be safely omitted for many older women with ER+, clinically node-negative, early-stage breast cancer. Nodal positivity declines with advancing age, and this suggests varied biology in older patients versus younger patients. [ABSTRACT FROM AUTHOR]

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. The severity of patient‐reported chemotherapy‐induced peripheral neuropathy (CIPN) varies by the regimen used in current clinical practice for the treatment of early breast cancer. The discrepancy between patient‐reported and clinician‐assessed CIPN underscores the need for both patient and clinician perspectives on this common, dose‐limiting, and potentially disabling side effect of chemotherapy. [ABSTRACT FROM AUTHOR]

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Purpose: A few previous studies report a direct relationship between older age and chemotherapy‐induced neuropathy. This study further evaluated this adverse event's age‐based risk. Methods: CALGB 40101 investigated adjuvant paclitaxel (80 mg/m2 once per week or 175 mg/m2 every 2 weeks) in patients with breast cancer and served as a platform for the current study that investigated age‐based differences in neuropathy. Grade 2 or worse neuropathy, as per Common Terminology Criteria for Adverse Events version 4, was the primary endpoint; patients were assessed at baseline, every 6 months for 2 years, and then annually for 15 years. Results: Among these 1,881 patients, 230 were 65 years of age or older, 556 were 55–64 years, and 1,095 were younger than 55; 1,226 neuropathy events (commonly grade 1 or 2) were reported in 65% of the cohort. The number of grade 2 or worse events was 63 (27%), 155 (28%), and 266 (24%) within respective age groups (p =.14). In univariate analysis, only motor neuropathy had a higher age‐based incidence: 19 (8%), 43 (8%), and 60 (5%), respectively (p =.04); in multivariate analyses, this association was no longer statistically significant. Other endpoints, such as time to onset of neuropathy (time from trial enrollment to neuropathy development) and time to improvement (time from maximal grade sensory neuropathy to a one‐category improvement), showed no statistically significant age‐based differences. In contrast, obesity was associated with neuropathy, and every 2‐week paclitaxel was associated with trends toward neuropathy. Conclusion: Although paclitaxel‐induced neuropathy is common, older age is not an independent risk factor. Clinical trial identification number. NCT00041119 (CALGB 40101). Implications for Practice: Age alone is not an independent risk factor for paclitaxel‐induced neuropathy. Mixed results have been reported regarding whether older cancer patients are at a greater risk for chemotherapy‐induced neuropathy. This article further evaluates the age‐based risk of this adverse event. [ABSTRACT FROM AUTHOR]

Background: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer.Methods: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade ≥ 3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined.Results: One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade ≥ 3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age ≥ 65 years (p < 0.01), decreased vision (p = 0.04), and poorer pretreatment physical function measures (p < 0.05) were found on univariate analysis to be significantly associated with increased incidence of grade ≥ 3 adverse events. Upon multivariate analysis, age ≥ 65 years (p = 0.01) and decreased vision (p = 0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade ≥ 3 adverse events.Conclusions: Age (≥ 65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring. [ABSTRACT FROM AUTHOR]

Objective Chemotherapy preference refers to a patient's interest in receiving chemotherapy. This study examined whether chemotherapy preference was associated with toxicity, efficacy, quality of life (QoL), and functional outcomes during and after completion of adjuvant chemotherapy in older women with breast cancer. Materials and Methods This study is a secondary analysis of CALGB 49907, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in patients age 65 years or older with breast cancer. A subset of 145 patients completed a questionnaire to describe chemotherapy preference pre-treatment. The association of this pre-treatment preference with the patient's perception of self-health, predicted and actual QoL, patient- and professional-reported toxicity, mental health, self-rated function, and survival was studied during and after treatment. Results The median age of patients was 71 years and 47% had a high preference for chemotherapy. On baseline demographics, the low preference group had a higher proportion of white patients (95% vs. 78%, p  = 0.004). Before treatment, low chemotherapy preference was associated with greater nausea/vomiting ( p  = 0.008). Mid-treatment, low preference was associated with lower QoL, worse social, emotional and physical function (all p  ≤ 0.02) and worse nausea/vomiting, cancer symptoms and financial worries (all p  < 0.05). The association noted mid-treatment, resolved after treatment completion except with financial worries which persisted at 24 months. Low preference was associated with higher rates of grade 3–5 adverse events (53% vs. 34%, p  = 0.02) but was not associated with survival. Conclusions Low chemotherapy preference prior to treatment initiation was associated with lower QoL, worse physical symptoms and self-rated function and more adverse events mid-treatment. There is no association of chemotherapy preference with survival. [ABSTRACT FROM AUTHOR]

Objective Actual weight-based (AWB) chemotherapy dosing is recommended for obese patients in the 2012 ASCO Clinical Practice Guideline. CALGB 49907, which utilized ABW-based adjuvant chemotherapy dosing, was a phase 3 trial in women age ≥ 65 years with early stage breast cancer, providing the opportunity to examine impact of such dosing on toxicities and outcome in older patients with breast cancer. Materials and Methods Adverse event data were available for 615 of 633 enrolled patients. Objectives were to assess grade ≥ 3 hematologic/non-hematologic toxicities by treatment arm, age, study entry BSA/BMI, and relapse-free (RFS) and overall survival (OS) by BSA/BMI. Results The 615 patients were sub-grouped by BSA (quartiles) and standard BMI categories, with BMI underweight/normal weight categories combined. Overall, grade ≥ 3 non-hematologic and hematologic toxicities occurred in 39.8% and 28.3% of patients, respectively. There were no significant differences in grade ≥ 3 toxicities among BSA quartiles. However, more grade ≥ 3 hematologic toxicities occurred in the underweight/normal weight BMI subgroup compared to overweight/obese subgroups (p = 0.048). Type of chemotherapy and age had no impact on toxicity occurrence by BSA/BMI categories. RFS was superior in the 25th–50th BSA percentile patients in univariate analysis (p = 0.042), as was OS in both univariate and multivariate analyses (p = 0.007, p = 0.009, respectively). No differences in RFS or OS were found by BMI categories. Conclusion Obesity was not correlated with adverse relapse or survival outcome, and grade ≥ 3 toxicities were not greater with ABW-based dosing. This supports safety and efficacy of ABW-based dosing as per the 2012 ASCO clinical practice guideline. ClinicalTrials.gov Identifier: NCT00024102 (49907). [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates weight trajectories in pre- versus postmenopausal breast cancer (BC) survivors diagnosed with hormone receptor-positive tumors, with a specific focus on discerning menopausal status and type of endocrine treatment (ET) as risk factors for weight gain during ET.Methods: We conducted a retrospective review of electronic medical records. Descriptive statistics and Chi-squared and t tests were used to compare pre- and postmenopausal women. Chi-squared tests and ANOVA were used for within-group associations between patient characteristics and weight trajectories. Log-binomial regression models were used to estimate relative risk for weight gain.Results: The final sample was 32% premenopausal (n = 140) and 68% postmenopausal (n = 298). Relative risk (RR) for weight gain during ET was highest in women who were premenopausal (RR = 1.29, 1.03–1.52) and had Stage 3 BC (RR = 2.12, 1.59–2.82), mastectomy (RR = 1.49, 1.19–1.88), axillary node dissection (RR = 1.39, 1.11–1.73), and chemotherapy (RR = 1.80, 1.37–2.36). For each kg of weight gained between BC diagnosis and start of ET, and for each additional year of age, RR of gaining weight during ET decreased (RR = 0.98, 0.97–0.99, and RR = 0.99, 0.98–0.99, respectively). Menopausal status and type of ET were not significant predictors of weight gain. In multivariable analysis, only weight loss between BC diagnosis and start of ET was significant.Conclusion: The association of weight loss prior to ET and subsequent substantial weight gain during ET warrants further investigation. [ABSTRACT FROM AUTHOR]

Background. In postmenopausal women diagnosed with breast cancer (BC), most BC tumors are hormone receptor positive and guidelines recommend adjuvant endocrine therapy that includes an aromatase inhibitor (AI). This study investigates the impact of a 6-week, home-based, self-directed walking program on the commonly reported side effect of AI-associated arthralgia (AIAA). Materials and Methods. In this phase II trial, consented BC patients were randomized to walking Intervention (n = 31) or Wait List Control (WLC; n = 31). Eligibility criteria included: stage 0-III BC, on AI for at least 4 weeks, ≥3 on a 5-point scale inquiring about joint symptom intensity "at its worst," and exercising ≤150 minutes per week. Outcomes were self-reported joint symptoms and psychosocial measures. Analyses comparing Intervention and WLC groups were conducted on an intention-to-treat basis to assess intervention impact at 6 weeks (postintervention) and at 6-months follow-up. Adjusted means were calculated to assess differences in two groups. Results. In our final sample (n = 62), mean age was 64 years, 74% were white, and 63% had a body mass index of 30 or higher. At postintervention, Intervention group participants reported significantly increased walking minutes per week, reduced stiffness, less difficulty with activities of daily living (ADL), and less perceived helplessness in managing joint symptoms. At 6-months follow-up (postwalking period in both Intervention and WLC), walking minutes per week had decreased significantly; however, improvements in stiffness and difficulty with ADLs were maintained. Conclusion. This study adds to the growing evidence base suggesting exercise as a safe alternative or adjunct to medications for the management of AIAA. [ABSTRACT FROM AUTHOR]