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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.

Abstract Background Medical mistrust, rooted in unethical research, is a barrier to cancer‐related health care for Black/African American (AA) persons. Understanding trust, mistrust, and health care experiences is crucial, especially in multiple myeloma (MM), which disproportionately burdens Black/AA persons in incidence and survival. Study Purpose This study qualitatively examines the experiences of Black/AA and White dyads (patient with MM and adult caregiver) to gain insights into these phenomena. Methods From November 2021 to April 2022, we recruited 21 dyads from the UNC Lineberger Comprehensive Cancer Center. Participants completed a sociodemographic survey and a 60–90 min semi‐structured interview. We used ATLAS.ti v9 for project management and to facilitate data analysis using the Sort and Sift, Think and Shift approach (ResearchTalk Inc). Results We interviewed 21 racially concordant dyads (11 Black/AA, 10 White) with mean patient ages of 70 (Black/AA) and 72 (White) at enrollment. Both Black/AA and White caregivers had a mean enrollment age of 68. The mean duration from MM diagnosis to enrollment for all patients was 5.5 years. Four key themes emerged: (1) knowledge and trust, (2) heightened emotions and discomfort, (3) differing mental constructs of health care experiences, and (4) mitigating mistrust, which varied by self‐identified race. Black/AA participants had greater knowledge of historical events like the U.S. Public Health Service Untreated Syphilis Study at Tuskegee and carried the emotional burden longer. They also emphasized self‐learning and self‐guided research about MM for informed medical decision‐making. Both Black/AA and White dyads emphasized the pivotal role of patient‐provider relationships and effective communication in fostering trust and addressing concerns. Conclusion Our study offers contextual insights into the enduring challenges of medical mistrust, particularly within the Black/AA community, and its implications for patients and caregivers accessing and receiving MM‐related care. Future studies should leverage these insights to guide the development of multilevel interventions addressing medical mistrust within the Black/AA community.

Abstract Background Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. Methods Patients with stage I–III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. Results Of 126 patients approached, 56 (44%) enrolled. Forty‐five (80%) received ≥1 dose of memantine and completed pre‐post assessments. Seventy‐six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty‐four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%–91% across objective cognitive domain composite measures. Sixty‐six percent self‐reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. Conclusions Memantine was well‐tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre‐ to post‐assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. Trial Registration ClinicalTrials.gov NCT04033419.

Abstract Identifying patients at higher risk of chemotherapy-induced peripheral neuropathy (CIPN) is a major unmet need given its high incidence, persistence, and detrimental effect on quality of life. We determined if the expression of p16, a biomarker of aging and cellular senescence, predicts CIPN in a prospective, multi-center study of 152 participants enrolled between 2014 and 2018. Any women with newly diagnosed Stage I–III breast cancer scheduled to receive taxane-containing chemotherapy was eligible. The primary outcome was development of grade 2 or higher CIPN during chemotherapy graded by the clinician before each chemotherapy cycle (NCI-CTCAE v5 criteria). We measured p16 expression in peripheral blood T cells by qPCR before and at the end of chemotherapy. A multivariate model identified risk factors for CIPN and included taxane regimen type, p16Age Gap, a measure of discordance between chronological age and p16 expression, and p16 expression before chemotherapy. Participants with higher p16Age Gap—higher chronological age but lower p16 expression prior to chemotherapy - were at the highest risk. In addition, higher levels of p16 before treatment, regardless of patient age, conferred an increased risk of CIPN. Incidence of CIPN positively correlated with chemotherapy-induced increase in p16 expression, with the largest increase seen in participants with the lowest p16 expression before treatment. We have shown that p16 expression levels before treatment can identify patients at high risk for taxane-induced CIPN. If confirmed, p16 might help guide chemotherapy selection in early breast cancer.

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. [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.

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

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]