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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. [ABSTRACT FROM AUTHOR]

This phase I/II trial investigates the safety and feasibility of six cycles of concurrent taxane, anthracycline and cyclophosphamide on a dose dense schedule. Patients with stage II/III breast cancer were treated with docetaxel (T) 75 mg/m2, epirubicin (E) 75 mg/m2 (cohort 1, n = 3) or 100 mg/m2 (cohort 2, n = 12), and cyclophosphamide (C) 500 mg/m2 IV on day 1, with pegfilgrastim 6 mg subcutaneously on day 2, every 2 weeks for six cycles. Patients were assessed for toxicity every 2 weeks; cardiac function and response (if neoadjuvant) were assessed after six cycles. All patients in cohort 1 received 100% planned dose intensity; in cohort 2, five of twelve patients received 100% and 11/12 received >80%. There were no dose reductions or delays for day 1 myelotoxicity. Dose reductions as a result of febrile neutropenia (FN) occurred in cohort 2, with six of twelve patients experiencing FN in seven of sixty-nine cycles. Six patients had anemia ≥grade 3; five received RBC transfusion and seven received an erythropoietic growth factor. Four patients required dose reductions for nonhematologic toxicity (two mucositis; one neurotoxicity; one diarrhea + cellulitis). Four patients developed thrombophlebitis, which was associated with FN in one of four. Two of fourteen evaluable patients had asymptomatic decreases in LVEF >10%; all remained within normal range. All four patients receiving neoadjuvant TEC had significant clinical responses (one CR, three PR). No pathologic CRs were seen. Conclusions: Dose dense TEC chemotherapy is feasible, has acceptable toxicity at doses equivalent to TAC (docetaxel 75 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 600 mg/m2), and has moderate but manageable toxicity using a higher epirubicin dose of 100 mg/m2, with FN occurring in six of twelve patients at the higher dose. [ABSTRACT FROM AUTHOR]

Background Senescent cells, which express p16INK4a, accumulate with aging and contribute to age-related pathology. To understand whether cytotoxic agents promote molecular aging, we measured expression of p16INK4a and other senescence markers in breast cancer patients treated with adjuvant chemotherapy. Methods Blood and clinical information were prospectively obtained from 33 women with stage I to III breast cancer at four time points: before anthracycline-based chemotherapy, immediately after anthracycline-based chemotherapy, 3 months after anthracycline-based chemotherapy, and 12 months after anthracycline-based chemotherapy. Expression of senescence markers p16INK4a and ARF mRNA was determined using TaqMan quantitative reverse-transcription polymerase chain reaction in CD3+ T lymphocytes, telomere length was determined by Southern analysis, and senescence-associated cytokines were determined by enzyme-linked immunosorbent assay. Findings were independently assessed in a cross-sectional cohort of 176 breast cancer survivors enrolled a median of 3.4 years after treatment; 39% previously received chemotherapy. All statistical tests were two-sided. Results In prospectively analyzed patients, expression of p16INK4a and ARF increased immediately after chemotherapy and remained elevated 12 months after treatment. Median increase in log2p16INK4a was 0.81 (interquartile range = 0.28–1.62; Wilcoxon signed-rank P < .001), or a 75% absolute increase in expression, equivalent to the increase observed over 14.7 years of chronological aging. ARF expression was comparably increased (P < .001). Increased expression of p16INK4a and ARF was associated with dose-dense therapy and hematological toxicity. Expression of two senescence-associated cytokines (VEGFA and MCP1) was durably increased by adjuvant chemotherapy. Telomere length was not affected by chemotherapy. In a cross-sectional cohort, prior chemotherapy exposure was independently associated with a log2-increase in p16INK4a expression of 0.57 (repeated measures model, P < .001), comparable with 10.4 years of chronological aging. Conclusions Adjuvant chemotherapy for breast cancer is gerontogenic, inducing cellular senescence in vivo, thereby accelerating molecular aging of hematopoietic tissues. [ABSTRACT FROM PUBLISHER]