Late effects in a high-risk population of breast cancer survivors.

PURPOSE: To better understand the impact of cancer and treatment on outcomes and guide program development, we evaluated breast cancer survivors at risk for long-term medical and psychosocial issues who participated in survivorship care visits (SVs) at Johns Hopkins Hospital. METHODS: We conducted a prospective survey study of women with stage I-III breast cancer who participated in SVs from 2010-2016. The same 56-item questionnaire administered at SV and follow-up included an assessment of symptoms, social factors, demographics, anxiety, depression, and comorbidities. We added the Godin Exercise questionnaire to the follow-up. RESULTS: In 2018, 74 participants were identified as disease-free and mailed a follow-up survey; 52 (70.3%) completed the survey. At a median follow-up time of 3.1 years after diagnosis, participants were less likely to be employed (54% vs. 67%) than at the SV. About two-thirds were sedentary, and this was associated with high body mass index (p = 0.02). Sufficiently active participants (≥ 150 min per week of moderate-intensity activity) were less likely to report pain (p = 0.02) or fatigue (p = 0.001). Although 19% had moderate/severe anxiety or depression at follow-up, participants who reported employment satisfaction were less likely to be depressed (p = 0.02). CONCLUSIONS: Awareness of issues faced by survivors is critical for enhancing care and developing models to identify patients who might benefit most from targeted long-term interventions. IMPLICATIONS FOR CANCER SURVIVORS: Interventions to address physical activity, persistent symptoms, and mental health are critical for breast cancer survivors.

Breast cancer survivorship care plans: what are they covering and how well do they align with national guidelines?

PURPOSE: Survivorship care plans (SCPs) provide key information about cancer treatment history and follow-up recommendations. We describe the completeness of breast cancer SCPs and evaluate guideline concordance of follow-up recommendations. METHODS: We analyzed 149 breast cancer SCPs from two sites, abstracting demographics, cancer/treatment details, surveillance plans, and health promotion advice. SCP recommendations and provided information were compared to American Cancer Society/American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines. RESULTS: SCP information provided in > 90% of the plans included patient age; relevant providers; cancer stage; treatment details; and physical exam, mammogram, and health promotion recommendations. SCP components completed less frequently included post-treatment symptoms/side effects (67%). All SCPs at the community site were uniform but had the potential for oversurveillance if visits occurred every 3 months in years 1-2 or every 6 months in years 3-5 with multiple cancer providers. The academic site recommended three predominant patterns of follow-up: (1) primary care provider every 6-12 months; (2) cancer team every 3-6 months (year 1), every 6-12 months (years 4-5); and (3) alternating oncology providers every 3-6 months (years 1-2) then every 6 months. Compared to guidelines, these patterns recommend under- and oversurveillance at various times. Mammography recommendations showed guideline concordance (annual) for 84%, oversurveillance for 10%, and were incomplete for 6%. SCPs of only 12/79 (15%) women on aromatase inhibitors recommended guideline-concordant bone density testing. CONCLUSIONS: SCP content is more complete for demographic and treatment summary information but has follow-up recommendation gaps. Efforts to improve follow-up recommendations are needed.

A Phase II study of the polyamine analog N1,N11-diethylnorspermine (DENSpm) daily for five days every 21 days in patients with previously treated metastatic breast cancer.

PURPOSE: Polyamines are ubiquitous intracellular polycationic molecules essential for cell growth and differentiation. Polyamine analogs down-regulate ornithine decarboxylase, induce spermidine/spermine N1-acetyltransferase, deplete natural polyamine pools, inhibit growth, and induce programmed cell death in breast cancer models. This study evaluated the activity of the first-generation analog DENSpm in women with metastatic breast cancer. EXPERIMENTAL DESIGN: The overall accrual goal was 34 patients (30 evaluable) in a two-stage design. The second stage of accrual was to proceed if > or =2 among first 15 evaluable patients were progression free at 4 months. The primary objective was to determine whether > or =20% of metastatic breast cancer patients treated with DENSpm as second- or third-line therapy remained progression free after 4 months. RESULTS: Sixteen patients (median age, 52 years; range, 34-65; median performance status, 1; range, 0-1) enrolled in the first stage received 43 cycles (median, 2; range, 1-6) of 100 mg/m2 DENSpm as a 15-min infusion i.v. on days 1-5 every 21 days. All 16 patients were evaluable for toxicity; 15 were evaluable for response. All patients had disease progression by 4 months, and the study closed after the first stage of accrual. The main toxicities included grade 1-2 abdominal pain, transient perioral numbness, nausea, and grade 1 thrombocytopenia. Two patients had grade 3 abdominal pain during cycle 2 infusion: one was hospitalized, and another was subsequently retreated at 80% dose without pain recurrence. CONCLUSIONS: Although this dose and administration schedule of DENSpm was quite tolerable, no evidence of clinical activity was detected. Encouraging preclinical activity of polyamine analogs alone and in combination with cytotoxic drugs supports the continued evaluation of newer-generation polyamine analogs for the treatment and prevention of breast cancer.