Abstract Physical inactivity and being overweight or obese are lifestyle factors that put breast cancer survivors at a higher risk for a cancer recurrence and/or development of other chronic ...diseases. Despite this, there is limited research that has identified effective lifestyle interventions aimed specifically at weight loss in breast cancer survivors. This pilot study is a single-arm experimental pre–post test design, conducted from November 2009 to July 2010, that tested the efficacy of a 24-week group-based lifestyle intervention modeled on the Diabetes Prevention Program in early stage breast cancer survivors (N=14). The intervention included 16 diet sessions led by a registered dietitian and 150 min/wk of moderate-to-vigorous exercise. Study outcome measures were completed at baseline, 24, and 36 weeks (nonintervention follow-up). The primary outcome was change in body weight, and secondary outcomes were change in body composition, aerobic fitness, dietary intake, and blood biomarkers. Overall, participants were postmenopausal women aged 54.6±8.3 years with obesity (body mass index 30.1±3.6), and had completed adjuvant cancer treatment 2 years prior. Results showed an average weight loss of 3.8±5.0 kg and a decrease in body mass index, percent body fat, and waist and hip circumferences at 24 weeks and an additional mean weight loss of 0.8±1.2 kg at 36 weeks. In exploratory analysis, participants who lost >7% body weight were older and attended a greater percentage of diet and supervised exercise sessions. There were no significant changes in any of the blood biomarkers at 24 and 36 weeks; however, the results provide a measure of expected effect size for future research studies. This pilot study demonstrated the efficacy of a lifestyle intervention based on the Diabetes Prevention Program in early stage breast cancer survivors and represents an innovative clinical intervention for dietetics practitioners to address the unmet need for programs.
Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein hs-CRP) associated with poor breast cancer outcomes. The NCIC Clinical Trials Group (NCIC CTG) ...MA.32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. Maintaining blinding of investigators to outcomes, we conducted a planned, Data Safety Monitoring Committee-approved, analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples.
Eligible nondiabetic subjects with T1-3, N0-3, M0 breast cancer who had completed surgery and (neo)adjuvant chemotherapy (if given) provided fasting plasma samples at random assignment and at six months. Glucose was measured locally; blood was aliquoted, frozen, and stored at -80°C. Paired plasma aliquots were analyzed for insulin, hs-CRP, and leptin. Spearman correlation coefficients were calculated and comparisons analyzed using Wilcoxon signed rank test. All statistical tests were two-sided.
Mean age was 52.1±9.5 years in the metformin group and 52.6 ± 9.8 years in the placebo group. Arms were balanced for estrogen/progesterone receptor, BMI, prior (neo)adjuvant chemotherapy, and stage. At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight -3.0%, glucose -3.8%, insulin -11.1%, homeostasis model assessment -17.1%, leptin -20.2%, hs-CRP -6.7%; all P values were less than or equal to .03. There was no statistically significant interaction of change in these variables with baseline BMI or insulin.
Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin.
The prevalence of breast cancer amongst older adults in Canada is increasing. This patient population faces unique challenges in the management of breast cancer, as older adults often have distinct ...biological, psychosocial, and treatment-related considerations. This paper presents an expert consensus of the Canadian treatment landscape, focusing on key considerations for optimizing selection of systemic therapy for advanced breast cancer in older adults. This paper aims to provide evidence-based recommendations and practical guidance for healthcare professionals involved in the care of older adults with breast cancer. By recognizing and addressing the specific needs of older adults, healthcare providers can optimize treatment outcomes and improve the overall quality of care for this population.
Adverse drug reactions such as ototoxicity, which occurs in approximately one-fifth of adult patients who receive cisplatin treatment, can incur large socioeconomic burdens on patients with ...testicular cancer who develop this cancer during early adulthood. Recent genome-wide association studies have identified genetic variants in
and
that are associated with cisplatin-induced ototoxicity. We sought to explore the role of these genetic susceptibility factors to cisplatin-induced ototoxicity in patients with testicular cancer.
Extensive clinical and demographic data were collected for 229 patients with testicular cancer treated with cisplatin. Patients were genotyped for two variants,
rs1872328 and
rs62283056, that have previously been associated with hearing loss in cisplatin-treated patients. Analyses were performed to investigate the association of these variants with ototoxicity in this cohort of adult patients with testicular cancer.
Pharmacogenomic analyses revealed that
rs1872328 was significantly associated with cisplatin-induced ototoxicity
= 2.83 × 10
, OR (95% CI):14.7 (2.6-84.2).
rs62283056 was not significantly associated with ototoxicity caused by cisplatin (
= 0.39); however, this variant was associated with hearing loss attributable to any cause
= 5.67 × 10
, OR (95% CI): 3.2 (1.4-7.7).
This study has provided the first evidence for the role of
rs1872328 in cisplatin-induced ototoxicity in patients with testicular cancer. These results support the use of this information to guide the development of strategies to prevent cisplatin-induced ototoxicity across cancers. Further, this study has highlighted the importance of phenotypic differences in replication studies and has provided further evidence for the role of
rs62283056 in susceptibility to hearing loss, which may be worsened by cisplatin treatment.
.
PURPOSEThe purpose of this study was to provide a rationale for “chemotherapy-periodized” exercise by characterizing cyclical variations in fatigue and exercise response across a chemotherapy cycle ...and comparing exercise adherence during chemotherapy between a prescription that is periodized according to chemotherapy cycle length and a standard linearly progressed prescription.
METHODSWomen with breast cancer who were prescribed taxane-based chemotherapy were randomly assigned to a supervised aerobic and resistance exercise program after a chemotherapy-periodized exercise prescription (n = 12) or to usual care during chemotherapy (n = 15). Fatigue and steady state exercise responses were assessed in both groups before the first taxane treatment and across the third treatment (i.e., 0–3 d prior and 3–5 d after the third treatment, and 0–3 d before the fourth treatment) to assess cyclical variations. Adherence to the chemotherapy-periodized exercise prescription was compared with adherence to a standard linear prescription from a prior study in a similar population (n = 51).
RESULTSFatigue increased from baseline (marginal mean ± standard error3.2 ± 0.4) to before the third treatment (4.1 ± 0.4, P = 0.025), then peaked at 3 to 5 d after the third treatment (5.1 ± 0.4, P = 0.001), before recovering before the fourth treatment (4.3 ± 0.5, P = 0.021). The peak in fatigue at 3 to 5 d post–third treatment corresponded to a decrease in steady state exercise oxygen consumption (V˙O2) (P = 0.013). Compared with a standard linear exercise prescription during chemotherapy, a chemotherapy-periodized exercise prescription resulted in higher attendance during the week after chemotherapy (57% ± 30% vs 77% ± 28%, P = 0.04) and overall attendance (63% + 25% vs 78% ± 23%, P = 0.05).
CONCLUSIONSFatigue and exercise V˙O2 vary across a chemotherapy cycle. A chemotherapy-periodized exercise prescription that accommodates cyclical variations in fatigue may increase adherence to supervised exercise.
The addition of pertuzumab to neoadjuvant trastuzumab and chemotherapy for women with early-stage, high-risk, HER2+ breast cancer has been observed to lead to higher pathologic complete response ...rates (pCR), and improved event-free survival compared to trastuzumab and chemotherapy alone. Based on available data, neoadjuvant pertuzumab is recommended by ESMO, ASCO, and NICE as well as by a Canadian Consensus Guideline Group. We discuss the implications for Canadian patients with HER2+ early breast cancer due to a second and final negative funding decision by the Canadian Agency for Drugs and Technologies in Health (CADTH) related to neoadjuvant pertuzumab. This decision will have adverse impacts for up to 1 in 6 women receiving neoadjuvant therapy for high-risk HER2+ breast cancer, due to suboptimal pCR rates and higher risks of invasive breast cancer recurrent events, resulting in the need for more toxic adjuvant therapy.
Background
Cardiovascular autonomic dysfunction is an early marker for cardiovascular disease. Anthracycline chemotherapy and left‐sided radiation for breast cancer are associated with negative ...autonomic function changes. This study's objectives were to characterize changes in, and the association of exercise training with, clinical indices of cardiovascular autonomic function across the trajectory of breast cancer therapy.
Subjects, Materials, and Methods
Seventy‐three patients receiving adjuvant chemotherapy participated to varying degrees in supervised aerobic and resistance exercise during chemotherapy ± radiation and for 20 weeks after. Resting heart rate (HRrest) and blood pressure were measured weekly during chemotherapy. HRrest, exercise heart rate recovery (HRrecovery), and aerobic fitness were measured at enrollment, end of chemotherapy ± radiation, and 10 and 20 weeks after treatment.
Results
During chemotherapy, HRrest increased in a parabolic manner within a single treatment and with increasing treatment dose, whereas systolic and diastolic blood pressure decreased linearly across treatments. Tachycardia and hypotension were present in 32%–51% of participants. Factors associated with weekly changes during chemotherapy included receiving anthracyclines or trastuzumab, days since last treatment, hematocrit, and exercise attendance. Receipt of anthracyclines, trastuzumab, and left‐sided radiation individually predicted impairments of HRrest and HRrecovery during chemotherapy ± radiation; however, aerobic fitness change and at least twice‐weekly exercise attendance predicted improvement. By 10 weeks after treatment, HRrest and blood pressure were not different from prechemotherapy.
Conclusion
In this study, chemotherapy resulted in increased HRrest and tachycardia, as well as decreased blood pressure and hypotension. Anthracyclines, trastuzumab, and left‐sided radiation were associated with HRrest elevations and impairments of HRrecovery, but exercise training at least twice a week appeared to mitigate these changes.
Implications for Practice
This study characterized changes in clinically accessible measures with well‐established prognostic value for cardiovascular disease, and investigated associations with cardiotoxic treatments and the positive influence of exercise. The chemotherapy‐related incremental increase in resting heart rate, with tachycardia occurring in one third of patients, and decrease in blood pressure, with hypotension occurring in one half of the patients, is relevant to oncology practitioners for clinical examination or patient report of related symptoms (i.e., dizziness). The weekly dose of two 60‐minute sessions of moderate‐intensity aerobic and resistance exercise that was identified as protective of cardiovascular autonomic impairments can easily be prescribed to patients by oncologists.
摘要
背景。心血管自主神经功能障碍是心血管疾病的早期指标。针对乳腺癌的蒽环类药物化疗和左侧放疗与自主神经功能的负面变化有关。本研究的目的是描述在乳腺癌治疗过程中心血管自主神经功能临床指标的变化，及这些指标与运动训练之间的关联。
受试者、材料和方法。接受辅助化疗的 73 名患者在化疗 ± 放疗期间及 20 周之后参加了不同程度的指导性有氧及抗阻运动。化疗期间每周测量静息心率 (HRrest) 和血压。我们会在报名时、化疗 ± 放疗结束时，以及治疗后 10 周和 20 周测量 HRrest、运动心率恢复 (HRrecovery) 和有氧适能。
结果。在化疗期间，HRrest 在单次治疗中以抛物线形式随着治疗剂量的增加而增加，而收缩压和舒张压会在治疗过程中呈线性下降。有 32%‐51% 的参与者出现心动过速和低血压。与化疗期间每周变化相关的因素包括接受蒽环类药物或曲妥单抗、上次治疗后的天数、血细胞比容和参加运动的人数。接受蒽环类药物、曲妥单抗和左侧放疗分别预示出化疗 ± 放疗期间 HRrest 和 HRrecovery的障碍；但是，有氧健身的变化和每周至少两次的运动预计会有所改善。到治疗后 10 周，HRrest 和血压与化疗前相比没有分别。
结论。在本研究中，化疗导致 HRrest 增加、心动过速、血压下降和低血压。蒽环类药物、曲妥单抗和左侧放疗与 HRrest 升高和 HRrecovery 障碍有关，但每周进行两次运动似乎可以减缓这些变化。
对实践的启示:本研究根据心血管疾病的确定预后值来表现临床上可利用措施的变化，同时研究了与心脏毒性治疗和运动的积极影响之间的关联。与化疗相关的静息心率逐步增加，导致 1/3 的患者出现心动过速，血压降低，导致 1/2 患者出现低血压，这些均与肿瘤医生进行临床检查或患者报告相关症状(即头晕)相关。肿瘤医生可轻易给患者开具处方，每周进行两次 60 分钟的中等强度有氧及抗阻运动，这些运动被认为可以避免心血管自主神经损伤。
Treatment for breast cancer, including chemotherapy and radiation can have cardiovascular side effects. This study's objectives were to characterize changes in, and the association of exercise training with, clinical indices of cardiovascular autonomic function across the trajectory of breast cancer therapy.
ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated ...positivity could indicate differential associations of positivity with breast cancer outcomes.
MA.27 (ClinicalTrials.gov identifier: NCT00066573) was a phase III adjuvant trial of exemestane versus anastrozole in postmenopausal women with early-stage breast cancer. Immunochemistry ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation and statistically standardized to mean 0 and standard deviation (SD) 1 after Box-Cox variance stabilization transformations of square for ER; for PgR, (1) natural logarithm (0.1 added to 0 HSCOREs and 0%+) and (2) square root. Our primary end point was MA.27 distant disease-free survival (DDFS) at a median 4.1-year follow-up, and secondary end point was event-free survival (EFS). Univariate survival with cut points at SDs about a mean of 0 (≤-1; (-1, 0; (0, 1; >1) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions had two-sided Wald tests and nominal significance
< .05.
Of 7,576 women accrued, 3,048 women's tumors had machine-quantitated image analysis results: 2,900 (95%) for ER, 2,726 (89%) for PgR, and 2,582 (85% of 3,048) with both ER and PgR. Higher statistically standardized ER and PgR HSCORE and %+ were associated with better univariate DDFS and EFS (
< .001). In multivariable assessments, ER HSCORE and %+ were not significantly associated (
= .52-.88) with DDFS in models with PgR, whereas higher PgR HSCORE and %+ were significantly associated with better DDFS (
= .001) in models with ER.
Adjunctive statistical standardization differentiated quantitated levels of ER and PgR. Patients with higher ER- and PgR-standardized units had superior DDFS compared with those with HSCOREs and %+ ≤-1.
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