Preferences for breast cancer survivorship care by rural/urban residence and age at diagnosis.

PURPOSE: Preferences for survivorship care among recently treated breast cancer survivors may vary by rural-urban residence and age, but potential differences have not been examined. METHODS: We conducted a cross-sectional survey of survivorship preferences among women treated for non-metastatic breast cancer 6-24 months prior to recruitment. RESULTS: We surveyed 203 women (66% response) with American Joint Committee on Cancer Stage I or II breast cancer. Rural residents comprised 36.5% of respondents (82.7% White, non-Hispanic; 52.5% < college education) and 29.6% were ≥ 65 years. More than 95% indicated that checking for recurrence, receiving additional treatment, evaluation of side effects, and identification of late effects were "very important" reasons for follow-up care. The most common topics identified as "very important" for survivorship care discussions were recommendations for healthy behaviors (65.3%), best sources for breast cancer information (65.3%), and effects on family (53.3%) and job (53.8%). Women 65 years and older preferred to discuss follow-up care at the time of diagnosis (p = 0.002), with younger women preferring during (32%) or after treatment (39.1%). Rural survivors were significantly more likely to identify follow-up care reasons not related to the initial breast cancer as "very important" than urban survivors, including screening for other cancers, and examinations or tests for non-cancer diseases (both p = 0.01). CONCLUSIONS: Survivorship care in accordance with national recommendations will likely be accepted by breast cancer survivors. Tailoring breast cancer survivorship care by timing, integration of primary care services, and specific psychosocial topics may best meet the needs of different ages and demographics.

National Institute on Aging /Alzheimer's Association criteria for Mild Cognitive Impairment applied to chemotherapy treated breast cancer survivors.

BACKGROUND: In this analysis we use the National Institute on Aging/Alzheimer's Association (NIA/AA) criteria to identify Mild Cognitive Impairment (MCI) in a sample of breast cancer survivors treated with chemotherapy. METHODS: Sixty women ages 39-79 on a prospective clinical trial of donepezil were assessed at baseline using a battery of standardized/validated neurocognitive measures. Cognitive status was adjudicated to identify MCI by a panel of dementia experts. RESULTS: Fifty percent were not cognitively impaired, 43% met the NIA/AA criteria for MCI, 2% had dementia, and 5% could not be classified. DISCUSSION: In this sample, nearly half of breast cancer survivors met the NIA/AA criteria for MCI. We propose these criteria be used to define cancer-related Mild Cognitive Impairment (cMCI), providing a framework for conducting additional studies to further characterize cMCI and identify clinical, imaging, and genetic factors associated with the progression of cMCI to more advanced stages of cognitive impairment.

Disparities in barriers to follow-up care between African American and White breast cancer survivors.

PURPOSE: Despite recommendations for breast cancer survivorship care, African American women are less likely to receive appropriate follow-up care, which is concerning due to their higher mortality rates. This study describes differences in barriers to follow-up care between African American and White breast cancer survivors. METHODS: We conducted a mailed survey of women treated for non-metastatic breast cancer in 2009-2011, 6-24 months post-treatment (N = 203). Survivors were asked about 14 potential barriers to follow-up care. We used logistic regression to explore associations between barriers and race, adjusting for covariates. RESULTS: Our participants included 31 African American and 160 White survivors. At least one barrier to follow-up care was reported by 62 %. Compared to White survivors, African Americans were more likely to identify barriers related to out-of-pocket costs (28 vs. 51.6 %, p = 0.01), other health care costs (21.3 vs. 45.2 %, p = 0.01), anxiety/worry (29.4 vs. 51.6 %, p = 0.02), and transportation (4.4 vs. 16.1 %, p = 0.03). After adjustment for covariates, African Americans were three times as likely to report at least one barrier to care (odds ratio (OR) = 3.3, 95 % confidence interval (CI) = 1.1-10.1). CONCLUSIONS: Barriers to care are common among breast cancer survivors, especially African American women. Financial barriers to care may prevent minority and underserved survivors from accessing follow-up care. Enhancing insurance coverage or addressing out-of-pocket costs may help address financial barriers to follow-up care among breast cancer survivors. Psychosocial care aimed at reducing fear of recurrence may also be important to improve access among African American breast cancer survivors.

Chronic statin administration may attenuate early anthracycline-associated declines in left ventricular ejection function.

BACKGROUND: Recent studies have shown an association between statin therapy and a reduced risk of heart failure among breast cancer survivors. Our goal was to evaluate whether statin therapy for prevention of cardiovascular (CV) disease would ameliorate declines in the left ventricular ejection fraction (LVEF) that is often observed during anthracycline-based chemotherapy (Anth-bC). METHODS: There were 51 participants (33 women and 18 men, aged 48 ± 2 years). We obtained cardiovascular magnetic resonance imaging (CMRI) measurements of LVEF before and 6 months after initiation of Anth-bC for patients with breast cancer, leukemia, or lymphoma. Fourteen individuals received statin therapy, and 37 patients received no statins. MR image analysts were blinded to participant identifiers. RESULTS: Individuals receiving statins were older and often had diabetes mellitus (DM), hypertension (HTN), and hyperlipidemia (HLD). For those receiving statins, LVEF was 56.6% ± 1.4% at baseline and 54.1% ± 1.3% 6 months after initiating anthracycline treatment (P = 0.15). For those not receiving statins, LVEF was 57.5% ± 1.4% at baseline and decreased to 52.4% ± 1.2% over a similar 6-month interval (P = 0.0003). In a multivariable model accounting for age, sex, DM, HTN, HLD, and cumulative amount of anthracycline received, LVEF remained unchanged in participants receiving a statin (+1.1% ± 2.6%) vs a -6.5% ± 1.5% decline among those not receiving a statin (P = 0.03). CONCLUSIONS: These data highlight the finding that individuals receiving statin therapy for prevention of cardiovascular disease may experience less deterioration in LVEF with early receipt of Anth-bC than individuals not receiving statins. Further studies with large numbers of participants are warranted to determine if statins protect against LVEF decline in patients receiving Anth-bC.

Feasibility of implementing a community-based randomized trial of yoga for women undergoing chemotherapy for breast cancer.

BACKGROUND: Treatment-related symptoms and decreased health-related quality of life (HRQoL) frequently occur during chemotherapy for breast cancer. Although research findings suggest that yoga can reduce symptoms and Improve HRQoL after treatment, potential benefits of yoga during chemotherapy have received minimal attention. OBJECTIVE: To estimate accrual, adherence, study retention, and preliminary efficacy of a yoga intervention compared with an active control group for breast cancer patients during chemotherapy. METHODS: Women with stage I-III breast cancer were recruited from 3 community cancer clinics and randomized to 10 weeks of gentle yoga or wellness education. Depressive symptoms, fatigue, sleep, and HRQoL were assessed at baseline, mid-intervention (Week 5), and after intervention (Week 10). RESULTS: 40 women aged 29-83 years (median, 48 years; 88% white) were randomized to yoga (n = 22) or wellness education (n = 18). The groups did not differ significantly on baseline characteristics, adherence, or study retention. Participant feedback was positive and comparable between groups. Meaningful within-group differences were identified For sleep adequacy and quantity in yoga participants and for somnolence in wellness-education participants. LIMITATIONS: Small sample size and lack of a usual-care control group. CONCLUSIONS: This study established Feasibility of a community-based randomized trial of yoga and an active comparison group for women undergoing chemotherapy for breast cancer. Preliminary efficacy estimates suggest that yoga improves sleep adequacy Symptom severity and interference remained stable during chemotherapy for the yoga group and snowed a trend toward increasing in the control group. The study highlighted obstacles to multisite yoga research during cancer treatment. FUNDING/SPONSORSHIP: National Cancer Institute (3U10 CA081851, PI; Shaw; R25 CA122061, PI: Avis); Translational Science Institute, Wake Forest School of Medicine.

Longitudinal assessment of concurrent changes in left ventricular ejection fraction and left ventricular myocardial tissue characteristics after administration of cardiotoxic chemotherapies using T1-weighted and T2-weighted cardiovascular magnetic resonance.

BACKGROUND: In a murine anthracycline-related cardiotoxicity model, increases in cardiovascular magnetic resonance myocardial contrast-enhanced T1-weighted signal intensity are associated with myocellular injury and decreases with left ventricular ejection fraction. We sought to determine whether T1- and T2-weighted measures of signal intensity associate with decreases in left ventricular ejection fraction in human subjects receiving potentially cardiotoxic chemotherapy. METHODS AND RESULTS: In 65 individuals with breast cancer (n=51) or a hematologic malignancy (n=14), we measured left ventricular volumes, ejection fraction, and contrast-enhanced T1-weighted and T2-weighted signal intensity before and 3 months after initiating potentially cardiotoxic chemotherapy using blinded, unpaired analysis of cardiovascular magnetic resonance images. Participants were aged 51 ± 12 years, of whom 55% received an anthracycline, 38% received a monoclonal antibody, and 6% received an antimicrotubule agent. Overall, left ventricular ejection fraction decreased from 57 ± 6% to 54 ± 7% (P<0.001) because of an increase in end-systolic volume (P<0.05). T1-weighted signal intensities also increased from 14.1 ± 5.1 to 15.9 ± 6.8 (P<0.05), with baseline values trending higher among individuals who received chemotherapy before study enrollment (P=0.06). Changes in T1-weighted signal intensity did not differ within the 17 LV myocardial segments (P=0.97). Myocardial edema quantified from T2-weighted images did not change significantly after 3 months (P=0.70). CONCLUSIONS: Concordant with previous animal studies, cardiovascular magnetic resonance measures of contrast-enhanced T1-weighted signal intensity occur commensurate with small but significant left ventricular ejection fraction declines 3 months after the receipt of potentially cardiotoxic chemotherapy. These data indicate that changes in T1-weighted signal intensity may serve as an early marker of subclinical injury related to the administration of potentially cardiotoxic chemotherapy in human subjects.

Cognitive factors associated with adherence to oral antiestrogen therapy: results from the cognition in the study of tamoxifen and raloxifene (Co-STAR) study.

Little is known about the cognitive factors associated with adherence to antiestrogen therapy. Our objective was to investigate the association between domain-specific cognitive function and adherence among women in a clinical prevention trial of oral antiestrogen therapies. We performed a secondary analysis of Co-STAR, an ancillary study of the STAR breast cancer prevention trial in which postmenopausal women at increased breast cancer risk were randomized to tamoxifen or raloxifene. Co-STAR enrolled nondemented participants ≥65 years old to compare treatment effects on cognition. The cognitive battery assessed global cognitive function (Modified Mini-Mental State Exam), and specific cognitive domains of verbal knowledge, verbal fluency, figural memory, verbal memory, attention and working memory, spatial ability, and fine motor speed. Adherence was defined by a ratio of actual time taking therapy per protocol ≥80% of expected time. Logistic regression was used to evaluate the association between cognitive test scores and adherence to therapy. The mean age of the 1,331 Co-STAR participants was 67.2 ± 4.3 years. Mean 3MS score was 95.1 (4.7) and 14% were nonadherent. In adjusted analyses, the odds of nonadherence were lower for those with better scores on verbal memory [OR (95% confidence interval): 0.75 (0.62-0.92)]. Larger relative deficits in verbal memory compared with verbal fluency were also associated with nonadherence [1.28 (1.08-1.51)]. Among nondemented older women, subtle differences in memory performance were associated with medication adherence. Differential performance across cognitive domains may help identify persons at greater risk for poor adherence.

Oral paricalcitol (19-nor-1,25-dihydroxyvitamin D2) in women receiving chemotherapy for metastatic breast cancer: a feasibility trial.

The vitamin D hormone, [1,25(OH) 2D, calcitriol], inhibits proliferation and angiogenesis in breast cancer but its therapeutic use is limited by hypercalcemia. Synthetic analogs of 1,25(OH) 2D that are less calcemic, such as paricalcitol (19-nor-1,25-Dihydroxyvitamin D 2), are used to treat hyperparathyroidism associated with chronic kidney disease. We sought to determine the safety and feasibility of taking oral paricalcitol with taxane-based chemotherapy in women with metastatic breast cancer (MBC). Oral paricalcitol was considered safe if it did not result in excessive toxicity, defined as grade 3 or higher serum calcium levels. It was considered feasible if the majority of women could take eight weeks of continuous therapy in the first three months. Serum calcium was monitored weekly and the paricalcitol dose was adjusted based on its calcemic effect. Intact parathyroid hormone (iPTH) was monitored as a marker of paricalcitol activity. Twenty-four women with MBC were enrolled. Twenty women (83%) received eight weeks of continuous therapy. Paricalcitol was well-tolerated with no instances of hypercalcemia grade 2 or greater. Fourteen women (54%) were able to escalate the dose. The dose range of paricalcitol in the first 3 mo was 2-7 ug/day. Serum iPTH levels at baseline were significantly higher in women with serum 25-Hydroxyvitamin D (25-OHD) levels less than 30 ng/ml (96.4 ± 40.9 pg/ml) vs. 46.2 ± 20.3 pg/ml (p = 0 0.001) (iPTH reference 12-72 pg/ml). We conclude that paricalcitol is safe and feasible in women with MBC who are receiving chemotherapy.

Phase I study and biomarker analysis of lapatinib and concurrent radiation for locally advanced breast cancer.

PURPOSE: This phase I study assessed the toxicity and safety of combining daily lapatinib with radiation therapy. Sequential tumor biopsies were obtained to evaluate changes in biomarkers, such as epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2) signaling pathways. METHODS: Eligibility for this dose-escalation study included unresectable and locally recurrent or chemotherapy-refractory and locally advanced breast cancer, and adequate organ function. Patients underwent three serial biopsies: at baseline, after 1 week of lapatinib alone, and after 1 week of lapatinib and radiation. Endpoints included determination of toxicity, maximum tolerated dose, and analysis of the effect of lapatinib with or without radiation on EGFR and HER2 signaling pathways by immunohistochemistry. RESULTS: Doses of lapatinib up to 1,500 mg/day were well tolerated. Toxicity of grade 3 or more was limited to radiation dermatitis and pain. Out of 19 patients treated, in field responses per response evaluation criteria in solid tumors criteria were complete in four patients and partial in six patients. Serial biopsies were obtained in 16 patients with no complications. Total Her2 was relatively unchanged while phospho-Her2, phospho-Akt, and phospho-ERK showed variable responses to both lapatinib alone and dual therapy with lapatinib and radiation. CONCLUSIONS: The combination of lapatinib and radiation was well tolerated in this patient cohort. Overall local response rates were comparable to those reported in other studies in this patient population. Biopsies were safely performed at all time points. Inhibition of HER2 and downstream signaling pathways was identified, although no strong correlation with response was seen.

Breast cancer subtype affects patterns of failure of brain metastases after treatment with stereotactic radiosurgery.

We investigate the variance in patterns of failure after Gamma Knife™ radiosurgery (GKRS) for patients with brain metastases based on the subtype of the primary breast cancer. Between 2000 and 2010, 154 breast cancer patients were treated with GKRS for brain metastases. Tumor subtypes were approximated based on hormone receptor (HR) and HER2 status of the primary cancer: Luminal A/B (HR+/HER2(-)); HER2 (HER2+/HR(-)); Luminal HER2 (HR+/HER2+), Basal (HR(-)/HER2(-)), and then based on HER2 status alone. The median follow-up period was 54 months. Kaplan-Meier method was used to estimate survival times. Multivariable analysis was performed using Cox regression models. Median number of lesions treated was two (range 1-15) with a median dose of 20 Gy (range 9-24 Gy). Median overall survival (OS) was 7, 9, 11 and 22 months for Basal, Luminal A/B, HER2, and Luminal HER2, respectively (p = 0.001), and was 17 and 8 months for HER2+ and HER(-) patients, respectively (p < 0.001). Breast cancer subtype did not predict time to local failure (p = 0.554), but did predict distant brain failure rate (76, 47, 47, 36 % at 1 year for Basal, Luminal A/B, HER2, and Luminal HER2 respectively, p < 0.001). An increased proportion of HER2+ patients experienced neurologic death (46 vs 31 %, p = 0.066). Multivariate analysis revealed that HER2+ patients (p = 0.007) independently predicted for improved survival. Women with basal subtype have high rates of distant brain failure and worsened survival. Our data suggest that differences in biologic behavior of brain metastasis occur across breast cancer subtypes.

A retrospective review of the metabolic syndrome in women diagnosed with breast cancer and correlation with estrogen receptor.

Women diagnosed with obesity and breast cancer have an increased risk of recurrence and death (Protani et al., Breast Cancer Res Treat 123:627-635, 1). Obesity is associated with the metabolic syndrome--a pathophysiologically distinct inflammatory process comprised of central obesity, insulin resistance, hypertension, and atherogenic dyslipidemia. The relationship of obesity as a risk factor for breast cancer is complex with a protective effect for younger women in contrast to a risk for older women (Kabat et al., Cancer Epidemiol Biomarkers Prev 18:2046-2053, 2; Ursin et al., Epidemiology 6:137-141, 3). The metabolic syndrome has been associated with the risk of cancer, and pro-inflammatory circulating factors may be associated with risk of more aggressive breast cancer (Capasso et al., Cancer Biol Ther 10:1240-1243, 4; Healy et al., Clin Oncol (R Coll Radiol) 22:281-288, 5; Laukkanen et al., Cancer Epidemiol Biomarkers Prev 13:1646-1650, 6). We conducted a retrospective review of 860 breast cancer patients to determine the relationship between estrogen receptor status and the metabolic syndrome. We collected the relevant metabolic diagnoses, medications, physical findings, and laboratory values and adapted the National Cholesterol Education Program criteria to define the metabolic syndrome retrospectively. No relationship was found between estrogen receptor status and the individual components of the metabolic syndrome. Based on findings in the medical records, 15% of the women with breast cancer had the metabolic syndrome, and 26% of the women were considered obese, 16% hyperglycemic, 54% hypertensive, and 30% dyslipidemic. The metabolic syndrome was associated with advanced age and African-American race (P < 0.001). When adjusted for age, race, and stage, the metabolic syndrome was marginally associated with estrogen receptor-positive tumors (P = 0.054). Our findings do not support the concern that the metabolic syndrome may contribute to more biologically aggressive breast cancer.

Current therapeutic options for breast cancer central nervous system metastases.

OPINION STATEMENT: Breast cancer metastases to the central nervous system (CNS) has devastating consequences for the individual. As treatment options for metastatic breast cancer expand and as quality of life and overall survival improve, researchers are targeting potential treatments for this sanctuary site. Attention is now being focused on defining the phenotype of breast cancer that has a propensity to metastasize to the CNS. Specific therapies that penetrate the blood brain barrier as well as adjuvant therapies that decrease recurrence in the CNS are currently being investigated. We will review current approaches to the diagnosis, evaluation, and treatment of CNS metastases in breast cancer patients.

Lavage and nipple aspiration of breast ductal fluids: a source of biomarkers for environmental mutagenesis.

The acquisition of breast ductal fluid by nipple aspiration and ductal lavage are simple noninvasive procedures to sample breast tissue. Nipple aspiration fluid (NAF) obtained with gentle suction and a simple syringe-adapted apparatus may evaluate the secretory components that bathe the ductal epithelial cells. Evaluations have included the quantification of soluble markers (carcinoembryonic antigen and prostatic-specific antigen), DNA amplification, protein gel electrophoresis, and mutagenesis assays. It has been suggested that environmental mutagens in the breast ductal system may contribute to carcinogenesis. The feasibility of mutagenesis assays on NAF has been limited by the small size of the samples obtained. Three small clinical studies detected mutagens in 6-14% of the samples using the Salmonella Ames assay. Ductal lavage collects more of a cellular aspirate from the ductal system utilizing a microcatheter. Early studies on ductal lavage fluid have included cytology and methylation-specific PCR. Ductal lavage in a high-risk group has identified cellular atypia in 21% of those sampled. Samples obtained through the nipple, by aspiration or lavage, are the proteinaceous secretions from the ductal system and ductal epithelial cells. The fluid represents the cellular events and the dynamic secretory process of the breast and may include potential initiators of the carcinogenesis process in the cellular microenvironment. Fluid obtained by ductal lavage may allow for more detailed studies of the role of mutagens in breast cancer.