Joanne Lester

Pilot Study of Rosiglitazone Therapy in Women with Breast Cancer: Effects of Short-term Therapy on Tumor Tissue and Serum Markers

Purpose: Peroxisome proliferator-activated receptor γ (PPARγ) is a steroid nuclear receptor that is activated by natural compounds such as specific fatty acids and synthetic drugs such as thiazolidinedione antidiabetic agents. Expressed in normal and malignant mammary epithelial cells, activation of PPARγ is associated with antiproliferative effects on human breast cancer cells in preclinical studies. The purpose of this study was to test the hypothesis that PPARγ ligand therapy might inhibit tumor growth and progression in human breast cancer. Experimental Design: We conducted a pilot trial of short-term (2-6 weeks) treatment with the thiazolidinedione rosiglitazone in 38 women with early-stage (Tis-T2, N0-1, M0) breast cancer, administered between the time of diagnostic biopsy and definitive surgery. Results: Short-term treatment with rosiglitazone (8 mg/d) did not elicit significant effects on breast tumor cell proliferation using Ki67 expression as a measure of cell proliferation and surrogate marker of tumor growth and progression. In pretreatment tumors notable for nuclear expression of PPARγ by immunohistochemistry, down-regulation of nuclear PPARγ expression occurred following rosiglitazone administration (P = 0.005). No PPARG mutations were identified, and the incidence of P12A and H446H polymorphisms did not differ relative to U.S. controls (P = 0.5). Treatment with rosiglitazone resulted in increased serum adiponectin (P < 0.001), decreased insulin levels (P = 0.005), and increased insulin sensitivity (P = 0.004). Rosiglitazone was well tolerated without serious adverse events. Conclusion: Our data indicate that short-term rosiglitazone therapy in early-stage breast cancer patients leads to local and systemic effects on PPARγ signaling that may be relevant to breast cancer.

ω-3 Fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition

BACKGROUND Preclinical evidence of the preventive benefits of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in breast cancer continues to fuel interest in the potential role of dietary fat content in reducing breast cancer risk. The dose of fish-oil/omega-3 PUFAs needed to achieve maximal target tissue effects for breast cancer prevention remains undefined. OBJECTIVE To determine the dose effects of omega-3 fatty acids on breast adipose tissue fatty acid profiles, we conducted a study of 4 doses of omega-3 PUFAs in women at high risk of breast cancer. DESIGN In this 6-mo randomized open-label study, 48 women with increased breast cancer risk received 1, 3, 6, or 9 capsules/d of an omega-3 PUFA supplement that provided 0.84, 2.52, 5.04, and 7.56 g docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) daily, respectively. Subjects made monthly visits, at which time pill counts were made and fasting blood samples were collected to determine fatty acid profiles; anthropometric measurements were made, breast adipose tissue samples were collected, and laboratory tests of toxicity (alanine aminotransferase, LDL cholesterol, and platelet function) were made at baseline and at 3 and 6 mo. RESULTS All doses led to increased serum and breast adipose tissue EPA and DHA concentrations, but the response to 0.84 g DHA+EPA/d was less than the maximum possible response with > or = 2.52 g/d. Body mass index attenuated the dose response for serum tissue DHA and EPA (P = 0.015 and 0.027, respectively) and breast adipose tissue DHA (P = 0.0022) in all of the treatment groups. The incremental increase in DHA and EPA correlated inversely with baseline fat and serum values. Compliance over 6 mo was 92.9 +/- 9.2% and was unaffected by treatment arm. No severe or serious toxicities were reported. CONCLUSIONS Daily doses up to 7.56 g DHA+EPA were well tolerated with excellent compliance in this cohort at high risk of breast cancer. Body mass index and baseline fatty acid concentrations modulated the dose-response effects of omega-3 PUFA supplements on serum EPA and DHA and breast adipose tissue DHA.

Breast Cancer in 2007: Incidence, Risk Assessment, and Risk Reduction Strategies

Research continues to advance breast health practices, risk assessment, risk reduction strategies, and early detection of breast cancer. Nurses must maintain a current knowledge base to appropriately screen, educate, and counsel women in their fight against the number-one cause of cancer in women and the second-largest source of cancer death in women in the United States (Jemal et al., 2007).

Atrophic Vaginitis in Breast Cancer Survivors: A Difficult Survivorship Issue

Management of breast cancer includes systematic therapies including chemotherapy and endocrine therapy can lead to a variety of symptoms that can impair the quality of life of many breast cancer survivors. Atrophic vaginitis, caused by decreased levels of circulating estrogen to urinary and vaginal receptors, is commonly experienced by this group. Chemotherapy induced ovarian failure and endocrine therapies including aromatase inhibitors and selective estrogen receptor modulators can trigger the onset of atrophic vaginitis or exacerbate existing symptoms. Symptoms of atrophic vaginitis include vaginal dryness, dyspareunia, and irritation of genital skin, pruritus, burning, vaginal discharge, and soreness. The diagnosis of atrophic vaginitis is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Lifestyle modifications can be helpful but are usually insufficient to significantly improve symptoms. Non-hormonal vaginal therapies may provide additional relief by increasing vaginal moisture and fluid. Systemic estrogen therapy is contraindicated in breast cancer survivors. Continued investigations of various treatments for atrophic vaginitis are necessary. Local estrogen-based therapies, DHEA, testosterone, and pH-balanced gels continue to be evaluated in ongoing studies. Definitive results are needed pertaining to the safety of topical estrogens in breast cancer survivors.

Safe Handling and Administration Considerations of Oral Anticancer Agents in the Clinical and Home Setting

The use of hormonal, chemotherapeutic, and targeted biologic oral agents has exponentially increased since the early 2000s. Oral therapies have the advantage of persistent exposure of the cytotoxic drug to tumor cells and the tumor environment. The use of oral anticancer agents provides therapeutic drug treatment for patients with cancer in the comfort of their home or alternative settings, such as retirement homes and assisted living or extended-care facilities. Practices to ensure safe storage, handling, administration, and disposal of oral agents are necessary to prevent additional exposure of hazardous substances to the environment, professionals, patients, family members, and caretakers. Providers should consider potential barriers to adherence and compliance, and develop strategies to ensure optimal therapeutic benefit prior to initiation of oral agents.

Women With Breast Cancer: Self-Reported Distress in Early Survivorship

PURPOSE/OBJECTIVES To identify and compare levels of distress and sources of problems among patients with breast cancer in early survivorship. DESIGN Descriptive, cross-sectional. SETTING A National Cancer Institute-designated comprehensive cancer center. SAMPLE 100 breast cancer survivors were selected to represent four time points in the cancer trajectory. METHODS Distress was self-reported using the Distress Thermometer and its 38-item problem list. Analysis of variance and chi-square analyses were performed as appropriate. MAIN RESEARCH VARIABLES Distress scores, problem reports, and time groups. FINDINGS Participants scored in range of the cutoff of more than 4 (range = 4.1-5.1) from treatment through three months post-treatment. At six months post-treatment, distress levels were significantly lower. Significant differences were found between groups on the total problem list score (p = 0.007) and emotional (p = 0.01) and physical subscale scores (p = 0.003). CONCLUSIONS Comparison of groups at different points in the cancer trajectory found similar elevated levels from diagnosis through three months. Distress remained elevated in early survivorship but significantly decreased at six months post-treatment. IMPLICATIONS FOR NURSING Interventions to reduce or prevent distress may improve outcomes in early survivorship.

Urogenital Atrophy in Breast Cancer Survivors

PURPOSE/OBJECTIVES To review the symptoms of urogenital atrophy in breast cancer survivors, influencing factors, and their effects on performance. DATA SOURCES Review of qualitative and quantitative research data that describe pain, function, satisfaction, and quality of life related to urologic, genital, and sexual function. DATA SYNTHESIS Breast cancer treatment can induce or exacerbate symptoms related to urogenital atrophy. The lower urinary and genital tracts are affected by physiologic alterations, the potential abrupt onset of menopause, and treatment side effects. Symptoms of urogenital atrophy often are more prevalent and severe in women treated for breast cancer than in age-matched women without breast cancer. CONCLUSIONS Symptoms related to urogenital atrophy are common in breast cancer survivors and can be affected by physiologic, situational, and psychological influences with negative effects on performance. Research is essential to the understanding of how transient or permanent hormonal alterations affect the urogenital system and the role of these symptoms on quality of life. IMPLICATIONS FOR NURSING Nurses must listen with sensitivity to breast cancer survivors and their descriptions of these significant and life-altering symptoms. Personalized discussion enables the nurse to explore issues, assess symptoms, recommend interventions, and evaluate at follow-up visits. Nurses are integral to the provision of survivorship care planning that can address the short- and long-term effects of a cancer diagnosis and related treatments.

A Self-Report Instrument That Describes Urogenital Atrophy Symptoms in Breast Cancer Survivors

Urogenital atrophy affects the lower urinary and genital tracts and is responsible for urinary, genital, and sexual symptoms. The accurate identification, measurement, and documentation of symptoms are limited by the absence of reliable and valid instruments. The Urogenital Atrophy Questionnaire was developed to allow self-reporting of symptoms and to provide clinicians and researchers an instrument to identify, measure, and document indicators of urogenital atrophy. A pilot study (n = 30) measured test–retest reliability (p < .05) of the instrument. Subsequently, a survey of women with (n = 168) and without breast cancer (n = 166) was conducted using the Urogenital Atrophy Questionnaire, Female Sexual Function Instrument, and Functional Assessment of Cancer Therapy, Breast, Endocrine Scale. Exploratory factor analysis (KMO 0.774; Bartlett’s test of sphericity 0.000) indicated moderate-high relatedness of items. Concurrent (p > .01) and divergent validity (p < .000) were established. A questionnaire resulted that enables women, regardless of sexual orientation, partner status, and levels of sexual activity to accurately report symptoms.

Reproducibility of Random Periareolar Fine Needle Aspiration in a Multi-Institutional Cancer and Leukemia Group B (CALGB) Cross-Sectional Study

Background: Random periareolar fine needle aspiration (RPFNA) is a research technique developed to assess short-term breast cancer risk in women at increased risk of breast cancer. Although there is increasing acceptance of RPFNA, neither the reproducibility nor the inter–institutional compatibility of RPFNA has been established. To address these key limitations, the Cancer and Leukemia Group B (CALGB) Prevention Group tested the reproducibility of RPFNA in a multi-institutional cross-sectional study. Methods: Sixty-three high-risk women from five CALGB institutions (Duke, Ohio State, Roswell Park, Dana Farber, and Vermont) underwent RPFNA from July 1, 2007 to June 30, 2008. Duplicate bilateral RPFNA was performed on each woman by a single investigator on a single day. Masood Cytology Index score was assessed by a single blinded cytopathologist. Results: There was a high degree of statistical agreement in the Masood Cytology Index scores of duplicate RPFNA samples from the same breast, with a Spearman correlation coefficient of 0.8312 (P < 0.0001). Importantly, although there was agreement in duplicate samples from the same breast, there was lack of agreement between duplicate samples from the opposite breast. Conclusions: This multi-institutional study shows that RPFNA is a highly reproducible measure of breast cytology in a cooperative group cross-sectional trial. RPFNA did not show a high degree of agreement between breasts, suggesting that breast cancer risk and progression may occur at different rates in individual breasts from a single woman. These studies provide proof-of-principle for future RPFNA-based cooperative group prevention studies. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1379–85)

Incorporation of eicosapentaenioic and docosahexaenoic acids into breast adipose tissue of women at high risk of breast cancer: A randomized clinical trial of dietary fish and n-3 fatty acid capsules

SCOPE The fatty acid profile of dietary lipids is reflected in mammary adipose tissue and may influence mammary gland biology and cancer risk. To determine the effects of fish consumption on breast adipose tissue fatty acids, we conducted a study of fish versus n-3 PUFA supplements in women at increased risk of breast cancer. METHODS AND RESULTS High risk women were randomized to comparable doses of marine n-3 PUFAs as canned salmon + albacore or capsules for 3 months. Pre- and posttreatment fatty acid profiles were obtained by GC. Dietary fish (n = 12) and n-3 PUFA capsules (n = 13) yielded increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plasma (p < 0.0001), erythrocyte membranes (p < 0.0001), and breast fat (p < 0.01) at 3 months. Women taking capsules had higher plasma and erythrocyte membrane EPA changes (∼four versus twofold, p = 0.002), without significant differences in DHA. Increases in breast adipose EPA, DHA were similar for both groups. Higher BMI correlated with smaller changes in plasma, erythrocyte membrane EPA, and breast adipose EPA, DHA. Adherence was excellent at 93.9% overall and higher in the fish arm (p = 0.01). CONCLUSION Fish provides an excellent source of n-3 PUFAs that increases breast adipose EPA, DHA similar to supplements and represents a well-tolerated intervention for future studies of the impact of n-3 PUFAs and dietary patterns on breast cancer.