Heather Greenlee

Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715)

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect of taxanes. Acetyl-L-carnitine (ALC) was unexpectedly found to increase CIPN in a randomized trial. We investigated the long-term patterns of CIPN among patients in this trial. Methods S0715 was a randomized, double-blind, multicenter trial comparing ALC (1000 mg three times a day) with placebo for 24 weeks in women undergoing adjuvant taxane-based chemotherapy for breast cancer. CIPN was measured by the 11-item neurotoxicity (NTX) component of the FACT-Taxane scale at weeks 12, 24, 36, 52, and 104. We examined NTX scores over two years using linear mixed models for longitudinal data. Individual time points were examined using linear regression. Regression analyses included stratification factors and the baseline score as covariates. All statistical tests were two-sided. Results Four-hundred nine subjects were eligible for evaluation. Patients receiving ALC had a statistically significantly (P = .01) greater reduction in NTX scores (worse CIPN) of -1.39 points (95% confidence interval [CI] = -2.48 to -0.30) than the placebo group. These differences were particularly evident at weeks 24 (-1.68, 95% CI = -3.02 to -0.33), 36 (-1.37, 95% CI = -2.69 to -0.04), and 52 (-1.83, 95% CI = -3.35 to -0.32). At 104 weeks, 39.5% on the ALC arm and 34.4% on the placebo arm reported a five-point (10%) decrease from baseline. For both treatment groups, 104-week NTX scores were statistically significantly different compared with baseline (P < .001). Conclusions For both groups, NTX scores were reduced from baseline and remained persistently low. Twenty-four weeks of ALC therapy resulted in statistically significantly worse CIPN over two years. Understanding the mechanism of this persistent effect may inform prevention and treatment strategies. Until then, the potential efficacy and harms of commonly used supplements should be rigorously studied.

Abstract P3-08-12: Influence of a clinic-based survivorship intervention on dietary change and lifestyle recommendations among Hispanic and non-Hispanic women following adjuvant therapy for breast cancer

BACKGROUND: In 2006, the IOM released a report citing the importance of “survivorship plans” to improve quality-of-life. Little has been done to evaluate their efficacy with regard to uptake of dietary and lifestyle recommendations. METHODS: Women with early-stage breast cancer were randomized within 6 weeks of completing adjuvant therapy to a survivorship intervention or a control group. Randomization was stratified by ethnicity and subjects were not aware that they were randomized. All subjects were provided the NCI publication, “Facing Forward: Life after Cancer Treatment.” The survivorship intervention group also met with a nurse (1 hour) and nutritionist (1 hour) to receive a treatment summary, surveillance and personalized lifestyle recommendations, based on guidelines from the American Cancer Society and American Institute for Cancer Research. At baseline, 3 and 6 months, both groups completed questionnaires on diet, lifestyle, and perceived health. Linear regression analyses adjusted for ethnicity evaluated the effects of the intervention on comprehension and uptake of lifestyle recommendations. Additional models were run to evaluate the interaction between intervention and ethnicity. RESULTS: Among 126 women (60 control group, 66 survivorship intervention) mean age was 54 yrs, 48% were Hispanic, and randomized groups were well-balanced by baseline characteristics. Of note, at baseline, compared to non-Hispanics, Hispanics reported lower SES, poorer knowledge of healthy lifestyle behaviors (e.g., diet, physical activity, weight, dietary supplements), lower intake of fruits and vegetables, less recreational physical activity, lower consumption of alcohol, and a lower overall health rating (all P<0.05). After adjusting for ethnicity, at month 3 the intervention group compared to the control group reported greater knowledge of how to eat a healthy diet (P = 0.047), greater knowledge of appropriate use of dietary supplements (P = 0.006), higher levels of physical activity (P = 0.03), and higher intake of fish (P = 0.005). At month 6, the only difference that persisted was greater knowledge of a healthy diet (P = 0.01). In models assessing an interaction between intervention condition and ethnicity, compared to Hispanics, the intervention had a stronger effect on increasing non-Hispanics’ belief that a healthy diet was important to prevent breast cancer recurrence (P = 0.02). CONCLUSIONS: Compared to only receiving written survivorship materials, a survivorship intervention that included written materials plus a 1 hour personalized lifestyle counseling session was associated with short-term increased knowledge of lifestyle recommendations, change in physical activity and change in dietary behaviors among a multi-ethnic group of breast cancer survivors. Behavioral effects were not observed beyond 3 months. A single 1 hour lifestyle consultation is likely not enough to achieve and maintain lifestyle recommendations. To facilitate long-term behavioral change among breast cancer survivors in the adjuvant setting, culturally competent behavioral interventions should be developed to increase knowledge of and the capabilities needed to meet lifestyle recommendations. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-12.

P4-11-06: Uptake of Selective Estrogen Receptor Modulators and Other Breast Cancer Prevention Strategies among High-Risk Women Seen in a Breast Center.

Background: Selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, are FDA-approved for breast cancer (BC) risk reduction. However, uptake has been poor in the prevention setting, partly due to a lack of knowledge in the medical community about BC prevention and public misconceptions about the risks of SERMs. We assessed demographic and clinical factors that influence SERM uptake among high-risk women seen in an academic breast center, where specialized risk counseling is provided by a breast surgeon or medical oncologist. Methods: Potential subjects included high-risk women seen for an initial consultation by Breast Surgery or Medical Oncology. Eligibility for SERM use included a 5-year Gail risk ≥1.67%, lobular carcinoma in situ (LCIS), BRCA mutation carrier, or estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive ductal carcinoma in situ (DCIS). Demographic and BC risk factor data was collected from self-administered questionnaires. Clinical data, including prior/current SERM use, was abstracted from medical chart review. Differences in distribution of risk factors, between women who ever took a SERM and those who did not, were examined using chi-square statistics or Fisher9s exact test. Multivariable logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals using SERM use as the dependent variable. Results: Among 247 high-risk women enrolled between March 2007 and January 2011, median age 51 (17-82); White/Hispanic/Black/Asian (%): 55/32/7/6. 85% of women were undergoing annual mammography, 94% had a breast biopsy, 19% genetic testing, and 71% Medical Oncology referral. Among 181 (73%) women eligible for a SERM, Gail risk ≥1.67%/LCIS/DCIS/BRCA mutation (%): 35/22/39/3; 83 (46%) ever took a SERM, including 62 on tamoxifen and 21 on raloxifene. Early SERM discontinuation was only 7%. In multivariable analysis, significant predictors of SERM uptake included risk category (DCIS vs. Gail risk ≥1.67%/LCIS/BRCA mutation), higher income, higher body mass index (BMI), and referral to Medical Oncology. In terms of this high-risk population meeting American Cancer Society (ACS) behavioral guidelines for cancer prevention, 53% had a BMI Conclusions: Among high-risk women seen at a specialized breast center, application of clinical recommendations such as screening mammography, genetic testing, and SERM uptake were relatively high, suggesting that a comprehensive approach to the management of high-risk women is feasible. However, meeting ACS nutrition and physical activity guidelines for cancer prevention was limited, perhaps due to a lack of reimbursable staff to implement these guidelines. Breast cancer risk assessment and available interventions for prevention among high-risk women are underutilized in the U.S. Future studies should focus on the development and delivery of breast cancer prevention strategies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-06.

Abstract PD4-05: Complementary and alternative medicine use and breast cancer chemotherapy initiation: The BQUAL study

PURPOSE: Adjuvant therapy is associated with improved survival for women with breast cancer, but not all women who could benefit initiate treatment. Women9s belief systems are related to treatment initiation. It has been hypothesized that complementary and alternative (CAM) use is associated with decreased initiation of standard oncology treatments because patients may be exploring alternative treatment approaches. However, there are limited data on the association between CAM use and cancer treatment initiation. We examined the association between CAM use and initiation of adjuvant breast cancer chemotherapy in a prospective cohort of early stage breast cancer patients. PATIENTS AND METHODS: Subjects participated in a multi-center prospective cohort study of women with early stage invasive breast cancer (n=1,156). National Comprehensive Cancer Network guidelines were used to define groups based on whether chemotherapy was indicated. Three subgroups were created: chemotherapy indicated for subjects RESULTS: Current CAM use was reported by 87% of women and 38% reporting current use of ≥3 modalities. The most commonly used CAM modalities were mind body therapies (63%) and other natural products (41%). In bivariate analyses, among women CONCLUSIONS: High use of CAM was associated with decreased chemotherapy initiation among women with breast cancer for whom chemotherapy was indicated. It is important for oncologists to discuss CAM use with their patients, especially since high CAM use is associated with negative expectations and beliefs about chemotherapy. Citation Format: Greenlee H, Neugut AI, Falci L, Hillyer GC, Buono D, Roh JM, Ergas IJ, Kwan ML, Lee M, Tsai WY, Shi Z, Lamerato L, Mandelblatt JS, Kushi LH, Hershman DL. Complementary and alternative medicine use and breast cancer chemotherapy initiation: The BQUAL study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD4-05.

Abstract P4-09-01: Impact of adherence to guidelines on nutrition and physical activity for breast cancer prevention in high-risk women

Background: Women who are at high-risk for breast cancer based upon their family history or benign breast disease are candidates for chemoprevention and other risk reduction strategies. Breast cancer risk factors such as obesity, lack of physical activity and alcohol consumption represent important modifiable behaviors to target for prevention due to their high prevalence and negative impact on multiple chronic diseases. We evaluated the effect of adherence to cancer prevention guidelines for body mass index (BMI), alcohol consumption, physical activity and diet on breast cancer development and predictors of adherence to these guidelines among high-risk women. Methods: From 1991-2011, 2674 participants were enrolled to a prospective cohort study called the Women at Risk registry at the Columbia University Medical Center (CUMC) breast clinic and 1600 evaluable patients had complete data and at least one follow-up visit. The study population included women who met one or more of the following criteria: 1) one or more first-degree relatives with premenopausal breast cancer; 2) two or more first-degree relatives with postmenopausal breast cancer; 3) known BRCA1 or BRCA2 deleterious mutation carrier; 4) a biopsy-proven history of atypical hyperplasia or lobular carcinoma in situ. Women completed a baseline epidemiologic questionnaire and were followed for an average of 4.5 years during routine clinic visits with breast surgery. Using unconditional logistic regression, we examined the association between adherence to the following lifestyle factors and breast cancer risk among 90 prospectively-ascertained breast cancer cases and 1510 unaffected controls: 1) BMI of 18.5-25 kg/m2, 2) alcohol consumption of Results: Median age: 47 years; race/ethnicity, White/Hispanic/Black/Asian/other/unknown (%): 76/7/4/2/5/6; first-degree family history of breast cancer: 57%; benign breast disease: 60%; BMI of 18.5-25 kg/m2: 66%; consumption of Conclusion: Among high-risk women, being overweight or obese was associated with a 2.7-fold increased breast cancer risk compared to those with a lean body weight. Older women and non-white women were less likely to adhere to cancer prevention guidelines. We have identified a potentially modifiable breast cancer risk factor and vulnerable populations to target for breast cancer prevention. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-09-01.

Abstract B02: ¡Cocinar Para Su Salud!: Long-term effects of a short-term culturally based dietary intervention among Hispanic breast cancer survivors

Background: Guidelines for cancer survivors from the American Cancer Society and the American Institute for Cancer Research recommend a diet high in fruits and vegetables and low in energy dense foods, with the goal of improving cancer outcomes. However, few effective and culturally relevant resources exist to assist minority cancer survivors, including Hispanics, in meeting and maintaining these dietary recommendations. We tested the effects of iCocinar Para Su Salud! (Cook For Your Health!), a short-term (9-week) culturally-based dietary intervention, on increasing fruit/vegetable (F/V) intake and decreasing dietary fat intake over 12 months among Hispanic breast cancer survivors. Methods: Eligible women included those with a prior diagnosis of stage 0-III breast cancer, completion of adjuvant treatment (hormonal therapy allowed), Hispanic and able to speak Spanish. At baseline, women completed three 24-hour diet recalls, detailed interviews, provided fasting blood and anthropometric measures. Subjects were randomized to: A) the control arm (dietary recommendation booklet for breast cancer survivors), or B) the iCocinar Para Su Salud! program, a 9-week culturally-based dietary intervention using group nutrition education, cooking classes and food shopping field trips to promote behavior change. The intervention was developed via a collaboration between academic and NYC-based community partners. All study activities were conducted in Spanish. Participants were followed for 12 months via monthly phone interviews and clinic visits (3, 6 and 12 months). The primary outcome was change at 6 months in daily F/V servings and % calories from fat. Month 12 outcomes are reported here. Change in dietary intake was analyzed using 2-sample t-tests. Results: From April 2011 to March 2012, 70 women were randomized (n=36 control, n=34 intervention). Baseline characteristics: mean age 56.6 yrs (SD 9.7), mean time since diagnosis 3.4 yrs (SD 2.7), mean body mass index (BMI) 30.6 kg/m 2 (SD 5.4), and 63% had an annual household income Conclusions: iCocinar Para Su Salud! is an effective program to increase fruit/vegetable intake among a diverse group of urban Hispanic breast cancer survivors. The benefit of the 9-week intervention was sustained at 12 months. Citation Format: Heather Greenlee, Ann Ogden Gaffney, Ana Corina Aycinena, Pam Koch, Isobel Contento, Wahida Karmally, John Richardson, Emerson Lim, Wei Yann Tsai, Katherine Crew, Matthew Maurer, Kevin Kalinsky, Dawn L. Hershman. iCocinar Para Su Salud!: Long-term effects of a short-term culturally based dietary intervention among Hispanic breast cancer survivors. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B02.