Death In Breast Cancer Survivors Research Articles

Abstract 841: Fine particulate matter exposure during breast cancer treatment among older women associated with increased mortality

Abstract Background: Fine Particulate Matter (PM2.5) is associated with higher mortality among people with chronic conditions. Breast cancer (BC) survivors may be particularly vulnerable during cancer treatment. We assessed the association between PM2.5 during 9-months following BC diagnosis and all-cause and BC-mortality using policy relevant PM2.5 cut-offs. Methods: Using SEER-Medicare linked with a high-resolution model-based PM2.5 by residential zipcode (2007-2016), we assembled a cohort of women ≥66 years with incident stage I-IV BC. We assessed PM2.5 exposure, categorized as <8 µg/m3 (low), 8-12 µg/m3 (moderate) and >12 µg/m3 (high—above air quality standard), and types of cancer treatments (surgery [SX], chemotherapy [CTX], radiation therapy [RTX]) during a 9-month landmark period. We identified all-cause and BC death within 5 years of diagnosis. We fit multivariable Cox proportional hazard models to assess associations with PM2.5 exposure adjusting for individual-level characteristics (demographics, tumor characteristics, comorbidities), neighborhood SES, SEER state, and long-term PM2.5 exposure. We also evaluated the association between PM2.5 exposure and mortality by treatment types (SX, SX + RTX, SX + CTX, SX + RTX + CTX, and RTX and/or CTX). We used multiple imputation to account for missing variables (race, ER status, HER2 status, grade). Results: Among 72,798 women (mean age 75 years, 83% white, 56% stage I, 32% II, 9.2% III, 2.9% IV), 41%, 32%, 13%, 8.4%, and 5.1% received SX + RTX, SX only, SX + Chemo + RTX, SX + Chemo, and CTX and/or RTX. The mean PM2.5 level was 8.8 µg/m3 [36%, 52% and 11% were exposed to <8, 8-12, and >12, respectively]. We observed 12,163 all-cause and 4,729 BC deaths during follow-up. Compared to those exposed to low levels, higher levels of PM2.5 exposure were associated with increased all-cause mortality for both moderate PM2.5 [HR 1.03 (95%CI:1.00-1.05)] and high PM2.5 [HR 1.09 (95%CI: 1.06-1.14)] but not BC-specific mortality. Among treatment subgroups, PM2.5 was associated with higher all-cause mortality in SX+RTX for moderate [HR 1.24 (95%CI:1.18-1.32)] and high PM2.5 [HR 1.36 (95%CI: 1.25-1.48)] and SX+RTX+CTX for high PM2.5 [HR 1.33 (95%CI: 1.17-1.51)]. There were no association between moderate/high PM2.5 with all-cause mortality in SX only and SX+CTX. Among the SX+RTX subgroup, BC-specific mortality was elevated for both moderate [HR 1.50 (95%CI:1.35-1.66)] and high PM2.5 [HR 1.81 (95%CI: 1.55-2.12)]. Conclusion: Even below EPA regulatory thresholds (PM2.5 <12 µg/m3), we observed increased risk of death in BC survivors who had high PM2.5 exposure during treatment period. The elevated mortality primarily occurred among women who received RTX and was present for all-cause and BC-specific mortality. The potential interaction between RTX and PM2.5 exposure, even after adjusting for tumor subtype and stage, warrants further evaluation. Citation Format: Benjamin Bates, Rachel Nethery, Melanie Rua, Hari Iyer, Elisa Bandera, Soko Setoguchi. Fine particulate matter exposure during breast cancer treatment among older women associated with increased mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 841.

Cardiopulmonary Protection for Bilateral Breast Irradiation: A Dosimetric Comparison between Proton and Photon Plans

Recent advances in cancer treatment improve cancer survivorship. Cardiovascular disease has become the leading cause of non-cancer death in breast cancer survivors. Therefore, risk of cardiopulmonary toxicities during multimodality treatment should be assessed carefully. It remains to be defined the best scenario for proton therapy to confer meaningful cardiovascular protection in the setting of breast irradiation. We hypothesized proton therapy plan provides optimal cardiopulmonary protection during bilateral breast irradiation. The study aimed to compare cardiopulmonary dosimetric parameters of proton and photon radiotherapy plans. We conducted a retrospective study and patients with bilateral breast cancer indicated for radiotherapy between January 01, 2010 and December 31, 2020 were included. All patients received whole breast or chest wall irradiation with or without regional nodal irradiation. The dose scheme was 50-50.4 Gy in 25-28 fractions. Boost was allowed if patients receiving breast conserving surgery or known risk factors. The dosimetric parameters included planning target volume, mean dose to the heart, the volume of whole lung receiving 5 Gy, 10 Gy, and 20 Gy. For photon therapy, volumetric modulated arc therapy using double partial arc plans was generated with Pinnacle 9.8, Elekta Synergy and tomotherapy helical plan was generated with Tomo Hi-Art planning system. For proton therapy, treatment planning was generated with Ray station 9A. All data was managed using SAS v.9.4 software. Analysis of variance (α = 0.05) was used to compute the dosimetry of different treatment modalities. The statistical significance was considered with a p-value <0.05. Thirty-one patients with bilateral breast cancer were included, including 12 bilateral breast irradiation patients and 6 bilateral chest wall irradiation patients. The mean dose of heart was 53.0±43.3 cGy in proton therapy while 736.6±225.1 cGy and 869.67±241.0 cGy in Tomotherapy and volumetric modulated arc therapy respectively. The volume of whole lung receiving 5 Gy was 15.4±7.91% in proton therapy while 46.1±10.8% and 46.3±2.5% in Tomotherapy and volumetric modulated arc therapy respectively. The volume of whole lung receiving 20 Gy was 7.7±4.3% in proton therapy while 15.4±5.6% and 19±3.5% in Tomotherapy and volumetric modulated arc therapy respectively. The effects of cardiopulmonary protection were more significant for chest wall irradiation over breast irradiation. Proton radiotherapy provided significant dose reduction for bilateral breast irradiation. The benefit is more significant is patients receiving bilateral chest wall irradiation. Further clinical validations will be warranted to confirm the clinical relevance of the finding.

A troubled heart: Mood disorder history longitudinally predicts faster cardiopulmonary aging in breast cancer survivorship.

Breast cancer survivors live longer due to more advanced cancer treatments; however, cardiovascular disease (CVD) is the leading non-cancer cause of death in breast cancer survivors. Previous studies have shown that depression is associated with an increased risk of CVD development. This study investigated whether depressive symptoms or mood disorder history, either independently or in combination with cardiotoxic treatments, predicted older cardiopulmonary age using a novel index-the Age Based on Exercise Stress Test (ABEST)-among breast cancer survivors. Breast cancer survivors (N = 80, ages 26-72, stage I-IIIA) were assessed an average of 53 days (SD = 26) post-surgery, but before adjuvant treatment, and again an average of 32 (SD = 6) months thereafter. At both visits, they reported depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D), completed the Structured Clinical Interview for DSM-V, and engaged in an exercise stress test to obtain ABEST scores. Controlling for treatment type, age, education, trunk fat, antidepressant use, and time between visits, longitudinal analyses showed that breast cancer survivors with a mood disorder history had worsening ABEST scores over time, compared to their peers without this history (p = .046). Change in physical activity between Visits 1 and 2 did not mediate this relationship (95% CI: -0.16-0.51). Ancillary analyses provided some additional support for the primary finding, such that those with a mood disorder history trended toward greater decreases in Vo2max, although results were marginally non-significant (p = .095). There were no cross-sectional relationships between depressive symptoms or mood disorder history and ABEST scores (ps>.20). Treatment type did not modulate observed relationships (ps>.22). Breast cancer survivors with a mood disorder history may experience faster cardiopulmonary aging compared to their peers without such a history, raising risk for CVD.

Abstract P3-03-15: Physical Activity and Risk of Death in Breast Cancer Survivors: A Prospective Study

Abstract BACKGROUND. Strong evidence exists supporting the protective effect of physical activity on the risk of developing breast cancer; however, its impact on survival after breast cancer diagnosis remains controversial with limited research in long-term survivors. The aim of the current study was to evaluate the association of physical activity and risk of all-cause mortality in long-term breast cancer survivors. METHODS. We conducted a prospective cohort of 315 post-menopausal breast cancer survivors who were at least 2 years post their initial diagnosis (median 6 years of survivorship). They initially were diagnosed with early stage (AJCC TNM Stages 0-II) breast cancer between January 1996-December 2012. Baseline interviews were conducted between August 2013 and March 2015, and participants were followed until date of death or study’s end (April 2022). Subjects were queried on physical activity and fatigue using validated questionnaires, Godin Leisure Physical Activity Scale (GLPAS) and Fatigue Symptom Inventory (FSI). Physical activity was defined in 3 levels (active, moderately active, insufficiently active). Cox proportional hazards regression model was used to estimate the association of physical activity with risk of all-cause mortality, adjusted for age at baseline, breast cancer stage, Charlson comorbidity index (CCI), years since cancer diagnosis, fatigue, race/ethnicity, lifetime history of insomnia and depression, and adjuvant cancer treatments (endocrine, chemotherapy and radiation). RESULTS. Of the 315 women, mean age at interview was 71 years (range: 57-86). The cohort included 30% women of color, mainly African American/Black and Asian/Pacific Islander women. Over a maximum follow-up of 8.7 years (median:7.8, IQR:7.3-8.3) after their baseline interview, 45 subjects (14.3%) died due to all causes. The mortality rates were: 12.9 per 1000 person years (PY) for active; 13.4 per 1000 PY for moderately active; and 32.9 per 1000 PY for insufficiently active. In multivariable analysis, compared to insufficiently active women, those who were active or moderately active had a markedly 60% decreased risk of death (active: HR=0.42, 95% CI: 0.21-0.85; moderately active: HR=0.40, 95% CI:0.17-0.95). CONCLUSION: We found that even moderate physical activity was associated with a significantly decreased risk of all-cause death in long-term breast cancer survivors. Survivorship care plans should consider incorporating physical activity because even moderate activity is vital for extending survival as well as health-related quality of life. Citation Format: Lie Hong Chen, Michael R. Irwin, Richard Olmstead, Reina Haque. Physical Activity and Risk of Death in Breast Cancer Survivors: A Prospective Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-15.

Changes in body composition and subsequent cardiovascular disease risk among 5-year breast cancer survivors.

Cardiovascular disease (CVD) remains a leading cause of death in breast cancer survivors, a growing population. The aim of this study was to determine whether changes in body composition, commonly observed in breast cancer survivors, is associated with subsequent CVD risk. This cohort study used the Korean National Health Insurance Service database. The study population included 73,271 5-year breast cancer survivors aged 40 years or above. To assess changes in body composition and its effect on the risk of CVD, validated prediction equations and multivariate Cox proportional hazards regression were used. Changes in metabolic markers (blood pressure, total cholesterol, and fasting serum glucose) according to changes in body composition were calculated by multiple linear regression. Having persistently high predicted lean body and appendicular skeletal muscle mass percentages (LBMP and ASMP, respectively) among breast cancer survivors was associated with 32% and 40% lower CVD risks than a persistently low predicted LBMP or ASMP, respectively. Conversely, persistently high predicted body fat mass percentage (BFMP) was associated with a higher CVD risk than persistently low predicted BFMP. Additionally, those with a low to high change in predicted BFMP had a higher risk of CVD than those with persistently low predicted BFMP. Changes in body composition were accompanied by changes in metabolic markers. Maintaining high percentages of lean body and appendicular skeletal muscle mass and preventing an increase in fat mass may be beneficial in preventing CVD in breast cancer survivors.

The effects of exercise and diet on sex steroids in breast cancer survivors.

Insufficient physical activity and obesity are associated with an increased risk of cancer recurrence and death in breast cancer survivors. Sex steroid hormones may mediate these associations. This study tested the hypothesis that exercise and diet, as compared to control, favorably change sex steroid hormones. This analysis of data from a subset of participants in a 2 × 2 factorial trial compares 269 postmenopausal breast cancer survivors who were insufficiently physically active and had overweight or obesity and were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. Secondary sex steroid hormone endpoints included estradiol, sex hormone-binding globulin (SHBG), and testosterone. Treatment effects were quantified using a mixed model for repeated measures. Compared to control, exercise alone did not significantly change estradiol (-1.9%; 95% CI: -12.6, 8.8), SHBG (2.4%; 95% CI: -9.9, 14.6), or testosterone (1.2%; 95% CI: -12.2, 14.5). Compared to control, diet alone did not significantly change estradiol (-7.8%; 95% CI: -17.6, 1.9), SHBG (8.2%; 95% CI: -4.2, 20.6), or testosterone (-0.8%; 95% CI: -13.6, 12.0). Compared to control, exercise plus diet did not significantly change estradiol (-6.3%; 95% CI: -16.3, 3.6), SHBG (8.8%; 95% CI: -4.0, 21.7), or testosterone (-5.3%; 95% CI: -18.0, 7.4). In postmenopausal breast cancer survivors who were insufficiently physically active and had overweight or obesity, randomization to exercise alone, diet alone, or exercise plus diet did not statistically significantly change sex steroid hormone concentrations at week 52.

Insulin sensitivity, cardiovascular function and bone health in women with early stage breast cancer before and after cancer treatment.

Cardiovascular disease is a leading cause of death in breast cancer survivors, but the underlying cause is not fully characterised. To determine whether insulin sensitivity, cardiovascular risk markers and body composition were perturbed in women treated with chemotherapy for early stage breast cancer and whether perturbations occurred before or after cancer treatment. Sixteen women with breast cancer and 17 control subjects were studied. Twelve breast cancer patients returned for a second visit following cancer treatment comprising chemotherapy (n=2), or chemotherapy and radiotherapy (n= 10). The Matsuda index to estimate insulin sensitivity, fasting lipids, pulse wave velocity (PWV), reactive hyperaemia index (RHI) and body composition by dual energy X-ray absorptiometry were measured. There were no significant differences in age (53 ± 9 vs 54 ± 11 years; P= 0.82) or body mass index (28 ± 7 vs 28 ± 6; P= 0.97) between patients with breast cancer and controls. Patients with breast cancer had higher triglycerides than controls (1.2 ± 0.1 vs 0.8 ± 0.1 mmol/L; P= 0.03), but there were no significant differences in the Matsuda index, PWV and RHI. Following cancer treatment, there was a lower Matsuda index (6.3 ± 1.2 vs 5.2 ± 1.0; P= 0.01), but this was not associated with a significant change in vascular function. Bone mass fell by 3% from 2.27 ± 0.11 to 2.20 ± 0.10 kg after cancer treatment (P= 0.03). Patients with breast cancer had higher triglycerides before treatment and a reduction in insulin sensitivity and bone mass following cancer treatment. Future larger and longer-term studies should characterise the effect of reduced insulin sensitivity on rates of diabetes, cardiovascular disease, cancer outcomes and fracture. ACTRN12614001055695.

The impact of high-intensity interval training exercise on breast cancer survivors: a pilot study to explore fitness, cardiac regulation and biomarkers of the stress systems

BackgroundCardiovascular disease (CVD) remains the largest cause of death in breast cancer survivors. The aim of this study was to explore the impact of exercise intensity on aerobic fitness and autonomic cardiac regulation (heart rate variability (HRV)) and salivary biomarkers of the stress systems (HPA-axis, cortisol; sympathetic nervous system, α-amylase) and mucosal immunity (secretory(s)-IgA), markers of increased risk of CVD in breast cancer survivors.MethodsParticipants were randomly assigned to; 1) high intensity interval training (HIIT); 2) moderate-intensity, continuous aerobic training (CMIT); or 3) a wait-list control (CON) for a 12-week (36 session) stationary cycling intervention. Cardiorespiratory fitness (VO2peak), resting HRV and salivary biomarkers were measured at baseline 2–4 d pre-intervention and 2–4 d post the last exercise session.ResultsSeventeen participants were included in this study (62 ± 8 years, HIIT; n = 6, CMIT; n = 5, CON; n = 6). A significant improvement (p ≤ 0.05) was observed for VO2peak in the HIIT group; 19.3% (B = 3.98, 95%CI = [1.89; 4.02]) and a non-significant increase in the CMIT group; 5.6% (B = 1.96, 95%CI = [− 0.11; 4.03]), compared with a 2.6% (B = − 0.64, 95%CI = [− 2.10; 0.82]) decrease in the CON group. Post intervention improvements in HRV markers of vagal activity (log (ln)LF/HF, LnRMSSD) and sympathetic nervous system (α-amylase waking response) occurred for individuals exhibiting outlying (> 95% CI) levels at baseline compared to general population.ConclusionHigh intensity interval training improved cardiovascular fitness in breast cancer survivors and improved cardiac regulation, and sympathetic nervous system (stress) responses in some individuals. High-intensity interval training was safe and effective for breast cancer survivors to participate in with promising results as a time efficient intensity to improve physical health and stress, reducing CVD risk.Trial registrationThis pilot study was retrospectively registered through the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12620000684921.

Circuit resistance training and cardiovascular health in breast cancer survivors.

Cardiovascular disease is the leading cause of death in breast cancer survivors. While evidence shows circuit resistance training (CRT) is effective for improving muscle and cardiorespiratory fitness, whether CRT is an efficacious therapy for decreasing cardiovascular risk in cancer survivors is unclear. Fifty-one breast cancer survivors were recruited to either 12weeks CRT (n=26), or a non-exercising wait-list control (n=25). Two supervised 60min CRT sessions per week were undertaken, comprising resistance and functional exercises, and aerobic exercise stations. Primary outcome measure was the gold-standard assessment of arterial stiffness, aortic pulse wave velocity (PWV). Secondary outcomes included: cardiorespiratory fitness (CRF), upper and lower body strength, arterial wave reflections, central blood pressure and rate pressure product. Compared to the control group, the CRT group had a statistically significant medium effect decrease in PWV 0.9m/s (95% CI: 0.1, 1.7). There were large effect improvements in VO2 max (4.3mlkg-1 min-1 , 95% CI: 5.8, 2.8), upper and lower body strength (3.7kg, 95% CI: 1.9, 5.6 and 10.4kg, 1.6, 19.1) respectively. Findings support the existing literature demonstrating that 12weeks CRT improves muscle and cardiorespiratory fitness and is also an effective strategy for decreasing a proven cardiovascular risk factor in breast cancer survivors.

Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer

IntroductionCardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for...

Effect of Rosuvastatin in Preventing Chemotherapy-Induced Cardiotoxicity in Women With Breast Cancer: A Randomized, Single-Blind, Placebo-Controlled Trial.

Chemotherapy-induced cardiotoxicity is a major and leading cause of death in breast cancer survivors. It can present decades after chemotherapy and can manifest in different ways; some chemotherapeutic agents have a powerful dose-dependent relationship with cardiotoxicity. The aim of this study was to investigate the effect of rosuvastatin on preventing chemotherapy-induced cardiotoxicity in patients with breast cancer. Our study was a randomized, single-blind, placebo-controlled trial that involved 89 women with newly diagnosed breast cancer who were scheduled to receive chemotherapy. Patients were randomly assigned to receive rosuvastatin or a placebo in a 1:1 ratio for 6 months. Echocardiography, using 2-dimensional (2D) Doppler, tissue Doppler, and speckle-tracking methods, was used to determine the absolute changes in the left ventricular systolic ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial (LA) diameter, transmitral Doppler early diastolic velocity (E wave), tissue Doppler early diastolic (e') and peak systolic (s') mitral annular velocities, E/e' ratio, and global longitudinal systolic strain. The LVEF was significantly reduced in the placebo group at the end of the study when compared with the baseline value. However, there was no significant difference in the LVEF in the intervention group (intergroup P = .012). Furthermore, compared with the intervention group at the end of the study, there was a significant increase in the 4- and 2-chamber LVESV, LA diameter, and E/e' ratio in the placebo group (intergroup P = .019, P = .024, P < .001, and P = .021, respectively) and a significant decrease in the e' and s' velocities in the placebo group (intergroup P < .001 and P < .006, respectively). The present study showed that the prophylactic use of rosuvastatin may prevent the development of chemotherapy-induced cardiotoxicity.

Pre- and postdiagnostic diet in relation to mortality among breast cancer survivors in the CPS-II Nutrition Cohort.

Due to the limited evidence on the role of diet and cause-specific mortality among breast cancer survivors, current nutrition guidelines for this population are consistent with those for cancer prevention. We evaluated whether diets consistent with the American Cancer Society recommendations for cancer prevention were associated with risk of death in breast cancer survivors. Participants reported information on diet and other factors at baseline in 1992-1993 and twice during follow-up. A nine-point score reflecting concordance with diet recommendations was calculated. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) for diet score in relation to overall and cause-specific mortality were computed using Cox proportional hazards regression methods. Among 4,452 women diagnosed with locally and regionally staged breast cancer after baseline and until 2011, 1,204 died during follow-up through 2012 (398 from breast cancer). Prediagnostic diet score was not associated with mortality from any cause. Postdiagnostic diet score was associated with neither breast cancer-specific mortality (RR 1.44, 95% CI 0.90-2.30 for scores 6-9 vs 0-2) nor cardiovascular disease mortality (RR 0.81, 95% CI 0.47-1.39), but compared to a score of 0-2, a score of 6-9 was associated with a borderline lower risk of other causes of death (RR 0.78, 95% CI 0.56-1.07, p trend=0.03; per two-point increase in score RR 0.88, 95% CI 0.79-0.99). Of diet score components, only limiting red and processed meat consumption was associated with statistically significantly lower risk of total, CVD, and other non-breast cancer mortality. Diets consistent with guidelines for cancer prevention were not associated with breast cancer-specific mortality. However, their association with other causes of mortality underscores the importance of consuming a healthy diet in this population.

ABCDE steps to prevent heart disease in breast cancer survivors.

Breast cancer is the most common invasive cancer diagnosed in women. Of every 8 women, 1 woman is diagnosed with breast cancer in her lifetime. In 2013, more than 230 000 women were diagnosed with breast cancer in the United States alone, resulting in nearly 40 000 deaths. Breast cancer can also occur in men, although the incidence is much lower, with a total of 2240 men diagnosed in 2013 (accounting for less than 1% of all breast cancers). Over the past 2 decades, death resulting from breast cancer has been declining each year. This decrease in mortality is due in part to improvements in cancer treatment. These treatments have come about as a result of collaborations among physicians in various specialties. These physicians include medical oncologists (who give systemic treatments like chemotherapy and hormonal therapy), surgeons (who perform surgery such as mastectomy and lumpectomy), and radiation oncologists (who treat patients with radiation therapy). Radiation therapy, in particular, has increasingly become an important part of management of most patients with breast cancer. Radiation therapy has been demonstrated not only to prevent recurrence of cancer in the breast or chest wall area but also to improve long-term survival in women. In addition, radiation therapy allows women to undergo a less radical form of surgery in which the breast tissue is conserved, thus improving body image for breast cancer survivors without compromising survival. As a result of this progress in treatment and improved detection of early breast cancer, in 2012, there were nearly 3 million breast cancer survivors in the United States alone, a number that will increase in the coming years. Women who survive breast cancer may face many health challenges, but the number 1 cause of death in breast cancer survivors (and, in fact, all women) remains heart disease. Unfortunately, although systemic …

Abstract P4-09-04: Weight loss and lipid-lowering efficacy of a low carbohydrate, calorie restricted diet intervention on postmenopausal breast cancer patients

Abstract Background: Obesity and weight gain are associated with higher rates of breast cancer recurrence and increased mortality. Cardiovascular disease is a leading cause of death in breast cancer survivors. Control of body weight and cardiovascular risk factors are key aspects in breast cancer survivorship. The purpose of our study was to see if a low carbohydrate, calorie restricted dietary intervention could be implemented in a group of obese postmenopausal breast cancer survivors to achieve weight loss and improved lipid profiles. Methods: Twenty-four postmenopausal estrogen receptor positive breast cancer patients were enrolled on a low carbohydrate, calorie restricted dietary intervention. The dietary intervention utilizes 0.5g protein/pound (actual body weight), less than 40 grams of carbohydrates, and 800-1200 calories per day. Body weight, body fat percentage, blood triglyceride level, and total cholesterol level were measured and monitored, during the dietary intervention. Results: The average weight loss spanned 23.8 weeks (varying from 5 to 59 weeks). When compared with the mean body weight prior to the dietary intervention, the mean body weight was reduced by 19.9% (equivalent to 43.7 pounds). The mean body fat percentage was reduced by 6.86%. In addition, the dietary intervention significantly decreased the patients’ blood triglyceride level by 33.8% (p = 0.00013). The mean total cholesterol level was decreased by 9.5% with the dietary intervention (p = 0.00498). Conclusion: This study demonstrated that a low carbohydrate, calorie restricted diet resulted in significant weight loss with improved lipid profiles. This study suggests that this dietary intervention is feasible in postmenopausal breast cancer survivors and a potential strategy for cardiovascular risk reduction. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-09-04.

Abstract 2286: Short term reduction in mammographic density predicts survival in breast cancer.

Abstract Back ground: Identification of the factors that predict response to treatment in breast cancer patients early after diagnosis is important in guiding the treatment strategy. High mammographic density (MD) is a risk factor for breast cancer. However no study has examined the association between change in MD and death in breast cancer survivors. We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting risk of death from breast cancer and all causes. Methods: We evaluated the relationship between reduction in MD and risk of death from all causes within the Health, Eating, Activity, and Lifestyle (HEAL) Study. In a prospective observational study, we studied 403 women diagnosed with primary invasive breast carcinoma between 1995 and 1998 and followed until death or September 2009. We collected mammograms and prognostic, demographic, and lifestyle factors as well as treatments at the time of diagnosis and two years after the diagnosis was made. Mammograms were digitized and MD was measured on cranio-caudal (CC) images of the unaffected breast using a computer assisted program developed at the University of Toronto. MD reduction (MDR) was evaluated based on two mammograms; the first was taken 12 months before diagnosis, and the second approximately 24 months after diagnosis. MDR was defined as the difference between the MD of these two images (% MDR = % preMD -% postMD). Reduction in MD was categorized into a binary variable as women who had a MDR ≥5% compared to those with less than 5% reduction in MD. Cox proportional hazards models were used to estimate the Hazard ratios and 95% confidence intervals. Results: Breast cancer patients with 5% or more reduction in MD were younger (mean age was 55.7 compared to 58.9), more likely to be premenopausal at diagnosis (36.7% compared to 24.0%), and more likely to have a history of oral contraception (73.9% compared to 63.3%). Women with MDR ≥5% were 49% less likely to die from any cause after adjustment for age, BMI, estrogen receptor status, progesterone receptor status, menopausal status at baseline, smoking, stage, tamoxifen use, chemotherapy, radiation therapy, and study center (HR=0.51 CI: 0.3-0.86). The results were stronger when we restricted the analysis to women who were premenopausal at diagnosis. When we restricted the analysis to women who had taken tamoxifen a similar direction was observed but the results were not statistically significant. Conclusion: Result from our data suggests that reduction in mammographic density few years after breast cancer diagnosis may be used as a predictor of overall survival. Citation Format: Ali Ozhand, Roberta Mckean-Cowdin, Leslie Bernstein, Rachel Ballard-Babash, Anne McTiernan, Kathy B. Baumgartner. Short term reduction in mammographic density predicts survival in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2286. doi:10.1158/1538-7445.AM2013-2286

Is it the time for metformin to take place in adjuvant treatment of Her-2 positive breast cancer? Teaching new tricks to old dogs

Breast cancer is the most common malignancy diagnosed among women. According to the new molecular subclassification, basal like and Her-2 positive breast cancers have the worst outcome and these are the ones in which chemotherapy is a must as a part of adjuvant treatment. New treatment options that could be used as an adjuvant maintenance treatment are still being investigated. Insulin hormone is one of the reasons of breast cancer recurrence and death in breast cancer survivors. Targeting insulin as a therapeutic modality in breast cancer could be an option in the adjuvant treatment of breast cancer. It seems that insulin may signal to activate a cascade of proliferative and anti-apoptotic events in the cancer cell. Metformin, an oral anti-diabetic known for 50 years, may also have direct effects on cancer cells. Metformin causes Her-2 suppression via the inhibition of mTOR in breast cancer cells. Thus, we believe that the time has arrived both to target insulin reduction and to alter Her-2 oncogene based molecular pathogenetic steps in breast cancer by using metformin as an adjuvant therapy in breast cancer patients.

Post-diagnosis mammographic density and risk of death in breast cancer survivors: The Health, Eating, Activity, and Lifestyle (HEAL) study

22095 Background: There is evidence that mammographic breast density (BD) is a strong risk factor for breast cancer; however, no study has examined the association between BD and death in breast cancer survivors. We examined the association between post- diagnosis BD and risk of all causes of death and breast cancer death in breast cancer survivors. Methods: Prospective observational study of 524 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study who were diagnosed with breast cancer between 1995 and 1998 and followed until death or September 2004. We collected a mammogram and prognostic, demographic, and lifestyle factors including measured weight and height during a clinic visit two to three years after diagnosis. Mammograms were digitized and the cranio-caudal view contralateral to the breast diagnosed with breast cancer was measured for percent density and dense area using a computer-assisted program developed at University of Toronto. Results: The age and BMI of women were 58.3 ± 10.6 yrs and 27.7 ± 6.7 kg/m2. Women were postmenopausal (81%); non-Hispanic White (59%), African American (25%) or Hispanic White (13%); and diagnosed with Stage I (72%) or Stage II (28%) breast cancer. Seventy-one % of women were diagnosed with tumors that were estrogen receptor-positive. In analyses adjusted for age, menopausal status, race, disease stage, hormone therapy, BMI, physical activity, smoking status, and family history of breast cancer, the adjusted hazard ratio (HR) and 95% confidence interval (CI) for women in the highest vs. the lowest tertile of amount of dense tissue and all causes of death was 2.47 (95% CI, 1.01–6.23), P for trend = 0.049. Similar, yet nonsignificant associations, were observed for amount of dense tissue and breast cancer deaths. The adjusted HR for women in the highest vs. the lowest tertile of percent dense tissue and all causes of death was 1.38 (95% CI, 0.57–3.31), P for trend = 0.48. Similar nonsignificant associations were observed between percent dense tissue and breast cancer deaths. Conclusions: Women with high amounts of dense tissue were at a 2.5 times greater risk of death compared to women with lower amounts of dense tissue. Increased BD may be a marker of tumor aggressiveness or response to therapy. No significant financial relationships to disclose.

Ovarian function and childbearing issues in breast cancer survivors

The increasing number of breast cancer survivors makes the issues of ovarian dysfunction and childbearing ability more and more relevant for the quality of life of these patients. The incidence of ovarian dysfunction is related to patient age, the specific agents used and the total dose administered, especially the dose of alkylating agents such as cyclophosphamide. Amenorrhea rates following combination chemotherapy consisting of cyclophosphamide + methotrexate + 5-flurouracil (CMF regimen) range from 21 to 71% in women aged 40 years and younger, and from 40 to 100% in older ones. In most series anthracycline-based adjuvant chemotherapy regimens appear to have a lower incidence of amenorrhea, which is probably due to the lower cumulative cyclophosphamide dose administered compared with that given in the CMF regimen. Few data are currently available regarding ovarian function in women treated with taxane-based chemotherapy. In a recent retrospective study on 191 patients, the amenorrhea rate was 64% for women who received doxorubicin + cyclophosphamide (AC regimen) followed by a taxane, compared with 55% (p = 0.05) for those treated with AC alone. Forty percent of women aged 40 years or younger resumed menstruation, whereas the amenorrhea was more likely to be irreversible in older women; however, the addition of a taxane did not change the reversibility rate. Ovarian reserve can be tested with serum assays of follicle-stimulating hormone, inhibin B, estradiol and anti-Müllerian hormone, as well as by ultrasound assessment of antral follicle count. A review of literature data failed to show that a subsequent pregnancy increases the risk of recurrence and death in breast cancer survivors, and some series have even detected longer survival for patients who get pregnant after breast cancer treatment. This apparent survival benefit, probably due to a selection bias called the ‘healthy mother effect’, suggests that breast cancer survivors who subsequently conceive are a self-selecting group of women with better prognosis. The little available information appears to show no increase in the incidence of prematurity, stillbirth or congenital malformations in their babies. In conclusion, future pregnancy is a viable option for a woman treated for early-stage breast cancer and does not appear to be detrimental to either the mother or her offspring.