Differential effect of obesity on comorbidity risk in younger and older women with early breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13601-e13601
Author(s):  
Michael Lorentsen ◽  
Allison Mary Deal ◽  
Hyman B. Muss ◽  
Yi Tang Chen ◽  
Tucker Brenizer ◽  
...  

e13601 Background: Overall survival in women with early breast cancer (EBC) (Stage I-III) has made great strides over the past several decades, with survivors more likely to die from causes other than breast cancer. This study investigates the differential effect of obesity on pre-treatment comorbidity risk in younger versus older women with EBC. Methods: This is a retrospective chart review of women with EBC, age 21 and older, seen at a single institution. Differences in 18 common comorbidities were assessed by age ( > = 65 vs < 65) and Body Mass Index/BMI ( > = BMI 30 vs < 30), with relative risks (RR) estimated from log-binomial regression. Results: In a sample of 590 women, 24% were age 65+, 32% non-white, and 39% had obesity. Patients age 65+ were more likely to report 2+ comorbidities compared to age < 65 (RR 1.62, 69% v 43%). Obese patients (BMI > = 30) were more likely to report 2+ comorbidities compared to BMI < 30 (RR: 1.73, 66% v 38%). Women with obesity were more likely to have hyperlipidemia (RR: 1.85, 28% v 15%) as well as diabetes (RR: 2.51, 17% v 7%). The impact of BMI on comorbidity risk (2+ v < 2) differed by age group (interaction p < 0.001). In the < 65 group, obese patients were more likely to have 2+ comorbidities compared to non-obese (RR: 2.12, 62% v 29%, p < 0.0001). The difference was not as large in the 65+ group (RR: 1.28, 81% v 63%, p = 0.02). Conclusions: This study demonstrates increased comorbidity burden, including hyperlipidemia and diabetes, in women with obesity and EBC, especially those < 65. Providers should ensure that patients with obesity and EBC are appropriately screened and treated for underlying comorbidities. Future research should assess the impact of weight loss on overall survival in EBC patients.

2019 ◽  
Vol 37 (26) ◽  
pp. 2338-2348 ◽  
Author(s):  
Hyman B. Muss ◽  
Mei-Yin C. Polley ◽  
Donald A. Berry ◽  
Heshan Liu ◽  
Constance T. Cirrincione ◽  
...  

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician’s choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer–specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor–negative patients (HR, 0.66; P = .02), but not among hormone receptor–positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease. Competing risks in this older population dilute overall survival benefits.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 514-514
Author(s):  
Georg Pfeiler ◽  
Robert Konigsberg ◽  
Christian Fesl ◽  
Brigitte Mlineritsch ◽  
Herbert Stoger ◽  
...  

514 Background: Zoledronic acid (ZOL) improves disease outcome in premenopausal patients with breast cancer (BC), especially in those with low estrogen environment. Obesity is associated with increased estrogen serum levels, which might influence the efficacy of ZOL. We investigated the impact of BMI on the efficacy of ZOL in premenopausal patients with BC. Methods: ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6 mg q28d SC) in combination with anastrozole (ANA) or tamoxifen (TAM) ± ZOL 4 mg IV q6mo) in premenopausal women with endocrine-responsive BC. BMI was calculated using the prospectively collected data on patients’ height and weight at study entry. BMI definitions of the WHO were used: normal 18.5-24.9 kg/m2, overweight: BMI 25-29.9 kg/m2, obese BMI ≥ 30 kg/m2). Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method and results were compared by using the log-rank test and Cox proportional hazard modeling. Results: Two thirds of the patients were normal weight (1,111) and one third was overweight (391) or obese (182). Normal weight patients treated with ZOL experienced the same benefit as overweight/obese patients treated with ZOL compared to patients without ZOL regarding disease free survival (HR 0.75, 95%CI 0.53 1.05 p = 0.09 and HR 0.71, 95%CI 0.46 1.1, p=0.12, respectively) as well as overall survival (HR 0.67, 95% CI 0.37 1.22, p=0.19 and HR 0.64, 95%CI 0.32 1.28, p=0.19, respectively). No difference regarding DFS and OS could be detected between normal weight and overweight/ obese patients treated with ZOL (HR 1.05, 95%CI 0.69 1.59, p=0.83 and HR 1.27, 95%CI 0.62 2.61, p= 0.51). Comparing normal weight patients with ZOL to obese patients with ZOL, again no difference could be observed. Conclusions: The significant outcome benefit of adjuvant zoledronic acid in ABCSG-12 can be demonstrated both in normal weight and overweight/obese premenopausal patients with early breast cancer, indicating that the bone marrow microenvironment changing impact of adjuvant bisphopshonate treatment does not correlate with patients’ BMI.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19061-e19061
Author(s):  
Kirsten A. Nyrop ◽  
Allison Mary Deal ◽  
Hyman B. Muss ◽  
Emily Damone ◽  
Michael Lorentsen ◽  
...  

e19061 Background: Both comorbidities and obesity (body mass index/BMI 30 or higher) are observed in women at the time of early breast cancer (EBC) diagnosis. This study investigates age and obesity and their association with disparities in comorbidities between black and white women at EBC diagnosis. Methods: This is a retrospective chart review of women with EBC (Stage I-III) treated at a single institution. Relative risk (RR) with 95% Confidence Interval (CI) for individual comorbidities are calculated for black compared to white patients, adjusted for age and BMI. Results: In a sample of 548 women, 26% are black and 74% are white. 18% of black patients vs 28% of white patients were age 65 or older (p = .01). 62% of black vs 33% of white patients had obesity (p < .0001). 63% of black vs 47% of white patients had 2 or more total comorbidities at diagnosis (p = .003). 33% of black vs 10% of white patients had 2 or more obesity-related comorbidities (p < .0001). 60% of black vs 32% of white patients had hypertension (p < .0001); 23% of black vs 6% of white patients had diabetes (p < .0001); and 28% of black vs 18% of white patients had high cholesterol (p = .02). In multivariable (MV) analysis adjusted for age and BMI, black women had 45% higher risk for hypertension [RR 1.45 (1.19-1.75), p = .0002)] and 44% higher risk for diabetes [RR 1.44 (1.02-5.86), p < .0001)] at EBC diagnosis. However, after adjustment, differences by race were no longer seen for > = 2 total comorbidities, > = 2 obesity-related comorbidities, heart disease, or thyroid disease. Conclusions: This study documents significant disparities between black and white women with EBC with regard to high rates of obesity, overall comorbidities and obesity-related comorbidities. Future research should assess the potential impact of weight management (avoiding weight gain) interventions in the first 2 years post diagnosis on improving OS and BCSS among patients with obesity and in reducing OS and BCSS disparities between black and white women.


Author(s):  
Qiao Li ◽  
Manran Liu ◽  
Yan Sun ◽  
Ting Jin ◽  
Pengpeng Zhu ◽  
...  

Abstract Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with poor prognosis and limited treatment options. Hypoxia is a key hallmark of TNBC. Metabolic adaptation promotes progression of TNBC cells that are located within the hypoxic tumor regions. However, it is not well understood regarding the precise molecular mechanisms underlying the regulation of metabolic adaptions by hypoxia. Methods RNA sequencing was performed to analyze the gene expression profiles in MDA-MB-231 cell line (20% O2 and 1% O2). Expressions of Slc6a8, which encodes the creatine transporter protein, were detected in breast cancer cells and tissues by quantitative real-time PCR. Immunohistochemistry was performed to detect SLC6A8 protein abundances in tumor tissues. Clinicopathologic correlation and overall survival were evaluated by chi-square test and Kaplan-Meier analysis, respectively. Cell viability assay and flow cytometry analysis with Annexin V/PI double staining were performed to investigate the impact of SLC6A8-mediated uptake of creatine on viability of hypoxic TNBC cells. TNBC orthotopic mouse model was used to evaluate the effects of creatine in vivo. Results SLC6A8 was aberrantly upregulated in TNBC cells in hypoxia. SLC6A8 was drastically overexpressed in TNBC tissues and its level was tightly associated with advanced TNM stage, higher histological grade and worse overall survival of TNBC patients. We found that SLC6A8 was transcriptionally upregulated by p65/NF-κB and mediated accumulation of intracellular creatine in hypoxia. SLC6A8-mediated accumulation of creatine promoted survival and suppressed apoptosis via maintaining redox homeostasis in hypoxic TNBC cells. Furthermore, creatine was required to facilitate tumor growth in xenograft mouse models. Mechanistically, intracellular creatine bolstered cell antioxidant defense by reducing mitochondrial activity and oxygen consumption rates to reduce accumulation of intracellular reactive oxygen species, ultimately activating AKT-ERK signaling, the activation of which protected the viability of hypoxic TNBC cells via mediating the upregulation of Ki-67 and Bcl-2, and the downregulation of Bax and cleaved Caspase-3. Conclusions Our study indicates that SLC6A8-mediated creatine accumulation plays an important role in promoting TNBC progression, and may provide a potential therapeutic strategy option for treatment of SLC6A8 high expressed TNBC.


Breast Cancer ◽  
2020 ◽  
Author(s):  
Yasser Alatawi ◽  
Richard A. Hansen ◽  
Chiahung Chou ◽  
Jingjing Qian ◽  
Vishnu Suppiramaniam ◽  
...  

2008 ◽  
Vol 26 (25) ◽  
pp. 4072-4077 ◽  
Author(s):  
Jennifer K. Litton ◽  
Ana M. Gonzalez-Angulo ◽  
Carla L. Warneke ◽  
Aman U. Buzdar ◽  
Shu-Wan Kau ◽  
...  

Purpose To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer. Patients and Methods From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI of 25 to < 30 kg/m2), or normal/underweight (BMI < 25 kg/m2). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer–specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided. Results Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years. Conclusion Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.


2017 ◽  
Vol 26 (12) ◽  
pp. 2094-2100 ◽  
Author(s):  
Maria Burton ◽  
Karen Kilner ◽  
Lynda Wyld ◽  
Kate Joanna Lifford ◽  
Frances Gordon ◽  
...  

2017 ◽  
Vol 35 (10) ◽  
pp. 1041-1048 ◽  
Author(s):  
Ian Smith ◽  
Denise Yardley ◽  
Howard A. Burris ◽  
Richard De Boer ◽  
Dino Amadori ◽  
...  

Purpose The Letrozole (Femara) Versus Anastrozole Clinical Evaluation (FACE) study compared the efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor (HR) –positive and node-positive early breast cancer (eBC). Methods Postmenopausal women with HR-positive and node-positive eBC were randomly assigned to receive adjuvant therapy with either letrozole (2.5 mg) or anastrozole (1 mg) once per day for 5 years or until recurrence of disease. Patients were stratified on the basis of the number of lymph nodes and human epidermal growth factor receptor 2 status. The primary end point was 5-year disease-free survival (DFS), and the key secondary end points were overall survival and safety. Results A total of 4,136 patients were randomly assigned to receive either letrozole (n = 2,061) or anastrozole (n = 2,075). The final analysis was done at 709 DFS events (letrozole, 341 [16.5%]; anastrozole, 368 [17.7%]). The 5-year estimated DFS rate was 84.9% for letrozole versus 82.9% for anastrozole arm (hazard ratio, 0.93; 95% CI, 0.80 to 1.07; P = .3150). Exploratory analysis showed similar DFS with letrozole and anastrozole in all evaluated subgroups. The 5-year estimated overall survival rate was 89.9% for letrozole versus 89.2% for anastrozole arm (hazard ratio, 0.98; 95% CI, 0.82 to 1.17; P = .7916). Most common grade 3 to 4 adverse events (> 5% of patients) reported for letrozole versus anastrozole were arthralgia (3.9% v 3.3%, and 48.2% v 47.9% for all adverse events), hypertension (1.2% v 1.0%), hot flushes (0.8% v 0.4%), myalgia (0.8% v 0.7%), dyspnea (0.8% v 0.5%), and depression (0.8% v 0.6%). Conclusion Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR-positive, node-positive eBC.


2016 ◽  
Vol 1 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Eleonora Mioranza ◽  
Cristina Falci ◽  
Maria Vittoria Dieci ◽  
Valentina Guarneri ◽  
Pierfranco Conte

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