scholarly journals Weight Gain, Metabolic Syndrome, and Breast Cancer Recurrence: Are Dietary Recommendations Supported by the Data?

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Colin E. Champ ◽  
Jeff S. Volek ◽  
Joshua Siglin ◽  
Lianjin Jin ◽  
Nicole L. Simone

Metabolic syndrome, which can include weight gain and central obesity, elevated serum insulin and glucose, and insulin resistance, has been strongly associated with breast cancer recurrence and worse outcomes after treatment. Epidemiologic and prospective data do not show conclusive evidence as to which dietary factors may be responsible for these results. Current strategies employ low-fat diets which emphasize supplementing calories with increased intake of fruit, grain, and vegetable carbohydrate sources. Although results thus far have been inconclusive, recent randomized trials employing markedly different dietary strategies in noncancer patients may hold the key to reducing multiple risk factors in metabolic syndrome simultaneously which may prove to increase the long-term outcome of breast cancer patients and decrease recurrences. Since weight gain after breast cancer treatment confers a poor prognosis and may increase recurrence rates, large-scale randomized trials are needed to evaluate appropriate dietary interventions for our breast cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1521-1521 ◽  
Author(s):  
Anne Marie McCarthy ◽  
Wei He ◽  
Susan Regan ◽  
Andrew T. Chan ◽  
Beverly Moy ◽  
...  

1521 Background: Aspirin or NSAID (A/N) use post diagnosis is associated with lower risk of breast cancer recurrence and mortality in cohort studies. A potential mechanism is that A/Ns may suppress cell growth and induce apoptosis in tumors driven by phosphatidylinositol 3 kinase ( PIK3CA), the most common oncogene mutation in breast cancer. An interaction of A/Ns and PIK3CA mutation has been observed for colorectal cancer prognosis, but has not been studied in breast cancer. The objective was to assess time to breast cancer recurrence (TTR) with respect to A/N use and PIK3CAmutation. Methods: Patients with HR+/HER2- breast cancer treated at Massachusetts General Hospital in 2009-2014 who received tumor genotyping were included. PIK3CA mutations, including 8 common hotspot mutations, were assessed by a high-throughput tumor genotyping assay using DNA from formalin-fixed, paraffin-embedded tumor tissue. A/N use beginning 6 months post diagnosis through metastasis was extracted from electronic medical records using coded data and natural language processing. Patients with de novo metastatic disease or progressive disease within 6 months of primary diagnosis were excluded. TTR was estimated using Cox proportional hazards models. Results: Among breast cancer patients (N=212), 60 (28%) used A/Ns and 69 (33%) had PIK3CA mutation (see Table). After adjusting for age, stage, adjuvant endocrine therapy, radiation, and chemotherapy, A/N users had significantly longer TTR (HR=0.65 p=0.01). The association was similar for wild type (HR=0.58 p=0.01) and PIK3CA mutated tumors (HR=0.60 p=0.06), with no significant interaction of A/N use and PIK3CA (p=0.34). Conclusions: Among HR+ breast cancer patients, those who used A/Ns following primary diagnosis had longer TTR than non-users, regardless of tumor PIK3CA mutation status. The study provides a model for how tumor genomics could be integrated into secondary chemoprevention studies. [Table: see text]


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1561-1561
Author(s):  
Sangeetha Meda Reddy ◽  
Maureen Sadim ◽  
Irene B. Helenowski ◽  
Jun Li ◽  
Nengjun Yi ◽  
...  

1561 Background: Obesity and weight gain in breast cancer patients has been associated with decreased quality of life, decreased response to chemotherapy, increased cancer recurrence, and higher all-cause mortality. Our study was designed to identify factors that contribute to this weight gain. Methods: Chart review was conducted on 565 breast cancer patients to obtain weights and BMIs over an 18 month period from diagnosis, tumor characteristics (ER/PR/Her2 status, grade, presence of LN metastases, stage), demographics (age, race), clinical factors (menopausal status), and treatment regimens (chemotherapy, hormone therapy, radiation). Blood samples were genotyped for polymorphisms in FTO (fat mass and obesity-associated protein) and the adiponectin pathway, two pathways found to be associated with obesity and breast cancer risk. Results: See table. For genetic analysis, one statistically significant epistatic and three gene x environmental interactions were detected for adiponectin SNPs: rs822396d x BMI at diagnosis (effect size 8.65), rs2232853a x age (2.75), rs1501299a x BMI at diagnosis (3.63), and rs266729d x rs7539542d (6.40). Conclusions: We have identified multiple clinical and genetic variables that are likely predictors of weight gain in breast cancer patients. We are conducting a prospective study of 200 breast cancer patients to validate the findings of this retrospective study. By identifying a high risk patient population, we hope to target them for aggressive lifestyle interventions to prevent weight gain and thereby improve their mortality and morbidity. [Table: see text]


2021 ◽  
Vol 12 ◽  
Author(s):  
Yifei Zhu ◽  
Tiange Wang ◽  
Yiwei Tong ◽  
Xiaosong Chen ◽  
Kunwei Shen

BackgroundComprehensive investigations of the associations between 21-gene recurrence assay and metabolic profiles in Chinese breast cancer patients are limited.MethodsWe evaluated the relations of the 21-gene recurrence risk score (RS) and the expression of cancer-related genes with metabolic factors and biomarkers of insulin and the insulin-like growth factor (IGF) axis, and examined the interactions between the 21-gene RS and these metabolic profiles on breast cancer recurrence in Chinese women with HR-positive, HER2-negative early-stage breast cancer.ResultsThe 21-gene RS was inversely associated with body mass index ([BMI]β: −0.178 kg/m2; P=0.040), the homeostasis model assessment of insulin resistance index ([HOMA-IR] β: −0.031; P=0.042), insulin (β: −0.036 uIU/ml; P=0.009), and C-peptide (β: −0.021 ug/L; P=0.014) and was positively associated with high-density lipoprotein cholesterol (β: 0.025 mmol/L; P=0.004), which were driven by the relation patterns between specific cancer-related genes and these metabolic profiles. Each 10-unit increase in the 21-gene RS was associated with 28% (95% CI: 5–47%) higher risk of breast cancer recurrence; this association was also observed in patients with favorable metabolic profiles in relevant to an absence of obesity, insulin resistance, hyperglycemia, hypertension, or dyslipidemia (28–44% higher risk) and among women with a low level of insulin, C-peptide, or the IGF1/IGFBP3 ratio (41–155% higher risk).ConclusionsThe 21-gene RS was related to favorable metabolic profiles including lower BMI, HOMA-IR, insulin, and C-peptide, and higher HDL in Chinese breast cancer patients, and its prognostic impact on breast cancer recurrence was more likely to present among patients with relatively favorable metabolic profiles.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Pang ◽  
Guoqiang Zhang ◽  
Na Yan ◽  
Jidong Lang ◽  
Yuebin Liang ◽  
...  

Tamoxifen (TAM) is the most commonly used adjuvant endocrine drug for hormone receptor-positive (HR+) breast cancer patients. However, how to accurately evaluate the risk of breast cancer recurrence and metastasis after adjuvant TAM therapy is still a major concern. In recent years, many studies have shown that the clinical outcomes of TAM-treated breast cancer patients are influenced by the activity of some cytochrome P450 (CYP) enzymes that catalyze the formation of active TAM metabolites like endoxifen and 4-hydroxytamoxifen. In this study, we aimed to first develop and validate an algorithm combining polymorphisms in CYP genes and clinicopathological signatures to identify a subpopulation of breast cancer patients who might benefit most from TAM adjuvant therapy and meanwhile evaluate major risk factors related to TAM resistance. Specifically, a total of 256 patients with invasive breast cancer who received adjuvant endocrine therapy were selected. The genotypes at 10 loci from three TAM metabolism-related CYP genes were detected by time-of-flight mass spectrometry and multiplex long PCR. Combining the 10 loci with nine clinicopathological characteristics, we obtained 19 important features whose association with cancer recurrence was assessed by importance score via random forests. After that, a logistic regression model was trained to calculate TAM risk-of-recurrence score (TAM RORs), which is adopted to assess a patient’s risk of recurrence after TAM treatment. The sensitivity and specificity of the model in an independent test cohort were 86.67% and 64.56%, respectively. This study showed that breast cancer patients with high TAM RORs were less sensitive to TAM treatment and manifested more invasive characteristics, whereas those with low TAM RORs were highly sensitive to TAM treatment, and their conditions were stable during the follow-up period. There were some risk factors that had a significant effect on the efficacy of TAM. They were tissue classification (tumor Grade < 2 vs. Grade ≥ 2, p = 2.2e−16), the number of lymph node metastases (Node-Negative vs. Node < 4, p = 5.3e−07; Node < 4 vs. Node ≥ 4, p = 0.003; Node-Negative vs. Node ≥ 4, p = 7.2e−15), and the expression levels of estrogen receptor (ER) and progesterone receptor (PR) (ER < 50% vs. ER ≥ 50%, p = 1.3e−12; PR < 50% vs. PR ≥ 50%, p = 2.6e−08). The really remarkable thing is that different genotypes of CYP2D6*10(C188T) show significant differences in prediction function (CYP2D6*10 CC vs. TT, p < 0.019; CYP2D6*10 CT vs. TT, p < 0.037). There are more than 50% Chinese who have CYP2D6*10 mutation. So the genotype of CYP2D6*10(C188T) should be tested before TAM therapy.


2020 ◽  
Vol 25 (12) ◽  
pp. 3186-3197 ◽  
Author(s):  
Xuan Wang ◽  
Neng Wang ◽  
Lidan Zhong ◽  
Shengqi Wang ◽  
Yifeng Zheng ◽  
...  

AbstractDepression and anxiety are common comorbidities in breast cancer patients. Whether depression and anxiety are associated with breast cancer progression or mortality is unclear. Herein, based on a systematic literature search, 17 eligible studies involving 282,203 breast cancer patients were included. The results showed that depression was associated with cancer recurrence [1.24 (1.07, 1.43)], all-cause mortality [1.30 (1.23, 1.36)], and cancer-specific mortality [1.29 (1.11, 1.49)]. However, anxiety was associated with recurrence [1.17 (1.02, 1.34)] and all-cause mortality [1.13 (1.07, 1.19)] but not with cancer-specific mortality [1.05 (0.82, 1.35)]. Comorbidity of depression and anxiety is associated with all-cause mortality [1.34 (1.24, 1.45)] and cancer-specific mortality [1.45 (1.11, 1.90)]. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety, being female and of younger age (<60 years), and shorter follow-up duration (≤5 years) were related to a poorer prognosis. Our study highlights the critical role of depression/anxiety as an independent factor in predicting breast cancer recurrence and survival. Further research should focus on a favorable strategy that works best to improve outcomes among breast cancer patients with mental disorders.


Author(s):  
Mark J. Haykowsky ◽  
Jessica M. Scott ◽  
Kathryn Hudson ◽  
Neelima Denduluri

As patients are living longer after a cancer diagnosis, survivorship is becoming increasingly important in cancer care. The sequelae of multimodality therapies include weight gain and decreased cardiorespiratory fitness, which increase cardiovascular risk. Evidence suggests that physical activity reduces the risk of breast cancer recurrence and death. Avoidance of weight gain after therapy also improves outcomes after a diagnosis of breast cancer. Prospective randomized trials must be performed to determine the benefits of specific physical activity and dietary habits for survivors of breast cancer. This review outlines the important physiologic changes that occur with antineoplastic therapy and the important role of exercise and diet.


2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA509-CRA509 ◽  
Author(s):  
V. Dezentje ◽  
N. J. Van Blijderveen ◽  
H. Gelderblom ◽  
H. Putter ◽  
M. P. Van Herk-Sukel ◽  
...  

CRA509 Background: The use of cytochrome P450 2D6 inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Concomitant use of CYP2D6 inhibitors, such as the commonly prescribed selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in breast cancer. The objectives were to relate concomitant CYP2D6 inhibitor use and tamoxifen adherence to breast cancer event free time (EFT). Methods: Data were used from PHARMO, a pharmacy database, PALGA, a nationwide pathology database and the Dutch Medical Register in the Netherlands. Breast cancer patients who were treated with tamoxifen as adjuvant therapy between 1994 and 2006 were included. A Cox proportional hazards model with a time-dependent definition for the CYP2D6 inhibitor exposure was used. Results: 1,990 breast cancer patients using tamoxifen were included, among whom 215 (10.8%) used a CYP2D6 inhibitor during tamoxifen treatment. No association between concomitant CYP2D6 inhibitor use and breast cancer recurrence was observed. Poor tamoxifen adherence was associated with lower EFT. Conclusions: This observational study did not show an association between concomitant CYP2D6 inhibitor use and breast cancer recurrence among patients treated with adjuvant tamoxifen. However, this study shows for the first time that poor tamoxifen adherence is associated with lower EFT. No significant financial relationships to disclose.


2020 ◽  
Vol 185 (Supplement_1) ◽  
pp. 669-675 ◽  
Author(s):  
Alakesh Bera ◽  
Eric Russ ◽  
Muthu Srinivasan ◽  
Ofer Eidelman ◽  
Michael Eklund ◽  
...  

ABSTRACT Introduction Breast cancer is the most frequent cancer detected for women, and while our ability to treat breast cancer has improved substantially over the years, recurrence remains a major obstacle. Standard screening for new and recurrent breast cancer involves clinical breast imaging. However, there is no clinically approved noninvasive body fluid test for the early detection of recurrent breast cancer. Materials and Method: In this study, we analyzed serum samples from both recurrent and nonrecurrent breast cancer patients by different proteomics methods to identify biomarkers in patients with recurrence of disease. Results Comparative data analysis identified several histone deacetylase (HDAC) proteins, which were found at significantly higher levels in the serum of recurrent breast cancer patients: HDAC9 (C-term) (P = 0.0035), HDAC5 (C-term) (P = 0.013), small ubiquitin-like modifier 1 (N-term) (P = 0.017), embryonic stem cell-expressed Ras (inter) (P = 0.018), and HDAC7 (C-term) (P = 0.020). Chronic inflammation plays a critical role in the development of the breast cancer recurrence, and we identified several proinflammatory cytokines that were present at elevated levels only in recurrent breast cancer patient serum. Conclusions Our data indicated that the epigenetic regulation of inflammatory processes plays a critical role in breast cancer recurrence. The identified proteins could lay the groundwork for the development of a serum-based breast cancer recurrence assay.


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