Atkinson R.L.,University of Houston |
Atkinson R.L.,MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic |
El-Zein R.,MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic |
El-Zein R.,University of Houston |
And 13 more authors.
Cancer Causes and Control | Year: 2016
Background: In this single-institution case–control study, we identified risk factors associated with inflammatory breast cancer (IBC) subtypes based on staining of estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth factor 2 (HER2neu) to determine distinct etiologic pathways. Methods: We identified 224 women with IBC and 396 cancer-free women seen at the MD Anderson Cancer Center. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between breast cancer risk factors and the IBC tumor subtypes: luminal (ER+ and/or PR+/HER2neu−), HER2neu+ (any ER and PR, HER2neu+), and triple-negative (ER−/PR−/HER2neu−). Results: In multivariable analysis, compared with women age ≥26 at first pregnancy, women age <26 had a higher risk of triple-negative IBC (OR 3.32, 95% CI 1.37–8.05). Women with a history of breast-feeding had a lower risk of triple-negative (OR 0.30; 95% CI 0.15–0.62) and luminal IBC (OR 0.35, 95% CI 0.18–0.68). A history of smoking was associated with an increased risk of luminal IBC (OR 2.37; 95% CI 1.24–4.52). Compared with normal-weight women, those who were overweight or obese (body mass index ≥25 kg/m2) had a higher risk of all three tumor subtypes (p < 0.01 for all subtypes). Conclusion: Overweight or obese status is important modifiable risk factor for IBC of any subtype. Modifiable risk factors, age at first pregnancy (≥26), breast-feeding, and smoking may be associated with specific IBC subtypes. These results highlight the importance of evaluating epidemiologic risk factors for IBC for the identification of subtype-specific prevention strategies. © 2016, Springer International Publishing Switzerland. Source
Loveland-Jones C.,Anderson Cancer Center at Cooper |
Lin H.,University of Houston |
Shen Y.,University of Houston |
Bedrosian I.,University of Houston |
And 10 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2016
Purpose Although radiation therapy improves locoregional control and survival for inflammatory breast cancer (IBC), it is underused in this population. The purpose of this study was to identify variables associated with the underuse of postmastectomy radiation therapy (PMRT) for IBC. Methods and Materials Using the 1998 to 2011 National Cancer Data Base, we identified 8273 women who underwent mastectomy for nonmetastatic IBC. We used logistic regression modeling to determine the demographic, tumor, and treatment variables associated with the underuse of PMRT. Results Although the use of PMRT increased over time, a total of 30.3% of our cohort did not receive PMRT. On multivariate analysis, variables associated with the underuse of PMRT for IBC included the following (all P<.05): Medicare insurance (odds ratio [OR] = 0.70), annual income <$34,999 (<$30,000: OR=0.79; $30,000-$34,999: OR=0.82), cN2 and cN0 disease (cN2: OR=0.71; cN0: OR=0.63), failure to receive chemotherapy and hormone therapy (chemotherapy: OR=0.15; hormone therapy: OR=0.35), treatment at lower-volume centers (OR=0.83), and treatment in the South and West (South: OR=0.73; West: OR=0.80). Greater distance between patient's residence and radiation facility was also associated with the underuse of PMRT (P=.0001). Conclusions Although the use of PMRT for IBC has increased over time, it continues to be underused. Disparities related to a variety of variables impact which IBC patients receive PMRT. A concerted effort must be made to address these disparities in order to optimize the outcomes for IBC. © 2016 Elsevier Inc. Source
Debeb B.G.,University of Houston |
Debeb B.G.,MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic |
Lacerda L.,University of Houston |
Lacerda L.,MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic |
And 13 more authors.
Oncotarget | Year: 2016
Purpose: We recently demonstrated that histone deacetylase (HDAC) inhibitors can "reprogram" differentiated triple-negative breast cancer cells to become quiescent stem-like cancer cells. We hypothesized that the metabolic state of such cells differs from that of their differentiated progeny. Results: In untreated cells, glucose uptake was higher in ALDH+ cells than in ALDH- cells (p = 0.01) but lactate production was not different; treating ALDH- or ALDH+ cells with VA or SAHA similarly increased glucose uptake without changing lactate production but upregulated G6PD, a rate-limiting enzyme in pentose phosphate pathway metabolism. NADPH production was higher in HDAC inhibitor-treated stem-like cells than in vehicle-treated cells (p < 0.05). Two G6PD inhibitors, 6-aminonicotinamide and dehydroepiandrosterone, decreased mammosphere formation efficiency and ALDH activity and 6-aminonicotinamide reduced the VAinduced increase in ALDH+ cells. Finally, patients expressing high G6PD mRNA had significantly worse overall survival (p < 0.001), and patients with high G6PD protein showed a similar trend towards worse disease-specific survival (p = 0.06). Methods: Glucose consumption, lactate and NADPH production, and reactive oxygen species generation were compared in aldehyde dehydrogenase (ALDH)-positive and -negative cells in the presence or absence of the HDAC inhibitors valproic acid (VA) or suberoylanilide hydroxamic acid (SAHA). Glucose-6-phosphate dehydrogenase (G6PD) expression was evaluated in a tissue microarray from 94 patients with nodepositive invasive breast carcinoma and in two publically available databases and correlated with overall survival. Conclusions: Energy metabolism in HDAC inhibitor-induced stem-like cancer cells differed sharply from that of differentiated cell types. HDAC inhibitor-induced dedifferentiation promoted metabolic reprogramming into the pentose phosphate pathway, which is targeted effectively by G6PD inhibition. These findings highlight a potential dual-therapy approach to targeting bulk differentiated cells with HDAC inhibitors and CSCs with G6PD inhibitors. Source