- Email: [email protected]
Endometrial cancer complications and survival in morbidly obese African American and white women
174
Abstracts / Gynecologic Oncology 133 (2014) 2–207
compared with 18% with BMI b25 (P b .001), and 88% of patients with BMI ≥40 having endometrioid tumors compared with 76% with BMI b25 (P = 0.005). Furthermore, obese women were less likely to have highrisk (HR) disease (+ lymph nodes, ovaries, cytology) or tumor features that met GOG 99 high-intermediate risk (HIR) criteria: 41% of BMI ≥40 were HR or HIR vs 58% of BMI b25 (P b .001). Adjuvant therapies (P = 0.151) and recurrence (P = 0.46) did not vary by weight. BMI (P = 0.016), age (P b 0.0001), race (P = 0.033), and risk group (P b 0.0001) predicted all-cause mortality. BMI was not predictive of disease-specific survival (P = 0.79); only age (P = 0.032) and risk group (P b .0001) remained significant factors. Conclusions: This study demonstrated that obese women inherently have lower-risk disease but suggested that EC in low BMI women may be higher risk than previously thought. BMI was associated with all-cause but not disease-specific mortality, again suggesting the detrimental effect of obesity independent of EC. Given the obesity epidemic, these findings suggest that weight management should be a consideration in risk stratification of EC. doi:10.1016/j.ygyno.2014.03.457
438 — Poster Session B Endometrial cancer complications and survival in morbidly obese African American and white women S.M. Seward1, M.L. Cote1, Q.F. Ahmed2, S. Bandyopadhyay2, J. Ruterbusch2, B. Alosh2, E. Abdulfatah2, R.T. Morris2, R. Ali-Fehmi2. 1 Karmanos Cancer Institute, Detroit, MI, USA, 2Wayne State University, Detroit, MI, USA. Objectives: The prevalence of morbid obesity, defined as a body mass index (BMI) ≥40, is increasing at twice the rate of obesity (BMI ≥30) in the United States. Obesity is the strongest modifiable exposure for endometrial cancer and is at least partially responsible for the increase in type I endometrial cancers. The aim of our study was to assess obesity as a risk factor in endometrial cancer. Methods: From our database of 800 endometrial cancer patients, we examined 89 African American (AA) and 97 white women with endometrial cancer who received a hysterectomy at our institution to determine whether the racial disparities seen in tumor characteristics and survival persisted in a morbidly obese population. All slides were reviewed by a gynecologic pathologist. The clinical data was retrieved from medical charts. Chi-square tests, Kaplan–Meier curves, and Cox regression models were used for statistical analysis. Results: The mean age at diagnosis was similar for whites (56.8 years) and AAs (56.9 years). The mean BMI in this morbidly obese population was slightly higher for AA women (mean BMI, 49.2) than for white women (mean BMI, 47.0) (P = 0.09). AA women were more likely to have a type II tumor than white women (33.7% vs 15.5%, P = 0.003) and to have higher-grade tumors (P b 0.001). On average, AA women had longer hospital stays after surgery (mean, 5.4 days) compared to white women (mean, 3.5 days) (P = 0.03). Other clinical variables, including FIGO stage, depth of invasion, lymph node involvement, myometrium involvement, postsurgical complications, and overall endometrial cancerspecific survival, were similar. Conclusions: Morbidly obese AA women had relatively high rates of type II cancers, suggesting that obesity may play a stronger role in type II tumors than previously reported. In addition, despite longer hospital stays in AA women, other comparable clinical characteristics, postsurgical complications, and survival did not differ by race.
doi:10.1016/j.ygyno.2014.03.458
439 — Poster Session B Predicting everolimus/letrozole treatment efficacy in patients with advanced or recurrent endometrial cancer: A biomarker study Y. Jiang1, B.M. Slomovitz2, Q. Zhang3, Y. Amin1, R. Broaddus3, R.L. Coleman3, K.H. Lu3. 1Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2 Women's Cancer Center, Carol G Simon Cancer Center, Morristown, NJ, USA, cThe University of Texas MD Anderson Cancer Center, Houston, TX, USA. Objectives: A phase II study using everolimus/letrozole demonstrated a high response rate for patients with advanced or recurrent endometrial cancer with a clinical benefit rate of 49% and objective response rate of 31%. The objective of this study is to determine whether various tumor biomarkers involved in the PI3K/mTOR and estrogen receptor (ER) signaling pathways can predict tumor response to the treatment. In our previous single agent everolimus trial, KRAS mutation was associated with non-response. Methods: Formalin fixed, paraffin-embedded (FFPE) primary tumor tissue from patients was used for biomarker studies via mutational analysis and immunohistochemistry (IHC). Hot spot mutations of KRAS, CTNNB1, and PIK3CA were performed using Sanger sequencing. IHC was used to access the expression level of biomarkers ER, progesterone receptor (PR), 4EBP1, phosphorylated (p-)4EBP1, S6RP, p-S6RP, p-mTOR, PTEN, p-AKT, PI3K, LKB1 and p-ERK1/2. Results: 20 out of 35 patients had FFPE tissue available for DNA testing and 16 had tissue available for IHC study. One out of 20 (5.0%) patients was found to carry a KRAS mutation. Of interest, this patient was a complete responder. Four out of 18 (22.2%) patients were found to carry CTNNB1 mutations, among which three were responders and one was a non-responder. Five out of 19 patients (26.3%) were found to carry PIK3CA mutations and there was no association between PIK3CA mutations and clinical outcome, which differs from the previous reports that PIK3CA mutations may be associated with better treatment response. In the IHC study, only combined ER/PR level was associated with clinical benefit (P b 0.05). Conclusions: Combined ER/PR level was significantly higher in responders, and CTNNB1 mutations were observed more frequently in responders than non-responders. A KRAS mutation was identified in one of the complete responders. Of interest, this patient was also on metformin, which we have demonstrated to act as an anti-KRAS therapeutic agent in preclinical studies. A phase II study of everolimus/ letrozole/metformin has recently been initiated and biomarker analysis will be integrated.
doi:10.1016/j.ygyno.2014.03.459
440 — Poster Session B Evaluation of slide storage and detection of molecular markers by immunohistochemistry (IHC) in formalin-fixed, paraffin embedded endometrial cancer tissues from a clinical trial: A GOG study T.A. Grushko1, V.L. Filiaci2, A.G. Montag3, M. Apushkin3, M.J. Gomez1, B. Marzullo2, L. Monovich4, N. Ramirez4, M.J. Birrer5, O.I. Olopade1, G. Fleming1. 1University of Chicago Medical Center, Chicago, IL, USA, 2 Gynecologic Oncology Group Statistical and Data Center, Buffalo, NY, USA, 3Department of Pathology, University of Chicago Medical Center, Chicago, IL, USA, 4Gynecologic Oncology Group Tissue Bank, Biopathology Center, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA, 5Massachusetts General Hospital Cancer Center, Harvard University, Boston, MA, USA. Objectives: To compare IHC staining for topoisomerase II alpha (TOP2A) on year old stored unstained slides with staining on freshly cut slides from stored blocks of tumor specimens on a clinical trial.
Abstracts / Gynecologic Oncology 133 (2014) 2–207
compared with 18% with BMI b25 (P b .001), and 88% of patients with BMI ≥40 having endometrioid tumors compared with 76% with BMI b25 (P = 0.005). Furthermore, obese women were less likely to have highrisk (HR) disease (+ lymph nodes, ovaries, cytology) or tumor features that met GOG 99 high-intermediate risk (HIR) criteria: 41% of BMI ≥40 were HR or HIR vs 58% of BMI b25 (P b .001). Adjuvant therapies (P = 0.151) and recurrence (P = 0.46) did not vary by weight. BMI (P = 0.016), age (P b 0.0001), race (P = 0.033), and risk group (P b 0.0001) predicted all-cause mortality. BMI was not predictive of disease-specific survival (P = 0.79); only age (P = 0.032) and risk group (P b .0001) remained significant factors. Conclusions: This study demonstrated that obese women inherently have lower-risk disease but suggested that EC in low BMI women may be higher risk than previously thought. BMI was associated with all-cause but not disease-specific mortality, again suggesting the detrimental effect of obesity independent of EC. Given the obesity epidemic, these findings suggest that weight management should be a consideration in risk stratification of EC. doi:10.1016/j.ygyno.2014.03.457
438 — Poster Session B Endometrial cancer complications and survival in morbidly obese African American and white women S.M. Seward1, M.L. Cote1, Q.F. Ahmed2, S. Bandyopadhyay2, J. Ruterbusch2, B. Alosh2, E. Abdulfatah2, R.T. Morris2, R. Ali-Fehmi2. 1 Karmanos Cancer Institute, Detroit, MI, USA, 2Wayne State University, Detroit, MI, USA. Objectives: The prevalence of morbid obesity, defined as a body mass index (BMI) ≥40, is increasing at twice the rate of obesity (BMI ≥30) in the United States. Obesity is the strongest modifiable exposure for endometrial cancer and is at least partially responsible for the increase in type I endometrial cancers. The aim of our study was to assess obesity as a risk factor in endometrial cancer. Methods: From our database of 800 endometrial cancer patients, we examined 89 African American (AA) and 97 white women with endometrial cancer who received a hysterectomy at our institution to determine whether the racial disparities seen in tumor characteristics and survival persisted in a morbidly obese population. All slides were reviewed by a gynecologic pathologist. The clinical data was retrieved from medical charts. Chi-square tests, Kaplan–Meier curves, and Cox regression models were used for statistical analysis. Results: The mean age at diagnosis was similar for whites (56.8 years) and AAs (56.9 years). The mean BMI in this morbidly obese population was slightly higher for AA women (mean BMI, 49.2) than for white women (mean BMI, 47.0) (P = 0.09). AA women were more likely to have a type II tumor than white women (33.7% vs 15.5%, P = 0.003) and to have higher-grade tumors (P b 0.001). On average, AA women had longer hospital stays after surgery (mean, 5.4 days) compared to white women (mean, 3.5 days) (P = 0.03). Other clinical variables, including FIGO stage, depth of invasion, lymph node involvement, myometrium involvement, postsurgical complications, and overall endometrial cancerspecific survival, were similar. Conclusions: Morbidly obese AA women had relatively high rates of type II cancers, suggesting that obesity may play a stronger role in type II tumors than previously reported. In addition, despite longer hospital stays in AA women, other comparable clinical characteristics, postsurgical complications, and survival did not differ by race.
doi:10.1016/j.ygyno.2014.03.458
439 — Poster Session B Predicting everolimus/letrozole treatment efficacy in patients with advanced or recurrent endometrial cancer: A biomarker study Y. Jiang1, B.M. Slomovitz2, Q. Zhang3, Y. Amin1, R. Broaddus3, R.L. Coleman3, K.H. Lu3. 1Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2 Women's Cancer Center, Carol G Simon Cancer Center, Morristown, NJ, USA, cThe University of Texas MD Anderson Cancer Center, Houston, TX, USA. Objectives: A phase II study using everolimus/letrozole demonstrated a high response rate for patients with advanced or recurrent endometrial cancer with a clinical benefit rate of 49% and objective response rate of 31%. The objective of this study is to determine whether various tumor biomarkers involved in the PI3K/mTOR and estrogen receptor (ER) signaling pathways can predict tumor response to the treatment. In our previous single agent everolimus trial, KRAS mutation was associated with non-response. Methods: Formalin fixed, paraffin-embedded (FFPE) primary tumor tissue from patients was used for biomarker studies via mutational analysis and immunohistochemistry (IHC). Hot spot mutations of KRAS, CTNNB1, and PIK3CA were performed using Sanger sequencing. IHC was used to access the expression level of biomarkers ER, progesterone receptor (PR), 4EBP1, phosphorylated (p-)4EBP1, S6RP, p-S6RP, p-mTOR, PTEN, p-AKT, PI3K, LKB1 and p-ERK1/2. Results: 20 out of 35 patients had FFPE tissue available for DNA testing and 16 had tissue available for IHC study. One out of 20 (5.0%) patients was found to carry a KRAS mutation. Of interest, this patient was a complete responder. Four out of 18 (22.2%) patients were found to carry CTNNB1 mutations, among which three were responders and one was a non-responder. Five out of 19 patients (26.3%) were found to carry PIK3CA mutations and there was no association between PIK3CA mutations and clinical outcome, which differs from the previous reports that PIK3CA mutations may be associated with better treatment response. In the IHC study, only combined ER/PR level was associated with clinical benefit (P b 0.05). Conclusions: Combined ER/PR level was significantly higher in responders, and CTNNB1 mutations were observed more frequently in responders than non-responders. A KRAS mutation was identified in one of the complete responders. Of interest, this patient was also on metformin, which we have demonstrated to act as an anti-KRAS therapeutic agent in preclinical studies. A phase II study of everolimus/ letrozole/metformin has recently been initiated and biomarker analysis will be integrated.
doi:10.1016/j.ygyno.2014.03.459
440 — Poster Session B Evaluation of slide storage and detection of molecular markers by immunohistochemistry (IHC) in formalin-fixed, paraffin embedded endometrial cancer tissues from a clinical trial: A GOG study T.A. Grushko1, V.L. Filiaci2, A.G. Montag3, M. Apushkin3, M.J. Gomez1, B. Marzullo2, L. Monovich4, N. Ramirez4, M.J. Birrer5, O.I. Olopade1, G. Fleming1. 1University of Chicago Medical Center, Chicago, IL, USA, 2 Gynecologic Oncology Group Statistical and Data Center, Buffalo, NY, USA, 3Department of Pathology, University of Chicago Medical Center, Chicago, IL, USA, 4Gynecologic Oncology Group Tissue Bank, Biopathology Center, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA, 5Massachusetts General Hospital Cancer Center, Harvard University, Boston, MA, USA. Objectives: To compare IHC staining for topoisomerase II alpha (TOP2A) on year old stored unstained slides with staining on freshly cut slides from stored blocks of tumor specimens on a clinical trial.