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Beta blocker use and ovarian cancer survival: A retrospective cohort study
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
Conclusions: Unless costs are significantly reduced, or overall survival is significantly increased, the U.S. would have difficulty absorbing the cost of CPB + B to only improve PFLY by an average of 3.8 months/per patient. doi:10.1016/j.ygyno.2011.12.264
264 Beta blocker use and ovarian cancer survival: A retrospective cohort study R. Eskander1, L. Randall1, L. Bessonova1, K. Ward2, H. Anton Culver1, T. Harrison3. 1University of California, Irvine Medical Center, Orange, CA, 2 University of California, San Diego Moores Cancer Center, La Jolla, CA, 3 Kaiser Permanente Medical Group, Los Angeles, CA. Objective: Beta-blockers have been shown to have a potential beneficial impact on survival in melanoma, breast and prostate cancer. These effects may be mediated through β-2 adrenergic blockade. We examined the association between beta-blocker use and ovarian cancer-specific overall survival (OS). Methods: After institutional review board approval, a retrospective study of patients diagnosed with stage I–IV epithelial ovarian cancer from 2007 to 2010 at Kaiser Permanente Southern California was performed utilizing a universal electronic medication record. Betablocker users for at least 30 days prior to diagnosis were matched 1:4 to non-users. Sample size calculation indicated that 115 users and 415 non-users would provide an 80% power to detect a 30% difference in OS. Statistical analysis was performed using Kaplan–Meier and Cox proportional hazards models. Results: A total of 680 patients were evaluated, including 144 beta-blocker users and 536 non-users. The mean age of beta-blocker users (67.8 years) was statistically greater than that of non-users (60.7 years, P=b 0.001). The mean OS was 23 months for all patients. Median OS was similar for beta-blocker users and non-users (23 months vs. 20 months respectively, P=0.0787), independent of age and stage. Long-term beta-blocker use (≥2.5 years of use prior to diagnosis) resulted in a hazard ratio (HR) of death of 0.711 (95% CI 0.315–1.608). After adjusting for age and stage, the HR for ovarian cancer-specific death was 0.529 (95% CI 0.233–1.200) for long-term users. Post-hoc power analysis showed 21% power to detect a HR of 0.70 with this subgroup sample size at α=0.05. This trend was not seen for short-term users (HR 1.101, 95% CI 0.803–1.510). Conclusions: In this patient cohort, long-term beta-blocker use was associated with a 47% reduction in risk of death, though this did not reach statistical significance. This provocative trend supports further study of long-term beta-blocker use in a larger patient cohort. doi:10.1016/j.ygyno.2011.12.265
265 Mullerian inhibiting substance (MIS) pathway as a therapeutic target in ovarian cancer: Deciphering the necessary components T. Ayeni, W. Sullivan, A. Weaver, W. Cliby. Mayo Clinic, Rochester, MN. Objective: Activation of mullerian inhibiting substance type II receptor (T2R) leads to dimerization with one of three candidate type I receptors (T1R) and growth inhibition of mullerian tissues. While T2R is commonly expressed in epithelial ovarian cancer (EOC), the prevalence of T1R is unknown; this data is critical because our in vitro studies suggest that biologic response is dependent upon which candidate T1R is involved in signaling. The aims of this research were to characterize the frequency of candidate T1R expression in EOC and determine if clinical outcomes are dependent on receptor expression.
S111
Methods: Tissue microarrays (TMA) were created from 323 consecutive patients with primary EOC. Expression of T1R (ALK2, ALK3, ALK6) and T2R was assessed with immunohistochemistry. Associations between T2R status and clinical characteristics were assessed using the chi-square test. The logrank test was used to evaluate associations between clinicopathologic features and recurrence-free survival (RFS, limited to patients disease-free after completion of chemotherapy) and overall survival (OS), respectively. Results: Analysis was restricted to 262 patients with serous, endometrioid, clear cell, mucinous or mixed histology and known status for at least one of the four receptors. The most common receptor combinations were: T2R-/Alk2,3,6 (16; 6%); T2R-/ALK2,3 (43; 16%); T2R+/ALK2,3 (81; 31%); and T2R+/ALK2,3,6 (84; 32%). There was no difference among these receptor combinations regarding survival (RFS p = 0.91; OS p = 0.89). Patients without T2R were more likely to have advanced stage disease (p = 0.04) and an inability to be cytoreduced to microscopic disease (p = 0.01), compared to patients with T2R present. The ALK6 protein was the least represented form of type I receptor and its expression was associated with death in early stage disease (p = .03), but not in late stage (p = 0.42). Conclusions: The downstream effect of therapy targeting the MIS pathway is dependent upon specific receptor pairing in EOC. We demonstrate for the first time that the majority of human EOC (70%) expresses the necessary candidate receptors for growth inhibition via the MIS pathway. We show that expression of specific receptors is associated with worse clinical outcomes. These results will facilitate future in vitro and in vivo investigations. doi:10.1016/j.ygyno.2011.12.266
266 Survey of physician awareness of oocyte and embryo cryopreservation in women with hereditary breast ovarian cancer (HBOC) syndrome A. West1, N. Noyes2, B. Pothuri2. 1New York University School of Medicine, New York, NY, 2New York University Medical Center, New York, NY. Objective: Risk reducing salpingo-oophorectomy may be offered to women with hereditary breast ovarian cancer syndrome with reduction in ovarian cancer mortality. This study evaluated physician awareness of oocyte and embryo cryopreservation procedures in this population. Methods: Physicians at academic centers in 45 states and D.C. caring for women at risk of developing ovarian cancer were invited to participate in an anonymous online survey. Physicians were recruited using email addresses publicized on institutional websites. Physicians received an email link to the 5-minute, 28-question survey, which evaluated demographic information and knowledge of fertility preservation (FP). Results: One-thousand-ninety-six physicians were invited to participate and 109 completed the questionnaire: OB/GYN 34 (31%), GynOnc 25 (23%), MedOnc 26 (24%), REI 8 (7%), Surgery 6 (6%), and other 10 (9%). Ninety-four (86%) physicians indicated they regularly care for women at risk of developing ovarian cancer and 92 (84%) are concerned about child bearing. In the experience of 62 (57%) physicians, greater than 25% of their patient population is interested in learning about FP options. Eighty-six (79%) of the physicians speak to women about FP options. Physicians who speak to patients about FP introduce oocyte cryopreservation 23 (21%), embryo cryopreservation 40 (37%), or both 23 (21%). Sixty-eight (62%) have referred HBOC patients for embryo cryopreservation and 58 (53%) have referred for oocyte cryopreservation. Ninety-eight
Conclusions: Unless costs are significantly reduced, or overall survival is significantly increased, the U.S. would have difficulty absorbing the cost of CPB + B to only improve PFLY by an average of 3.8 months/per patient. doi:10.1016/j.ygyno.2011.12.264
264 Beta blocker use and ovarian cancer survival: A retrospective cohort study R. Eskander1, L. Randall1, L. Bessonova1, K. Ward2, H. Anton Culver1, T. Harrison3. 1University of California, Irvine Medical Center, Orange, CA, 2 University of California, San Diego Moores Cancer Center, La Jolla, CA, 3 Kaiser Permanente Medical Group, Los Angeles, CA. Objective: Beta-blockers have been shown to have a potential beneficial impact on survival in melanoma, breast and prostate cancer. These effects may be mediated through β-2 adrenergic blockade. We examined the association between beta-blocker use and ovarian cancer-specific overall survival (OS). Methods: After institutional review board approval, a retrospective study of patients diagnosed with stage I–IV epithelial ovarian cancer from 2007 to 2010 at Kaiser Permanente Southern California was performed utilizing a universal electronic medication record. Betablocker users for at least 30 days prior to diagnosis were matched 1:4 to non-users. Sample size calculation indicated that 115 users and 415 non-users would provide an 80% power to detect a 30% difference in OS. Statistical analysis was performed using Kaplan–Meier and Cox proportional hazards models. Results: A total of 680 patients were evaluated, including 144 beta-blocker users and 536 non-users. The mean age of beta-blocker users (67.8 years) was statistically greater than that of non-users (60.7 years, P=b 0.001). The mean OS was 23 months for all patients. Median OS was similar for beta-blocker users and non-users (23 months vs. 20 months respectively, P=0.0787), independent of age and stage. Long-term beta-blocker use (≥2.5 years of use prior to diagnosis) resulted in a hazard ratio (HR) of death of 0.711 (95% CI 0.315–1.608). After adjusting for age and stage, the HR for ovarian cancer-specific death was 0.529 (95% CI 0.233–1.200) for long-term users. Post-hoc power analysis showed 21% power to detect a HR of 0.70 with this subgroup sample size at α=0.05. This trend was not seen for short-term users (HR 1.101, 95% CI 0.803–1.510). Conclusions: In this patient cohort, long-term beta-blocker use was associated with a 47% reduction in risk of death, though this did not reach statistical significance. This provocative trend supports further study of long-term beta-blocker use in a larger patient cohort. doi:10.1016/j.ygyno.2011.12.265
265 Mullerian inhibiting substance (MIS) pathway as a therapeutic target in ovarian cancer: Deciphering the necessary components T. Ayeni, W. Sullivan, A. Weaver, W. Cliby. Mayo Clinic, Rochester, MN. Objective: Activation of mullerian inhibiting substance type II receptor (T2R) leads to dimerization with one of three candidate type I receptors (T1R) and growth inhibition of mullerian tissues. While T2R is commonly expressed in epithelial ovarian cancer (EOC), the prevalence of T1R is unknown; this data is critical because our in vitro studies suggest that biologic response is dependent upon which candidate T1R is involved in signaling. The aims of this research were to characterize the frequency of candidate T1R expression in EOC and determine if clinical outcomes are dependent on receptor expression.
S111
Methods: Tissue microarrays (TMA) were created from 323 consecutive patients with primary EOC. Expression of T1R (ALK2, ALK3, ALK6) and T2R was assessed with immunohistochemistry. Associations between T2R status and clinical characteristics were assessed using the chi-square test. The logrank test was used to evaluate associations between clinicopathologic features and recurrence-free survival (RFS, limited to patients disease-free after completion of chemotherapy) and overall survival (OS), respectively. Results: Analysis was restricted to 262 patients with serous, endometrioid, clear cell, mucinous or mixed histology and known status for at least one of the four receptors. The most common receptor combinations were: T2R-/Alk2,3,6 (16; 6%); T2R-/ALK2,3 (43; 16%); T2R+/ALK2,3 (81; 31%); and T2R+/ALK2,3,6 (84; 32%). There was no difference among these receptor combinations regarding survival (RFS p = 0.91; OS p = 0.89). Patients without T2R were more likely to have advanced stage disease (p = 0.04) and an inability to be cytoreduced to microscopic disease (p = 0.01), compared to patients with T2R present. The ALK6 protein was the least represented form of type I receptor and its expression was associated with death in early stage disease (p = .03), but not in late stage (p = 0.42). Conclusions: The downstream effect of therapy targeting the MIS pathway is dependent upon specific receptor pairing in EOC. We demonstrate for the first time that the majority of human EOC (70%) expresses the necessary candidate receptors for growth inhibition via the MIS pathway. We show that expression of specific receptors is associated with worse clinical outcomes. These results will facilitate future in vitro and in vivo investigations. doi:10.1016/j.ygyno.2011.12.266
266 Survey of physician awareness of oocyte and embryo cryopreservation in women with hereditary breast ovarian cancer (HBOC) syndrome A. West1, N. Noyes2, B. Pothuri2. 1New York University School of Medicine, New York, NY, 2New York University Medical Center, New York, NY. Objective: Risk reducing salpingo-oophorectomy may be offered to women with hereditary breast ovarian cancer syndrome with reduction in ovarian cancer mortality. This study evaluated physician awareness of oocyte and embryo cryopreservation procedures in this population. Methods: Physicians at academic centers in 45 states and D.C. caring for women at risk of developing ovarian cancer were invited to participate in an anonymous online survey. Physicians were recruited using email addresses publicized on institutional websites. Physicians received an email link to the 5-minute, 28-question survey, which evaluated demographic information and knowledge of fertility preservation (FP). Results: One-thousand-ninety-six physicians were invited to participate and 109 completed the questionnaire: OB/GYN 34 (31%), GynOnc 25 (23%), MedOnc 26 (24%), REI 8 (7%), Surgery 6 (6%), and other 10 (9%). Ninety-four (86%) physicians indicated they regularly care for women at risk of developing ovarian cancer and 92 (84%) are concerned about child bearing. In the experience of 62 (57%) physicians, greater than 25% of their patient population is interested in learning about FP options. Eighty-six (79%) of the physicians speak to women about FP options. Physicians who speak to patients about FP introduce oocyte cryopreservation 23 (21%), embryo cryopreservation 40 (37%), or both 23 (21%). Sixty-eight (62%) have referred HBOC patients for embryo cryopreservation and 58 (53%) have referred for oocyte cryopreservation. Ninety-eight