Response to chemotherapy, recurrence and survival in advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish BRCA mutations, compared to those without

Objectives. Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish (AJ) BRCA founder mutations, compared to sporadic ovarian cancer patients. The purpose of this study was to determine if this association exists in ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations. In addition, we sought to account for possible "survival bias" by minimizing any lead time that may exist between diagnosis and genetic testing. ^ Methods. Patients with stage III/IV ovarian, fallopian tube, or primary peritoneal cancer and a non-Ashkenazi Jewish BRCA1 or 2 mutation, seen for genetic testing January 1996-July 2007, were identified from genetics and institutional databases. Medical records were reviewed for clinical factors, including response to initial chemotherapy. Patients with sporadic (non-hereditary) ovarian, fallopian tube, or primary peritoneal cancer, without family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. When possible, 2 sporadic patients were matched to each BRCA patient. An additional group of unmatched, sporadic ovarian, fallopian tube and primary peritoneal cancer patients was included for a separate analysis. Progression-free (PFS) & overall survival (OS) were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Matched pairs were treated as clusters. Stratified log rank test was used to calculate survival data for matched pairs using paired event times. Fisher's exact test, chi-square, and univariate logistic regression were also used for analysis. ^ Results. Forty five advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations, 86 sporadic-matched and 414 sporadic-unmatched patients were analyzed. Compared to the sporadic-matched and sporadic-unmatched ovarian cancer patients, non-AJ BRCA mutation carriers had longer PFS (17.9 & 13.8 mos. vs. 32.0 mos., HR 1.76 [95% CI 1.13–2.75] & 2.61 [95% CI 1.70–4.00]). In relation to the sporadic- unmatched patients, non-AJ BRCA patients had greater odds of complete response to initial chemotherapy (OR 2.25 [95% CI 1.17–5.41]) and improved OS (37.6 mos. vs. 101.4 mos., HR 2.64 [95% CI 1.49–4.67]). ^ Conclusions. This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. Our efforts to account for "survival bias," by matching, will continue with collaborative studies. ^

The role of cardiovascular comorbidities in ovarian cancer survival

Objective. One facet of cancer care that often goes ignored is comorbidities, or diseases that exist in concert with cancer. Comorbid conditions may affect survival by influencing treatment decisions and prognosis. The purpose of this secondary data analysis was to identify whether a history of cardiovascular comorbidities among ovarian cancer patients influenced survival time at the University of Texas M. D. Anderson Cancer Center. The parent study, Project Peace, has a longitudinal design with an embedded randomized efficacy study which seeks to improve detection of depressive disorders in ovarian, peritoneal, and fallopian tube cancers. ^ Methods. Survival time was calculated for the 249 ovarian cancer patients abstracted by Project Peace staff. Cardiovascular comorbidities were documented as present, based upon information from medical records in addition to self reported comorbidities in a baseline study questionnaire. Kaplan-Meier survival curves were used to compare survival time among patients with a presence or absence of particular cardiovascular comorbidities. Cox Regression proportional models accounted for multivariable factors such as age, staging, family history of cardiovascular comorbidities, and treatment. ^ Results. Among our patient population, there was a statistically significant relationship between shorter survival time and a history of thrombosis, pericardial disease/tamponade, or COPD/pulmonary hypertension. Ovarian cancer patients with a history of thrombosis lived approximately half as long as patients without thrombosis (58.06 months vs. 121.55 months; p=.001). In addition, patients who suffered from pericardial disease/tamponade had poorer survival than those without a history of pericardial disease/tamponade (48 months vs. 80.07 months; p=.002). Ovarian cancer patients with a history of COPD or pulmonary hypertension had a median survival of 60.2 months, while the median survival for patients without these comorbidities was 80.2 months (p=.014). ^ Conclusion. Especially because of its relatively lower survival rate, greater emphasis needs to be placed on the potential influence of cardiovascular comorbid conditions in ovarian cancer.^