William J. Lowery

Oral Contraceptive Use and Risk of Breast, Cervical, Colorectal, and Endometrial Cancers: A Systematic Review

Oral contraceptives may influence the risk of certain cancers. As part of the AHRQ Evidence Report, Oral Contraceptive Use for the Primary Prevention of Ovarian Cancer, we conducted a systematic review to estimate associations between oral contraceptive use and breast, cervical, colorectal, and endometrial cancer incidence. We searched PubMed, Embase, and Cochrane Database of Systematic Reviews. Study inclusion criteria were women taking oral contraceptives for contraception or ovarian cancer prevention; includes comparison group with no oral contraceptive use; study reports quantitative associations between oral contraceptive exposure and relevant cancers; controlled study or pooled patient-level meta-analyses; sample size for nonrandomized studies ≥100; peer-reviewed, English-language; published from January 1, 2000 forward. Random-effects meta-analyses were conducted by estimating pooled ORs with 95% confidence intervals (CIs). We included 44 breast, 12 cervical, 11 colorectal, and 9 endometrial cancers studies. Breast cancer incidence was slightly but significantly increased in users (OR, 1.08; CI, 1.00–1.17); results show a higher risk associated with more recent use of oral contraceptives. Risk of cervical cancer was increased with duration of oral contraceptive use in women with human papillomavirus infection; heterogeneity prevented meta-analysis. Colorectal cancer (OR, 0.86; CI, 0.79–0.95) and endometrial cancer incidences (OR, 0.57; CI, 0.43–0.77) were significantly reduced by oral contraceptive use. Compared with never use, ever use of oral contraceptives is significantly associated with decreases in colorectal and endometrial cancers and increases in breast cancers. Although elevated breast cancer risk was small, relatively high incidence of breast cancers means that oral contraceptives may contribute to a substantial number of cases. Cancer Epidemiol Biomarkers Prev; 22(11); 1931–43. ©2013 AACR.

Oral Contraceptives and Risk of Ovarian Cancer and Breast Cancer Among High-Risk Women: A Systematic Review and Meta-Analysis

PURPOSE To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. METHODS We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. RESULTS From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. CONCLUSION Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.

Loss of ARID1A-associated Protein Expression Is a Frequent Event in Clear Cell and Endometrioid Ovarian Cancers

Background Inactivating somatic mutations in the ARID1A gene are described in a significant fraction of clear cell and endometrioid ovarian cancers leading to loss of the corresponding protein (BAF250a). Expression of BAF250a was examined in clear cell and endometrioid cancers accrued as part of the North Carolina Ovarian Cancer Study, a population-based case-control study, to determine whether loss of expression is associated with clinical and epidemiological features. Methods Immunostaining for BAF250a was performed using 212 clear cell and endometrioid ovarian cancers. Associations between loss of BAF250a and clinical and epidemiological features were examined. Variables were analyzed by logistic regression. Results Loss of BAF250a expression was noted in 96 (45%) of 212 cancers: 34 (41%) of 82 clear cell cases and 62 (48%) of 130 endometrioid cases. There was no relationship between the loss of BAF250a and stage, grade, survival, or epidemiological variables. Conclusions These data confirm that loss of the ARID1A-encoded protein BAF250a is a frequent event in the genesis of clear cell and endometrioid ovarian cancers. Loss of BAF250a was not associated with clinical or epidemiologic characteristics. One explanation for these findings is that inactivation of the chromatin remodeling pathway may be a requisite event in the development of these cancers.

Hospice enrollment for terminally ill patients with gynecologic malignancies: Impact on outcomes and interventions

OBJECTIVE To determine survival and interventions for patients with non-curative gynecologic malignancies based on supportive care enrollment. METHODS An IRB approved retrospective review identified patients with recurrent/persistent gynecologic cancers from 2002 to 2008. Demographics, therapy, clinicopathologic data, hospice utilization, surgical/invasive procedures and survival were collected. Patients were considered hospice enrollees if they enrolled following recommendation from their provider (HOSPICE); however, patients that declined hospice when recommended were considered (NO HOSPICE), regardless if they ultimately received supportive care. Standard statistical tests including: t-test and Kaplan-Meier with Log Rank were used. RESULTS Eighty-one patients were identified: 29 patients (36%) NO HOSPICE and 52 (64%) HOSPICE. Mean age was 61. Most patients had ovarian cancer (54.3%), were white (61.7%) and had disease recurrence (72%). Patients utilized a median of 3 anti-neoplastic therapies (range 0-10) for recurrent or progressive/persistent disease. Median time receiving hospice care was 1week for NO HOSPICE patients versus 8weeks HOSPICE patients (p<0.0005). In a subset of patients with recurrent disease, median overall survival for NO HOSPICE patients was 9months (95% CI 5.9-12.1months) versus 17months (95% CI 11.1-22.9months) for HOSPICE patients (p=0.002). NO HOSPICE patients were more likely to have a procedure performed (55% vs. 31%) within 4weeks of their death, including the administration of chemotherapy OR 2.4 (95% CI 1.1-7.1, p=0.036). CONCLUSIONS While retrospective reviews evaluating hospice are challenging, our data suggest no detrimental impact on survival for hospice patients. Continued evaluation for patients at the end-of-life is necessary in order to optimize resource utilization.

Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer.

OBJECTIVE To determine if early palliative care intervention in patients with recurrent, platinum-resistant ovarian cancer is potentially cost saving or cost-effective. METHODS A decision model with a 6 month time horizon evaluated routine care versus routine care plus early referral to a palliative medicine specialist (EPC) for recurrent platinum-resistant ovarian cancer. Model parameters included rates of inpatient admissions, emergency department (ED) visits, chemotherapy administration, and quality of life (QOL). From published ovarian cancer data, we assumed baseline rates over the final 6 months: hospitalization 70%, chemotherapy 60%, and ED visit 30%. Published data from a randomized trial evaluating EPC in metastatic lung cancer were used to model odds ratios (ORs) for potential reductions in hospitalization (OR 0.69), chemotherapy (OR 0.77), and emergency department care (OR 0.74) and improvement in QOL (OR 1.07). The costs of hospitalization, ED visit, chemotherapy, and EPC were based on published data. Ranges were used for sensitivity analysis. Effectiveness was quantified in quality adjusted life years (QALYs); survival was assumed equivalent between strategies. RESULTS EPC was associated with a cost savings of

Cost of care using prophylactic negative pressure wound vacuum on closed laparotomy incisions

1285 per patient over routine care. In sensitivity analysis incorporating QOL, EPC was either dominant or cost-effective, with an incremental cost-effectiveness ratio (ICER) <

Palliative and hospice care in gynecologic cancer: a review.

50,000/QALY, unless the cost of outpatient EPC exceeded

Metastatic adenocarcinoma after laparoscopic supracervical hysterectomy with morcellation: A case report.

2400. Assuming no clinical benefit other than QOL (no change in chemotherapy administration, hospitalizations or ED visits), EPC remained highly cost-effective with ICER

Surgical outcomes and national comprehensive cancer network compliance in advanced ovarian cancer surgery in a low volume military treatment facility

37,440/QALY. CONCLUSION Early palliative care intervention has the potential to reduce costs associated with end of life care in patients with ovarian cancer.

Surgical staging for endometrial cancer in the elderly — Is there a role for lymphadenectomy?

OBJECTIVE We wished to determine the reduction in the rate of wound complications that would render the use of prophylactic negative pressure wound vacuum therapy (NPWT) cost saving compared to routine incision care (RC) following laparotomy for gynecologic malignancy. METHODS A decision tree was designed from a payer perspective to compare strategies for incision management following laparotomy for gynecologic malignancy: (1) RC; (2) prophylactic NPWT. Rates of wound complication, antibiotic use, re-hospitalization, re-operation, and home health use were obtained from a published cohort of 431 women who underwent laparotomy for endometrial cancer 2002-2007. Costs were estimated using Medicare reimbursements; cost of NPWT (