be a reflection of older, medically infirm patients with advanceddisease rather than an inherently inferior treatment option.

doi:10.1016/j.ygyno.2014.07.009

Every-three-week versus dose dense weekly paclitaxel neoadjuvantchemotherapy for advanced stage ovarian, fallopian tube, andperitoneal cancersM. Auera, I. Wilkinson-Ryanb, L. Chenb, K. Fuhb, A. Hagemannb,P. Thakerb, M. Powellb, L. Massadb, D. Mutchb. aCleveland ClinicFoundation/MetroHealthMedical Center, Cleveland, OH, USA, bWashingtonUniversity School of Medicine, Saint Louis, MO, USA.

Objectives: The aim of this study was to compare operative data,toxicity, and survival between weekly dose dense (ddT) and every 3-week (q3wT) paclitaxel given with carboplatin as neoadjuvantchemotherapy (NACT) for advanced ovarian cancer.Methods: We performed a retrospective study of stage III–IV ovarian,fallopian tube, or peritoneal cancers treated with NACT followed byinterval cytoreduction from January 2009 to present. Carboplatin(AUC 5-6) was given every 3 weeks with ddT (paclitaxel 80 mg/m2)or q3wT (paclitaxel 175 mg/m2). Chi-square, Student's t test, Kaplan–Meier method, and log-rank statistics were used.Results: Eleven women treated with ddT, and 51 women treated withNACT met inclusion criteria. There were no demographic differences.Median agewas 64. Fifty-nine percent of patients had stage IIIC and 41%stage IVdisease. Therewas nodifference inmean cycles of NACT (3.6 forddT v. 3.8 q3wT), proportion achieving a 50% decline in CA-125 (91% ofddT v. 94% of q3wT p= 0.51), or radiologic response (100% ddT v. 72%q3wT, p = 0.12). Ten ddT women (91%) and 28 q3wT women (55%)had no gross residual disease after interval cytoreduction (OR 8.21, 95%CI 0.98–69). Mean operative time (181 min ddT v. 166 min q3wT,p = 0.46), EBL (416 cc ddT v. 358 cc q3wT, p = 0.49), and rate ofpostoperative complications (9% ddT v. 18% q3wT, p = 0.43) weresimilar. Eighty-two percent of ddT v. 51% q3wT experienced grade 1–2anemia (p= 0.043) and 55% of ddT v. 14% of q3wT had a grade 1–2leukopenia or neutropenia (p= 0.029). One ddT patient had grade 3hypokalemia and one q3wT patient had grade 3 anemia. A similarnumber of patients in each group was treated with G-CSF (36% ddT v.55% q3wT, p = 0.26). Median progression-free survival was 16 monthsfor ddT v. 15 months for q3wT, (p= 0.69); overall survival has not beenreached. After a median of 15 months, 9% ddT women have died and27% are alive with the disease. After a median of 21 months, 44% q3wTwomen have died and 27% are alive with the disease. The remainingpatients have no evidence of disease.Conclusion: ddT has similar outcomes with a trend toward increasedrate of cytoreduction to no gross residual disease compared to q3wT.Future studies evaluating survival benefit and symptom controlbetween these regimens in the NACT setting are needed.

doi:10.1016/j.ygyno.2014.07.010

Germline mutations in cancer susceptibility genes in brca1 andbrca2 negative families with ovarian and breast cancerB. Norquista, M. Harrellb, T. Walshb, J. Mandellb, K. Agnewb, M. Leeb,K. Penningtona, M.C. Kingb, E. Swishera,b. aDivision of GynecologicOncology, University ofWashington, Seattle, WA, USA, bDivision of MedicalGenetics, University of Washington, Seattle, WA, USA.

Objectives: Germline mutations in cancer susceptibility genes otherthan BRCA1 and BRCA2 (BRCA1/2) are found in approximately 6% ofwomen with ovarian, fallopian tube, or primary peritoneal cancer. Ourobjective was to sequence BRCA1/2-negative ovarian cancer patients

with a family history of ovarian or breast cancer to identify inheritedmutations that may explain the familial risk.Methods: Weused a targeted capture,massively parallel sequencing testcalled BROCAon ovarian cancer probandswith a family history of ovarianor breast cancer, or a personal history of breast cancer. BROCA testingincluded all known breast and ovarian cancer genes. Only the clear loss offunctionmutationswere included. 118probandswere ascertained fromagynecologic oncology tissue bank or outside referrals and providedinformed consent. A family history of ovarian cancer was defined ashaving a first or second degree relative with ovarian cancer. A familyhistory of breast cancer was defined as having a first or second degreerelative with pre-menopausal breast cancer, or 2 or more regardless ofmenopausal status. Subjects were only included in one category.Results: Of 118 ovarian cancer probands, 22 (18.6%) were found tocarry deleterious mutations in non-BRCA1/2 cancer susceptibilitygenes. 8/29 (27.6%) ovarian cancer patients with a personal history ofbreast cancer hadmutations in 7 genes (2 CHEK2, 2 RAD51D, 1 BRIP1, 1TP53, 1 ATM, and one with both PALB2 and PMS2). This includedmutations found in 2/5 (40%) who also had a family history of ovariancancer and 4/10 (40%)who also had a family history of breast cancer. 38patients had a family history of ovarian cancer with no personal historyof breast cancer; 9/38 (23.7%) had mutations in 5 genes (3 BRIP1, 3RAD51C, 1 RAD51D, 1 TP53, and 1 ATM). Finally, 5/51 (9.8%) ovariancancer patients with a family history of breast cancer and no personalhistory of breast cancer hadmutations in 5 genes (1MSH6, 1 FAM175A,1 NBN, 1 PALB2, and 1 CHEK2).Conclusion: Germline mutations in DNA-repair genes are present in asubstantial fraction of BRCA1/2-negative ovarian cancer patients with apersonal or family history suggestive of inherited disease. Thesewomenmay benefit from multiplex gene testing. The detection of inheritedmutations in these women may be useful to identify the risk of othercancers, to inform familymembers of possible risk, and to direct therapyby suggesting candidates for PARP inhibitor therapy.

doi:10.1016/j.ygyno.2014.07.011

Hereditary predisposition to ovarian cancer, looking beyondBRCA1/BRCA2L. Miniona, J. Dolinskyb, E. Chaoc, B. Monkd. aMaricopa Medical Center,Phoenix, AZ, USA, bAmbry Genetics, Aliso Viejo, CA, USA, cUniversity ofCalifornia Irvine, Irvine, CA, USA, dUniversity of Arizona Cancer Center,Phoenix, AZ, USA.

Objectives: Genetic predisposition to ovarian cancer is well docu-mented. To date, the majority of testing has focused on BRCA1/BRCA2 germ-line mutations but these genes do not entirely explainhereditary risk. We sought to investigate the contribution of 19additional genes identified from the scientific literature that havebeen suggested to increase the risk of ovarian cancer.Methods: Between March 2012 and September 2013, 974 patients(without known BRCA1/BRCA2 mutations) were referred for multi-genetesting with OvaNext TM, a commercially available panel including ATM,BARD1, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6,MUTYH, NBN, PALB2, PMS2, PTEN, RAD50, RAD51C, STK11 and TP53.Illumina next generation sequencingwas performed andmutationswereverified with Sanger sequencing. Deletion/duplication analyses wereperformed using custom targeted array comparative genomic hybridiza-tion for all genes. EPCAM was analyzed for deletion/duplications only.Data regarding personal and/or family history of cancer were abstractedfrom test requisition forms.Results: Eighty-six women (8.8%) were found to carry a pathogenicor likely pathogenic mutation(s) in one of 16 additional genes. Threegenes (EPCAM, RAD50, STK11) did not contain identified mutations.Mutations were identified in 16 of the 19 additional genes (ATM,

Abstracts 383