title: Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma.
abstract: OBJECTIVE
  Metastatic pancreatic adenocarcinoma is considered a uniformly fatal disease with a median survival of 1 year with modern chemotherapy. While a subset of patients achieve prolonged survival, few of the factors that define this group of patients are known.
  
  
  METHODS
  For the determination of overall survival (OS), 549 patients with histologically confirmed metastatic pancreatic adenocarcinoma were evaluated. Emphasis was placed on treatment history and family history of breast, ovarian, and pancreatic cancers. To ensure a uniform metastatic population, patients treated with prior locoregional therapies (i.e., surgery or radiotherapy) were excluded as were patients with a prior history of stage I-III disease.
  
  
  RESULTS
  Patients with family history or pedigree history of cancer had superior OS. This was especially true in patients with three or more relatives with either breast, ovarian, or pancreatic cancers [hazard ratio (HR) 0.49, 95 % confidence interval (CI) 0.30-0.80, p = 0.003]. First-line platinum chemotherapy was associated with a poor survival (hazard ratio for death 1.74, 95% CI 1.12-2.71, p = 0.01) for patients without a family history of these cancers but not for those without such a history (p = 0.31). In fact, as the number of relatives with these cancers increased, the OS survival improved for individuals receiving first-line platinum therapy (HR 0.76, 95 % CI 0.65-0.89, p = 0.0004), which was not the case for those receiving other therapies (p = 0.98).
  
  
  CONCLUSIONS
  Treatment with platinum chemotherapy in patients with a family history of breast, ovarian, or pancreatic cancers was associated with a longer survival, whereas platinum use in patients without such a family history of cancer was associated with poor survival. These findings suggest that family history may serve as a predictive marker for platinum use in patients with metastatic pancreatic adenocarcinoma.
authors.affiliation: Department of G.I. Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA.|University of Texas/M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77096, USA.
authors.forename: David
authors.initials: D
authors.lastname: Fogelman
authors.affiliation: Sidney Kimmel Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.|Departments of Biostatistics and Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.|Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E3537, Baltimore, MD 21205, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sugar
authors.affiliation: Sidney Kimmel Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.|6300 Harry Hines Blvd. Ste 265, Dallas, TX 75235, USA.
authors.forename: George
authors.initials: G
authors.lastname: Oliver
authors.affiliation: Department of G.I. Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA.|Staten Island University Hospital, 475 Seaview Avenue, Staten Island, NY 10305, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Shah
authors.affiliation: Departments of Pathology and Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, 1650 Orleans St., Rm G89, Baltimore, MD 21231-1000, USA.|Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.|Johns Hopkins Bloomberg School of Public Health, 1650 Orleans Street, CRB I Room 590, Baltimore, MD 21231, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Klein
authors.affiliation: Departments of Pathology and Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.|Department of Medical Oncology, NCI-National Cancer Institute, 10 Center Dr, Bldg 10/12N226, Bethesda, MD 20892, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Alewine
authors.affiliation: 1515 Holcombe Blvd., Unit 0085, Houston, TX 77030, USA.
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of G.I. Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA.|University of Texas/M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77096, USA.
authors.forename: Milind
authors.initials: M
authors.lastname: Javle
authors.affiliation: Department of G.I. Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA.
authors.forename: Rachna
authors.initials: R
authors.lastname: Shroff
authors.affiliation: Department of G.I. Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA.|University of Texas/M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77096, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Department of G.I. Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA.|Division of Medical Oncology, Duke University, 10 Searle Drive, 445 Seeley G Mudd Building, Durham, NC 27710, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.affiliation: Sidney Kimmel Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, 1650 Orleans St., Rm G89, Baltimore, MD 21231-1000, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Laheru
authors.affiliation: Swim Across America Laboratory, Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins, 1650 Orleans Street, CRB I Room 590, Baltimore, MD 21231, USA.|Sidney Kimmel Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology
chemical_list: D009944:Organoplatinum Compounds