title: Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience.
abstract: OBJECTIVE
  Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN).
  
  
  METHODS
  We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed.
  
  
  RESULTS
  Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years.
  
  
  CONCLUSIONS
  In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy.
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX. awolff@jhmi.edu.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Blackford
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Goldstein
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Keith
authors.initials: K
authors.lastname: Stockerl-Goldstein
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Leigh
authors.initials: L
authors.lastname: Neumayer
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Terry S
authors.initials: TS
authors.lastname: Langbaum
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Theriault
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Hughes
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Weeks
authors.affiliation: Antonio C. Wolff, Amanda L. Blackford, Kala Visvanathan, Terry S. Langbaum, and Judith E. Karp, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Hope S. Rugo, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA; Beverly Moy, Massachusetts General Hospital Cancer Center; Melissa E. Hughes and Jane C. Weeks, Dana-Farber Cancer Institute, Boston, MA; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Keith Stockerl-Goldstein, Siteman Cancer Center at Washington University School of Medicine, St Louis, MO; Leigh Neumayer, Huntsman Cancer Center at University of Utah School of Medicine, Salt Lake City, UT; and Richard L. Theriault, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Karp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019046:Bone Marrow Neoplasms / Q000145:classification / Q000453:epidemiology* / Q000209:etiology; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008408:Mastectomy / Q000009:adverse effects / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D012307:Risk Factors; D018426:SEER Program / Q000706:statistics & numerical data; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology; D055815:Young Adult