title: Circulating neuregulin during the transition from stage A to stage B/C heart failure in a breast cancer cohort.
abstract: BACKGROUND
  Breast cancer (BC) treatments can cause heart failure (HF) in a subset of patients. ACC/AHA guidelines classify patients receiving cardiotoxic medications as stage A, a high-risk population for the development of HF. Circulating neuregulin (NRG) correlates with outcomes in stage C and D HF. We examined the levels of NRG in a BC cohort receiving cardiotoxic chemotherapy and its relationship with adverse cardiac effects during the transition from stage A to stage B or C HF.
  
  
  RESULTS
  In an ongoing prospective study, a planned interim analysis of 78 BC women receiving either anthracycline (AC) or trastuzumab (Tsz) was performed. Biometric data, cardiac risk factors, and NRG levels, were collected before chemotherapy and after completion of AC therapy and/or 3 months into Tsz therapy. Cardiac function was measured by left ventricular ejection fraction (LVEF) by echocardiography at the above time points and longitudinally as standard of care. The interim cohort was predominately white with stage II BC and a median age of 50 years. A reduction of >10 absolute percentage points in LVEF was observed in 21.4% of the cohort, representing a transition from stage A to stage B or C HF. A statistically significant drop in plasma NRG was observed in women treated with AC and/or Tsz (P < .001). Additionally, baseline NRG correlated with the maximal change in LVEF.
  
  
  CONCLUSIONS
  More than 20% of women experienced cardiac dysfunction, detected by decline in LVEF, and were reclassified as stage B or C HF. Plasma NRG levels were reduced after exposure to cardiotoxic chemotherapy, suggesting a loss in a cardioprotective growth factor. Higher baseline NRG levels were observed in those with the greatest decline in LVEF, supporting the continued investigation of NRG as a potential prognostic marker in early-stage HF.
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6300, USA. carrie.geisberg@vanderbilt.edu
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Geisberg
authors.forename: Wissam M
authors.initials: WM
authors.lastname: Abdallah
authors.forename: Monica
authors.initials: M
authors.lastname: da Silva
authors.forename: Cheri
authors.initials: C
authors.lastname: Silverstein
authors.forename: Holly M
authors.initials: HM
authors.lastname: Smith
authors.forename: Vandana
authors.initials: V
authors.lastname: Abramson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mayer
authors.forename: Julie
authors.initials: J
authors.lastname: Means-Powell
authors.forename: Darla
authors.initials: D
authors.lastname: Freehardt
authors.forename: Brenda
authors.initials: B
authors.lastname: White
authors.forename: Daniel
authors.initials: D
authors.lastname: Lenihan
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Sawyer
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D020880:Neuregulins / Q000097:blood* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D000068878:Trastuzumab
chemical_list: D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015415:Biomarkers; D020880:Neuregulins; D000068878:Trastuzumab