title: Hypertension as a predictive marker for bevacizumab in metastatic breast cancer: results from a retrospective matched-pair analysis.
abstract: BACKGROUND
  Several phase-III studies have shown improvements in terms of progression-free survival (PFS) with bevacizumab when added to chemotherapy in advanced breast cancer. However, the extent of improvement varied and none of the trials showed benefit in terms of overall survival (OS).
  
  
  METHODS
  All patients with metastatic breast cancer treated with bevacizumab at our Institution between 2005 and 2011 were retrospectively analyzed. A control group was matched according to the following variables: receptor status, treatment line, type of chemotherapy, presence of visceral disease and age.
  
  
  RESULTS
  All 212 patients were evaluable for toxicity, and 198 for response; 430 controls allowed a complete matching for 85 bevacizumab-treated patients. The addition of bevacizumab to chemotherapy significantly prolonged PFS (9.3 vs. 7.6 months, hazard ratio [HR]=0.70, 95% confidence interval [CI]=0.51-0.97, p=0.031) and OS (28.9 vs. 22.6 months, HR=0.67, 95% CI=0.45-0.99, p=0.043). Clinical benefit rate (overall response rate + stable disease for at least six months) was significantly better in the bevacizumab group (75% vs. 59%, p=0.002), while ORR did not differ significantly (48% vs. 35%, p=0.21). Patients developing hypertension during treatment had a more favourable outcome (PFS 13.7 vs. 6.6 months, HR=0.34, 95% CI=0.23-0.49 p<0.001; 2-year OS 78% vs. 30%, HR=0.20, 95% CI=0.12-0.35, p<0.001).
  
  
  CONCLUSIONS
  Bevacizumab in addition to chemotherapy prolonged PFS and OS in a non-selected, partly intensively pre-treated breast cancer population. Hypertension induced by bevacizumab predicted therapy efficacy.
authors.affiliation: Third Medical Department, Salzburg Cancer Research Institute, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, 5020 Salzburg, Austria. r.greil@salk.at.
authors.forename: Simon Peter
authors.initials: SP
authors.lastname: Gampenrieder
authors.forename: Franz
authors.initials: F
authors.lastname: Romeder
authors.forename: Claudia
authors.initials: C
authors.lastname: Muß
authors.forename: Magdalena
authors.initials: M
authors.lastname: Pircher
authors.forename: Sigrun
authors.initials: S
authors.lastname: Ressler
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rinnerthaler
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
authors.forename: Claudia
authors.initials: C
authors.lastname: Sattlberger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mlineritsch
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000175:diagnosis*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: Breast cancer; bevacizumab; hypertension; matched pair; metastatic disease; predictive markers; survival