title: Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer.
abstract: OBJECTIVE
  To evaluate the pathologic complete response (pCR) and safety of bevacizumab (B) with chemotherapy in the neoadjuvant setting of breast cancer (BC).
  
  
  METHODS
  A prospective single-arm, single-institution phase II trial for women with stage IIA-B/IIIA-B-C BC. Patients received neoadjuvant docetaxel, cyclophosphamide, B every 3 weeks for 4 cycles followed by doxorubicin every 3 weeks for 4 cycles followed by surgery. After healing, B was given every 3 weeks for 9 cycles. Radiation therapy, trastuzumab and endocrine therapy were given as indicated.
  
  
  RESULTS
  Thirty-nine of 40 patients were evaluable. Median age of participants was 45 years (range, 26 to 72 y). The most serious grade ≥3 adverse events were infection (4), congestive heart failure (2), and pulmonary embolism (1). Thirty-eight of 39 patients underwent surgery. The pCR rate was 41% (16/39), significantly higher than the null-hypothesis rate of 25% (P=0.0204). Rates of pCR were 52% (15/29) in ductal carcinoma compared with 10% (1/10) in nonductal disease (P=0.021), and 59% (10/17) in estrogen receptor-/progesteron receptor- patients compared with 27% (6/22) among patient with at least one positive hormone receptor (P=0.047). African Americans (AA) had 75% pCR (9/12), whereas Whites had only 28% pCR (7/25; P=0.0069), possibly in part because 100% of AA (12/12) had ductal carcinoma compared with only 64% (16/25) of Whites (P=0.017).
  
  
  CONCLUSIONS
  Chemotherapy with B improved pCR in BC patients, but was associated with significant toxicity and rare but very serious complications. The improvement was more pronounced in AA patients, those with ductal carcinoma, and those with estrogen receptor-/progesteron receptor - BC.ClinicalTrials.gov Identifier: NCT00203502.
authors.affiliation: *Hematology/Oncology Division Departments of †Breast Surgical Oncology ‡Pathology §Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR.
authors.forename: Issam
authors.initials: I
authors.lastname: Makhoul
authors.forename: Vicki Suzanne
authors.initials: VS
authors.lastname: Klimberg
authors.forename: Soheila
authors.initials: S
authors.lastname: Korourian
authors.forename: Ronda S
authors.initials: RS
authors.lastname: Henry-Tillman
authors.forename: Eric R
authors.initials: ER
authors.lastname: Siegel
authors.forename: Kent C
authors.initials: KC
authors.lastname: Westbrook
authors.forename: Laura F
authors.initials: LF
authors.lastname: Hutchins
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008408:Mastectomy; D015412:Mastectomy, Segmental; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D044465:White People
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; D003520:Cyclophosphamide