Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Chemotherapy in Treating Women With Breast Cancer That Can Be Surgically Removed

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed Any age NCI NSABP-B-27 NCT00002707

Objectives

I.  Compare overall and disease-free survival in patients with operable 
adenocarcinoma of the breast treated with 4 courses of preoperative 
doxorubicin and cyclophosphamide (AC) alone vs 4 courses of preoperative or 
postoperative docetaxel (TXT) following 4 courses of preoperative AC.

II.  Evaluate whether the addition of preoperative TXT to preoperative AC 
results in improved rates of clinical and pathologic locoregional tumor 
response.

III.  Assess whether the addition of preoperative TXT to preoperative AC 
results in improved rates of breast conservation.

IV.  Assess whether postoperative TXT improves disease-free and overall 
survival in patients who receive preoperative AC, especially in certain 
subgroups of patients (e.g., those with pathologically positive nodes).

Entry Criteria

Disease Characteristics:

Histologically or cytologically proven invasive adenocarcinoma of the breast
 Fine-needle aspiration is acceptable
 Core or Tru-cut biopsies are preferable
 No more than 63 days between initial diagnosis and randomization

Tumor palpable on clinical exam and confined to the breast and ipsilateral
axilla

If clinically negative axillary nodes (N0):  primary tumor greater than 1 cm
(T1c-T3)

If clinically positive axillary nodes (N1):  any size primary tumor (T1-3)

No N2 disease, i.e., ipsilateral nodes clinically fixed to one another or to
other structures

No skeletal pain unless:
 Bone scan and/or roentgenologic exam negative for metastatic disease
 Suspicious findings confirmed as benign by x-ray, MRI, or biopsy

No ulceration, erythema, skin infiltration (complete fixation), or peau
d'orange, or skin edema of any magnitude
 Tethering or dimpling of skin or nipple inversion allowed

No bilateral malignancy
 Suspicious contralateral mass proven benign on biopsy allowed

None of the following unless proven benign on biopsy:
 Suspicious palpable nodes in contralateral axilla
 Palpable supraclavicular or infraclavicular nodes

Hormone receptor status:
 Any status

Prior/Concurrent Therapy:

No prior therapy for breast cancer

No prior anthracyclines for any malignancy

No concurrent sex hormones (e.g., birth control pills or ovarian replacement
therapy)

Patient Characteristics:

Age:
 Any age

Sex:
 Female

Menopausal status:
 Not specified

Performance status:
 Not specified

Life expectancy:
 At least 10 years (exclusive of cancer diagnosis)

Hematopoietic:
 WBC at least 4,000/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin normal
 AST/ALT normal
 Alkaline phosphatase normal

Renal:
 Creatinine normal

Cardiovascular:
 No active cardiac disease that would preclude doxorubicin, e.g.:
  Documented myocardial infarction
  History of congestive heart failure
  Angina pectoris requiring medication
  Valvular disease with documented cardiac function compromise
  Arrhythmia associated with heart failure or cardiac dysfunction
  Poorly controlled hypertension, i.e., diastolic blood pressure greater
   than 100 mm Hg
  Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG unless left
   ventricular ejection fraction at least 45% by MUGA

Other:
 No other malignancy within the past 10 years except:
  Segmentally resected lobular carcinoma in situ of the ipsilateral or
   contralateral breast
  Effectively treated nonmelanomatous skin cancer
  Surgically treated carcinoma in situ of the cervix
 No systemic disease that would preclude therapy
 No psychiatric or addictive disorder that would preclude informed consent
 Geographically accessible for follow-up
 Not pregnant 

Expected Enrollment

Approximately 2,400 patients will be accrued for this study within 5 years.

Outline

This is a randomized, multicenter study. Patients are stratified according to 
age (under 50 vs 50 and over), clinical tumor size (less than 2.1 cm vs 
2.1-4.0 cm vs greater than 4.0 cm), clinical nodal status (negative vs 
positive), and participating center. Patients are randomized to one of three 
treatment arms.  

Arm I: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 
minutes to 2 hours on day 1 every 21 days for 4 courses. Patients receive oral 
tamoxifen daily for 5 years, starting on day 1. After completion of 
chemotherapy, patients are offered surgery (e.g., lumpectomy with axillary 
node dissection, or modified radical mastectomy). Post-operative radiotherapy 
is given post-lumpectomy.

Arm II: Patients receive doxorubicin IV followed by cyclophosphamide IV over 
30 minutes to 2 hours followed by docetaxel IV over 1 hour on day 1 once every 
21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, 
starting on day 1. After the completion of chemotherapy, surgery is offered 
(as in arm I). Radiotherapy follows surgery in post-lumpectomy patients.

Arm III: Patients receive doxorubicin IV followed by cyclophosphamide IV over 
30 minutes to 2 hours on day 1 every 21 days for 4 courses. Patients receive 
oral tamoxifen daily for 5 years, starting on day 1. After completion of 
chemotherapy, surgery is offered (as in arm I). After surgical recovery, 
docetaxel IV is given over 1 hour once every 21 days for 4 courses. 
Radiotherapy follows docetaxel in post-lumpectomy patients.  

Chemotherapy is repeated every 21 days for 4 courses in the absence of disease 
progression or unacceptable toxicity.

Patients are followed every 6 months for 5 years, and then annually thereafter.

Bear HD, Anderson S, Smith RE, et al.: Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 24 (13): 2019-27, 2006.[PUBMED Abstract]

Julian T, Anderson S, Fourchotte V, et al.: Is invasive lobular breast cancer a prognostic factor for neoadjuvant chemotherapy response and long term outcomes? [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3065, S146, 2006.

Mamounas EP, Brown A, Anderson S, et al.: Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 23 (12): 2694-702, 2005.[PUBMED Abstract]

Bear HD, Anderson S, Smith RE, et al.: A randomized trial comparing preoperative (preop) doxorubicin/cyclophosphamide (AC) to preop AC followed by preop docetaxel (T) and to preop AC followed by postoperative (postop) T in patients (pts) with operable carcinoma of the breast: results of NSABP B-27. [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-26, 2004.

Bear HD, Anderson S, Brown A, et al.: The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21 (22): 4165-74, 2003.[PUBMED Abstract]

Mamounas EP, Brown A, Smith R, et al.: Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: updated results from NSABP B-27. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-140, 2002.

Rastogi P, Anderson SJ, Bear HD, et al.: Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol 26 (5): 778-85, 2008.[PUBMED Abstract]

Soran A, Nesbitt L, Mamounas EP, et al.: Centralized medical monitoring in phase III clinical trials: the National Surgical Adjuvant Breast and Bowel Project (NSABP) experience. Clin Trials 3 (5): 478-85, 2006.[PUBMED Abstract]

Heys SD, Sarkar T, Hutcheon AW: Primary docetaxel chemotherapy in patients with breast cancer: impact on response and survival. Breast Cancer Res Treat 90 (2): 169-85, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Harry Bear, MD, PhD, Protocol chair		Ph: 804-828-9325 Email: hdbear@vcu.edu

Registry Information
Official Title		A RANDOMIZED TRIAL COMPARING PREOPERATIVE DOXORUBICIN (ADRIAMYCIN)/CYCLOPHOSPHAMIDE (AC) TO PREOPERATIVE AC FOLLOWED BY PREOPERATIVE DOCETAXEL (TAXOTERE) AND TO PREOPERATIVE AC FOLLOWED BY POSTOPERATIVE DOCETAXEL IN PATIENTS WITH OPERABLE CARCINOMA OF THE BREAST
Trial Start Date		1995-12-20
Registered in ClinicalTrials.gov		NCT00002707
Date Submitted to PDQ		1995-12-20
Information Last Verified		2008-02-09
NCI Grant/Contract Number		U10-CA12027

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