Four Versus Six Cycles of Cyclophosphamide/Doxorubicin or Paclitaxel in Adjuvant Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: AC regimen; cyclophosphamide; doxorubicin hydrochloride; paclitaxel
Intervention description: Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 3871.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IB breast cancer; stage II breast cancer

Summary:

      This randomized phase III trial studies cyclophosphamide and doxorubicin hydrochloride
      compared with paclitaxel as adjuvant therapy in treating breast cancer in women with 0-3
      positive axillary lymph nodes. Giving additional cancer treatment after surgery may help to
      lower the risk that the cancer will come back (adjuvant therapy). Drugs used in chemotherapy,
      such as cyclophosphamide, doxorubicin hydrochloride, and paclitaxel, work in different ways
      to stop the growth of tumor cells, either by killing the cells, by stopping them from
      dividing, or by stopping them from spreading. It is not yet known whether the standard
      adjuvant therapy of cyclophosphamide and doxorubicin hydrochloride is more effective than
      paclitaxel in treating women with breast cancer
    

Eligibility criteria:

        Eligibility Criteria:

          -  Patients must have histologically confirmed invasive carcinoma of the female breast,
             with 0-3 positive axillary lymph nodes

          -  Patients must have 0-3 positive axillary lymph nodes to be eligible for this study;
             patients with node-negative breast cancer should have sufficiently "high risk" disease
             to warrant chemotherapy; as general guidelines, node-negative patients with tumors of
             >= 1 cm or estrogen or progesterone receptor negative tumors of any size may be
             eligible; ultimately though, the definition of "high risk" may be determined by the
             treating physician, and if the treating physician feels the patient warrants
             chemotherapy, the patient is eligible; for patients with 1-3 positive axillary nodes,
             the patient is eligible regardless of primary breast tumor characteristics, if in the
             opinion of the treating physician, chemotherapy is deemed potentially beneficial to
             the patient

          -  If the patient has had a negative sentinel node biopsy, then no further axillary
             dissection is required, and the patient is determined to be node-negative; if an
             axillary dissection, without a sentinel node biopsy, is performed to determine nodal
             status, at least six axillary lymph nodes must be removed and analyzed and negative
             for the patient to be considered node-negative; axillary nodes with single cells or
             tumor clusters =< 0.2 mm by either hematoxylin and eosin stain (H&E) or
             immunohistochemistry (IHC), will be considered node-negative; lymph nodes positive for
             polymerase chain reaction (PCR) with tumor cells/clusters =< 0.2 mm will be considered
             node-negative; any axillary lymph node with tumor clusters > 0.2 mm will be considered
             positive

          -  If the patient has a sentinel node biopsy and one of the sentinel nodes is positive,
             as defined by tumor clusters > 0.2 mm, an axillary dissection must be performed; a
             total of at least 6 axillary lymph nodes, including sentinel nodes plus the subsequent
             dissection, must be removed for the patient to be eligible; of all the lymph nodes
             removed from both the sentinel node procedure and the axillary dissection, 1-3 must be
             positive for the patient to be eligible as a node-positive patient; if an axillary
             dissection is done without a sentinel node procedure, at least 6 lymph nodes must be
             removed and a 1-3 nodes must be positive for the patient to be considered
             node-positive and eligible for this study

          -  Determination of involvement of axillary nodes with metastatic cancer will follow the
             revised tumor-node-metastasis (TNM) staging system: axillary nodes with single cells
             with tumor clusters =< 0.2 mm, by either H&E or immunohistochemistry (IHC), will be
             considered negative axillary node; lymph nodes positive for PCR with tumor
             cells/clusters < 0.2 mm will be considered negative axillary node; any axillary lymph
             node with clusters > 0.2 mm will be considered to be positive

          -  Patients with estrogen-receptor and/or progesterone receptor negative, positive, or
             unknown tumors are eligible; estrogen-receptor (ER) and progesterone receptor (PgR)
             assays should be performed by immunohistochemical methods according to the local
             institution's standard protocol

          -  Patients with human epidermal growth factor receptor 2 (HER2) positive, negative or
             unknown disease are eligible for this trial; patients whose tumors are HER2 positive
             by either immunohistochemistry 3+ staining or demonstrate gene amplification by
             fluorescence in situ hybridization (FISH) may receive trastuzumab

          -  There must be negative tumor margins for invasive cancer and ductal carcinoma in situ
             (DCIS) in the case of mastectomy or lumpectomy; lobular carcinoma in situ (LCIS) is
             acceptable at the margin

          -  Patients with multi-centric breast cancer are eligible as long as all known disease is
             resected with negative margins, and have 0-3 positive axillary lymph nodes

          -  Patients must be registered within 84 days of the last breast surgery; patients must
             have undergone either modified radical mastectomy or lumpectomy; for patients
             undergoing sentinel node sampling or axillary dissection a simple mastectomy is
             acceptable; lumpectomy patients must receive radiation therapy; for patients treated
             with radiation therapy prior to chemotherapy, the patients should be registered on
             this study after the conclusion of radiation, with chemotherapy administration
             beginning within 7 days of registration

             * All primary breast and axillary node surgery must be completed prior to enrollment
             on study

          -  No previous trastuzumab, chemotherapy or hormonal therapy for this malignancy, except
             for tamoxifen therapy

          -  No previous anthracycline chemotherapy for any disease

          -  Patients with locally advanced breast cancer, inflammatory breast cancer or metastatic
             breast cancer are not eligible; patients with involvement of dermal lymphatics on
             pathology are not eligible, even if there are no clinical signs of inflammatory cancer

          -  Patients with bilateral, synchronous invasive breast cancer are eligible as long as
             both primary tumors; if a patient has an invasive cancer on one side that meets the
             eligibility criteria, and DCIS or LCIS on the contralateral side, the patient is
             eligible; DCIS or LCIS should be managed according to institutional guidelines

          -  Patients must be disease free from prior malignancies for > 5 years, except for
             curatively treated basal cell or squamous cell carcinoma of the skin or
             carcinoma-in-situ of the cervix; patients with a history of invasive breast cancer, or
             DCIS are eligible if they have been disease free for > 5 years; patients with a
             history of LCIS are eligible regardless of the interval from diagnosis

          -  Common Toxicity Criteria (CTC) performance status 0-1

          -  Women must not be pregnant or nursing

          -  Concomitant exogenous hormone therapy, including oral contraceptives, post-menopausal
             hormone replacement therapy, and raloxifene must be stopped before patients can be
             enrolled

          -  Patients may have received up to 4 weeks of tamoxifen therapy for this malignancy and
             still be eligible for this study; patients who received tamoxifen or another selective
             estrogen receptor modulator (SERM) for prevention or for other indicators (e.g.
             osteoporosis) are eligible; tamoxifen therapy or other SERMs must be discontinued
             before the patient is enrolled on this study

             * The use of bisphosphonates for the treatment of osteoporosis is permitted; the use
             of raloxifene is not permitted are enrollment on this study

          -  Patients must have adequate organ function including no active congestive heart
             failure, and no myocardial infarction < 6 months from time of registration

          -  Absolute neutrophil count (ANC) >= 1,000/mm^3

          -  Platelet count >= 100,00/mm^3

          -  Creatinine =< 2.0 mg/dl

          -  Bilirubin =< 1.5 x upper limits of institutional normal

          -  Patients may be enrolled on adjuvant bisphosphonate studies; patients may be enrolled
             concurrently or sequentially on 40101 and bisphosphonate trials

          -  Patients may be enrolled on adjuvant hormonal studies approved by CALGB or Cancer
             Trials Support Unit (CTSU), such as the Suppression of Ovarian Function Trial (SOFT)
             and Tamoxifen and Exemestane Trial (TEXT) trials