Combination Chemotherapy and Filgrastim Before Surgery in Treating Patients With HER2-Positive Breast Cancer That Can Be Removed By Surgery

• Combined rate of microscopic pCR and macroscopic pathologic complete response (mCR) [ Time Frame: At the end of part II, before surgical resection ] [ Designated as safety issue: No ]
  Microscopic pCR: No evidence of microscopic invasive tumor at the primary site or in the regional lymph nodes at the time of definitive surgical resection. mCR: The examining pathologist cannot identify gross residual tumor mass in the surgical specimen. This differs from a pCR where the specimen must also be negative for invasive tumor by microscopy. For this study, we are using a definition of mCR that will make the trial more translatable to other institutions. For this study, mCR will be defined as no focus of invasive cancer >= 1 cm.
  
  

• Number and percent of patients reporting grade 2, 3, 4, or fatal toxicities of these regimens, need for dose reduction, or treatment interruption or discontinuation [ Time Frame: From the initiation of study treatments to 30 days after the end of neoadjuvant treatment or adjuvant treatment if received ] [ Designated as safety issue: Yes ]
  
• Correlation of molecular markers with response [ Time Frame: After completion of neoadjuvant therapy ] [ Designated as safety issue: No ]
  
• Relapse rate in patients with operable breast cancer treated with neoadjuvant chemotherapy for 12 weeks followed by weekly paclitaxel for 12 weeks and adjuvant chemotherapy [ Time Frame: Every 4-8 weeks and then every 3 months for 2 years, every 6 months for 2 years and then annually after completion of study treatment ] [ Designated as safety issue: No ]
  
• Time to progression [ Time Frame: Baseline, monthly, and then every 3 months for 2 years, every 6 months for 2 years and then annually after completion of study treatment ] [ Designated as safety issue: No ]
  
• OS in patients with operable breast cancer treated with neoadjuvant chemotherapy for 12 weeks followed weekly paclitaxel for 12 weeks and adjuvant chemotherapy with XMN [ Time Frame: Baseline, monthly and then every 3 months for 2 years, every 6 months for 2 years and then annually after completion of study treatment ] [ Designated as safety issue: No ]
  
• Disease-free survival [ Time Frame: Baseline, monthly and then every 3 months for 2 years, every 6 months for 2 years and then annually after completion of study treatment ] [ Designated as safety issue: No ]
  
• Clinical response to neoadjuvant therapy [ Time Frame: Every 4-8 weeks during Part I ] [ Designated as safety issue: No ]
  
• Clinical response to paclitaxel [ Time Frame: Every 4-8 weeks during Part II ] [ Designated as safety issue: No ]
  
• Clinical response to adjuvant therapy [ Time Frame: Every 4-8 weeks during Part III ] [ Designated as safety issue: No ]
  

PRIMARY OBJECTIVES:

I. To assess the pathologic response rate in patients with operable breast cancer treated with a two part, neoadjuvant regimen consisting of weekly doxorubicin (doxorubicin hydrochloride) and daily oral cyclophosphamide given with G-CSF (filgrastim) support for 12 weeks followed weekly paclitaxel for 12 weeks.

SECONDARY OBJECTIVES:

I. To assess the clinical response rate in patients with surgically resectable breast cancer treated with weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 12 weeks.

II. To assess the clinical response rate in patients with surgically resectable breast cancer treated with weekly paclitaxel for 12 weeks.

III. To assess the relapse rate, overall and disease-free survival in patients with operable breast cancer treated with neoadjuvant chemotherapy consisting of weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 12 weeks followed weekly paclitaxel for 12 weeks and adjuvant chemotherapy with Xeloda (capecitabine), Methotrexate and Navelbine (vinorelbine tartrate) (XMN).

IV. To assess the toxicity associated with these regimens. V. To assess whether the phenotype of breast cancer changes with treatment. VI. To assess whether phenotypic changes in breast tumors predict outcome.

OUTLINE:

PART I: Patients receive doxorubicin hydrochloride intravenously (IV) on day 1 of each week, cyclophosphamide orally (PO) once daily (QD), and filgrastim subcutaneously (SC) QD on days 2-7 of each week. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

PART II: Patients* receive paclitaxel IV over 1 hour on day 1 of each week. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo definitive surgical resection by partial mastectomy (lumpectomy) or mastectomy after completion of neoadjuvant chemotherapy.

PART III: Patients** unable to achieve complete pathologic response (pCR) or disease that has been down-staged to =< 1 cm with no positive nodes following surgery receive capecitabine PO twice daily (BID) on days 1-14, methotrexate IV on days 1, 8 and 15, and vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients with HER2/neu-positive disease also receive trastuzumab IV over 30-90 minutes once weekly or every 3 weeks for 1 year beginning in Part II.

NOTE: **Patients with hormone receptor-positive disease also receive tamoxifen PO QD for 5 years (premenopausal) OR letozole PO QD or tamoxifen PO QD for 5 years (postmenopausal) beginning in Part III.

After completion of study treatment, patients are followed up every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.