Neoadjuvant Chemotherapy + Herceptin in HER2 Positive Stage II-III Breast Cancer Patients

Toxicities are evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. Grade refers to the severity of the adverse event (AE). Generally, grade 1 = mild AE; grade 2 = moderate AE; grade 3 = severe AE; grade 4 = life-threatening or disabling AE; grade 5 = death related to AE.

Time frame: Toxicities are evaluated every 2 weeks during neoadjuvant treatment and assessed once during the post-treatment follow-up period, up to 25 weeks.

Feasibility will be determined by evaluating the percentage of subjects able to complete the neoadjuvant portion of the study on time with \> 85% of the protocol-specified dose.

Time frame: From the start of treatment through the neoadjuvant treatment period (approximately 20 weeks)

Clinical response was assessed via physical exam every 2 weeks during neoadjuvant treatment and via imaging prior to definitive surgery. Clinical complete response was defined as no evidence of cancer in breast by exam or imaging. Clinical partial response was defined as \>= 50 % reduction in sum of diameters to measurement of primary lesion compared to pretreatment by exam or imaging. Clinical stable disease was defined as \< 50% reduction in sum of diameters to measurement of primary lesion compared to pretreatment by exam or imaging, and \< 25% increase in sum of diameters.

Time frame: Assessed every 2 weeks during neoadjuvant treatment and prior to definitive surgery, up to 23 weeks.

Population: Clinical response assessment was available for 27 patients at the time of surgery.

LVEF was assessed by echocardiogram (ECHO) or multigated angiogram (MUGA) during neoadjuvant treatment and during follow-up.

Time frame: At screening, prior to cycle 5, prior to surgery, and then during follow-up at Month 6, 12, 24, and 36

Population: Note that the number of participants analyzed changes with the study interval. At Screening n=30, after Epirubicin/Cyclophosphamide n=30, Pre-surgery n=28, Follow-up Month 6 n=28, Follow-up Month 12 n=20, Follow-up Month 24 n=9, and Follow-up Month 36 n=1.

Overall survival is defined as the time from treatment start until death from any cause. The median overall survival time is used to measure OS.

Time frame: Measured from day 1 of treatment until time of death, assessed up to 48 months.

Pathologic response was assessed at time of definitive surgery, scheduled to occur 20-24 weeks after study treatment start. Pathologic complete response was defined as no invasive carcinoma in surgical specimen of breast, but residual ductal carcinoma in situ may be present. Pathologic partial response was defined as \>= 50% decrease in sum of diameters in pathologic cancer size compared to pretreatment clinical size. Stable disease was defined as \< 50% decrease in sum of diameters in pathologic cancer size compared to pretreatment clinical size, and \< 25% increase in sum of diameters.

Time frame: At completion of neoadjuvant treatment period, up to 24 weeks.

Population: 28 patients went to surgery, so 28 patients were included in the surgery sample. Note that 4 patients in the pathologic complete response (pCR) group had residual ductal carcinoma in situ (DCIS).

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.

Time frame: PFS was measured from day 1 of treatment until time of progression or death, whichever comes first, assessed up to 48 months.