Study of Dasatinib (BMS-354825) in Patients With Advanced Estrogen/Progesterone Receptor-positive (ER+/PR+) or Her2/Neu-positive (Her2/Neu+)Breast Cancer

Percentage of Response-evaluable Participants With Disease Control (DCR)

Disease control was defined in response-evaluable participants as having a best response of objective response (CR or PR) or SD at/after 16 Weeks.

Time frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment.

Number of Participants Who Progressed

PFS was defined as time from first dosing date until the first date that Progressive Disease (PD) was observed.

Time frame: From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45)

Median Progression Free Survival (PFS)

PFS was defined as time from first dosing date until the first date that PD was observed. The distribution of PFS was estimated using the Kaplan-Meier product limit method. A two-sided 95% confidence interval (Brookmeyer and Crowley method) for the median PFS was computed.

Time frame: From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45)

Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25

PFS was defined as time from first dosing date until the first date that progressive disease (PD) was observed.

Time frame: At Weeks 9, 17, and 25

Duration Of Objective Response

Duration of objective response was defined as the time (in weeks) between the first date that criteria for CR or PR were met and the first date that progressive disease (PD) or clinical progressive disease (cPD) was observed. Date of death was used as PD date for participants who died before reporting PD. Participants who neither progressed nor died were censored at the date of their last tumor assessment.

Time frame: the time (in weeks) between the first date that criteria for PR were met and the first date that PD or cPD was observed

Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.

Time frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug

Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities

Normal ranges for laboratory abnormalities: granulocytes=1.5x10\^3-8x10\^3 mm\^3 (range may have varied by institution); hemoglobin=12-16 g/dL; platelets=150-440x10\^9c/L; partial thromboplastin time=27-37.1 seconds; alkaline phosphatase=38-126 U/L; alanine aminotransferase=15-48 U/L; aspartate aminotransferase=14-38 U/L; creatine=0.7-1.1 mg/dL; hypokalemia (potassium \[K\])=3.5-5mEq/L; hyponatremia (sodium \[Na\])=135-145 mEq/L; phosphorous=2.4-4.5 mg/dL; bilirubin=0-1.2. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening/disabling, Gr 5=Death.

Time frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug

Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs

AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to CTCAE Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

Time frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug

Number Of Participants With Notable Drug-related AEs

Notable drug-related AEs for dasatinib include gastrointestinal symptoms (diarrhea, nausea, vomiting and abdominal pain), fatigue, lethargy, headache, rash, fever, pleural effusion, and dyspnea.

Time frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug

Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3

Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.

Time frame: PK assessment was performed at Week 3 visit (Day 15 ±4 days). Blood samples were obtained at Time = 0 hours, and at 1, 3 and 6 hours after each dose, and a trough sample was obtained immediately prior to any dose (~12 hours).

PK: Plasma Concentration of Dasatinib at Week 7 or Week 9

Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.

Time frame: PK assessment was performed at Week 7 or 9 visit. Blood samples were obtained at Time = 0 hours, and at 1, 3 and 6 hours after each dose, and a trough sample was obtained immediately prior to any dose (~12 hours).

Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR

Collagen Type IV is a circulating marker related to the modulation of the vascular endothelial growth factor (VEGF)-pathway. An assay of Collagen Type IV in plasma was performed by ELISA.

Time frame: At Baseline and Week 3 of treatment (Day 15 ±4 days)

Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR

Collagen Type IV is a circulating marker related to the modulation of the vascular endothelial growth factor (VEGF)-pathway. An assay of Collagen Type IV in plasma was performed by ELISA.

Time frame: Week 5

Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR

VEGF-stimulated disruption of the cadherin-catenin complex leads to tumor cell invasion and metastasis. VEGFR2 plasma levels were assayed by ELISA as a marker of VEGF pathway modulation.

Time frame: At Baseline and Week 3 of treatment (Day 15 ±4 days)

Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR

VEGF-stimulated disruption of the cadherin-catenin complex leads to tumor cell invasion and metastasis. VEGFR2 plasma levels were assayed by ELISA as a marker of VEGF pathway modulation.

Time frame: At Baseline and Week 5 of treatment