Table 4: Adjusted model for risk of death.

CharacteristicAdjusted HR (95% CI)P-Value

Metastases present at trastuzumab initiationBone1.17 (0.75–1.84)0.49
Liver2.03 (1.55–2.64)<0.001
Lung/chest1.36 (1.04–1.78)0.02
Other0.72 (0.53–0.96)0.03

Diagnosed with metastases after start of trastuzumab*CNS2.49 (1.84–3.37)<0.001
Bone1.34 (0.93–1.94)0.12
Liver2.72 (1.93–3.84)<0.001
Lung/Chest1.39 (0.98–1.97)0.07
Other1.91 (1.31–2.78)0.001

Discontinued trastuzumab therapy*No1.00 (ref)<0.001
Yes2.44 (1.90–3.15)

Hospital inpatient*No1.00 (ref)<0.001
Yes7.04 (5.32–9.32)

Age at start of trastuzumab66–691.00 (ref)
70–741.17 (0.80–1.69)0.42
75–791.17 (0.80–1.72)0.42
≥801.24 (0.84–1.81)0.28

Race/ethnicityWhite1.00 (ref)0.22
Non-White1.21 (0.89–1.63)

Time from MBC diagnosis to trastuzumab initiationPer ln (days)1.07 (0.98–1.15)0.12

NCI comorbidity score at start of trastuzumab01.00 (ref)
11.27 (0.80–2.01)0.31
≥20.95 (0.48–1.85)0.87

Cardiovascular disease*Yes3.23 (2.43–4.30)<0.001

Stage at diagnosisRecurrent Stage 0–III1.00 (ref)0.23
Incident Stage IV0.86 (0.66–1.10)

ER/PR StatusHormone Positive1.00 (ref)
Hormone Negative1.06 (0.81–1.40)0.67
Unknown1.40 (0.96–2.05)0.08

Asterisk (*) indicates time varying covariate. All listed covariates were included in one model. Nonwhite race includes Black, Hispanic and Other as a combined category. Baseline defined as the date of trastuzumab initiation. Year of trastuzumab initiation (not significant) was also included as a covariate but results are not shown. Discontinuation was defined to be at least 60 days with no therapy. Reference group for cardiovascular disease and for each metastasis covariate is the absence of the condition (HR = 1.0).