A Study of the Safety of Subcutaneously Administered Trastuzumab (Herceptin) in Participants With Early and Locally Advanced Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the AEs occurring from starting on the day of or after first administration of trastuzumab and within 28 days after last dose of trastuzumab. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

Time frame: Day 1 up to 28 days after last dose of trastuzumab (up to approximately 1 year)

Population: Safety population

Actual dose (mg) administered = (sum over all cycles of actual dose received \[mg\] divided by number of cycles). Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

Time frame: Day 1 up last dose of trastuzumab (up to approximately 1 year)

Population: Safety Population

DFS was defined as the time from the first treatment to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first). Kaplan-Meier estimates were used for analysis. Participants who were disease-free were censored at the data cut off date. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

Time frame: Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first [up to approximately 4.5 years])

Population: m-ITT population. Here, 'Number of Participants Analyzed' = participants who were evaluable for this outcome measure.

Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

Time frame: Day 1 up last dose of trastuzumab (up to approximately 1 year)

Population: Safety Population

Overall survival was defined as the time from the first treatment to death from any cause. Kaplan-Meier estimates were used for analysis. Participants who did not die were censored on the date they were last known to be alive. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

Time frame: Day 1 up to death due to any cause (up to approximately 4.5 years)

Population: m-ITT population

Percentage of HCPs providing responses to various questions related to overall ease of study drug administration was reported in different categories, where categories indicate all possible responses to such questions.

Time frame: After at least 4 participants completed 5 cycles of adjuvant treatment (1 cycle = 21 days; maximum up to 1 year)

Population: HCPQ population included all investigators and study nurses who completed the questionnaire at each site when at least 4 participants from their site had received at least 5 cycles of adjuvant study treatment (52 and 50, respectively for Vial and SID groups).

Participants were asked the following 5 questions: (1) Following the first injection given by the physician/nurse and training on how to use the SID, I felt comfortable injecting the study drug by myself; (2) The SID was convenient and easy to use; (3) I am confident giving myself an injection in the thigh with the SID; (4) Taking all things into account, I find self-administration using the SID satisfactory; (5) If given the opportunity, I would choose to continue self-injecting the study drug using the SID at home. Response to each question was recorded as either of the following options: Unknown, Strongly Disagree, Disagree, Unsure, Agree, Strongly Agree. Percentage of participants who provided responses to above questions was reported. Data for this outcome measure were analyzed and reported only for Trastuzumab (SID) arm.

Time frame: After at least 14 cycles (1 cycle = 21 days; maximum up to 1 year)

Population: PSQ population included all enrolled participants from trastuzumab (SID) group who were able to use SID and had completed a minimum of 14 administrations of trastuzumab subcutaneously using SID (at least 10 of which were self-administered). Here, 'Number of Participants Analyzed' = participants who were evaluable for this outcome measure.

Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

Time frame: Day 1 up to death due to any cause (up to approximately 4.5 years)

Population: m-ITT population

Time frame: Screening (Day -28 to -1) up to 2.5 years

Population: Safety Population

A participant was considered as disease free if the participant was free from local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first). Percentage of participants with event at the cut off date were reported. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

Time frame: Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first [up to approximately 4.5 years])

Population: m-ITT population. Here, 'Number of Participants Analyzed' = participants who were evaluable for this outcome measure.

In the neoadjuvant setting, the activity of two sequential drug regimens, doxorubicin-containing chemotherapy followed by paclitaxel or docetaxel chemotherapy in combination with trastuzumab, was assessed as the percentage of participants with pCR in breast and nodes using mammography. pCR was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after preoperative treatment. Data for this outcome measure were analyzed and reported only for neoadjuvant groups within each treatment arm.

Time frame: Day 1 up to 24 weeks

Population: Modified intent-to-treat (m-ITT) population included all enrolled participants satisfying criteria for eligibility.