A Study of Trastuzumab Emtansine (T-DM1) Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage Herceptin (HER)2-positive Breast Cancer

The following percentages of participants are reported: At least 1 adverse event while receiving T-DM1; at least 1 serious adverse event while receiving T-DM1; an adverse event leading to discontinuation, dose delay, or dose reduction of trastuzumab emtansine treatment; symptomatic cardiac dysfunction; and asymptomatic decline in left ventricular ejection fraction (LVEF). An asymptomatic LVEF decline was defined as a LVEF \< 50% and a maximum decrease ≥ 10% from Baseline. The percentage of participants who died is reported.

Time frame: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)

Population: Safety-evaluable population: All participants who received at least 1 dose of trastuzumab emtansine.

A cardiac event was defined as death from a cardiac cause or severe congestive failure (New York Heart Association \[NYHA\] Class III or IV) with a decrease in left ventricular ejection fraction (LVEF) of ≥ 10% from Baseline to an LVEF of \< 50%.

Time frame: Baseline to 12 weeks after the start of trastuzumab emtansine treatment

Population: Cardiac-safety evaluable population: All participants who received at least 1 dose of T-DM1 and met either of the following 2 criteria: (1) Had an echocardiogram/multiple-gated acquisition assessment by 12 weeks after the first dose of T-DM1 or (2) discontinued study treatment because of cardiac toxicity prior to completion of 4 cycles of T-DM1.

Disease-free survival was defined as the time from date of first protocol treatment for adjuvant patients or date of surgery for neoadjuvant patients to disease recurrence, occurrence of invasive contralateral breast cancer, other second primary cancer (excluding non-breast second primary), or death, whichever occurred first.

Time frame: From the start of trastuzumab emtansine for adjuvant patients and from the date of surgery for neoadjuvant patients to 12 months later

Population: Safety-evaluable population: All participants who received at least 1 dose of trastuzumab emtansine.~Due to too few events, the analysis of disease-free survival was not performed.

Time frame: From the start to the end of radiotherapy treatment (up to 51 weeks)

Population: Safety-evaluable population: All participants who received at least 1 dose of trastuzumab emtansine. Only participants who received concurrent radiotherapy and who had radiotherapy dose information reported were included in the analysis.

Participants were to receive up to a total of 17 cycles of trastuzumab emtansine. If trastuzumab was given concurrently with either the optional docetaxel or optional radiation, then the number of 3-week cycles of trastuzumab therapy was subtracted from the planned 17 cycles of trastuzumab emtansine therapy.

Time frame: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)

Population: Safety-evaluable population: All participants who received at least 1 dose of trastuzumab emtansine.

Time frame: From the start to the end of concurrent hormonal therapy (up to 51 weeks)

Population: Safety-evaluable population: All participants who received at least 1 dose of trastuzumab emtansine. Only participants who received concurrent hormonal therapy were included in the analysis.

Time frame: From the start to the end of concurrent radiotherapy (up to 51 weeks)

Population: Safety-evaluable population: All participants who received at least 1 dose of trastuzumab emtansine. Only participants who received concurrent radiotherapy were included in the analysis.

Pathological complete response was defined as the absence of invasive neoplastic cells at microscopic examination of the primary tumor and lymph nodes after surgery following primary systemic therapy. Pathological complete response was evaluated in participants treated with neoadjuvant therapy doxorubicin/cyclophosphamide-5-fluorouracil/epirubicin/cyclophosphamide followed by 1 or more doses of trastuzumab emtansine and who underwent surgery.

Time frame: Day of surgery

Population: Efficacy analysis population: All participants who enrolled in the neoadjuvant setting and received surgery, after completing 4 cycles of trastuzumab emtansine treatment.