T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)

Inclusion Criteria

• HER2-positive Stage I histologically confirmed invasive carcinoma of the breast
• ER/PR determination is required
• HER2 positive, confirmed by central testing: IHC 3+, FISH HER2/CEP17 /=6.0, or FISH HER2/CEP17 >/= 2.0
• Bilateral breast cancers that individually meet eligibility criteria are allowed
• Subjects with multifocal or multicentric disease are eligible as long as each tumor individually meets eligibility criteria
• Subjects with a history of ipsilateral DCIS are eligible if they were treated with wide-excision alone, without radiation therapy; Patients with a history of contralateral DCIS are not eligible.
• Should have tumor tissue available and a tissue block of sufficient size to make 15 slides, which must be sent to a DFCI site for testing
• Less than or equal to 90 days since most recent breast surgery for this breast cancer
• All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy) with either a sentinel node biopsy or axillary dissection
• All margins should be clear of invasive cancer or DCIS
• May have received up to 4 weeks of tamoxifen therapy or other hormonal therapy, for adjuvant therapy for this cancer
• Prior oophorectomy for cancer prevention is allowed
• Subjects who have undergone partial breast radiation (duration </= 7 days) prior to registration are eligible. Partial breast radiation must be completed prior to 2 weeks before starting protocol therapy.
• Must have discontinued any investigational drug at least 2 weeks prior to participation
• Willing to use one highly effective from of nonhormonal contraception or two effective forms of nonhormonal contraception while on study and for 7 months after end of study treatment
• Subjects undergoing lumpectomy must have no contraindications to radiation therapy

Exclusion Criteria

• Pregnant or breastfeeding
• Use of potent CYP3A4 inhibitors during the study treatment period
• Excessive alcohol intake (more than 3 alcoholic beverages per day)
• Locally advanced tumors at diagnosis
• History of previous invasive breast cancer
• History of prior chemotherapy in the past 5 years
• History of prior trastuzumab or prior paclitaxel therapy
• Active, unresolved infection
• Active liver disease
• History of a different malignancy except for the following: disease free for at least 5 years and at low risk for recurrence; cervical cancer in situ, basal or squamous cell carcinoma of the skin
• Active cardiac disease