[Lani]

All patients diagnosed with HER2-positive MBC and treated with at least 21 days of trastuzumab or lapatinib in the metastatic setting at the University of Michigan (U-M) Comprehensive Cancer Center between 1991 and 2015 were included. Potentially eligible patients were identified through review of pharmacy records. Patients with distant metastatic disease were included; those with locoregional recurrence (including axillary or supraclavicular nodal disease) or second primary tumors were excluded. Those patients who received only a single 3-week dose or fewer than 4 weekly doses of trastuzumab were excluded (Supplemental Fig. 1). Biopsies of suspected metastatic sites were performed at the discretion of the treating physician. HER2 status was determined clinically at the time of primary or metastatic diagnosis using immunohistochemistry and/or fluorescence in situ hybridization (FISH) according to period-appropriate institutional guidelines. This retrospective, single-institutional study was approved by the Institutional Review Board, which granted a waiver of informed consent.
Clinicopathologic characteristics of eligible patients were abstracted from the electronic medical record by two reviewers (PM, NLH), including demographics; dates of diagnosis of primary breast cancer, MBC and first progression; tumor characteristics at the time of original diagnosis and at the time of disease recurrence; initial sites of metastatic disease; systemic treatments received in the adjuvant and metastatic settings; date of last follow-up at U-M; and date of death, if applicable. Site(s) of metastatic disease at the time of diagnosis of MBC were grouped into four categories based on the findings demonstrated on imaging studies: single organ involvement (bone, viscera, and central nervous system (CNS)) and multi-organ involvement.