Study selection
Clinical trials that met the following criteria were included for
analysis : (i) prospective, randomized, controlled phase 2 or 3 trials
involving breast cancer patients; (ii) random assignment of participants
to dual HER2 blockade or anti-HER2 monotherapy (lapatinib or trastuzumab
or pertuzumab or T-DM1) with or without concomitant therapy in cancer
patients regardless of treatment setting and (iii) available data
regarding events or incidence of cardiac events and sample size. For
trials with multiple intervention arms (for example, three-arms trials
with two anti-HER2 monotherapy arms and one combined anti-HER2 therapy
arm), we merged the two relevant (anti-HER2 monotherapy) arms into one
group, then compared the merged group with dual HER-2 blockade group as
previously reported[12].
Additionally, we used the five-item Jadad scale including randomization,
double-blinding, and withdrawals as previously described to assess the
quality of included trials. the final score was reported between 0 and
5[14].