Sub-group analysis
Firstly, we carried out a subgroup risk analysis stratified according to
treatment settings. Our results demonstrated that risk of LVEF decline
and CHF was comparable between dual HER-2 blockade and anti-HER2
monotherapy in neoadjuvant or metastatic setting (bothp >0.05, table 2). However, the addition of dual HER2
blockade to adjuvant treatment in breast cancer significantly increased
the risk of developing CHF (OR 2.00, 95%CI: 1.23-3.24, p =0.005)
and LVEF decline (OR1.17, 95%CI: 1.00-1.38, p =0.048, table 2).
The concomitant treatment with anti-HER-2 therapy might impact the ORs
of cardiac toxicities. Our combined results demonstrated that
concomitant hormonal therapy with dual HER2 blockade in breast cancer
significantly increased risk of developing LVEF decline in comparison
with hormonal therapy plus anti-HER2 monotherapy (OR 4.51,
95%CI:1.24-16.40, p =0.022), while no concomitant treatment or
concomitant chemotherapy with dual HER-2 blockade did not increase the
risk of developing LVEF decline(p =0.19 and p =0.11,
respectively). As for CHF events, concomitant chemotherapy with dual
HER2 blockade treatment significantly increased the risk of developing
CHF when compared to anti-HER2 monotherapy plus chemotherapy (OR 1.47,
95%CI: 1.00-2.16, p =0.052), while no concomitant treatment or
concomitant hormonal therapy with dual HER-2 blockade did not increase
the risk of CHF (p =0.22 and p =0.59, respectively).
We also did sub-group analysis according to anti-HER-2 monotherapy. Our
result showed that dual HER-2 blockade significantly increased the risk
of developing LVEF decline (OR 1.49, 95%CI: 1.14-1.96, p =0.004)
when compared to lapatinib, but not for CHF (OR 2.62, 95%CI: 0.90-2.94,p =0.11). In comparison with trastuzumab alone, no significantly
increased risk of developing LVEF decline(p =0.37) and CHF
(p =0.24, table 2) was observed in dual HER-2 blockade group.