Fourth, an analysis of the ALTTO trial (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation study, a phase III clinical trial of two targeted therapies for HER2-positive breast cancer) reported an incidence of amenorrhea of 72.1% for trastuzumab monotherapy, 72.1% for trastuzumab followed by lapatinib (oral anti-HER2 therapy), 74.8% in the trastuzumab plus lapatinib and 74.0% for the lapatinib monotherapy. Here, ERBB2 is linked to amenorrhea.