CYP19A1 and breast cancer: During the 12 years of the observation period trastuzumab was shown to be effective in second and third lines of treatment, also new drugs were developed and the combination of trastuzumab with these drugs have improved survival and time on treatment of breast cancer patients in the metastatic setting, as for example the combinations of trastuzumab with lapatinib [45], aromatase inhibitors [46] or pertuzumab [47].