In CYP2D6 PM patients, increasing the standard tamoxifen dose two-fold or three-fold raises endoxifen concentrations to levels similar to those of patients with EM phenotype.

<p>Supplementary Data</p>

<div>AbstractPurpose:<p>To assess palbociclib in combination with trastuzumab with or without endocrine therapy in patients with HER2-positive advanced breast cancer.</p>Patients and Methods:<p>PATRICIA is a prospective, open-label, multicenter phase II trial. Patients had received 2–4 prior lines of anti-HER2–based regimens. Treatment consisted of palbociclib 200 mg daily for 2 weeks and 1 week off plus trastuzumab. The study was based on a Simon two-stage design comprising three cohorts: estrogen receptor (ER)-negative (cohort A), ER-positive (cohort B1), and ER-positive with letrozole (cohort B2). ER-positive patients were randomized to cohorts B1 or B2. Primary endpoint was progression-free survival rate at 6 months (PFS6). Secondary objectives included safety and evaluation of the PAM50 intrinsic subtypes.</p>Results:<p>Seventy-one patients were recruited (<i>n</i> = 15 in cohort A and 28 in each cohort B). The PFS6 rate in cohorts A, B1, and B2 was 33.3% (5/15), 42.8% (12/28), and 46.4% (13/28), respectively. Regarding safety, grade 1–2 and 3–4 toxicities occurred in 97.7% and 84.4% of patients, respectively. The most common grade 3–4 toxicities were neutropenia (66.4%) and thrombocytopenia (11.3%). Regarding PAM50, 59 (83.1%) tumors were profiled. Luminal disease defined by PAM50 was found independently associated with longer PFS compared with non-luminal disease (10.6 vs. 4.2 months median PFS; adjusted hazard ratio = 0.40; <i>P</i> = 0.003).</p>Conclusions:<p>Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pretreated ER-positive/HER2-positive advanced breast cancer with a PAM50 Luminal A or B subtype. The enrollment was stopped prematurely, and a new randomized cohort was opened in this population.</p></div>

<div>AbstractPurpose:<p>To assess palbociclib in combination with trastuzumab with or without endocrine therapy in patients with HER2-positive advanced breast cancer.</p>Patients and Methods:<p>PATRICIA is a prospective, open-label, multicenter phase II trial. Patients had received 2–4 prior lines of anti-HER2–based regimens. Treatment consisted of palbociclib 200 mg daily for 2 weeks and 1 week off plus trastuzumab. The study was based on a Simon two-stage design comprising three cohorts: estrogen receptor (ER)-negative (cohort A), ER-positive (cohort B1), and ER-positive with letrozole (cohort B2). ER-positive patients were randomized to cohorts B1 or B2. Primary endpoint was progression-free survival rate at 6 months (PFS6). Secondary objectives included safety and evaluation of the PAM50 intrinsic subtypes.</p>Results:<p>Seventy-one patients were recruited (<i>n</i> = 15 in cohort A and 28 in each cohort B). The PFS6 rate in cohorts A, B1, and B2 was 33.3% (5/15), 42.8% (12/28), and 46.4% (13/28), respectively. Regarding safety, grade 1–2 and 3–4 toxicities occurred in 97.7% and 84.4% of patients, respectively. The most common grade 3–4 toxicities were neutropenia (66.4%) and thrombocytopenia (11.3%). Regarding PAM50, 59 (83.1%) tumors were profiled. Luminal disease defined by PAM50 was found independently associated with longer PFS compared with non-luminal disease (10.6 vs. 4.2 months median PFS; adjusted hazard ratio = 0.40; <i>P</i> = 0.003).</p>Conclusions:<p>Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pretreated ER-positive/HER2-positive advanced breast cancer with a PAM50 Luminal A or B subtype. The enrollment was stopped prematurely, and a new randomized cohort was opened in this population.</p></div>

<p>Supplementary Data</p>