Cancer Res Treat.  2021 Jul;53(3):695-702. 10.4143/crt.2020.1246.

Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL)

  • 1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 2Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
  • 3Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
  • 4Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 5Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea
  • 6Center for Breast Cancer, National Cancer Center, Goyang, Korea
  • 7Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
  • 8Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea


YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC.
In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.


Breast neoplasms; Tamoxifen; CDK4/6 inhibitor; Palbociclib; Endocrine therapy


  • Fig. 1 Forest plot of subgroup analysis for progression-free survival. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; ET, endocrine therapy; PS, performance status.

  • Fig. 2 Progression-free survival curves according to tamoxifen sensitivity for ITT population (20.2 months vs. 15.1 months) (A), palbociclib plus endocrine therapy arm (20.5 months vs. 20.1 months) (B), and capecitabine arm (12.6 months vs. 14.5 months) (C). (D) Progression-free survival curves according to tamoxifen sensitivity and treatment arms. CI, confidence interval; ET, endocrine therapy; HR, hazard ratio; ITT, intention-to-treat; NA, not available.



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