Table 4.

Randomized clinical trials investigating the clinical utility of Ki67 and PEPI scores

Study	Profile	Initial treatment	Randomization	Primary endpoint(s)
NCT01953588	Phase IIb–III (n = 2820)	A: Anastrozole	4/12 weeks	Modified PEPI + Ki67 at 4/12 weeks
ALTERNATE	T2–T4	B: Fulvestrant	Ki67 <10% → ET × 24 weeks
	Allred 6–8	C: Fulvestrant + anastrozole	Ki67 >10% → CT × 24 weeks
			After surgery
			PEPI 0 → ET × 5 years
NCT00265759	Phase III (n = 610)	A: Anastrozole	2–4 weeks	ORR
ACOSOG Z1031-B	Stage II–III	B: Exemestane	Ki67 <10% → ET	pCR for CT arm
	Allred 6–8	C: Letrozole	Ki67 >10% → CT or surgery
			After surgery
			PEPI 0 → ET alone
NCT01779206	Phase III (n = 4,000)	ET	3 weeks	RFS
ADAPT HR⁺/HER2⁻	N0-1 and Oncotype RS 12–25		Ki67 <10% → ET
			Ki67 >10% → CT
NCT02592083	Phase II (n = 200)	ET	4 weeks	ORR at 16 weeks
PREDIX-A	Pre- and postmenopausal		Ki67 decrease ≥20%: A: ET × 10 weeks B: ET + palbociclib × 10 weeks
	Luminal A: ER ≥50% and Ki67 ≤20%		Ki67 decrease <20%: C: ET + palbociclib × 10 weeks
NCT02603679	Phase II (n = 200)	A: Paclitaxel	12 weeks	ORR at 24 weeks
PREDIX-B	Luminal B or Luminal A (Ki67 >20%) and age <40 years or N1	B: ET + palbociclib	If not progressive disease: A → B × 12 weeks B → A × 12 weeks
NCT01613560	Phase II (n = 404)	ET	16–20 weeks	RFS
	T2–3		PEPI 0–1 → ET × 5 years
	ER or PR >50%		PEPI 2–4 → randomized to: A: ET × 5 years B: CT + ET × 5 years