Clinical Study of Adjuvant Therapy on Post-menopausal Women With Breast Cancer Under the Guidance of the Results of Preoperative Endocrinotherapy

This is a phase II, prospective, multi-center, open-label, non-randomized, controlled study. The objective of this study is to prospectively verify the relation of efficacy of neoadjuvant hormonal therapy, and preliminarily explore the clinical value of complementary adjuvant chemotherapy to predict poor prognosis malignant breast cancer after neoadjuvant endocrinotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: AI+chemotherapy adjuvant therapy; Drug: AI adjuvant therapy

Detailed Description

In the decision-making process of a systemic adjuvant therapy for ER-positive/HER2-negative breast cancer, to avoid adjuvant chemotherapy is an attractive but hard choice. On one hand, the result of tamoxifen endocrine therapy combined with adjuvant chemotherapy is superior to tamoxifen endocrine therapy alone for ER-positive breast cancer patients; on the other hand, the benefit that adjuvant chemotherapy provides to breast cancer with high hormone receptor expression is not clear and the tolerance of chemotherapy is much lower than that of endocrinotherapy.

St. Galen consensus on adjuvant therapy for early breast cancer recommends adopting simple endocrinotherapy and avoiding adjuvant chemotherapy for medium- and low- risk breast cancer with hormone receptor highly expressed. However, the results of study P024 and IMPACT suggest that hormone receptor expression is insufficient to predict the effect of endocrinotherapy.

At present, the proven clinical value of neoadjuvant endocrinotherapy is to assist surgery. Consensus recommends neoadjuvant endocrinotherapy for the patients with postmenopausal breast cancer who plan to receive simple adjuvant endocrinotherapy. The current study results show that neoadjuvant endocrinotherapy may be used as an experimental treatment platform, i.e., it can predict the results of adjuvant endocrinotherapy through comprehensive analysis of multiple indexes of the surgery samples after neoadjuvant endocrinotherapy.

By using P024 and IMPACT samples, Ellis et al studied the relation between survival and the test results of surgery samples after neoadjuvant endocrinotherapy, and obtained PEPI (the preoperative endocrine prognostic index). They have preliminarily proved that the PEPI score is relative to RFS (relapse-free survival) of postmenopausal ER-positive breast cancer treated with simple endocrinotherapy and to BCSS (breast cancer-specific survival).

A retrospective study，performed by breast prevention and treatment center in Peking University Cancer Hospital，shows that RFS in PEPI score ≤ 1 group is superior to the PEPI > 1 group after 16 weeks of neoadjuvant endocrinotherapy(p = 0.037), and RFS in effective group (Miller&Payne G1G2G3) is better than that in ineffective group (p=0.001) in terms of pathological evaluation.

The objective of this study is to prospectively verify the relation of efficacy of neoadjuvant hormonal therapy, and preliminarily explore the clinical value of complementary adjuvant chemotherapy to predict poor prognosis malignant breast cancer after neoadjuvant endocrinotherapy.

• Study Type: Interventional
• Enrollment (Actual): 404
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Peking University First Hospital
    • Beijing, Beijing, China
      • Beijing Hospital
    • Beijing, Beijing, China
      • 307 Hospital of PLA
    • Beijing, Beijing, China, 100142
      • Peking Cancer Hospital & Institute
    • Beijing, Beijing, China
      • 301 Hospital of Pla
    • Beijing, Beijing, China
      • Beijing Chao-Yang Hospital
    • Beijing, Beijing, China
      • Cancer Institution and Hospital.Chinese Academy of Medical Sciences
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • The 2nd Affiliated Hospital of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
  • Jilin
    • Changchun, Jilin, China
      • the First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China
      • The First Hospital of China Medical University
  • Shandong
    • Jinan, Shandong, China
      • The Second Hospital of Shandong University
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China
      • Shanghai Ruijin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female, not more than 75 years old, judged to have been in menopause by the investigator when enrolled. Refer to the following criteria to determine whether they are postmenopausal breast cancer.

  • Spontaneous amenorrhea for more than 12 months Age ≥ 60 Age < 60, but FSH and E2 reach postmenopausal level.
  • Received bilateral ovariectomy previously
  • Not to define the women using LHRH agonists or antagonists as in postmenopausal state.
• Evidence of primary invasive breast cancer is confirmed by histopathological diagnosis.
• Clinical stage is T2-3N0M0
• ER or PgR are expressed in more than 50 percent of tumour cells, and HER2 is negative.
• No abnormal axillary nodes in ultrasound examination; no evidence of cancer metastasis confirmed by abnormal lymph node puncture pathological examination
• With plan of receiving simple endocrinotherapy and avoiding adjuvant chemotherapy
• No previous breast cancer treatment history
• No other tumors previously; no unstable complications or uncontrolled infection.
• No contraindication for endocrinotherapy with 3rd generation of aromatase inhibitors
• Participate in the trial voluntarily and sign the informed consent form.

Exclusion Criteria:

• Evidence of distant breast cancer metastasis by pathological and imaging diagnosis
• Patients who have a history of other malignant tumors
• With contraindications for 3rd generation of aromatase inhibitors
• Physical condition can not bear the experiment
• Patients who have potential mental, psychological, familial, social, geographic, or other factors that can hinder study regime performance.
• Patients who were treated or are treated with other anti-tumor measures before or during this trial, or planed to participate in other clinical trials.
• Patients who refuse to participate in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PEPI：2-4 group-A	Drug: AI+chemotherapy adjuvant therapy; preoperative endocrinotherapy was performed by AI for 4-6 months;surgery;pathological evaluation after surgery;AI adjuvant therapy for 5 years after adjuvant chemotherapy
ACTIVE_COMPARATOR: PEPI：2-4 group-B	Drug: AI adjuvant therapy; preoperative endocrinotherapy was performed by AI for 4-6 months;surgery;pathological evaluation after surgery;AI adjuvant therapy for 5 years
ACTIVE_COMPARATOR: PEPI：0-1group	Drug: AI adjuvant therapy; preoperative endocrinotherapy was performed by AI for 4-6 months;surgery;pathological evaluation after surgery;AI adjuvant therapy for 5 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFS	RFS events includes local recurrence, regional recurrence, and distant metastasis resulted from breast cancer	after a follow up of 5 years
DDFS	DDFS events includes distant metastasis due to breast cancer	after a follow up of 5 years
BCSS	BCSS events includes death for breast cancer	after a follow up of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse reaction	incidence rate of Ⅲ or Ⅳ adverse reaction(according to NCI classification)	during the period of trial (up to 7 years)

Collaborators and Investigators

• Sponsor: Tao OUYANG
• Investigators: Study Chair: Tao Ouyang, Doctor, Peking University Cancer Hospital Breast Center

Publications and helpful links

General Publications

• Wang X, Fan Z, Wang X, He Y, Liu Y, Wang X, Zhang B, Jiang Z, Wang T, Yu Z, Wang F, Liu Y, Li Y, Zhang J, Luo B, Jiang H, Wang T, Xie Y, Li J, Ouyang T. Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study. Breast Cancer Res Treat. 2022 Oct;195(3):301-310. doi: 10.1007/s10549-022-06686-1. Epub 2022 Aug 2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 5, 2012
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: May 27, 2012
• First Submitted That Met QC Criteria: June 6, 2012
• First Posted (ESTIMATE): June 7, 2012

Study Record Updates

• Last Update Posted (ACTUAL): November 29, 2021
• Last Update Submitted That Met QC Criteria: November 26, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BCP08