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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: AI adjuvant therapy
* Drug: AI+chemotherapy adjuvant therapy
* Drug: AI adjuvant therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEPI：2-4 group-A<br> | Drug: AI+chemotherapy adjuvant therapy<br>* preoperative endocrinotherapy was performed by AI for 4-6 months;surgery;pathological evaluation after surgery;AI adjuvant therapy for 5 years after adjuvant chemotherapy<br>|
| Active Comparator: PEPI：2-4 group-B<br> | Drug: AI adjuvant therapy<br>* preoperative endocrinotherapy was performed by AI for 4-6 months;surgery;pathological evaluation after surgery;AI adjuvant therapy for 5 years<br>|
| Active Comparator: PEPI：0-1group<br> | Drug: AI adjuvant therapy<br>* preoperative endocrinotherapy was performed by AI for 4-6 months;surgery;pathological evaluation after surgery;AI adjuvant therapy for 5 years<br>|

What is the study measuring?
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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) |