Comparative Evaluation of Efficacy and Safety of Toremifene, Tamoxifen, and Aromatase Inhibitor Plus Ovarian Function Suppression in Hormone Receptor-Positive Early Breast Cancer Among Non-Low-Risk Premenopausal Women: A Real-World Study

Comparative Evaluation of Efficacy and Safety of Toremifene, Tamoxifen, and Aromatase Inhibitor Plus Ovarian Suppression in Hormone Receptor-Positive Early Breast Cancer Among Non-Low-Risk Premenopausal Women: A Real-World Study

This study aims to enroll premenopausal patients, with early breast cancer who are non-low-risk and hormone receptor-positive and have undergone prior surgical intervention at the Breast Cancer Center of Sun Yat-sen Memorial Hospital, Sun Yat-sen University. These participants, receiving tamoxifen (TAM), toremifene (TOR), or aromatase inhibitors (AI) as adjuvant endocrine therapy and undergoing ovarian function suppression (OFS) treatment, will be divided into three groups, namely TOR+OFS, TAM+OFS, AI+OFS. The study will compare the efficacy and safety of TOR+OFS to that of TAM+OFS or AI+OFS in premenopausal estrogen receptor-positive breast cancer patients by comparing the 5-year disease-free survival (DFS) and quality of life etc. The objective is to evaluate whether TOR+OFS is non-inferior to TAM+OFS or AI+OFS in this specific patient population.

Study Overview

• Status: Not yet recruiting
• Conditions: Premenopausal Breast Cancer; Hormone-receptor-positive Breast Cancer; Breast Cancer Patients at Intermediate to High Risk; Ovarian Function Suppression Combined With Aromatase Inhibitor or Tamoxifen or Torimefen
• Intervention / Treatment: Drug: Aromatase inhibitor; Procedure: ovarian function suppression (Oophorectomy, Ovarian irradiation, Gonadotropin-releasing hormone agonist); Drug: Tamoxifen; Drug: toremifene

Detailed Description

Selective estrogen receptor modulators (SERM), tamoxifen (TAM) and toremifene (TOR), have been proven to be effective in premenopausal estrogen receptor positive breast cancer patients with similar outcomes. In addition, many large-scale long-term follow-up clinical tials, such as ABCSG XII, SOFT, TEXT, ASTRRA, and ZIPP, have confirmed that premenopausal patients with hormone-receptor-positive breast cancer at intermediate to high risk could benefit from ovarian function suppression (OFS) combined with aromatase inhibitor (AI) or TAM. The Asian Breast Cancer Cooperative Group (ABCCG) also recommends OFS+TAM or OFS+AI for the treatment in this specific patient population. Notably, the therapeutic efficacy and safety profile of OFS in conjunction with TOR have yet to be investigated, nor has its comparative effectiveness with OFS plus TAM or OFS plus AI been established.

This study aims to enroll premenopausal patients, with early breast cancer who are non-low-risk and hormone receptor-positive and have undergone prior surgical intervention at the Breast Cancer Center of Sun Yat-sen Memorial Hospital, Sun Yat-sen University. These participants, receiving tamoxifen (TAM), toremifene (TOR), or aromatase inhibitors (AI) as adjuvant endocrine therapy and undergoing ovarian function suppression (OFS) treatment, will be divided into three groups, namely TOR+OFS, TAM+OFS, AI+OFS. The study will compare the efficacy and safety of TOR+OFS to that of TAM+OFS or AI+OFS in premenopausal estrogen receptor-positive breast cancer patients by comparing the 5-year disease-free survival (DFS) and quality of life etc. The objective is to evaluate whether TOR+OFS is non-inferior to TAM+OFS or AI+OFS in this specific patient population.

• Study Type: Observational
• Enrollment (Anticipated): 700

Contacts and Locations

• Study Contact: Name: Chang Gong, doctor; Phone Number: 13925089353; Email: gchang@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
      • Contact: Gong Chang, doctor; Phone Number: 02034070499; Email: changgong282@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

1. Female, age ≥ 18
2. Premenopausal patients with early hormone receptor-positive breast cancer at intermediate to high risk (Low risk is defined as having the following 6 items at the same time: lesion size (pT) in the specimen <= 2cm; histological grade 1; no vessel carcinoma embolus; ER and/or PR positive; HER2 gene without overexpression or amplification; age >=35 years old)
3. Completed radical surgery for breast cancer
4. Undergoing postoperative endocrine therapy (toremifene, tamoxifen, aromatase inhibitorI) at least five years at Sun Yat-sen Memorial Hospital of Sun Yat-sen University since 2010
5. Undergoing ovarian function suppression (Oophorectomy, Ovarian irradiation, Gonadotropin-releasing hormone agonist)

Description

Inclusion Criteria:

1. Female, aged 18-60
2. Premenopausal patients with early hormone receptor-positive breast cancer at intermediate to high risk (Low risk is defined as having the following 6 items at the same time: lesion size (pT) in the specimen <= 2cm; histological grade 1; no vessel carcinoma embolus; ER and/or PR positive; HER2 gene without overexpression or amplification; age >=35 years old)
3. Completed radical surgery for breast cancer
4. Undergoing postoperative endocrine therapy (toremifene, tamoxifen, aromatase inhibitorI) at least five years at Sun Yat-sen Memorial Hospital of Sun Yat-sen University since 2010
5. Undergoing ovarian function suppression (Oophorectomy, Ovarian irradiation, Gonadotropin-releasing hormone agonist)

Exclusion Criteria:

1. Imaging or pathology suggestive of metastatic breast cancer (chest wall, lung, bone, liver, brain)
2. Patients with a second primary tumor
3. Hepatic insufficiency at baseline
4. Known history of psychotropic substance abuse or drug abuse;

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
OFS+AI; patients undergoing ovarian function suppression (OFS) combined with aromatase inhibitor (AI)	Drug: Aromatase inhibitor; Aromatase inhibitor includes Arimidex, Aromasin, Femara.; Procedure: ovarian function suppression (Oophorectomy, Ovarian irradiation, Gonadotropin-releasing hormone agonist); Gonadotropin-releasing hormone agonist includes Buserelin, Goserelin, Leuprorelin, Nafarelin, Triptorelin
OFS+TAM; patients undergoing ovarian function suppression (OFS) combined with tamoxifen (TAM)	Procedure: ovarian function suppression (Oophorectomy, Ovarian irradiation, Gonadotropin-releasing hormone agonist); Gonadotropin-releasing hormone agonist includes Buserelin, Goserelin, Leuprorelin, Nafarelin, Triptorelin; Drug: Tamoxifen; tamoxifen,10mg, bid
OFS+TOR; patients undergoing ovarian function suppression (OFS) combined with torimifene (TOR)	Procedure: ovarian function suppression (Oophorectomy, Ovarian irradiation, Gonadotropin-releasing hormone agonist); Gonadotropin-releasing hormone agonist includes Buserelin, Goserelin, Leuprorelin, Nafarelin, Triptorelin; Drug: toremifene; toremifene, 60 mg, qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease free survival	The time from the beginning of treatment to the recurrence of the disease or death from any cause or the end of the visit	5 years
The score of life quality questionnaire assessed by SPF 36	The score of SPF 36	1 month
The score of life quality questionnaire assessed by EQ-5D-5L	The score of EQ-5D-5L	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of adverse events	Incidence of adverse outcome events (such as musculoskeletal symptoms，osteoporosis, fragile, bone mineral density loss, hepatic insufficiency, dyslipidemia, endometrial hyperplasia, uterine fibroids, ovarian cyst, adenomyosis, hot flashes, night sweats etc.)	5 years

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Study Chair: Chang Gong, docto, Sun Yat-sen Memorial Hospital of Sun Yat-sen Univeristy

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: March 26, 2023
• First Submitted That Met QC Criteria: April 5, 2023
• First Posted (Actual): April 6, 2023

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: May 17, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Eye Diseases; Neurologic Manifestations; Breast Diseases; Sensation Disorders; Breast Neoplasms; Vision Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Hormones; Tamoxifen; Aromatase Inhibitors; Toremifene
• Other Study ID Numbers: SYSKY-2022-445-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No