Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Immune System Diseases

Breast Neoplasms

Hypersensitivity

Breast Diseases

Skin Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Bone Density Conservation Agents

Antineoplastic Agents

Anesthetics

Tamoxifen

Hormones

Estrogens

Anesthetics, Local

Goserelin

Progesterone

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Patients should be premenopausal women ,prior to the start of chemotherapy, less than or equal to 45 years of age with oestrogen receptor positive ± progesterone receptor positive who have undergone a primary mass excision, received an neo-/adjuvant chemotherapy ± radiotherapy for their stage I, II or III breast cancer. This arm is ovarian suppression group which have a various starting time of ovarian function suppression after neo-/adjuvant chemotherapy.

Ovarian function suppression will be done by administration of LHRH agonist (ZOLADEXTM) for 2 years. After that, the patients will complete taking tamoxifen 20mg/day for 5 years.

Patients, less than or equal to 45 years of age with hormone receptor positive breast cancer will be enrolled. Included All the patients have already treated by surgery, neo- or adjuvant chemotherapy ±and/or radiotherapy before enrolment. At 0, 6, 12, 18 and 24 months since the baseline asTsessment(0), the ovarian function status will be evaluated by menstruation status or serum FSH level. If the patients are regarded as the premenopausal women, they will be randomized into the additional ovarian function suppression group or tamoxifen only group. The latter will complete taking tamoxifen 20mg/day for 5 years.

Patients, less than or equal to 45 years of age with hormone receptor positive breast cancer will be enrolled. Included All the patients have already treated by surgery, neo- or adjuvant chemotherapy ±and/or radiotherapy before enrolment. Eligible patients except for premenopausal status at the baseline will be followed up until 2 years after the baseline assessment for evaluating the menopausal status. This group still remains to postmenopausal status and will taking tamoxifen 20mg/day for 5 years if they remain in the study.

Patients, less than or equal to 45 years of age with hormone receptor positive breast cancer will be enrolled. Included All the patients have already treated by surgery, neo- or adjuvant chemotherapy ±and/or radiotherapy before enrolment. At 6, 12, 18 and 24 months since the baseline assessment (0), the ovarian function status will be evaluated by menstruation status or serum FSH level. If the patients are regarded as the premenopausal women, they will be randomized into the additional ovarian function suppression group or tamoxifen only group. This group, patients are premenopausal women, they will be randomized into tamoxifen only group, complete taking tamoxifen 20mg/day for 5 years.

Patients, less than or equal to 45 years of age with hormone receptor positive breast cancer will be enrolled. Included All the patients have already treated by surgery, neo- or adjuvant chemotherapy ±and/or radiotherapy before enrolment. At 6, 12, 18 and 24 months since the baseline assessment (0), the ovarian function status will be evaluated by menstruation status or serum FSH level. If the patients are regarded as the premenopausal women, they will be randomized. This group, patients are premenopausal women, they will be randomized into the additional ovarian function suppression group. Ovarian function suppression will be done by administration of LHRH agonist (ZOLADEXTM) for 2 years. Then, Patients will complete taking tamoxifen 20mg/day for 5 years.

1. Zoladex™ administration:

   Zoladex™ depot is available as a sterile disposable syringe. The depot is administered subcutaneously under the abdominal skin under sterile conditions. If necessary the injection site may be pre-treated with a local anaesthetic.
2. Sequence of administration Zoladex depot:

   The substance is administered for 24 months (2 years) at 28-day intervals (a period of 34 days between 2 administrations must not be exceeded).
3. Dosage:

   Each depot contains 3.6mg Zoladex. The substance Zoladex is contained in a while cylindrical rodlet .
4. Storage instructions for Zoladex™ Zoladex™ is kept a room temperature.

goserelin

1. Dose and period of Tamoxifen therapy:

   Tamoxifen is administered in tablet form. Each day 2 X 10 mg or 1 X 20 mg Tamoxifen are taken in the form of the respective tablet.
2. Storage instructions for Tamoxifen Tamoxifen is stored at room temperature away from light.

tamoxifen

Woo-Chul Noh, MD.PhD

The purpose of this study is to compare 5-year disease free survival rate (DFS rate) between the hormone receptor positive breast cancer patients who were added Goserelin to Tamoxifen for ovarian function suppression after neo-/adjuvant cytotoxic chemotherapy and the hormone receptor positive breast cancer patients who were treated with Tamoxifen.

* To compare overall Survival(OS) between the patients added Goserelin(ZOLADEXTM) to Tamoxifen and the patients treated with Tamoxifen alone in premenopausal status
* To compare 5-year disease free survival rate (DFS rate) between the patients who took tamoxifen only in postmenopause and the patients added Goserelin(ZOLADEXTM) to Tamoxifen for inducing ovarian function suppression in premenopause
* To determine the tolerability and safety of Tamoxifen with or without concomitant Zoladex

Evaluating the Role of the Addition of Ovarian Function Suppression (OFS) to Tamoxifen in Young Women

A Randomised Phase III Study for Evaluating the Role of the Addition of Ovarian Function Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain in Premenopause or Regain Menstruation After Chemotherapy

Korean Breast Cancer Study Group

Woo-Chul, Noh

Reproductive Control Agents

Exemestane

Leuprolide

Aromatase Inhibitors

Enzyme Inhibitors

Patients receive exemestane from week 1 to week 26 and Tucidinostat BIW from week 3 to week 26. Courses continue in the absence of disease progression or unacceptable toxicity. If the patient is premenopausal, leuprorelin or goserelin will be prescribed.

Tucidinostat: 30 mg BIW (Monday and Thursday) from week 3 to week 26

Tucidinostat

Exemestane: 25 mg QD from week 1 to week 26.

If the patient is premenopausal, leuprorelin 3.75mg or goserelin 3.6 mg will be injected every 28 days.

Ovarian function suppression

Ying Lin, MD

This study is to evaluate the efficacy of tucidinostat combined with exemestane as neoadjuvant strategy in estrogen receptor-positive early breast cancer patients and explore the genetic model which can predict neoadjuvant endocrine therapeutic results.

This study is to evaluate the efficacy of tucidinostat combined with exemestane as neoadjuvant strategy in estrogen receptor-positive early breast cancer patients.This study will recruit 30 patients. The 30 patients will receive 25 mg exemestane QD for 26 weeks. Tucidinostat will be prescribed 30 mg BIW from week 3 to week 26. During neoadjuvant treatment biopsy, CEUS and MRI will be perfomed according to protocol to evaluate the therapeutic results. Genetic testing will also be performed before and after neoadjuvant treatment to explore the predictive value. MRI evaluated ORR is primary end point. CEUS evaluated ORR, pCR, AE and RCB are secondary end point.

Neoadjuvant Tucidinostat and Exemestane in Early Breast Cancer

Neoadjuvant Tucidinostat and Exemestane in Estrogen Receptor-Positive Early Breast Cancer （NeoTEE）

ORR is defined as percentage of participants with Complete Response and Partial Response, assessed by the investigators using MRI according to the Response Evaluation Criteria in Solid Tumors (RECIST)

Contrast-enhanced ultrasound will also be performed to assess ORR

The percentage of participants with pathologically assessed ypT0 and ypTis of breast disease.

All advese effect events related with Tucidinostat and Exemestane.

Pathologilly assessed residual cancer burden according to MD Anderson protocol.

First Affiliated Hospital, Sun Yat-Sen University

Vice Director of Department of Breast Surgery

Antirheumatic Agents

Docetaxel

Cyclophosphamide

Epirubicin

Anastrozole

Six months of exemestane or anastrozole plus goserelin.

Six cycles of docetaxel plus epirubicin and cyclophosphamide(TEC).

Goserelin: 3.6mg, d1, hypodermic injection , q28d\*7 plus exemestane: 25mg, po, qd\*24w, or anastrozole: 1mg, po, qd\*24w

Neoadjuvant endocrine therapy

Docetaxel: 75mg/m2, d1, q3w\*6, Epirubicin 75mg/m2, d1, q3w\*6 and Cyclophosphamide: 500mg/m2, d1, q3w\*6

Neoadjuvant chemotherapy

Li Zhu, Prof

To compare the efficacy and safety of neoadjuvant aromatase inhibitor plus ovarian suppression with chemotherapy in premenopausal patients with hormone receptor-positive breast cancer.

Neoadjuvant therapy is nowadays the standard treatment for both early stage and locally advanced breast cancer, and exhibited similar benefit compared with adjuvant therapy in terms of disease free and overall survival. Patients achieved pathological complete response(pCR) after neoadjuvant chemotherapy have superior outcome compared with those with residual tumors in breast and/or axilla. pCR is now the most wildly accepted surrogate marker for long-term survival of patients, especially in those with triple negative or human epidermal growth factor receptor-2(HER2)-positive breast cancer. However, in luminal HER2-negative breast cancer, neoadjuvant chemotherapy is not as effective as in other subtypes of breast cancer, pCR is less noted and seems barely correlated to long-term survival benefit.

In postmenopausal patients with hormone receptor-positive breast cancer, neoadjuvant endocrine therapy of aromatase inhibitor achieved similar clinical response rate compared with neoadjuvant chemotherapy, and in premenopausal hormone receptor-positive, HER2-negative breast cancer patients, neoadjuvant aromatase inhibitor plus ovarian function suppression(OFS) has showed more pronounced efficacy than tamoxifen plus OFS.

In adjuvant setting, aromatase inhibitor combined with OFS in premenopausal patients with hormone receptor-positive breast cancer has demonstrated superior benefit in terms of disease free survival, and has been established as one of the routine options of adjuvant endocrine therapy. Notwithstanding the remarkable performance of combination of aromatase inhibitor and OFS in adjuvant therapy, the role of this treatment strategy in neoadjuvant setting has yet not been proved when compared with neoadjuvant chemotherapy.

The aim of this study is to prospectively compare the efficacy and safety of neoadjuvant aromatase inhibitor plus OFS with chemotherapy in premenopausal patients with hormone receptor-positive HER2-negative breast cancer.

Neoadjuvant Aromatase Inhibitor(AI) With Ovarian Suppression Versus Chemotherapy in Premenopausal Breast Cancer Patients

Comparison of Neoadjuvant Aromatase Inhibitors With Ovarian Suppression Versus Chemotherapy in Premenopausal Patients With Hormone Receptor-positive Breast Cancer (COMPETE): a Randomized Phase 3 Trial

Overall response rate(ORR) is defined as complete response rate plus partial response rate.

Ruijin Hospital

Professor

Symptoms and General Pathology

Amenorrhea

Menstruation Disturbances

Toremifene

Patients who didn't have CIA receive oral toremifene daily. Treatment continues for 5 years in the absence of disease progression or unacceptable toxicity

Patients who had CIA receive toremifene as in arm I

Patients without CIA receive oral toremifene and goserelin for ovarian function suppression

Patients with CIA receive oral toremifene and goserelin for ovarian function suppression.

Yidong ZHOU, Master

Changjun WANG, Doctor

Compare the potential benefits of adjuvant toremifene with or without goserelin in premenopausal women with stage I-IIIA, hormonal receptor positive breast cancer accompanied with or without chemotherapy induced amenorrhoea.

This is a single center, randomized, controlled study. Patients undergo surgical resection with standard Doxorubicin/Cyclophosphamide Followed by Docetaxel (AC-T).

Chemotherapy begins within 4 weeks after surgery for patients randomized to arm I-IV. Arm I: patients who didn't have CIA receive oral toremifene daily. Treatment continues for 5 years in the absence of disease progression or unacceptable toxicity. Arm II: patients who had CIA receive toremifene as in arm I. Arm III: patients without CIA receive oral toremifene and goserelin for ovarian function suppression. Arm IV: patients with CIA receive oral toremifene and goserelin for ovarian function suppression. Patients are followed every 6 months for 5 years and annually thereafter.

Adjuvant Toremifene With or Without Goserrelin in Premenopausal Women With Stage I-IIIA, Hormonal Receptor Positive Breast Cancer Accompanied With or Without Chemotherapy Induced Amenorrhoea

Study of Adjuvant Toremifene With or Without Goserrelin in Premenopausal Women With Stage I-IIIA, Hormonal Receptor Positive Breast Cancer Accompanied With or Without Chemotherapy Induced Amenorrhoea

measured by dual energy X-ray absorptiometry scans at every 12 months and by serum biomarkers

Peking Union Medical College Hospital

HR-positive premenopausal female patients whose doctors believe that they can benefit from continued use of OFS after 5 years should be included in the trial group.

The control group did not need to continue to use OFS, either leuprolide or goserelin

Patients included in the group continued or discontinued to use goserelin or leuprolide after 5 years use.

OFS continues to use group after 5 years use

Enrolled patients must be HR-positive premenopausal breast cancer patients

Immunohistochemical detection of HR status

Hongmei Zheng, Doctor

Xinhong Wu, Doctor

xinhong wu, Dr

To observe and evaluate the clinical efficacy and safety of continuous use of OFS for premenopausal patients with early breast cancer after 5 years use of OFS.

This study is a multicenter, prospective, observational, non randomized controlled, open-label real world study based on hospital medical record system data, aimed at evaluating the benefits of continuing to use OFS after 5 years of use. The retrospective analysis plan includes patient data from September 1, 2023 to September 1, 2026. Join two cohorts: the continued use group and the discontinued use group after 5 years of OFS, respectively.

The Benefits of Continued Use of Ovarian Function Suppression After 5 Years

A Multicenter, Open-label, Non-randomized Controlled Real World Study Comparing the Benefits of Continued Use of Ovarian Function Suppression After 5 Years

Quality of life score was evaluated by European Organization of Research and treatment of Cancer-Questionnaire of Life Quality-C30 Version 3 (EORTC-QLQ-C30 V3), which conduct a series of questions about the patients' physical condition, activity of daily life, adverse reaction and mood condition. The range in the questionnaire for the score is from 1 to 4, in which 1 stands for having no discomfort and 4 stands for having great discomfort.

The main effect evaluation index was invasive disease-free survival (iDFS)

Overall survival for years, which means the rate of patients alive in the whole patients at the same group will be calculated with kaplan meier survival curves.

Hongmei Zheng

vice director

Patients who were anticipated to receive adjuvant OFS+AI endocrine therapy according to MDT discussion results were randomized to this arm,they will receive OFS+Anastrozole.

Patients who were anticipated to receive adjuvant OFS+AI endocrine therapy according to MDT discussion results were randomized to this arm,they will receive OFS+Exemestane.

Ovarian function suppression can be achieved by choice of goserelin at a dose of 3.6 mg administered by means of subcutaneous injection every 28 days,bilateral oophorectomy,or bilateral ovarian irradiation.

Patients will take anastrozole 1mg qd.

OFS + Anastrozole

Patients will take exemestane 25mg qd. Ovarian function suppression can be achieved by choice of goserelin at a dose of 3.6 mg administered by means of subcutaneous injection every 28 days,bilateral oophorectomy,or bilateral ovarian irradiation.

OFS + Exemestane

Kunwei Shen, Professor

To compare safety of adjuvant OFS combined with anastrozole versus OFS combined with exemestane in Chinese premenopausal hormonal receptor(HR) positive breast cancer patients.

Safety of OFS Combined With AI Endocrine Therapy in Chinese Premenopausal Breast Cancer Patients

Safety of Ovarian Function Suppression(OFS)Combined With Different Aromatase Inhibitors(AIs) Endocrine Therapy in Chinese Premenopausal Breast Cancer Patients：A Randomized, Controlled, Prospective, Observational Study

Bone and joint pains are measured by National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI CTCAE) classification v4.0 every 3 months.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluating the Role of the Addition of Ovarian Function Suppression (OFS) to Tamoxifen in Young Women	NCT00912548	Breast Cancer	goserelin tamoxifen	18 Years - 45 Years	Korean Breast Cancer Study Group
Neoadjuvant Tucidinostat and Exemestane in Early Breast Cancer	NCT04465097	Breast Cancer	Tucidinostat Exemestane Ovarian functio...	18 Years -	First Affiliated Hospital, Sun Yat-Sen University
Neoadjuvant Aromatase Inhibitor(AI) With Ovarian Suppression Versus Chemotherapy in Premenopausal Breast Cancer Patients	NCT02532400	Breast Cancer	Neoadjuvant end... Neoadjuvant che...	18 Years -	Ruijin Hospital
Adjuvant Toremifene With or Without Goserrelin in Premenopausal Women With Stage I-IIIA, Hormonal Receptor Positive Breast Cancer Accompanied With or Without Chemotherapy Induced Amenorrhoea	NCT02132390	Breast Cancer Chemotherapy In... Ovarian Functio...	Goserelin Toremifene	18 Years - 45 Years	Peking Union Medical College Hospital
Adjuvant Toremifene With or Without Goserrelin in Premenopausal Women With Stage I-IIIA, Hormonal Receptor Positive Breast Cancer Accompanied With or Without Chemotherapy Induced Amenorrhoea	NCT02132390	Breast Cancer Chemotherapy In... Ovarian Functio...	Goserelin Toremifene	18 Years - 45 Years	Peking Union Medical College Hospital
The Benefits of Continued Use of Ovarian Function Suppression After 5 Years	NCT06050109	Breast Cancer F... Endocrine Thera...	OFS continues t... Immunohistochem...	18 Years - 60 Years	Hubei Cancer Hospital
Safety of OFS Combined With AI Endocrine Therapy in Chinese Premenopausal Breast Cancer Patients	NCT02440230	Breast Cancer	OFS + Anastrozo... OFS + Exemestan...	18 Years -	Shanghai Jiao Tong University School of Medicine
Safety of OFS Combined With AI Endocrine Therapy in Chinese Premenopausal Breast Cancer Patients	NCT02440230	Breast Cancer	OFS + Anastrozo... OFS + Exemestan...	18 Years -	Shanghai Jiao Tong University School of Medicine

Spots Global Cancer Trial Database for ovarian function suppression