Effect of Endocrine Therapy Duration on Clinical Outcome of Patients With HR+ Intraductal Carcinoma of the Breast

Effect of Endocrine Therapy Duration on Clinical Outcome of Patients With Hormone Receptor-positive Intraductal Carcinoma of the Breast: A Multicenter, Retrospective, Real-world Study

This study will investigate the relationship between the endocrine therapy and the survival of patients with hormone receptor positive intraductal carcinoma of the breast, and the optimal duration of medication. This study will also analyze the risk factors of recurrence and metastasis of hormone receptor positive intraductal carcinoma of the breast and establish a prognosis model to further clarify the specific reasons for recurrence and metastasis, adverse reactions, and drug withdrawal in patients with hormone receptor positive intraductal carcinoma of the breast after endocrine therapy.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tamoxifen; Drug: Toremifene; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane

Detailed Description

Intraductal carcinoma of the breast accounts for 20% of newly diagnosed breast cancer. In addition to necessary surgical treatment, 5-year endocrine therapy is also essential for patients with hormone receptor positive ductal carcinoma of the breast. Commonly used drugs include selective estrogen receptor modulators (Tamoxifen, Toremifene) and aromatase inhibitors (Exemestane, Anastrozole, Letrozole). Although these drugs can effectively reduce the recurrence and metastasis of ductal carcinoma of the breast, the adverse reactions of the above drugs significantly reduce the quality of life and treatment compliance of the patients. Therefore, the choice of endocrine therapy for intraductal carcinoma of the breast has been widely discussed. Is it possible for de-escalation of endocrine treatment intensity to reduce adverse reactions and improve patient compliance? Recently, a phase 3 clinical trial found that compared with placebo group, the adverse reactions of Tamoxifen group treated with 5 mg/d (conventional dose 20 mg/d) Tamoxifen for 3 years had less adverse reactions and achieved significant efficacy. This study revealed the reliable efficacy and safety of Tamoxifen, a low-dose drug for treatment of hormone receptor positive intraductal carcinoma of the breast. However, little is reported on the reasonable duration of Aromatase inhibitors for endocrine therapy in patients with intraductal carcinoma of the breast.

This study will investigate the relationship between the endocrine therapy and the survival of patients with hormone receptor positive intraductal carcinoma of the breast, and the optimal duration of medication. This study will also analyze the risk factors of recurrence and metastasis of hormone receptor positive intraductal carcinoma of the breast and establish a prognosis model to further clarify the specific reasons for recurrence and metastasis, adverse reactions, and drug withdrawal in patients with hormone receptor positive intraductal carcinoma of the breast after endocrine therapy.

• Study Type: Observational
• Enrollment (Anticipated): 1354

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

patients with hormone receptor-positive ductal carcinoma of the breast

Description

Inclusion Criteria:

• (1)Female patients aged ≥ 18 years and ≤ 85 years

• (2)The primary lesions and lymph nodes of the breast must meet all of the following conditions:

  1. Histologically confirmed intraductal carcinoma of the breast, accompanied by microinvasion, with the infiltration range ≤ 1 mm;
  2. Have received radical resection or breast conserving surgery;
  3. Patients who have received breast conserving surgery must undergo pathological examination to confirm there is no residual cancer tissue on the cutting edge and receive postoperative radiotherapy within the prescribed dose and range;
  4. No lymph node metastasis (including micrometastasis) is detected by postoperative pathological examination;
  5. Immuno
  6. Immunohistochemical staining results are positive for estrogen receptor (ER) or progesterone receptor (PR), which is defined as ER or PR immunoreactivity intensity ≥1+ or expression percentage ≥ 1%.
• (3)A volunteer to participate in the study and willing to cooperate with follow-up

Exclusion Criteria:

• (1)Patients with newly diagnosed metastatic breast cancer or other malignant tumors without breast intraductal carcinoma;
• (2) Patients who have other malignant tumors before the initial diagnosis of intraductal carcinoma of the breast
• (3) Patients who have received endocrine therapy with drugs including Toremifene, Tamoxifen, Anastrozole, Letrozole or Exemestane before the initial diagnosis of intraductal carcinoma of the breast
• (4) Patients who have a serious comorbidity or other comorbidities that interfere with the conduct of the study, or those who are considered not suitable for participation in this study

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Drug Group; Endocrine therapy drugs include selective estrogen receptor modulators (Tamoxifen, Toremifene) and aromatase inhibitors (Anastrozole, Letrozole, Exemestane), which have been widely used in the adjuvant treatment of hormone receptor positive breast cancer.

Drug: Tamoxifen; 20 mg/d, oral administration; Drug: Toremifene; 60 mg/d, oral administration; Drug: Anastrozole; 1 tablet (1 mg) per day, oral administration; Drug: Letrozole; Adjuvant therapy with letrozole for 5 years or until the disease relapses. Patients who have received tamoxifen adjuvant therapy for 5 years should continue to take Letrozole until the disease relapses. The recommended dose of Letrozole tablets is one 2.5 mg tablet administered once a day, without regard to meals. For patients with advanced breast cancer, treatment with Letrozole should continue until tumor progression is confirmed. Patients with liver and/or renal dysfunction (creatinine clearance rate ≥ 10 mL/min) do not need to adjust the dosage.; Drug: Exemestane; The recommended dose of Exemestane for adult and older patients with early and advanced breast cancer is one 25 mg tablet administered orally once a day after a meal. After 2-3 years of tamoxifen treatment, patients with early breast cancer should continue to use Tamoxifen in the case of no recurrence or contralateral breast cancer, until the completion of 5-year sequential adjuvant therapy with tamoxifen and exemestane. Patients with advanced breast cancer should continue to take Exemestane until the tumor progresses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival up to 16 years	Disease-free survival refers to the time from the first disease-free day (i.e. the operation day) to the day at which relevant event occurs.	Time from the first disease-free day to the end of the last follow-up, assessed up to 16 years
Invasive disease-free survival up to 16 years	Invasive disease-free survival refers to the time from the first disease-free day (i.e. the operation day) to the day at which intraductal carcinoma of the breast recurs. The recurrent diseases include ipsilateral or contralateral breast cancer, local and distant recurrence of breast cancer, and death due to any reason.	Time from the first disease-free day to the end of the last follow-up, assessed up to 16 years
Distant disease-free survival up to 16 years	Distant disease-free survival refers to the time from the first disease-free day (i.e. the operation day) to the day at which distant metastasis occurs.	Time from the first disease-free day to the end of the last follow-up, assessed up to 16 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival up to 16 years	Overall survival refers to the first disease-free day to the time of death caused by any reason.	Time from the first disease-free day to the end of the last follow-up, assessed up to 16 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events of endocrine therapy up to 16 years	The incidence, nature, and severity of adverse events (including serious adverse events)	Time from the first disease-free day to the end of the last follow-up, assessed up to 16 years

Collaborators and Investigators

• Sponsor: First Hospital of China Medical University
• Collaborators: Jilin Provincial Tumor Hospital; The First Hospital of Jilin University; Second Hospital of Jilin University; China-Japan Union Hospital, Jilin University; The First Affiliated Hospital of Dalian Medical University; The Second Affiliated Hospital of Dalian Medical University; The Affiliated Zhongshan Hospital of Dalian University; The Fifth People's Hospital of Shenyang; General Hospital of Benxi Steel & Iron (Group) Co., Ltd; Affiliated Hospital of Hebei University of Engineering; Fourth People's Hospital of Shenyang
• Investigators: Principal Investigator: Bo Chen, MD, First Hospital of China Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 15, 2021

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): December 14, 2020
• Last Update Submitted That Met QC Criteria: December 10, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: breast cancer; recurrence; hormone receptor; metastasis; aromatase inhibitor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Breast Carcinoma In Situ; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; 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; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Tamoxifen; Anastrozole; Exemestane; Toremifene
• Other Study ID Numbers: FirstHCMU_CB_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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