Endocrine Therapy Base on 21-gene RS (CUSTOM)

Comparison of Endocrine Therapy Plus Ovarian Function Suppression and Chemotherapy Based on 21-gene RS in Young Age (≤ 50) Women (CUSTOM): Multi-center Registry Study

Among patients aged ≤50 years with hormone receptor-positive, HER2-negative breast cancer and pathologic nodal stage pN0-1-limited to those with an Oncotype DX® Recurrence Score (RS) of 11-25 for pN0 and ≤25 for pN1-, we will investigate the followings:

i) Real-world patterns of adjuvant therapy (systemic chemotherapy and endocrine therapy) and radiotherapy according to N stage and Oncotype DX® RS.

ii) Clinicopathologic characteristics of each patient subgroup by adjuvant treatment modality and RS category.

iii) Survival outcomes and independent prognostic factors according to RS. iv) Survival analyses by adjuvant treatment modality, stratified by RS category, clinical risk, and N stage.

Through these analyses, we aim to establish clinical evidence on whether endocrine therapy combined with ovarian function suppression (OFS) can substitute for adjuvant chemotherapy in HR+/HER2- patients with pN0-1 disease within the above RS ranges, and-if so-to define the patient subsets for whom this substitution is appropriate.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: Oncotype DX

• Study Type: Observational
• Enrollment (Estimated): 4000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study included the patients aged ≤ 50 years with hormone receptor-positive, HER2-negative breast cancer and pathologic nodal stage pN0-1 and those with an Oncotype DX® Recurrence Score (RS) of 11-25 for pN0 and ≤25 for pN1.

Description

Inclusion Criteria:

1. Histologically confirmed breast cancer.
2. Age ≤50 years at initial diagnosis.

3. Premenopausal at diagnosis, defined as any of the following:

   A. History of menstruation within 6 months prior to diagnosis. B. Serum FSH < 30 mIU/mL. C. If criteria A or B are unavailable, women aged ≤50 years are considered premenopausal.

4. Underwent curative-intent breast cancer surgery between January 2012 and December 2021.
5. Pathologic tumor stage pT1-pT3 after surgery.
6. Pathologic nodal stage pN0-pN1 after surgery.
7. Hormone receptor-positive disease by immunohistochemistry (IHC): estrogen receptor (ER) and/or progesterone receptor (PR) positive (≥1% positive cells or Allred score ≥3).
8. HER2-negative disease per ASCO/CAP guidelines: IHC 0 or 1+; if IHC 2+, in situ hybridization (FISH or SISH) negative.
9. Oncotype DX® performed, meeting one of the following Recurrence Score (RS) ranges:

A. pN0: RS 11-25. B. pN1: RS ≤25.

Exclusion Criteria:

1. Evidence of distant (systemic) metastasis at diagnosis.

2. Postmenopausal status at diagnosis, defined as any of the following:

   A. Prior bilateral oophorectomy before the breast cancer diagnosis (considered postmenopausal).

   B. Prior unilateral oophorectomy alone is not considered postmenopausal (classified as premenopausal).

   C. Bilateral oophorectomy performed after breast cancer surgery for therapeutic purposes is not an exclusion; such patients will be categorized as having received ovarian function suppression (OFS).

   D. Serum FSH ≥ 30 mIU/mL.

3. Hormone receptor-negative or HER2-positive disease.
4. Insufficient or unclear data regarding the type of adjuvant therapy received.
5. History of another malignancy treated before the breast cancer diagnosis, except for thyroid cancer and non-melanoma skin cancer.
6. Bilateral breast cancer.
7. Receipt of neoadjuvant systemic therapy prior to surgery.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
invasive disease-free survival	5 years after breast cancer diagnosis

Collaborators and Investigators

• Sponsor: Gangnam Severance Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Breast cancer; Chemotherapy; Hormone receptor-positive; Oncotype DX; Ovarian function suppression
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: KBCSG 38

Drug and device information, study documents

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