Skipping Hormone Therapy in Low-Risk Early Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-04-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

National funding (PHRC)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine if women ≥ 60 years of age with clear margins of excision after surgery for node-negative breast cancer with tumors ≤ 1 cm and Luminal A characteristics (ER and PR
positive, HER2⁻, and Ki67 ≤ 15%) who are treated with adjuvant radiotherapy (if they underwent breast-conserving surgery, BCS) and forgo adjuvant ET have an acceptable low risk of relapse or death from breast cancer.

Secondary objectives 4

1. To compare the prognosis of the included participants to that of an external synthetic control arm.
2. To compare the risk of ipsilateral ductal carcinoma in situ (DCIS), contralateral DCIS and invasive breast cancer incidence to an external synthetic control arm.
3. To describe the HRQOL (EORTC QLQC30 and EORTC QLQ-BR42, HADS) of the included participants.
4. To describe the cardiovascular health and incidence of bone events and osteopenia/osteoporosis diagnosis

Conditions and MedDRA coding

Postmenopausal patients with small (pT1a-b pN0) hormone receptor positive (HR⁺) and HER2 negative (HER2⁻) early breast cancer with a Luminal A phenotype and at low risk of recurrence.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Postmenopausal (underwent bilateral oophorectomy or non-chemo induced amenorrhea for 12 or more months) female participant ≥60 years of age.
2. New diagnosis of invasive carcinoma of the breast (ductal, tubular or mucinous) with primary tumor ≤1 cm on microscopic exam (pT1a-b), with no evidence of nodal or distant metastatic disease.
3. Contralateral breast described as BI-RADS 1 or 2 in diagnostic imaging.
4. Negative axillary node involvement by sentinel node biopsy or axillary node dissection (pN0). or Clinically negative axillary node involvement (cN0) after mandatory ultrasound exploration without surgical exploration of the axilla if BCS was performed.
5. ER positive (≥ 50%) and PR positive (> 20%), Ki67 low (≤15%) and HER2 negative (IHC or In Situ Hybridization approach) according to ASCO criteria.
6. Histological grade scored on the invasive component, 1 or 2 if pT1a or grade 1 if pT1b.
7. Treated by mastectomy or BCS with microscopically clear resection margins defined as “no-ink on tumor” or ≥1 mm for invasive and non-invasive disease or no residual disease on re-excision.
8. If BCS was performed, participants must have received or have scheduled adjuvant local radiotherapy within 3 months after surgery, as follows : - whole breast adjuvant radiotherapy, - with appropriate fractionation (15, 5, 16 or 25 fractions), as per current standards - with or without a boost to the tumor bed, - delivered in a sequential or simultaneous manner, as per radiation oncologist’s choice. - whole breast irradiation volumes will be defined as per current guidelines
9. No indication of adjuvant chemotherapy.
10. The participant is willing and able to comply with the protocol for the duration of the study, including scheduled visits, treatment strategy, laboratory tests and other study procedures.
11. Participants must be affiliated with a Social Security System (or equivalent).
12. The participant must have signed a written informed consent form before any trialspecific procedures. When the participant is physically unable to give written consent, an impartial witness of her choice, independent from the investigator or the sponsor, can confirm the participant’s consent in writing.

Exclusion criteria 15

1. Have received any neo-adjuvant treatment, including hormone therapy and chemotherapy.
2. Have received or are eligible for adjuvant chemotherapy.
3. Absolute contraindication for RT in case of BCS or patients who were treated with partial breast irradiation.
4. Have been treated with mastectomy and with adjuvant radiotherapy received or scheduled.
5. Invasive lobular breast cancer.
6. Bilateral breast cancer or history of other invasive ipsi- or contralateral breast cancer.
7. Multifocal or multicentric disease.
8. Disease limited to microinvasion only (< 1 mm).
9. Evidence of lymphovascular invasion.
10. History of non-breast cancer malignancies if not disease-free for > 5 years and considered low risk of recurrence except for treated carcinoma in situ of the cervix, endometrium or colon, melanoma in situ and basal or squamous cell carcinoma of the skin.
11. Non-malignant severe disease associated with a life expectancy < 10 years.
12. Women with BRCA1, BRCA2 or other high-risk breast cancer predisposing deleterious germline mutations.
13. Enrolled in another therapeutic study within 30 days prior to inclusion.
14. Unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
15. Persons deprived of their liberty or under protective custody or guardianship.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Relapse-free interval (RFI) is defined as the delay between initial treatment and the first occurrence of i) ipsilateral breast tumor recurrence, ii) distant or locoregional recurrence or iii) death from breast cancer, according to the STEEP system definition version 2.0 (Tolaney SM et al., JCO 2021)

Secondary endpoints 4

1. RFI of participants treated with adjuvant hormone therapy in the CANTO study
2. Incidence of Ipsilateral DCIS, Contralateral DCIS, Invasive contralateral breast cancer at 5, 8 and 10 years*, Distant disease free survival (DDFS) and relapse free survival (RFS) rates at 5, 8, 10 years and overall survival (OS) at 5, 10 years * (RFI, DDFS, RFS and OS defined as per standardized STEEP v2.0 criteria)
3. EORTC QLQC30 and EORTC QLQ-BR42, HADS questionnaires
4. Bone-related events and osteopenia/osteoporosis diagnosis, dyslipidemia (hypercholesterolemia and hypertriglyceridemia) and cardiovascular events (myocardial infarction, stroke, and thromboembolic events), as per CTCAE v6.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 41 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications