Skipping Hormone Therapy in Low-Risk Early Breast Cancer (NoELA)
No Endocrine Therapy in Small HR⁺/HER2- Low Risk Luminal A Early Breast Cancer, a Single-arm De-escalation Trial
The goal of this clinical trial is to determine whether a selected population of women with early-stage, low-risk breast cancer can avoid hormone therapy without increasing their risk of relapse. It will also evaluate the prognosis of these participants compared to participants who received standard treatment with hormone therapy in another study, estimate the risk of specific recurrence, cardiovascular and bone health, and participants' quality of life.
All participants will have undergone surgery and possibly radiation therapy, but unlike standard care, they will not receive hormone therapy afterward. Participants will be enrolled for two years and followed for up to five years after the last participant is enrolled in the trial to monitor for long-term cancer recurrence.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Breast cancer is the most frequently diagnosed cancer among women worldwide. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) tumors represent the predominant subtype and are generally associated with favorable outcomes. Adjuvant endocrine therapy (ET), including tamoxifen and aromatase inhibitors, constitutes a cornerstone of treatment for HR+/HER2- early breast cancer and has demonstrated reductions in recurrence and mortality in large randomized trials and meta-analyses. However, these benefits were mainly established in populations including patients with a broader spectrum of recurrence risk.
The implementation of mammography screening programs has increased the detection of small, early-stage breast cancers, including tumors with excellent prognosis and very low risk of recurrence. In postmenopausal women with small node-negative Luminal A tumors, recurrence rates are particularly low, raising concerns regarding potential overtreatment and the balance between treatment benefit and toxicity.
Although ET is effective, its long-term administration is associated with substantial treatment burden and persistent toxicities, including musculoskeletal symptoms, vasomotor symptoms, fatigue, sexual dysfunction, mood disturbances, and bone loss. These adverse effects may significantly affect quality of life and contribute to treatment discontinuation. Observational data have suggested that ET-related quality-of-life impairment may persist longer than chemotherapy-related effects, particularly in postmenopausal women.
Retrospective studies have suggested that the absolute benefit of ET may be limited in selected patients with very low-risk disease, especially among older women with small, low-grade HR+/HER2- tumors. Furthermore, simulation models estimating individualized treatment benefit indicate that the absolute overall survival gain associated with ET in some low-risk subgroups may be minimal, with high numbers needed to treat.
Advances in biological characterization have enabled identification of Luminal A tumors, characterized by strong hormone receptor expression, low proliferative activity, and favorable prognosis. Combining biological characteristics with clinicopathological features such as age, tumor size, grade, and nodal status allows the identification of a subgroup of postmenopausal patients with exceptionally low risk of relapse.
NoELA was developed to prospectively evaluate a therapeutic de-escalation strategy consisting of omission of adjuvant ET in postmenopausal women presenting with very low-risk HR+/HER2- early breast cancer with Luminal A phenotype. The study focuses on patients expected to derive limited benefit from ET while remaining exposed to its long-term toxicity burden.
The study also aims to generate evidence supporting more individualized treatment strategies and improved shared decision-making by better quantifying the risk-benefit balance of ET omission in this population. In addition, comparison with external real-world data derived from patients treated with standard ET will help contextualize outcomes and improve the external validity of the findings.
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiekontakt
- Navn: Unicancer Project Leader
- Telefonnummer: 0033 6 58 43 58 94
- E-post: a-poitou@unicancer.fr
Studiesteder
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
- Postmenopausal (underwent bilateral oophorectomy or non-chemo induced amenorrhea for 12 or more months) female participant ≥60 years of age.
- New diagnosis of invasive carcinoma of the breast (ductal, tubular or mucinous) with primary tumor ≤1 cm on microscopic exam with no evidence of nodal or distant metastatic disease.
- Contralateral breast described as BI-RADS (Breast Imaging-Reporting And Data System) 1 or 2 in diagnostic imaging.
- 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 Breast Conservative Surgery (BCS) was performed.
- Estrogen Receptor (ER) positive (≥ 50%) and Progesterone Receptor(PR) positive (> 20%), Ki67 low (≤15%) and HER2 negative (IHC or In Situ Hybridization approach) according to ASCO (American Society of Clinical Oncology) criteria.
- Histological grade scored on the invasive component, 1 or 2 if pT1a or grade 1 if pT1b.
- 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.
- If BCS was performed, participants must have received or have scheduled adjuvant local radiotherapy (RT) within 3 months after surgery
- No indication of adjuvant chemotherapy.
- 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.
- Participants must be affiliated with a Social Security System (or equivalent).
- The participant must have signed a written informed consent form before any trial-specific 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:
- Have received any neo-adjuvant treatment, including hormone therapy and chemotherapy.
- Have received or are eligible for adjuvant chemotherapy.
- Absolute contraindication for RT in case of BCS or patients who were treated with partial breast irradiation.
- Have been treated with mastectomy and with adjuvant radiotherapy received or scheduled.
- Invasive lobular breast cancer.
- Bilateral breast cancer or history of other invasive ipsi- or contralateral breast cancer.
- Multifocal or multicentric disease.
- Disease limited to microinvasion only (< 1 mm).
- Evidence of lymphovascular invasion.
- 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.
- Non-malignant severe disease associated with a life expectancy < 10 years.
- Women with BRCA1, BRCA2 or other high-risk breast cancer predisposing deleterious germline mutations.
- Enrolled in another therapeutic study within 30 days prior to inclusion.
- Unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
- Persons deprived of their liberty or under protective custody or guardianship.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: No Endocrine Therapy
The endocrine therapy will not be received by the participant during the study.
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The standard of care endocrine therapy (Tamoxifene, Letrozole, Anastrozole or Exemestane) will not be received by the participant during the study.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Relapse-free interval
Tidsramme: At 5 years after the last treatment
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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., J Clin Oncol 2021)
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At 5 years after the last treatment
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Incidence of Ipsilateral Ductal Carcinoma In Situ (DCIS)
Tidsramme: At 5 years after the last treatment
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At 5 years after the last treatment
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|
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Incidence of invasive contralateral breast cancer
Tidsramme: At 5 years after the last treatment
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At 5 years after the last treatment
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Distant disease free survival (DDFS)
Tidsramme: At 5 years after the last treatment
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Distant disease free survival is defined as the delay between date of inclusion and distant tumor relapse or death from any cause, whichever occurs first.
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At 5 years after the last treatment
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Relapse free survival (RFS)
Tidsramme: 5 years after the last treatment
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Relapse-free survival is defined as the delay between date of inclusion and tumor relapse (local, regional, or distant) or death from any cause, whichever occurs first.
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5 years after the last treatment
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Overall survival (OS)
Tidsramme: At 5 years after the last treatment
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The overall survival is the length of time from randomization that patients enrolled in the study are still alive.
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At 5 years after the last treatment
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Quality of life questionnaire - Core 30 (QLQ-C30)
Tidsramme: At baseline, 6 months, 1 year, and then annually until 5 years after the last inclusion
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Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. |
At baseline, 6 months, 1 year, and then annually until 5 years after the last inclusion
|
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Quality of Life Questionnaire - Breast cancer module (QLQ-BR42)
Tidsramme: At baseline, 6 months, 1 year, and then annually until 5 year after the last inclusion
|
This EORTC breast cancer specific questionnaire is intended to supplement the QLQ-C30. The QLQ-BR42 incorporates nine multi-item scales to assess body image, sexual functioning, breast satisfaction, systemic therapy side effects, arm symptoms, breast symptoms, endocrine therapy symptoms, skin mucosis symptoms, endocrine sexual symptoms. In addition, single items assess sexual enjoyment, future perspective and being upset by hair loss. All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale. Higher scores indicate more severe symptoms or problems for all items. |
At baseline, 6 months, 1 year, and then annually until 5 year after the last inclusion
|
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Hospital anxiety and depression scale (HADS)
Tidsramme: At baseline, 6 months, 1 year, and then annually until 5 year after the last inclusion
|
The HADS is a 14 items questionnaire: 7 items related to anxiety and 7 items related to depression scored on a scale.
Scores for items in each subscale of the HADS are summed to produce an anxiety score (HADS-A) or a depression score (HADS-D), or can be added to produce a total score corresponding to emotional distress (HADS-T).
Each item is rated on a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), for a total score ranging from 0-21 for each subscale.
The entire scale (emotional distress) range from 0 to 42, with higher scores indicating more distress.
|
At baseline, 6 months, 1 year, and then annually until 5 year after the last inclusion
|
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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
Tidsramme: Throughout study completion, up to 5 years after the last inclusion
|
The National Cancer Institute-Common Terminology Criteria for Adverse Events version 6 (NCI-CTCAE v6) is widely accepted in the community of oncology research as the leading rating scale for adverse events.
This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.
|
Throughout study completion, up to 5 years after the last inclusion
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Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Jean-Yves PIERGA, MD, Institut Curie
- Hovedetterforsker: José Luis SANDOVAL, MD, University Hospital, Geneva
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- UC-BCG-2513
- 2025-523683-20-00 (Ctis)
Plan for individuelle deltakerdata (IPD)
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IPD-planbeskrivelse
Legemiddel- og utstyrsinformasjon, studiedokumenter
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