Deescalation of Endocrine Therapy Duration in Women With HR+ HER2- Breast Cancer at Very Low Risk

Phase 2RecruitingNCT05297617

UNICANCER696 enrolled

Overview

Hormone therapy is recommended for five years in all patients with hormone receptor-positive breast cancer, but there is no consensus on its duration in low-risk tumours and especially in postmenopausal women. Adjuvant endocrine therapy (ET) is associated with substantial side effects and long-term decreased quality of life. Moreover, while it has been shown that ET provides a real benefit in reducing the relapse rate over time, the deterioration in quality of life may also have a negative effect on patient adherence to treatment. It is therefore important to offer treatment to women with low-risk cancer less intensive treatment strategies. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. The 5-year duration appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among high-risk patients. However shorter treatments of 2-3 years were already associated with substantial benefits and may be enough for very low risk patients.

Adjuvant ET is the cornerstone treatment of localized hormone-receptor positive breast cancer, with demonstrated benefits on overall survival (30-40% relative decrease in mortality) but also on the risk of local and contralateral relapse (43-50% relative decrease). While the relative benefit of 5 years ET is identical for small tumors as compared to larger ones, the absolute benefit is much lower, and the risk-benefit ratio may therefore become very questionable given the frequent and impactful side effects of ET. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. Five years appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among rather high-risk patients. However shorter treatments of 2-3 years were already associated with substantial benefits and may be enough for very low risk patients. The purpose of this study is to demonstrate that adjuvant hormone therapy limited to 2 years of antiaromatase in postmenopausal women with a good prognosis can ensure very high survival without metastatic relapse and allows a reduction of side effects and a better quality of life. The 5-year DMFS was excellent in patients with low risk Luminal A tumors who received endocrine therapy.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: FEMALEMin age: 51 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Postmenopausal women: Postmenopausal status is defined by any of the following: * Prior bilateral oophorectomy * Age ≥60 years * Age \>50 and \<60 years and amenorrheic for at least 12 months, and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range 2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 3. Women with histologically proven invasive unilateral breast cancer Note: In case of a multifocal invasive tumor, all lesions (maximum 3 infiltrating lesions allowed) must be of identical phenotype and low biological risk 4. M0: Not clinically nor radiologically detectable metastases at time of inclusion 5. Primary tumor completely resected and adequate axillary surgery performed, according to current standards 6. IHC expression of the estrogen receptor and/or progesterone receptor ≥50% 7. HER2 negative according to ASCO criteria in immunohistochemistry and/or genomic analysis (HER2 negativity is defined as IHC 0-1+, or \[IHC 2+ and FISH or CISH nonamplified\]) 8. No indication of adjuvant chemotherapy 9. pT1 (tumor ≤20 mm), pN0, Grade 1 or Grade 2 OR pT2 (tumor ≤30 mm) and pN0, Grade 1 or Grade 2 Note 1: patient with Grade 2 pT2pN0 tumor must be aged under 70 years of age and should receive a genomic test as part of standard care (RIHN reimbursement) 10. Patient considered has having a luminal A ultralow risk of metastatic recurrence (i.e.less than 5% risk of metastatic relapse at 10 years) according to MammaPrint® and Blueprint® tests. Note 1: To be eligible, MammaPrint index score should be \> +0.355 11. Patients eligible to receive or have recently started (with a maximum of 4 months of adjuvant hormone therapy prior to enrollment) an adjuvant hormone therapy (letrozole, anastrozole, or exemestane) 12. Patient is willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures 13. Patients must be affiliated to a Social Security System (or equivalent) 14. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent. Exclusion Criteria: 1. Patients who received a neo-adjuvant hormone therapy, a neo-adjuvant or adjuvant chemotherapy or preoperative medical treatment 2. Any local or regional recurrence or metastatic disease 3. Non-invasive carcinoma 4. Bilateral breast cancer (except in case of contralateral DCIS), or history of other invasive ipsi- or contralateral breast cancer 5. Patients with a history of another malignancy, except for properly treated cervical carcinoma in situ, and non-melanoma cancer of the skin 6. Women with high-risk breast cancer predisposing deleterious germline mutations 7. Contra-indications to the administration of anti-aromatase inhibitors 8. Patients enrolled in another therapeutic study within 30 days prior to inclusion 9. Patients with any other disease or illness, which requires hospitalization or is incompatible with the trial treatment 10. Patients unwilling or unable to comply with trial obligations for geographic, social, physical or psychological reasons, or who are unable to understand the purpose and procedures of the trial 11. Persons deprived of their liberty or under protective custody or guardianship

Outcomes

Primary Outcomes

Distant relapse-free interval (DRFI)

Distant relapse-free interval (DRFI) is defined as the time from date of beginning of hormonotherapy to the date of first event of distant recurrence or breast cancer related death

Time frame: From date of beginning of hormonotherapy to onset of metastases or death, up to 5-years.

Secondary Outcomes

Distant Disease-Free Survival (DDFS)

DDFS is defined as the time from date of beginning of hormonotherapy to the date of first event of distant recurrence, death from any cause or secondary non-breast cancer.

Time frame: From date of beginning of hormonotherapy to the date of first event of distant recurrence, death from any cause or secondary non-breast cancer up to 10 years

Invasive disease free survival (iDFS)

Invasive disease free survival is defined as duration of time from date of registration until first appearance of invasive local, regional, or distant recurrence (including invasive ipsilateral breast cancer recurrence), invasive contralateral breast cancer, second primary non breast invasive cancer (excluding non-melanoma skin cancer), or death from any cause.

Time frame: From date of beginning of hormonotherapy to onset of invasive event, second cancer, or death, up to 10 years.

Invasive breast cancer-free survival (iBCFS)

Invasive disease free survival is defined as the delay between date of inclusion and first appearance of invasive local, regional, or distant recurrence (including invasive ipsilateral breast cancer recurrence), invasive contralateral breast cancer, or death from any cause.

Time frame: From date of beginning of hormonotherapy to onset of invasive event or death, up to 10 years.

Breast cancer-specific survival (BCSS)

Breast cancer-specific survival is defined as the time from inclusion to death from breast cancer.

Time frame: From date of beginning of hormonotherapy to death from breast cancer, up to 10 years.

Overall survival (OS)

The overall survival is the length of time from inclusion to death from any cause.

Time frame: From date of beginning of hormonotherapy to death from any cause, up to 10 years.

Quality of life (QoL) questionnaire - Core 30 (QLQ-C30)

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.