Optimal Personalized Treatment of Early Breast Cancer Using Multi-parameter Analysis: Focus on YOUNGer Women

Plain English Summary

Optimising Adjuvant Chemotherapy Prescription in Young Patients With Hormone-dependent Breast Cancer Using Genomic Tests is a Phase 3 clinical trial sponsored by UNICANCER studying Early Breast Cancer, Premenopausal Breast Cancer, HR+/HER2- Breast Cancer. This trial tests if a genetic test can help decide if younger women with early hormone-driven breast cancer need chemotherapy. It is for women aged 35 and older who have early-stage, hormone-sensitive, HER2-negative breast cancer. Participation involves surgery, a genetic test on the tumor, and then receiving either chemotherapy plus hormone therapy or hormone therapy alone, based on the test results. Alternatives include standard treatment (chemotherapy plus hormone therapy) or hormone therapy alone, depending on the cancer's characteristics and doctor's recommendation. The trial aims to enroll 3380 participants.

Official Summary

Rationale: Around 70 to 80% of breast cancers are so-called "hormone-dependent" (HR+)/HER2-. For more than 50 years, studies have shown that chemotherapy and optimised hormonal treatments (hormone therapy), including a drug associated with ovarian suppression (OFS), improve survival in patients with these cancers, which are characterised by a high risk of relapse. However, younger patients suffer more side effects than older women, particularly from chemotherapy. This can affect their quality of life and reduce their ability to work. For post-menopausal women, genetic tests exist to assess whether chemotherapy is really necessary in addition to hormonal treatment. However, for high-risk premenopausal patients, chemotherapy is still systematically recommended, as no study has proved that it can be safely avoided. Clinical trials based on risk stratification using genetic tests have not been conclusive, but the majority of premenopausal women included had not received optimal hormone treatment. It is possible that the beneficial effect of chemotherapy is partly due to the artificial menopause it induces. Some experts believe that, for patients with a high clinical risk but a low genetic risk, an optimised hormonal treatment (drug + OFS) could suffice, without the need for chemotherapy. Objectives: Main objective: The aim of the study is to determine whether the use of a genetic test (Prosigna®) to decide whether or not to administer chemotherapy produces results as good as standard treatment (systematic chemotherapy) in premenopausal women with hormone-dependent (HR+) breast cancer/HER2-, by assessing their risk of cancer recurrence. The secondary objectives include verifying whether, in patients with a low Prosigna® score (around 70% of cases), optimised hormonal treatment (including suppression of ovarian function) is as effective as chemotherapy combined with hormonal in treatment preventing cancer recurrence. The study also seeks to compare the efficacy of tr

Who Can Participate

Here is what you need to know about eligibility for this trial. Women aged 35 or older with early-stage, hormone-receptor-positive, HER2-negative invasive breast cancer. Patients must have had breast and lymph node surgery within 12 weeks of starting the trial. Women who have gone through menopause are not eligible. Patients must be fit enough to receive chemotherapy. This trial is studying Early Breast Cancer, Premenopausal Breast Cancer, HR+/HER2- Breast Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures if the cancer stays away or if the patient survives, showing whether the personalized treatment approach is as effective as standard chemotherapy. The specific primary outcome measures are: invasive breast cancer free survival (IBCFS) (Time from the date of randomization to the date of the first event (ipsilateral loco-regional invasive breast or distant breast cancer recurrence, contralateral new invasive primary breast cancer or death from any cause), assessed up to 120 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to reduce unnecessary chemotherapy in younger women with early breast cancer, improving quality of life by avoiding harsh side effects while maintaining high survival rates. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Early Breast Cancer, Premenopausal Breast Cancer, HR+/HER2- Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial addresses a significant unmet need in early breast cancer treatment for premenopausal women, potentially impacting a large market segment and offering a more targeted approach than current Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 3380 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if this trial is right for you and what the Prosigna® test results mean. Participation involves regular clinic visits for assessments and treatment, which may include chemotherapy and hormone therapy. Be prepared for potential side effects from treatment and discuss any concerns with your healthcare team. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 3,380 participants

Interventions

• DRUG: test-directed treatment: allocated treatment will depend on the PAM50 score result (centrally assessed) : chemo-endocrine therapy or endocrine therapy alone — In this experimental arm, the treatment is driven by the score of the Prosigna test. If the score is superior to 60, the patient is considered at hight risk so the patient will receive chemo-endocrine therapy. If the result is under or equal to 60, only endocrine therapy will be prescribed to the patient.
• DRUG: In the control arm, the treatment will be as standard of care : chemo-endocrine therapy — Standard treatment: Chemotherapy followed by endocrine therapy

Primary Outcomes

• invasive breast cancer free survival (IBCFS) (Time from the date of randomization to the date of the first event (ipsilateral loco-regional invasive breast or distant breast cancer recurrence, contralateral new invasive primary breast cancer or death from any cause), assessed up to 120 months)

Secondary Outcomes

• Invasive Breast Cancer Free Survival (IBCFS) in the population with tumours for which the Prosigna® score is below 60 (Time from the date of randomization to the date of the first event (ipsilateral loco-regional invasive breast or distant breast cancer recurrence, contralateral new invasive primary breast cancer or death from any cause), assessed up to 120 months)
• Distant recurrence free interval (DRFI) (time from the date of randomization to the date of the first event of distant recurrence of breast cancer or death from breast cancer in the global population, assessed up to 120 months)
• Distant recurrence free survival (DRFS) (time from the date of randomization to the date of the first event of distant recurrence of breast cancer or death from any cause in the global population, assessed up to 120 months)
• Breast cancer specific survival (BCSS) (time from the date of randomization to the date of death from breast cancer in the global population, assessed up to 120 months)
• Overall survival (OS) (time from the date of randomization to the date of death from any cause in the global population, assessed up to 120 months)

Full Eligibility Criteria

Inclusion Criteria:

1. Patient must have signed a written informed consent 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 signing the patient's consent;
2. . Premenopausal defined by patient that are not post-menopaused
3. Female
4. Age ≥ 35 years
5. Diagnosis of invasive HR-positive (ER≥10% of tumour cells stained positive and any PR expression) HER2-negative (IHC score 0-1+ or 2+ with negative/non-amplified ISH) invasive breast cancer; ER and HER2 determination will be assessed according to latest ASCO/CAP or national guidelines;
6. Breast and axillary surgery completed ≤ 12 weeks from study entry and randomization;
7. Availability of a Formalin-Fixed Paraffin-Embedded (FFPE) tumour sample from surgery to perform Prosigna® analysis or slides.

   Note: in case of receipt of neoadjuvant endocrine therapy the Prosigna® test must be done on the baseline biopsy. Performing the test on the surgical piece or on on-treatment biopsy is not permitted.
8. Tumour size and axillary lymph node status. One of the following must apply:

   1. 1-3 lymph nodes involved AND any invasive tumour size.
   2. node negative (including micrometastases in at least 1 node \[i.e. deposit \>0.2-2mm diameter\]) AND invasive tumour size ≥ 50mm.
9. Multiple ipsilateral breast cancers are permitted provided that at least one tumour meets the tumour size and axillary lymph node entry criteria, and none meet any of the exclusion criteria.
10. Bilateral breast cancers are permitted provided the tumour(s) in one breast meets the eligibility criteria and the other, contralateral tumour is not ER negative and/or HER2 positive and not clinically significant, defined by both of the following:

    1. The contralateral tumour does not fulfil the tumour size and lymph node eligibility criteria required for trial entry; i.e. the following are not acceptable:

       .i. presence of lymph node macro-metastases; .ii. tumour size ≥50mm when there is no lymph node involvement.
    2. The treating physician does not consider that the characteristics of the contralateral tumour alone justify consideration of adjuvant chemotherapy.
11. Fitness to receive adjuvant chemotherapy, as judged by the treating physician;
12. Short term pre-surgical treatment with endocrine therapy, including in combination with non-cytotoxic agents, is allowed providing that the duration of treatment did not exceed 8 weeks;
13. Patients affiliated with or a beneficiary of the local social security system, health social security system, or other local regulatory requirements
14. Patients must agree to use adequate contraception methods for the duration of study treatment and for the duration specified in the SmPC after completing the treatment, unless agreed with the treatment physician the safety of attempt a pregnancy, which could be possible after at least 18 months of endocrine therapy.

Note : patient with extracapsular nodular transgression are eligible. NOTE: If neoadjuvant endocrine therapy was received, the Prosigna® test must be realized on the baseline biopsy. Performing the test on the surgical specimen or on biopsy taken during treatment is not permitted.

NOTE: Re-excision or complementary mastectomy for close/positive surgical margins should be postponed after chemotherapy completion, if chemotherapy is given; breast reconstruction is allowed after trial entry.

NOTE: The use of approved adjuvant targeted agents (abemaciclib, ribociclib and olaparib) combined to adjuvant endocrine therapy is allowed according to local practice recommendations and availability.

Exclusion Criteria:

* 1\. Postmenopausal women. Women who fulfil the following criteria at trial entry will be considered postmenopausal:

  1. Age \>45 and natural amenorrhoea of at least 1 year's duration.
  2. Bilateral surgical oophorectomy.
  3. For amenorrhoea not fulfilling the above criteria the diagnosis of postmenopausal status should be supported by hormone measurement: FSH levels must be \> 25IU/L with low oestradiol (i.e. within the locally defined postmenopausal range), in the event of doubt measured on 2 occasions preferably 4-6 weeks apart. This applies to women who have undergone hysterectomy without bilateral surgical oophorectomy and are age \<60; those ≥60 may be considered postmenopausal.

     NOTE: Hormonal contraception will suppress FSH and oestradiol levels. In those taking oral contraception, levels will recover rapidly on discontinuation. Depo-Provera injectable contraception lasts many months: all women receiving this agent should be considered premenopausal.

     2\. Stage IV breast cancer; 3. Start of adjuvant systemic treatment (except for neoadjuvant endocrine therapy for a duration ≤ 8 weeks) before trial entry\*; 4. Previous diagnosis of malignancy except:

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  1. Previous ductal carcinoma in situ (DCIS

Trial Locations

• Institut Jules Bordet, Brussels, Belgium
• Cliniques Universitaires Saint-Luc, Brussels, Belgium
• Grand Hôpital de Charleroi, Charleroi, Belgium
• CHU Helora Hôpital de La Louvière - Site Jolimont, Haine-Saint-Paul, Belgium
• CHU UCL Namur - Site Sainte Elisabeth, Namur, Belgium
• Clinique Saint Pierre, Ottignies, Belgium
• CHR Verviers, Verviers, Belgium
• Centre Hospitalier d'Auxerre, Auxerre, France
• Sainte Catherine - Institut du Cancer Avignon-Provence, Avignon, France
• Centre Hospitalier de la Côte Basque, Bayonne, France
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Early Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• HER2-Negative Breast Cancer
• Premenopausal Breast Cancer
• Adjuvant Therapy
• Oncology
• Genomic Testing in Cancer
• Personalized Medicine
• Cancer Recurrence

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