Low-dose exemestane versus low-dose tamoxifen for postmenopausal women at high risk of breast cancer

Randomized Double Blind Phase II Trial of Baby Exemestane vs Baby Tamoxifen in Post-menopausal Women at High Risk for Breast Cancer.

This trial will test whether taking low-dose exemestane or low-dose tamoxifen for one year changes menopausal quality of life in postmenopausal women at high risk for breast cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Sex: Female
• Sponsor: Ente Ospedaliero Ospedali Galliera (Academic / other)
• Drugs / interventions: denosumab
• Locations: 1 site (Genova, Italy)
• Trial ID: NCT06364267 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, double-blind phase II trial that assigns eligible postmenopausal high-risk women 1:1 to low-dose exemestane (25 mg every other day) or low-dose tamoxifen (10 mg every other day) for 12 months. Blinding is maintained by over-encapsulation of active tablets, and study medication is provided free by the sponsor. Quality of life is measured with the MENQOL questionnaire at baseline, 6 months, and 12 months, with clinical visits and blood collection for centralized biomarker storage. Additional safety and compliance checks occur at interim telephone/video contacts and during regular clinic assessments.

Who should consider this trial

Good fit: Postmenopausal women at elevated breast cancer risk—for example recent ER-positive DCIS treated with breast-conserving therapy, high-risk lesions (ADH/LCIS/ALH) within three years, or meeting specified 5- or 10-year risk thresholds—are ideal candidates.

Not a fit: Women who are premenopausal, do not meet high-risk criteria, or have contraindications to endocrine therapy (such as prior thromboembolic events or other specific medical exclusions) are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the trial could identify a lower-dose endocrine option that preserves or improves menopausal quality of life while offering breast cancer risk reduction for high-risk postmenopausal women.

How similar studies have performed: Previous large prevention trials have shown that standard-dose tamoxifen and exemestane reduce breast cancer incidence and smaller studies have explored low-dose tamoxifen with encouraging tolerability, but a direct randomized head-to-head comparison of low-dose exemestane versus low-dose tamoxifen for quality-of-life outcomes is novel.

Eligibility criteria

Inclusion Criteria:

1. Postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post- menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

   Any of the following criteria must be met:
   1. Recent (within 12 months from date of consent form signature) histologic diagnosis of ER+ve (\>5%) DCIS (patients with DCIS should have undergone breast-conserving therapy i.e. lumpectomy to remove the tumor with negative surgical margins followed by radiotherapy) or diagnosis within 3 years of HRL (ADH, LCIS, ALH), or:
   2. At least 3% breast cancer risk at 5 years (or 5% risk at 10yrs) per one of the following risk models: the Breast Cancer Surveillance Consortium risk calculator V3 or Tyrer-Cuzick model V8 or:
   3. Known carriers of a germline pathogenic/likely pathogenetic variant in the following moderate penetrance genes (CHEK2 or ATM), or women with chest wall irradiation before age of 30 years.
2. Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) 0-1.
3. Able to swallow oral medications.
4. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Specifically, all cancers diagnosed since 3 years or longer except for breast and endometrial are eligible.
5. Ability to understand and the willingness to sign a written informed consent document.
6. Mammography performed up to 6 months before the trial consent form signature.
7. DEXA performed up to 12 months before the trial consent form signature.
8. Patients with life expectancy ≥ 10 years.
9. Patients with normal liver function tests and blood cell count.
10. Negative gynaecological examination performed up to 6 months before the trial consent form signature.

Exclusion Criteria:

1. Pre/perimenopausal women
2. History of DVT or PE.
3. Endometrial cancer.
4. Macular disorders.
5. Inability to comply with study procedures.
6. Prior use of antiestrogens within 12 months from the date of the trial consent form signature.
7. Use of hormone replacement therapy (HRT) within 3 months from the date of the trial consent form signature.
8. Severe osteoporosis (T score ≤ 2.5 at either spine or hip), or recent vertebral fracture (within 6 months) not treated with zolendronic acid or denosumab.
9. Use of terbinafine, quinidine, cinacalcet, rifampicin, phenytonin, carbamazepine, phenobarbital, and St. John's wort, warfarin, erythromycin, cyclosporin, nifepidine and any concomitant coumarin-type anticoagulant therapy.
10. Patients with moderate or severe renal impairment.
11. Patients with a known hypersensitivity to study drugs.

Where this trial is running

Genova, Italy

• E.O. Ospedali Galliera — Genova, Italy, Italy (Recruiting)

Study contacts

• Study coordinator: Andrea U De Censi, MD

Conditions Breast Cancer; Breast cancer, menopause, exemestane, tamoxifen, MenQol, Low dose; babytam, babyexe