Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer

What this trial studies

This phase IIA trial compares the effect of acolbifene versus low dose tamoxifen in preventing breast cancer in premenopausal women at high risk for developing breast cancer. The usual approach for patients at increased risk for breast cancer is to undergo yearly breast magnetic resonance imaging or ultrasound in addition to yearly mammogram. Premenopausal women at very high lifetime risk for breast cancer (greater than 50%) can consider preventive removal (mastectomy) of both breasts. Premenopausal women age 35 or older with a prior diagnosis of atypical hyperplasia, lobular carcinoma in situ, or an estimated 10-year risk of greater than or equal to 3% or estimated 10-year risk of greater than or equal to 2-5 times that of the average woman (depending on age) may be advised to consider five years of standard dose tamoxifen.

Conditions in scope

• Breast Atypical Hyperplasia
• Breast Carcinoma
• Breast Ductal Carcinoma In Situ
• Breast Lobular Carcinoma In Situ

Interventions

• Acolbifene Hydrochloride (Drug) — Given PO
• Biospecimen Collection (Procedure) — Undergo collection of blood
• Mammography (Procedure) — Undergo 3D mammography
• Questionnaire Administration (Other) — Ancillary studies
• Random Periareolar Fine-Needle Aspiration (Procedure) — Undergo RPFNA
• Tamoxifen (Drug) — Given PO

Who can join

Women only · Ages 35 Years and up

Inclusion criteria

• Age \>= 35 years
• Considered clinically premenopausal
• Having regular menstrual cycles (between 21 and 35 days) unless a contraceptive device such as progestin containing intrauterine device (IUD) (e.g., Mirena IUD) is being used which suppresses menstrual periods, or premenopausal women who have undergone a hysterectomy, but ovaries are intact
• Not considering pregnancy for at least 12 months
• Women of child-bearing potential capacity must be willing to have used effective birth control precautions for 8 weeks prior to fine needle aspiration and be willing to continue for 8 weeks after study completion as tamoxifen may have teratogenic effects on the developing fetus. Reproductive and developmental toxicity studies have not been conducted with acolbifene. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must stop study drug and inform her study physician immediately.
• For women not using oral contraceptive (progestin alone or estrogen plus a progestin), two of the following are recommended but woman must agree to at least one of the following methods:
• IUD non-hormonal or hormone containing (usually a progestin) intrauterine device (IUD) or rings. Any of these should have been inserted at least 8 weeks prior to RPFNA.
• Barrier method (such as condoms and diaphragms or cervical caps with or without a spermicide)

Exclusion criteria

• Bilateral breast implants (danger of implant puncture with RPFNA)
• Women who are pregnant
• Currently breastfeeding (concern that tamoxifen or acolbifene may be in breast milk) or nursing within the past 12 months (concern about milk fistula with RPFNA)
• Prior invasive breast cancer within the past 5 years
• Other prior invasive cancer \> T1 stage (other than non-melanoma skin) within the past 5 years
• Pathogenic or likely pathogenic germline mutation in BRCA1/2 or PALB2 (These latter individuals are likely to undergo yearly ovarian screening and enlarging cysts could raise concern about ovarian cancer and lead to unnecessary diagnostic procedures)
• Type I or Type II diabetes mellitus requiring treatment with prescription medication
• Prior deep vein thrombosis, pulmonary embolus, or stroke

Eligibility wording paraphrased from the public record. View the full criteria on ClinicalTrials.gov before contacting a site.

Where it’s happening

Status & timeline

• Overall status: Recruiting
• Study type: Interventional
• Phase: PHASE2
• Start date: 2024-08-23
• Primary completion: 2027-08-23
• Last update posted: 2026-04-13
• First posted: 2023-07-12

Sponsor & contact

Lead sponsor: National Cancer Institute (NCI) (Nih)

For trial site contact information, use the official record at ClinicalTrials.gov. Contact details change frequently and the public record is the source of truth.

Outcome measures

Primary outcomes

• Change in the relative abundance of the specific sequence of messenger ribonucleic acid that codes for AGR2 (Baseline up to 6 months)
  Will be assessed in benign breast tissue acquired by random periareolar fine-needle aspiration. Change over the intervention period is expressed as the ratio of the relative abundance values (6-month value: baseline value) and then this fold change value is log transformed (base 2) for analysis. For this variable, values of zero indicate no change in the relative abundance of AGR2;…

Related ClearedRx care

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