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. Standard dose tamoxifen is four times the dose used in this study. Estrogen can cause the development and growth of breast cancer cells. Acolbifene and tamoxifen blocks the use of estrogen by breast cells. This study may help researchers measure the effects of acolbifene and low dose tamoxifen on markers of breast cancer risk in mammogram imaging, breast tissue, and in blood samples.
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) or oral contraceptives is being used which suppresses menstrual periods, or premenopausal women who have undergone a hysterectomy, but have at least one intact ovary
Not considering pregnancy for at least 12 months
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
Parallel
Acolbifene Hydrochloride
DrugGiven PO
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood
Mammography
Procedure/SurgeryUndergo 3D mammography
Questionnaire Administration
Other interventionAncillary studies
Random Periareolar Fine-Needle Aspiration
Procedure/SurgeryUndergo RPFNA
Tamoxifen
DrugGiven PO
Change in the relative abundance of the specific sequence of messenger ribonucleic acid that codes for AGR2
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; positive values indicate an increase in the relative abundance; and negative values a decrease in the relative abundance.
Change in Estrogen Response Gene Index (ERGI)
The genes assayed for this index are: ESR1, ESR2, GREB1, progesterone receptor (PGR), and TFF1. The log2-transformed values of the ratio of relative abundance (6-month value: baseline value) for GREB1, PGR, TFF1, and the ratio of ESR1:ESR2 are averaged to produce the ERGI. In cases where a specific gene or ratio cannot be evaluated for change over time, it is omitted from the average.
Relative change in mammographic absolute fibroglandular volume
Will be assessed via the completely automated Volpara™ software program. This will be performed from Digital Imaging and Communications in Medicine image files analyzed on a Research Server to which the Volpara™ algorithm has been loaded. The Volpara™ score card with volumetric assessments will be automatically generated. Alternatively, a Volpara Data Manager (VDM) program running the same algorithm may be used to generate an Excel file which stores at least all variables provided by the Score Card. The volumetric measures may be less susceptible to technical variance (such as compression) than area of density. Will evaluate absolute change and relative change between baseline and 6-month assessments.
Relative change in mammographic percentage (%) dense volume
Will be assessed via the completely automated Volpara™ software program. This will be performed from Digital Imaging and Communications in Medicine image files analyzed on a Research Server to which the Volpara™ algorithm has been loaded. The Volpara™ score card with volumetric assessments will be automatically generated. Alternatively, a VDM program running the same algorithm may be used to generate an Excel file which stores at least all variables provided by the Score Card. The volumetric measures may be less susceptible to technical variance (such as compression) than area of density. Will evaluate absolute change and relative change between baseline and 6-month assessments.
Change in Menopause-Specific Quality of Life (MENQOL)
The responses to the 32 questions (will ask about symptoms over prior week) are clustered into four domains (vasomotor, psychosocial, physical, sexual). Worsening of problems (higher scores) over the course of the intervention will assessed by average scores for each of the four individual domains as well as the total MENQOL score.
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