| Eligibility |
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 must be willing to use effective birth control
methods (precautions) during study and for 8 weeks prior to fine needle aspiration and
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 should inform her study physician immediately.
Two of the following are recommended but woman must agree to at least one of the
following methods:
- Hormonal-impregnated intrauterine device (IUD) or rings
- Non-hormonal IUD
- Barrier method (such as condoms and diaphragms or cervical caps with or without a
spermicide)
- Partner has had a vasectomy
- Must have increased breast cancer risk as predicted by any one or more of the
conditions listed below or increased model calculated risk as below:
- Any one or more of the following conditions associated with increased risk
(condition must be documented in electronic medical record or copy of relevant
pathology or genetic testing reports submitted with the eligibility checklist)
- A prior biopsy at any time in the past showing ductal carcinoma in situ
(DCIS), lobular carcinoma in situ (LCIS), atypical hyperplasia. (If DCIS
must have been treated by mastectomy or local excision +/- radiation with
this treatment completed at least 3 months prior to screening with RPFNA)
- High or moderate penetrance risk pathogenic or likely pathogenic germline
gene mutation in ATM, BARD1, BRIP1, CDH1, CHEK2, MSH6, NBN, NF1, PTEN, PMS2,
RAD51C, RAD51D, or TP53
- High polygenic risk score (Life-time risk of >= 2x average or 25%)
- Breast cancer in a first or second degree relative (female or male) with
onset under age 50. First degree relative is defined as parent, sibling, or
child. Second degree relative is defined as grandparent, uncle, aunt,
nephew, niece, half-sibling, grandchild or first cousin
- Two or more affected first or second-degree relatives from either the
maternal or paternal lineage without regard to age
- Bilateral breast cancer or breast and ovarian cancer in the same first or
second degree relative without regard to age.
- High mammographic density defined as either visual estimate of area of
density (VAS) > 50%, or Volpara (Trademark) >= 15% dense volume (Volpara d)
or Breast Imaging Reporting and Data System (BIRADS) assessment of extremely
dense (BIRADs D)
- Alternatively, instead of Conditions listed above, , increased risk of breast
cancer as calculated by standard models (Breast Cancer Risk Assessment Tool
[BCRAT] Version 2, IBIS Version 8, Breast Cancer Surveillance Consortium)
- 5-year BCRAT Version 2.0 >= 1.66%
- 10-year IBIS Version 8 of >= 3% or Breast Cancer Surveillance Consortium
Version 2 of >= 3%
- 10 -year IBIS Version 8 age specific relative risk of
- Age 35-39 10-year relative risk of >= 5X that for age group
- Age 40-44 10-year risk of >= 4X that for age group
- Age 45 and up 10-year risk of >= 2X
- IBIS Version 8 Remaining lifetime risk of >= 25% or >= 2X that of population
- A copy of the output of model calculations from IBIS Version 8
(http://www.emstrials.org/riskevaluator/), BCRAT Version 2.0
(https://dceg.cancer.gov/tools/riskassessment/bcra) or BCSC version 2.0
(https://tools.bcsc-scc.org/BC5yearRisk/calculator.htm) online tools, if used for
qualifying risk assessment, or polygenetic risk score should be submitted with
the eligibility checklist. Otherwise, these risk qualifying factors need to be
documented in the medical record if that is considered the source document
- Women must have at least 1 unaffected untreated breast for fine needle aspiration.
Women may have had prior unilateral breast radiation or mastectomy for DCIS
- Eastern Cooperative Oncology Group (ECOG) current performance status =2 as documented
within 3 months prior to randomization (Karnofsky score >= 60%)
- Total bilirubin =< 1.5 x institutional upper limit of normal (measured within 180 days
prior to randomization)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase]) =< 1.5
x institutional upper limit of normal (measured within 180 days prior to
randomization)
- Creatinine =< 2.0 mg/dL (measured within 180 days prior to randomization)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are
eligible
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures
- Ability to understand and the willingness to sign a written informed consent document
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
- History of chronic liver disease including NASH (nonalcoholic steatohepatitis) and
chronic hepatitis C
- Current use of prescription anticoagulants such as Coumadin (warfarin), direct-acting
oral anticoagulants such as Xarelto (rivaroxaban) or Eliquis (apixaban), or heparin
- Women who would not be able to or do not wish to discontinue daily use of aspirin (81
mg or higher) and aspirin containing products (81 mg or higher) at least 3 weeks prior
to each RPFNA are not eligible. Women who would be able to stop daily use of aspirin
and aspirin containing products at least 3 weeks prior to each RPFNA are eligible
- NOTE: Women may resume daily use of aspirin and aspirin containing products 3
days after each RPFNA procedure
- Starting or stopping hormonal progestin IUDs within 8 weeks of baseline RPFNA
- Current use or use within the prior 8 weeks of progesterone/progestin injections,
progestin implants or oral contraceptives either combined estrogen + progestin or
progestin only (due to concerns about high levels of progestin and lack of safety and
efficacy data with low dose tamoxifen)
- Current use of other investigational agents
- Prior treatment with acolbifene for more than 2 months
- Prior treatment with tamoxifen for more than 2 months
- Current use of prescription immunosuppressive drugs
- History of allergic reactions attributed to tamoxifen or acolbifene or compounds of
similar chemical composition
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study
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