Low-Dose Tamoxifen Citrate in Reducing Breast Cancer Risk in Radiation-Induced Cancer Survivors
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Tamoxifen Citrate; Placebo; Digital mammography; immunohistochemistry staining method; pharmacological study; laboratory biomarker analysis; protein expression analysis; pharmacogenomic studies; questionnaire administration; Fine needle aspiration; Quality of Life Assessment
Intervention description: 5 mg PO Daily; 1 tablet daily; Correlative studies; Correlative Studies; Correlative Studies; Correlative Studies; correlative studies; correlative studies; Ancillary studies; Ancillary Studies
Intervention MeSH terms: Tamoxifen
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 84.0
Sex: Female
Minimum age: 25 Years
Healthy volunteers: No
Keywords: Cancer survivors; Low Dose Tamoxifen; Breast Cancer Risk Reduction

Summary:

      Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate
      may fight breast cancer by blocking the use of estrogen by the tumor cells

      This phase IIb trial studies how well low-dose tamoxifen citrate works in reducing breast
      cancer risk in radiation-induced cancer survivors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Exposure to radiation therapy (RT) delivered to the chest, axilla, and/or
             supraclavicular areas at a cumulative dose of 12 Gy or more by age 40 years; in
             addition, patients who received total body irradiation by age 40 may be considered

          -  No evidence of active disease from their primary cancer for at least 2 continuous
             years prior to registration; the indication for RT is not specified but cannot be for
             primary breast cancer; common examples include, but are not limited to: lymphoma,
             leukemia, sarcoma, and Wilms tumor occurring in pediatric patients, and lymphoma,
             leukemia, and sarcoma occurring in young adults; primary cancer therapy must have been
             completed at least 6 months prior to registration

          -  Well-defined menopausal status falling into one of the following categories:

               -  Premenopausal, defined as age at registration 45 years old or younger with
                  regular monthly period for at least 6 consecutive months prior to registration

               -  Postmenopausal, defined as continuous absence of menstruation for 12 months OR
                  status-post bilateral oophorectomy OR follicle stimulating hormone (FSH) level in
                  the postmenopausal range

        Exclusion Criteria:

          -  Subsequent malignant neoplasm (SMN) other than those listed below diagnosed within 2
             years of study entry; patients with the listed indolent or pre-invasive neoplasms may
             be eligible if diagnosed within 2 years and all treatment was completed at least 6
             months prior to registration:

               -  Non-melanoma cancers of the skin

               -  Thyroid cancer

               -  Cervical cancer confined to the cervix or cervical intraepithelial neoplasia
                  (CIN)

               -  Ductal carcinoma in situ (DCIS) or breast intraepithelial neoplasia (IEN)
                  (includes atypical hyperplasia and lobular carcinoma in situ [LCIS]), or

               -  Superficial or non-invasive transitional cell carcinoma of the bladder

          -  For women with a prior history of DCIS or breast IEN, only one breast could have been
             involved and all therapy must have been completed at least 6 months prior to
             registration; in addition women with a prior history of invasive breast cancer may
             also be eligible, as long as only one breast was involved, they were diagnosed at
             least 2 years prior to study entry, and therapy was completed at least 6 months prior
             to study entry

          -  Bilateral breast implants or status-post bilateral prophylactic mastectomy

          -  Evidence of malignant breast disease on any form of breast imaging; the study only
             requires annual mammography; however, annual breast magnetic resonance imaging (MRI)
             is considered standard of care in this patient population (per Children's Oncology
             Group [COG] or National Comprehensive Cancer Network [NCCN] follow-up guidelines), and
             breast ultrasound may be indicated if a palpable lesion is detected on screening
             clinical breast exam; abnormal imaging may require additional radiographs and/or
             breast biopsy; patients who are found to have benign breast disease with or without
             atypia may continue on study as long as there is no evidence of malignancy; if there
             is evidence of malignancy, and only one breast is involved, they may be reapproached 6
             months after completion of therapy for consideration of the trial

          -  Baseline categorical mammographic density scored as BIRAD 1, or extremely fatty, in
             both breasts; if the patient has a prior history of IEN (DCIS, LCIS, or atypical
             hyperplasia), the contralateral breast must not have a mammographic density score of
             BIRAD 1; this determination will be made at the local site

          -  Current or recent use (within 6 months of registration or baseline mammogram,
             whichever is first) of any of the following: systemic hormone replacement therapy
             (includes oral or transdermal formulations); Vagifem and Estring, two formulations of
             locally applied vaginal estrogen associated with minimal systemic absorption, may be
             allowed; other estrogen-containing vaginal creams, while not an exclusion, should be
             avoided whenever possible; patients with a history of hormone modifying herbal
             supplements are eligible, but patients will be asked to avoid their use after on study

          -  Current or recent use (within 6 months of registration or baseline mammogram,
             whichever is first) of any of the following: hormonal forms of contraception (includes
             oral, transdermal, implanted, and injectable formulations): selective estrogen
             receptor modifiers; aromatase inhibitors; GnRH analogs; androgens or antiandrogens

          -  Concurrent use of warfarin and strong inhibitors or CYP2D6 will not be allowed

          -  A personal history or a strong family of thromboembolism, including deep venous
             thrombosis (DVT), pulmonary embolus (PE), or cerebrovascular accident (CVA); a
             personal history of transient ischemic attack (TIA) or retinal vein thrombosis will
             also not be allowed; in addition, patients with a condition known to increase
             hypercoagulability, such as Factor V Leiden disease, will be excluded; patients with
             atrial fibrillation will be excluded, due to risk of CVA, but patients with coronary
             artery disease or congestive heart failure without atrial fibrillation will be allowed
             to participate

          -  Current intrauterine pregnancy or plans to become pregnant within two years; in
             addition, currently nursing mothers will be excluded

          -  Serum creatinine > 2X the institutional norm

          -  Total bilirubin > 2X the institutional norm

          -  Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase
             (SGPT) > 2X the institutional norm

          -  Unable to provide consent