Low-Dose Tamoxifen Citrate in Reducing Breast Cancer Risk in Radiation-Induced Cancer Survivors

Inclusion Criteria

• Exposure to radiation therapy (RT) delivered to the chest, axilla, and/or supraclavicular areas at a cumulative dose of 12 Gray (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 of primary cancer diagnosis 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 Breast Imaging Reporting and Data System (BIRAD) 1, or extremely fatty, in both breasts; if the patient has a prior history of IEN (DCIS, lobular carcinoma in situ [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 * Hormonal forms of contraception (includes oral, transdermal, implanted, and injectable formulations) * Selective estrogen receptor modifiers (such as tamoxifen and raloxifene) * Aromatase inhibitors * Gonadotropin-releasing hormone (GnRH) analogs * Prolactin inhibitors, or * Androgens or antiandrogens
• Concurrent use of warfarin and strong inhibitors or cytochrome P450, family 2, subfamily D, polypeptide 6 (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 one-time personal history of catheter-associated DVT may be allowed, as long as there were no subsequent venous thromboembolic (VTE) events and a strong family history is not present; examples of a strong family history includes (but is not limited to): one first degree relative with no more than one VTE event in the same individual, and two family members in the same lineage with unexplained VTE or two VTE events in the same individual; if a family history is present, but it is not clear whether or not it is clinically significant, consideration of genetic testing to rule out a hereditary clotting syndrome (e.g. Factor V Leiden [FVL], prothrombin G2010A mutations) may be considered; concurrent warfarin use for any reason is not allowed; patients with atrial fibrillation may not participate; however, patients with coronary artery disease or congestive heart failure without atrial fibrillation may be allowed to participate; patients with a personal history of a cerebrovascular accident (CVA), transient ischemic attack (TIA) or retinal vein thrombosis will not 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 greater than 2 x the institutional norm
• Total bilirubin greater than 2 x the institutional norm
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) greater than 2 x the institutional norm
• Unable to provide consent