Tamoxifen Citrate, Anastrozole, or Fulvestrant in Treating Patients with Stage I-III Invasive Lobular Breast Cancer
- Histologically confirmed invasive lobular breast cancer, that is hormone receptor-positive and HER2-negative, measuring at least 1 centimeter (cm) radiographically or clinically, clinical stages I-III; invasive lobular histology will be diagnosed at the enrolling institution for purposes of study participation; subsequently, invasive lobular histology will be confirmed by central pathology review, but this central review will not be required prior to patient enrollment
- Prior to initiation of study agents, study participants will be highly encouraged to undergo a baseline research core biopsy of their breast tumor; if this is not possible or the patient refuses, the pre-treatment tumor sample must be obtained from their archival diagnostic core biopsy; if definitive surgery is not performed at day 21-27 after study treatment, a second post-treatment research core biopsy will need to be obtained from their breast tumor; for patients undergoing surgery, the second biopsy will be removed from the breast tumor tissue excised during their operation; Note: In the event that the baseline breast tumor biopsy performed for research purposes does not yield adequate tumor tissue for analysis of the primary and secondary endpoints, tissue will be requested from the patient's archival clinical diagnostic core biopsy if it is available; the patient will still remain on study and complete protocol therapy as planned in this unlikely event
- Hormone receptor (HR) status of the invasive component must be documented before trial enrollment; the tumor must be HR-positive; HR will be considered positive if staining is 1% or greater for ER and/or PR; this will be determined at the enrolling institution for purposes of study participation and enrollment onto the trial; subsequently, HR status will be confirmed by central pathology review, but this central review will not be required prior to enrolling the patient; HER2 status will be determined locally only, based upon current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
- Participants must be fully postmenopausal
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Leukocytes >= 3,000/mm^3
- Absolute neutrophil count >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- Total bilirubin within normal laboratory limits
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times the laboratory upper limit of normal
- Creatinine within normal laboratory limits
- Prior use of hormone contraceptives and replacement therapy is allowed (e.g., estrogen and/or progestin), but must have been discontinued at least 30 days prior to the study enrollment; vaginal preparations (e.g., Vagifem or Estring) are allowed
- Participant must be aware of the nature of her malignancy, understand the study requirements and risks and be able and willing to sign a written informed consent document
- Prior or concurrent use of hormonal therapy, chemotherapy, radiation therapy, or novel therapy to treat the current breast cancer, including any history of prior irradiation to the ipsilateral breast; additionally, the patient must not have had hormonal therapy for breast cancer treatment or for breast cancer prevention within 2 years prior to study enrollment; Note: Synchronous breast, cancer (including bilateral breast cancer) at separate sites is permissible, provided the patient does not receive medical treatments for breast cancer or radiation therapy to the ipsilateral breast during the 21 day study intervention period
- Concurrent use of any other investigational agents
- History of allergic reactions/hypersensitivity attributed to compounds of similar chemical or biologic composition to tamoxifen, anastrozole, or fulvestrant or any of their ingredients
- History of thromboembolic disease or uterine cancer that is considered a contraindication to tamoxifen
- Active hepatitis viral infections
- Uncontrolled current 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 requirements
- HER-2 positivity
District of Columbia
I. To determine the change from baseline to post-treatment Ki67 values in hormone receptor (HR)-positive, HER2-negative invasive lobular carcinoma (ILC) tissue derived from postmenopausal women awaiting definitive surgery or further neoadjuvant treatment who are randomized to 21-27 days of neoadjuvant endocrine treatments with fulvestrant (two 250 mg intramuscular [IM] injections given on day 1 and 15), anastrozole (1 mg given orally daily), or tamoxifen citrate (tamoxifen) (20 mg given orally daily).
I. To compare between arms Ki67 values following neoadjuvant therapy.
II. To evaluate estrogen receptor (ER) protein expression in ILC tissues at baseline and following neoadjuvant endocrine therapy.
III. To evaluate progesterone receptor (PR) protein expression in ILC tissues at baseline and following neo-adjuvant endocrine therapy.
IV. To evaluate ER-related and ILC-specific candidate gene messenger ribonucleic acid (mRNA) expression in ILC tissues at baseline and following neoadjuvant endocrine therapy in an effort to identify biomarkers of endocrine response and putative drivers of endocrine resistance in ILC.
V. To evaluate associations between changes in Ki67 in ILC tissues following neoadjuvant endocrine therapy with ER and PR protein expression, or ER and candidate gene mRNA expression at baseline and post-treatment.
I. To evaluate deoxyribonucleic acid (DNA) methylation in ILC tissues at baseline and following neoadjuvant endocrine therapy.
II. To evaluate associations between germline and somatic DNA sequence variants with changes in Ki67 in ILC tissues following neoadjuvant endocrine therapy.
III. To evaluate the activity of signaling pathways in ILC tissues by immunohistochemical or other protein analyses, such as histone modifications, at baseline and following neoadjuvant endocrine therapy.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I: Patients receive fulvestrant IM on days 1 and 15 in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive anastrozole orally (PO) once daily (QD) for 21-27 days in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive tamoxifen citrate PO QD for 21-27 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Trial Phase Phase II
Trial Type Treatment
University of Pittsburgh Cancer Institute (UPCI)
Rachel C. Jankowitz
- Primary ID 13-164
- Secondary IDs NCI-2018-00191, TBCRC037
- Clinicaltrials.gov ID NCT02206984