Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

Status: Recruiting
Phase: Phase 3
Diagnosis: Breast: Early Stage Disease
NCT ID: NCT01953588 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID:


This randomized phase III trial has several primary objectives. One primary objective is to compare the efficacy of 3 different endocrine therapies, the estrogen receptor down regulator fulvestrant and the aromatase inhibitor anastrozole, either alone or in combination, in reducing cancer growth before surgery (neoadjuvant) in postmenopausal women with clinical stage II-III estrogen receptor positive and HER2 negative breast cancer. Another primary objective is to evaluate whether patients who achieved a modified PEPI (Preoperative Endocrine Prognostic Index) score of 0, defined by tumor size <5 cm, N0, Ki67<2.7% (by central testing), at surgery post 6 months of neoadjuvant endocrine therapy predict excellent long term outcome, for whom chemotherapy is unnecessary.


Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Beth-Israel Deaconess Medical Center

Overall PI:
Daniel Morganstern, MD, Faulkner Hospital

Site-responsible Investigators:
Steven Come, MD, Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute: Breast Cancer Nursing Team, 617-632-3478
Beth-Israel Deaconess Medical Center: Cancer Trials Call Center, 617-667-3060

Eligibility Criteria

Inclusion Criteria: 1. Female ≥18 years of age 2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 3. Postmenopausal, verified by: - post bilateral surgical oophorectomy or - no spontaneous menses ≥ 1 year or - no menses for < 1 year with follicle-stimulating hormone (FSH) and estradiol levels in postmenopausal range, according to institutional standards 4. Pathologic confirmation of invasive breast cancer diagnosed by core needle biopsy 5. Clinical T2-T4c, any N, M0 invasive breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to complete excision of the tumor in the breast and the lymph node. The extent of disease is a solitary lesion where the lesion is: - palpable - its size can be measured bidimensional by tape, ruler or caliper technique and - its largest tumor diameter is at least 2.0 cm (that is considered measurable by the WHO criteria) Note: - Patients with contralateral ductal carcinoma in situ and/or invasive breast cancer are not eligible. - Patients with multifocal/multi-lesional breast cancer are not eligible if more than one lesion is invasive breast cancer in the same breast. 6. Invasive breast cancer is estrogen receptor positive with an Allred score of 6, 7 or 8 by local institution standard protocol. If an Allred Score is not reported on the diagnostic pathology report, ER positivity in > 66% cells is eligible. If ER positivity is < 66%, the staining intensity (weak, intermediate, strong) is needed to calculate the Allred Score to determine eligibility. 7. Invasive breast cancer is Human Epidermal Growth Factor Receptor 2 (HER2) negative defined as 0 or 1+ by immunohistochemistry (IHC) or with a fluorescence in situ hybridization (FISH) ratio (HER2 gene copy/chromosome 17) < 2 if IHC 2+ by local institution standard protocol. 8. Documentation of mammogram and ultrasound (including ductal carcinoma in situ (DCIS) and invasive cancer) of the diseased breast performed within 42 days prior to registration. Mammogram for the unaffected contralateral breast is required within 12 months prior to registration. 9. Laboratory values ≤ 14 days prior to registration: 1. Absolute Neutrophil Count (ANC) > 1000/mm^3 2. Platelet Count > 100,000/mm^3 3. Total Bilirubin < 1.5 x upper limits of normal (ULN) 4. Creatinine < 1.5 x ULN 5. Serum alanine transaminase (ALT) < 2.5 x ULN 10. Tissue acquisition: Patient must agree to provide the required research biopsies at baseline, week 4 and at surgery for biomarker and correlative studies. Exclusion Criteria: 1. Premenopausal status 2. Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d' orange without erythema). 3. An excisional biopsy of this breast cancer. 4. Hormone replacement therapy of any type, megestrol acetate, or raloxifene within one week prior to registration. 5. Tumor estrogen receptor (ER) Allred score between 0-5 or HER2 positive by IHC (3+) or amplified by FISH > 2.0. 6. Surgical axillary staging procedure prior to study entry. Note: Fine needle aspiration (FNA) or core needle biopsy of axillary node is permitted. 7. Clinical or radiographic evidence of metastatic disease. Metastatic workup is not required, but is recommended for patients with clinical stage III disease. Note: Isolated ipsilateral supraclavicular node involvement is permitted. 8. Breast implants are contraindicated only if the implant precludes the required research biopsies. Patients who have previously had implants removed within 6 weeks prior to registration are eligible. 9. Treatment for this cancer including surgery, radiation therapy, chemotherapy, biotherapy, hormonal therapy or investigational agent prior to study entry. 10. History of invasive breast cancer or contralateral DCIS.
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