Arimidex With or Without Faslodex In Postmenopausal Women With HR Positive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Arimidex; Faslodex
Intervention description: Aromatase inhibitors; Hormone Receptor
Intervention MeSH terms: Fulvestrant; Anastrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer; HORMONE RECEPTOR POSITIVE BREAST CANCER

Summary:

      Over the last 3 decades, a steady shift has occurred in the management of breast cancer.
      Because it was traditionally viewed as a local disease, many advocated the use of radical
      surgery to achieve maximum survival benefit. This view has been slowly replaced by a broader
      biologic view that recognizes the often systemic nature of breast cancer, even when it
      appears to be localized to the breast. Results from randomized clinical trials have
      demonstrated that less extensive surgery, or lumpectomy plus radiation therapy, are optimal
      for local management of early breast cancer. In addition to the less radical approach to
      surgical treatment of breast cancer, other randomized clinical trials have established the
      value of postoperative systemic therapy in improving overall survival by eradicating
      micrometastatic disease, the major cause of mortality from breast cancer. Despite the
      well-documented benefits of adjuvant systemic therapy, it is not effective in preventing
      death from breast cancer in all patients who are candidates for such treatment. The worth of
      such therapy can only be judged in retrospect upon disease relapse, a time when breast cancer
      is nearly always incurable. Currently, there are few reliable methods to predict the success
      or failure of a particular postoperative treatment modality, and better ways to predict and
      optimize outcome are needed.

      Combination endocrine therapy: Using endocrine agents with different mechanisms of action
      together has the potential advantage of more effectively blocking ER signaling, thus
      improving the efficacy of such agents against breast cancer. In the past, attempts to combine
      endocrine agents for ER-positive breast cancer have had mixed results, depending on the
      setting and the patient population studied.

      Endocrine agents without any agonist effect could potentially be used in combination with
      aromatase inhibitors, under the rationale that the combination would maximally blockade
      estrogen receptor signaling, thus potentially improving the antitumor effect. Fulvestrant
      (FASLODEX) is a pure estrogen antagonist with no known agonist effect; thus, it has the
      potential to provide additional benefit when combined with an aromatase inhibitor. This
      concept provides the rationale for using the combination of anastrazole and fulvestrant in
      this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All subjects must be female.

          -  Postmenopausal status, defined as any one of the following criteria:

               -  Documented history of bilateral oophorectomy.

               -  Age 60 years or more.

               -  Age 45 to 59 and satisfying one or more of the following criteria:

                    -  Amenorrhea for at least 12 months and intact uterus.

                    -  Amenorrhea for less than 12 months and a follicle stimulating hormone (FSH)
                       and estradiol concentration within postmenopausal range including: patients
                       who have had a hysterectomy and patients who have received hormone
                       replacement.

          -  Patients must have histologically confirmed invasive breast cancer with a primary
             tumor of 3 cm or more in greatest dimension as measured by clinical examination.

          -  Estrogen receptor and/or progesterone receptor positive disease.

          -  Patients must not have received any prior treatment for current or newly diagnosed
             breast cancer.

          -  Patients must have not received previous treatment with any of the study medications
             or similar drugs.

          -  No use of selective estrogen receptor modulators (SERM) such as raloxifene or similar
             agents in the past 2 years.

          -  WHO performance status of 0, 1, or 2.

          -  Adequate organ function defined as follows:

               -  Adequate renal function, defined by a serum creatinine within 3 times the upper
                  limits of normal.

               -  Adequate liver function, defined by total bilirubin, AST, ALT, and alkaline
                  phosphatase within 3 times the upper limits of normal.

               -  Adequate bone marrow function, defined as a WBC greater than 3.0 ml, PLT greater
                  than 75,000/ul, Hb greater than 9 gm/l.

          -  Willing to undergo breast core biopsies as required by the study protocol. - Ability
             to understand and sign a written informed consent for participation in the trial.

          -  Life expectancy of at least 1 year.

        Exclusion Criteria:

          -  Premenopausal status.

          -  Other coexisting malignancies with the exception of basal cell carcinoma or cervical
             cancer in situ.

          -  Patients with brain metastasis.

          -  WHO performance status of 3 or 4.

          -  Is judged by the investigator, uncontrolled intercurrent illness including, but not
             limited to, ongoing or active infection, symptomatic congestive heart failure,
             unstable angina pectoris, significant cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements.

          -  Evidence of any other significant clinical disorder or laboratory finding that makes
             it undesirable for the subject to participate in the clinical trial. - Concurrent
             treatment with estrogens or progestins. Patients must stop these drugs at least two
             weeks prior to study entry.

          -  Treatment with a non-approved or investigational drug within 30 days before Day 1 of
             study treatment.

          -  Platelet count less than 75,000.

          -  In the opinion of the investigator, bleeding diathesis or anticoagulation therapy that
             would preclude intramuscular injections.

          -  History of hypersensitivity to castor oil.

          -  Any evidence of clinically active interstitial lung disease (patients with chronic
             stable radiographic changes who are asymptomatic need not be excluded) - Patients with
             recurrent breast cancer.

          -  Patients with contralateral second primary breast cancers are eligible.