Letrozole in Treating Postmenopausal Women Who Have Received Hormone Therapy for Hormone Receptor-Positive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Letrozole; Placebo
Intervention description: Letrozole 2.5 mg taken orally once daily for 5 years; Placebo tablet taken orally once daily for 5 years
Intervention MeSH terms: Letrozole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 3966.0
Sex: Female
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer

Summary:

      RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using
      letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is
      not yet known whether letrozole is more effective than a placebo in treating patients with
      hormone receptor-positive breast cancer.

      PURPOSE: This randomized phase III trial is studying letrozole to see how well it works
      compared with a placebo in treating postmenopausal women who have received hormone therapy
      for hormone receptor-positive breast cancer.
    

Eligibility criteria:

        Eligibility Criteria

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 or 1 (0 = fully active, able to carry on all pre-disease performance without
             restriction; 1 = restricted in physically strenuous activity but ambulatory).

          -  Patients must be postmenopausal at the time of randomization. (Note: Premenopausal or
             perimenopausal women requiring therapy with luteinizing hormone-releasing hormone
             [LHRH] analogs to suppress ovarian function are not eligible.) For study purposes,
             postmenopausal is defined as: age 56 or older with no spontaneous menses for at least
             12 months prior to study entry, or age 55 or younger with no spontaneous menses for at
             least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy)
             AND with a documented estradiol level in the postmenopausal range according to local
             institutional/laboratory standards, or a prior documented bilateral oophorectomy.

          -  The patient must have remained disease-free from the time of initial breast cancer
             diagnosis until the time of randomization.

          -  The patient must have had histologically-confirmed invasive carcinoma of the breast by
             diagnostic core needle biopsy or by final pathologic evaluation of the surgical
             specimen.

          -  Patients who received neoadjuvant chemotherapy must have been clinical Stage I, II, or
             IIIA. For patients who received adjuvant chemotherapy, the primary tumor must have
             been T1-3 on pathologic evaluation and ipsilateral nodes must have been pN0, pN1
             (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b.

          -  The primary tumor must have been estrogen receptor (ER)-positive and/or progesterone
             receptor (PgR)-positive. (Patients who had a tumor that was considered to be
             borderline for hormone receptor positivity and who were treated with tamoxifen and/or
             an aromatases inhibitor (AI) are eligible for this study.)

          -  Patients must have undergone either a lumpectomy with axillary nodal staging followed
             by breast radiotherapy or a total mastectomy with axillary nodal staging. (Acceptable
             axillary nodal staging procedures include sentinel node biopsy alone, if sentinel
             nodes were negative on hematoxylin and eosin (H&E) staining.)

          -  The duration of the patient's hormonal therapy following breast cancer diagnosis must
             have been 57-63 months from the first dose regardless of the number of missed doses.
             Hormonal therapy must have consisted of an AI or a combination of up to 3 years of
             tamoxifen followed by an AI. Tamoxifen may not have been given during years 4 and 5 of
             the 5 years of adjuvant hormonal therapy. (Note: Patients must discontinue their
             adjuvant AI therapy at the time of randomization.)

          -  Optional Letrozole Registration Program for patients who have not yet completed 5
             years of hormonal therapy. (Note: As of September 5, 2008, the optional NSABP B-42
             Registration Program closed to patient enrollment. Accrual and data collection for the
             NSABP B-42 randomized treatment trial continues as planned.) In order to have a
             predominantly letrozole-treated population for B-42 study entry, patients who have had
             a minimum of 2 years of hormonal therapy and who are currently on tamoxifen (for up to
             3 years) or an AI may be offered letrozole at no cost until they complete 5 total
             years of initial adjuvant hormonal therapy.

          -  B-42 randomization must be within 6 months following completion of 5 years (57-63
             months) of initial adjuvant hormonal therapy.

          -  At the time of randomization, the patient must have had the following: history and
             physical exam within 3 months demonstrating no findings suggestive of recurrent breast
             cancer; bilateral mammogram within 1 year (unilateral if patient had a mastectomy);
             mammogram not required if patient had a prophylactic contralateral mastectomy; bone
             mineral density (BMD) testing within 1 year; and fasting lipid profile (total
             cholesterol, LDL-C, HDL-C, and triglycerides) with a total cholesterol value less than
             or equal to grade 1 (according to CTCAE v3.0), with or without cholesterol-lowering
             therapy.

               -  within 1 year if the patient has a history of hypercholesterolemia controlled
                  with cholesterol-lowering therapy and/or therapeutic lifestyle changes or if the
                  patient has a history of one or more of the following risk factors for future
                  cardiovascular events: diabetes, hypertension, obesity, tobacco use,
                  hypertriglyceridemia, documented coronary artery disease, or family history of
                  premature coronary heart disease.

               -  within 2 years for all other patients.

        Ineligibility Criteria

          -  Patients with one or more of the following conditions will be ineligible for this
             study:

          -  History of non-traumatic osteoporotic fracture of wrist, hip, or spine.

          -  Diagnosis of bilateral breast cancer including ductal carcinoma in situ
             (DCIS)[(synchronous or metachronous].

          -  Other malignancies unless the patient is considered to be disease-free for 5 or more
             years prior to randomization, and is deemed by their physician to be at low risk for
             recurrence. Patients with the following cancers are eligible if diagnosed and treated
             within the past 5 years: carcinoma in situ of the cervix, colon carcinoma in situ,
             melanoma in situ, and basal cell and squamous cell carcinoma of the skin.

          -  Sex hormonal therapy, e.g., estrogen- or progesterone-replacement therapy or oral
             contraceptives. These patients are eligible only if this therapy is discontinued prior
             to randomization.

          -  Therapy with any hormonal agent such as raloxifene for management of osteoporosis.
             Patients are eligible only if these medications are discontinued prior to study entry.

          -  Administration of any investigational agent within 30 days before study entry.