Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer
Condition: Breast Ductal Carcinoma In Situ; Invasive Breast Carcinoma; Multicentric Breast Carcinoma; Multifocal Breast Carcinoma; Synchronous Bilateral Breast Carcinoma
MeSH terms: Carcinoma; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Ductal, Breast
Intervention: Anastrozole; Exemestane; Laboratory Biomarker Analysis; Letrozole; Quality-of-Life Assessment; Systemic Chemotherapy; Tamoxifen Citrate
Intervention description: Given PO; Given PO; Correlative studies; Given PO; Ancillary studies (closed as of 12/1/12); Given IV; Given PO
Intervention MeSH terms: Tamoxifen; Letrozole; Anastrozole; Exemestane
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5018.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III clinical trial studies how well tamoxifen citrate, anastrozole,
      letrozole, or exemestane with or without chemotherapy work in treating patients with breast
      cancer that has spread from where it began in the breast to surrounding normal tissue
      (invasive). Estrogen can cause the growth of breast cancer cells. Hormone therapy, using
      tamoxifen citrate, may fight breast cancer by blocking the use of estrogen by the tumor
      cells. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, may fight breast
      cancer by lowering the amount of estrogen the body makes. Drugs used in chemotherapy work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. It is not yet known whether giving
      tamoxifen citrate, anastrozole, letrozole, or exemestane is more effective with combination
      chemotherapy in treating patients with breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes)
             invasive breast carcinoma with positive estrogen and/or progesterone receptor status,
             and negative HER-2 status; estrogen and progesterone receptor positivity must be
             assessed according to American Society of Clinical Oncology (ASCO)/College of American
             Pathologists (CAP) guidelines as either estrogen receptor (ER) or progesterone
             receptor (PR) >= 1% positive nuclear staining; HER-2 test result negativity must be
             assessed as per ASCO/CAP 2013 guidelines using immunohistochemistry (IHC), in situ
             hybridization (ISH) or both; HER-2 is negative if a single test (or all tests)
             performed in a tumor specimen show: a) IHC negative (0 or 1+) or b) ISH negative using
             single probe or dual probe (average HER-2 copy number < 4.0 signals per cell by single
             probe or HER-2/CEP ration < 2.0 with an average copy number < 4.0 signals per cell by
             dual probe); if HER-2 IHC is 2+, evaluation for gene amplification (ISH) must be
             performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+; HER-2
             equivocal is not eligible

          -  Patients with multifocal, multicentric and synchronous bilateral breast cancers are
             allowed

               -  Multifocal disease is defined as more than one invasive cancer < 2 cm from the
                  largest lesion within the same breast quadrant; (NOTE: the Oncotype DX testing
                  must be completed on the largest lesion)

               -  Multicentric disease is defined as more than one invasive cancer >= 2 cm from the
                  largest lesion within the same breast quadrant or more than one lesion in
                  different quadrants (NOTE: Oncotype DX testing should be completed on all tumors
                  and the determination for eligibility should be made on the highest recurrence
                  score)

               -  Synchronous bilateral disease is defined as invasive breast cancer with positive
                  lymph nodes (axillary or intramammary) in at least one breast, diagnosed within
                  30 days of each other; (NOTE: the Oncotype DX testing should be completed on both
                  tumors and the tumor with the highest recurrence score should be used)

          -  Patients will have undergone axillary staging by sentinel node biopsy or axillary
             lymph nodes dissection (ALND); patients must have at least one, but no more than three
             known positive lymph nodes (pN1a, pN1b or pN1c); patients with micrometastases as the
             only nodal involvement (pN1mi) are not eligible; patients with positive sentinel node
             are not required to undergo full axillary lymph node dissection; this is at the
             discretion of the treating physician; axillary node evaluation is to be performed per
             the standard of care at each institution

          -  Patients with a prior diagnosis of contralateral ductal carcinoma in situ (DCIS) are
             eligible if they underwent a mastectomy or lumpectomy with whole breast radiation;
             prior partial breast irradiation, including brachytherapy, is not allowed; patients
             with a prior diagnosis of ipsilateral DCIS or invasive breast cancer who received
             radiation to that breast are not eligible

          -  Patients must have had either breast-conserving surgery with planned radiation therapy
             or total mastectomy (with or without planned postmastectomy radiation); patients must
             have clear margins from both invasive breast cancer and DCIS (as per local
             institutional guidelines); lobular carcinoma in situ (LCIS) at the margins is allowed

          -  Registration of patients who have not yet undergone Oncotype DX screening must occur
             no later than 56 days after definitive surgery; (for all patients, Step 2 Registration
             must occur within 84 days after definitive surgery); if the Oncotype DX Breast Cancer
             Assay has not been performed, patients must be willing to submit tissue samples for
             testing to determine the Recurrence Score value; a representative block or unstained
             sections from the representative block are sent directly to Genomic Health for
             Oncotype DX Breast Cancer Assay which will be performed according to the standard
             commercial process

               -  If the Oncotype DX Recurrence Score is already known and is 25 or less, the
                  patient must be registered to Step 2 immediately following Step 1 registration;
                  if the Oncotype DX Recurrence Score is already known and is greater than 25, the
                  patient is ineligible

          -  Patients must be females >= 18 years of age. As the Oncotype DX recurrence score has
             not been validated in men with breast cancer, men are not eligible for this study

          -  Patients must have a complete history and physical examination within 28 days prior to
             registration

          -  Patients must have a performance status of 0-2 by Zubrod criteria

          -  Patients must be able to receive taxane and/or anthracycline based chemotherapy

          -  Patients must not have received an aromatase inhibitor (AI) or a selective estrogen
             receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to
             registration

          -  No other prior malignancy is allowed except for adequately treated basal cell (or
             squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the
             patient has been disease-free for 5 years

          -  The Quality of Life and Economic Substudy is permanently closed to accrual effective
             12/1/12; patients who consented to QOL prior to 12/1/12 should continue to complete
             QOL forms per their expectation report; patients who are able to complete a
             questionnaire in English must be offered the opportunity to participate in the Quality
             of Life and Economic Substudy; (The Quality of Life and Economic Substudy is available
             to U.S. INSTITUTIONS ONLY); patients who are not able to complete a questionnaire in
             English are registered to S1007 without participating in the Quality of Life and
             Economic Substudy

               -  Patients who consent to participate in the Quality of Life and Economic Substudy
                  and who do not yet know the results of their Oncotype DX screening must agree to
                  complete the S1007 Health-Related Quality of Life Questionnaire: Enrollment
                  between 14 days prior to and 7 days after Step 1 Registration

               -  Patients who consent to participate in the Quality of Life and Economic Substudy
                  and who do already know their Oncotype DX Recurrence Score (and it is 25 or less)
                  will proceed to Step 2 Registration without completing the S1007 Health-Related
                  Quality of Life Questionnaire Enrollment Form (but will complete the S1007
                  Health-Related Quality of Life Questionnaire: Randomized Study Form)

          -  Patients or their legally authorized representative must be informed of the
             investigational nature of this study and must sign and give written informed consent
             in accordance with institutional and federal guidelines; for Step 1 registration of
             patients who have not yet submitted specimens for the Oncotype DX Breast Cancer Assay,
             the appropriate consent form is the Step 1 Consent Form; for both Step 1 and Step 2
             registration of patients whose Recurrence Score is already known and is 25 or less,
             the appropriate consent form is the Step 2 Consent Form

          -  As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered in the system

          -  STEP 2 REGISTRATION

          -  Recurrence score (RS) by Oncotype DX must be =< 25

          -  Step 2 Registration must take place within 84 days after definitive surgery; patients
             must not have begun chemotherapy or endocrine therapy for their breast cancer prior to
             randomization

          -  Patients randomized to either arm may also co-enroll in phase III trials that compare
             local therapies, or compare systemic therapies (such as chemotherapy, if randomized to
             Arm I of S1007)

          -  The Quality of Life and Economic Substudy is permanently closed to accrual effective
             12/1/12; patients at U.S. INSTITUTIONS who consent to participate in the Quality of
             Life and Economic Substudy must agree to complete the S1007 Health-Related Quality of
             Life Questionnaire: Randomized Study Form after Recurrence Score results and
             randomized treatment status are known but before treatment has been initiated

          -  Patients or their legally authorized representative must be informed of the
             investigational nature of this study and must sign and give written informed consent
             in accordance with institutional and federal guidelines; for all patients the
             appropriate consent form for this registration is the Step 2 Consent

          -  STEP 3 REGISTRATION CBALR TM Substudy

          -  Patients must be disease-free, with no prior invasive recurrence at time of
             registration to Step 3

          -  Patients must be registered to Step 3 no more than 8 years after randomization (Step 2
             Registration) and must agree to have samples drawn within 28 days after registration
             to Step 3

          -  Patients must agree to have blood samples collected at up to 3 timepoints: 1) within
             28 days after registration to Step 3, 2) 2-3 years after time of registration to Step
             3, and 3) At time of invasive recurrence (if applicable). Patients must also agree to
             have tissue submitted at time of invasive recurrence (if applicable) from the invasive
             recurrence biopsy (where tissue is available)

        Exclusion Criteria:

          -  Patients must not have inflammatory breast cancer and must not have metastatic disease

          -  Patients must not have begun chemotherapy or endocrine therapy for their breast cancer
             prior to registration

          -  Patients must not require chronic treatment with systemic steroids (inhaled steroids
             are allowed) or other immunosuppressive agents

          -  Patients must not be pregnant or nursing; women of reproductive potential must have
             agreed to use an effective contraceptive method; a woman is considered to be of
             "reproductive potential" if she has had menses at any time in the preceding 12
             consecutive months; in addition to routine contraceptive methods, "effective
             contraception" also includes heterosexual celibacy and surgery intended to prevent
             pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
             bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
             previously celibate patient chooses to become heterosexually active during the time
             period for use of contraceptive measures outlined in the protocol, he/she is
             responsible for beginning contraceptive measures