Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)
Condition: Breast Adenocarcinoma; Hormone Receptor Positive; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIB Breast Cancer AJCC v7
MeSH terms: Breast Neoplasms
Intervention: Anastrozole; Exemestane; Laboratory Biomarker Analysis; Letrozole; Quality-of-Life Assessment; Radiation Therapy; Tamoxifen Citrate
Intervention description: Given PO; Given PO; Correlative studies; Given PO; Ancillary studies; Undergo radiation therapy or partial breast irradiation; 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: 10273.0
Sex: Female
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies the best individual therapy for women who have
      node-negative, estrogen-receptor positive breast cancer by using a special test (Oncotype
      DX), and whether hormone therapy alone or hormone therapy together with combination
      chemotherapy is better for women who have an Oncotype DX recurrence score of 11-25. Estrogen
      can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by
      blocking the use of estrogen by the tumor cells or 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. Giving hormone therapy together with more than one chemotherapy drug (combination
      chemotherapy) has been shown to reduce the chance of breast cancer recurrence, but the
      benefit of adding chemotherapy to hormone therapy for women with node-negative,
      estrogen-receptor positive breast cancer is small. New tests may provide information about
      which patients are more likely to benefit from chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with operable histologically confirmed adenocarcinoma of the female breast
             who have completed primary surgical treatment and meet the following criteria:

               -  ER and/or progesterone receptor (PR)-positive: Estrogen and/or progesterone
                  receptor positive disease (as defined by local pathology laboratory)

               -  Negative axillary nodes: As assessed by a sentinel lymph node biopsy, an axillary
                  dissection, or both, and as defined by the Sixth Edition of the American Joint
                  Committee on Cancer (AJCC) staging criteria

               -  Tumor size 1.1-5.0 cm (or 5 mm-1.0 cm plus unfavorable histological features):

                    -  Unfavorable features defined as intermediate or poor nuclear and/or
                       histologic grade, or lymphovascular invasion

                    -  NOTE: Definition of tumor size: The tumor size used for determination of
                       eligibility is the pathologic tumor size, which is usually determined by the
                       size of the tumor as measured by inspection of the gross specimen; if the
                       tumor size is measured microscopically and the tumor includes ductal
                       carcinoma in-situ, the measurement should include only the invasive
                       component of the tumor

               -  The tumor must be human epidermal growth factor receptor 2 (Her2)/neu negative by
                  either fluorescent in-situ hybridization (FISH) or immunohistochemistry (e.g. 0
                  or 1+ by DAKO Herceptest)

          -  The patient and physician must be agreeable to initiate standard chemotherapy and
             hormonal therapy as adjuvant therapy

          -  A tissue specimen from the primary breast cancer has been located and is ready to be
             shipped to the appropriate laboratory after consent is obtained and within 3 days
             following pre-registration; NOTE: For determination of the Oncotype Recurrence Score,
             tissue must be shipped to Genomic Health; if the Oncotype DX Recurrence Score was
             previously performed by Genomic Health (prior to pre-registration), tissue must be
             submitted to the Eastern Cooperative Oncology Group (ECOG)-American College of
             Radiology Imaging Network (ACRIN) Central Biorepository and Pathology Facility upon
             randomization

          -  Leukocyte count >= 3500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Serum creatinine =< 1.5 mg/dL

          -  Serum aspartate transaminase (AST) that is =< 3-fold the upper institutional limits of
             normal

          -  Patients must be disease-free of prior invasive malignancies for >= 5 years with the
             exception of curatively-treated basal cell or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix; patients with a previous ipsilateral or contralateral
             invasive breast cancer, or with bilateral synchronous cancers, are not eligible;
             patients with previous ipsilateral or contralateral ductal in situ carcinoma (DCIS)
             are not eligible

          -  Prior treatment

               -  Mandatory prior surgery criteria:

                    -  Patient must pre-register within 84 days from the final surgical procedure
                       required to adequately treat the primary tumor (please note that if margins
                       are not clear and a resection has to be conducted after pre-registration but
                       before randomization, the patient will be deemed to be within the 84 day
                       window allowed by protocol and therefore eligible)

                    -  All tumors should be removed by either a mastectomy or local excision plus
                       an acceptable axillary procedure (i.e., sentinel lymph node biopsy, axillary
                       dissection, or both); there must be adequate (at least 1 mm if margin width
                       specified) tumor-free margins of resection (for invasive and ductal
                       carcinoma in-situ) in order for the patients to be eligible; patients with
                       lobular carcinoma in-situ involving the resection margins are eligible

               -  Criteria re: other prior treatments:

                    -  No prior chemotherapy for this malignancy

                    -  No prior radiation therapy for this malignancy; this includes no prior
                       MammoSite Brachytherapy radiation therapy (RT)

                    -  Hormonal therapy: Patients who develop breast cancer while receiving a
                       selective estrogen-receptor modulator (SERM; e.g., tamoxifen, toremifene,
                       raloxifene) or an aromatase inhibitor (e.g., anastrazole, letrozole,
                       exemestane) for breast cancer prevention or a SERM for other indications
                       (e.g., raloxifene for osteoporosis) are not eligible; however, patients may
                       have received up to 8 weeks of a SERM or aromatase inhibitor for this
                       malignancy and still be eligible for study entry

          -  Patients must have an anticipated life expectancy of at least 10 years

          -  Patients with the following medical conditions should not be enrolled on the study:

               -  Chronic obstructive pulmonary disease requiring treatment

               -  Chronic liver disease (e.g., cirrhosis, chronic active hepatitis)

               -  Previous history of a cerebrovascular accident

               -  History of congestive heart failure or other cardiac disease that would represent
                  a contraindication to the use of an anthracycline (e.g., doxorubicin or
                  epirubicin)

               -  Chronic psychiatric condition or other condition that would impair compliance
                  with the treatment regimen

          -  Women must not be pregnant or breast-feeding; all females of childbearing potential
             must have a blood test or urine study within 2 weeks prior to pre-registration to rule
             out pregnancy

               -  Women of childbearing potential must be strongly advised to utilize an accepted
                  and effective form of non-hormonal contraception (e.g. intrauterine device,
                  condoms, diaphragm, abstinence)

          -  Patients must not have previously had the Oncotype DX Assay performed, with the
             exception of patients who have had the assay performed and have a recurrence score of
             11-25