Program for the Assessment of Clinical Trial Test (PACCT-1):Trial Assigning Individualized Options for Treatment- the TAILORx Trial

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.

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