Prediction of Response to Neoadjuvant Chemotherapy in Women With Operable Breast Cancer

Inclusion Criteria

Inclusion Criteria

Female subjects who satisfy the following conditions will be considered for enrollment
into the study:

1. The subject must consent to be in the research study and must have signed an approved
consent form conforming to institutional guidelines prior to study entry.

2. The diagnosis of breast cancer can be made by FNA or biopsy (other than incisional or
excisional). The tumor specimen must demonstrate a diagnosis of invasive
adenocarcinoma.

3. The primary breast cancer must be operable and measurable "greater than or equal to"
2.0 cm by use of physical exam and/or ultrasound, MRI, CT scan, or mammogram.

4. T1c, T2, T3, or T4 patients clinically staged as M0 (non-inflammatory) are eligible.

5. Patients with a prior diagnosis and treatment for DCIS are eligible.

6. Patients with multi-focal breast cancer are eligible.

7. The tumor must be confined to either the breast or to the breast and ipsilateral
axilla.

8. The subject must be 18 years or older.

9. The interval between initial cytologic or histologic diagnosis of breast cancer and
registration must be no more than 10 weeks.

10. ECOG Performance Status of 0 or 1 (see Appendix A) is required.

11. The subject must receive standard of care chemotherapy regimens consisting of either
doxorubicin (A), cyclophosphamide (C), and a taxane (T) such as docetaxel,
paclitaxel, or nab-paclitaxel administered in any sequence and combination the
treating physician determines or docetaxel (T) plus cyclophosphamide (C).

Exclusion Criteria

Male subjects are not eligible for this study as the incidence of breast cancer in male
subjects is significantly lower than female subjects. Those subjects who are strongly
HER2-positive will be excluded as they will require treatment by biological agents for
which the ChemoResponse Assay has not yet been validated. Subjects with evidence of
distant metastatic disease are excluded as these subjects would not be good candidates for
neoadjuvant therapy. Women who have had an excisional or incisional biopsy prior to entry
would not have sufficient tumor sample to test or to be measured by physical exam for the
study. Women who have nonmalignant comorbid conditions and diseases that would preclude
them from being treated with doxorubicin (A), cyclophosphamide (C), and a taxane (T), and
from completing the study are also excluded. Women with psychiatric or addictive
disorders are excluded to protect those vulnerable subjects who may not be able to
adequately give informed consent.

Women with one or more of the following conditions will be ineligible for this study:

1. Tumor determined to be strongly HER2-positive by immunohistochemistry (3+) or by
fluorescent in situ hybridization (positive for gene amplification)

2. Definitive clinical or radiologic evidence of distant metastatic disease.

3. Excisional or incisional biopsy for this primary breast tumor.

4. Inflammatory breast cancer.

5. Synchronous contra-lateral breast cancer.

6. Multi-centric breast cancer.

7. Participation in the NSABP B-40 study.

8. Prior therapy for invasive breast cancer, including irradiation, chemo-, immuno-,
and/or hormonal therapy.

a. Note: the only exception is hormonal therapy, which may have been given anytime
after diagnosis and before study entry as long as the hormonal therapy is
discontinued at or before registration. After surgery, hormonal therapy may be
re-started, at the discretion of the treating physician.

9. Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other
selective estrogen receptor modulator (SERM), either for osteoporosis or breast
cancer prevention, or sex hormonal therapy such as birth control pills, ovarian
hormonal replacement therapy, etc. These patients are eligible IF these medications
are discontinued prior to registration.

10. Surgical axillary staging procedure prior to study entry.

a. Note: exceptions include FNA of an axillary node and pre-neoadjuvant sentinel
lymph node biopsy for patients with clinically negative axillary nodes.

11. Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would
preclude the woman from being treated with doxorubicin (A), cyclophosphamide (C), and
a taxane (T), and from completing the study.

12. Psychiatric or addictive disorders that would preclude obtaining informed consent.