- Inclusion Criteria:

A patient will be considered for enrollment in this study if all of the following criteria
are met:

1. Female patients 18 years of age.

2. Have either:

1. locally advanced TNBC defined as invasive ductal cancer; ER- tumors with <10% of
tumor nuclei immunoreactive; PR- tumors with <10% of tumor nuclei
immunoreactive; T3 or T4 disease, regardless of nodal status (T2 disease is
eligible if there are positive lymph nodes present by physical exam or imaging
evaluation or histological evaluation, OR

2. High-risk ER+ breast cancer defined as grade 3 invasive ductal or mixed
ductal/lobular cancers, or grade 2 with Ki67 20%; node positive as evidenced by
physical exam or imaging evaluation or histological evaluation.
3. HER2- negative breast cancer. If HER2-, it is defined as follows:

1. FISH-negative (FISH ratio <2.0), or

2. IHC 0-1+, or

3. IHC 2+ AND FISH-negative (FISH ratio<2.0)

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 5. Adequate
hematologic function, defined by:

1. Absolute neutrophil count (ANC) >1500/mm3

2. Platelet count 100,000/mm3

3. Hemoglobin >9 g/dL (in the absence of red blood cell transfusion) 6. Adequate liver
function, defined by:

a. AST and ALT 2.5 x the upper limit of normal (ULN) b. Total bilirubin 1.5 x ULN 7.
Adequate renal function, defined by:

a. Serum creatinine 1.5 x ULN or calculated creatinine clearance of 60 ml/min 8.
Patients with previous history of invasive cancers (including breast cancer) are eligible
if definitive treatment was completed more than 5 years prior to initiating current study
treatment, and there is no evidence of recurrent disease. 9. Eligible for treatment with
paclitaxel, doxorubicin, cyclophosphamide and carboplatine. 10.Patient must be accessible
for treatment and follow-up. 11.Patients must be willing to undergo research biopsies to
obtain breast cancer tissue for whole exome sequencing and evaluation of tumor immune
microenvironment. 12.All patients must be able to understand the investigational nature of
the study and give written informed consent prior to study entry.

- Exclusion Criteria:

A patient will be ineligible for inclusion in this study any of the following criteria are
met:

1. Evidence of metastatic disease on bone scan and CT scan of chest/abdomen (or PET CT
scan). Patients with intrathoracic metastatic adenopathy are eligible.

2. Active infection or unexplained fever >38.5C during screening.

3. Active infections including viral hepatitis and HIV.

4. Active asthma or other condition requiring steroid therapy.

5. Autoimmune disease including lupus erythematosus or rheumatoid arthritis. Topical or
inhaled corticosteroids are allowed.

6. Patients who are currently receiving or who have received previous systemic therapy
for breast cancer (eg, chemotherapy, antibody therapy, targeted agents).The use of an
LHRH agonist during chemotherapy in premenopausal women who wish to preserve ovarian
function is allowed, but is not required.

7. Women who are pregnant or lactating. All patients with reproductive potential must
agree to use effective contraception from time of study entry until at least 3 months
after the last administration of study drug.

8. Have a NYHA Class III or IV CHF or LVEF <55%. Patients with significant cardiac
disease history within 1 year or ventricular arrhythmias requiring medication are
also excluded.

9. Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation such as:

1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of
the normal predicted value and/or O2 saturation that is 88% or less at rest on
room air

2. uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

3. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class
C).

10. History of any other disease, physical examination finding, or clinical laboratory
finding giving reasonable suspicion of a disease or condition that contraindicates
use of an investigational drug, or that might affect interpretation of the results of
this study, or render the patient at high risk for treatment complications.

11. Any other investigational or anti-cancer treatments while participating in this
study.

12. Any other cancer

Minimum Eligible Age: 18 Years

Maximum Eligible Age: 80 Years

Eligible Gender: Female