PENN-Surveillance Markers of Utility for Recurrence After (Neo)Adjuvant Therapy for Breast Cancer

Inclusion Criteria:

- Histologically-confirmed primary invasive breast cancer within 5 years of study entry

- Pathologically-confirmed invasive breast cancer in axillary lymph nodes or tumor with
triple negative subtype: negative estrogen receptor (ER), progesterone receptor (PR)
and Her2-overexpression by ASCO-CAP guidelines or tumor with a Breast Cancer
Recurrence Score of ≥ 18 per the Genomic Health Oncotype DX breast cancer test, or
residual disease after neoadjuvant chemotherapy.

- Completed all primary therapy (surgery, (neo)adjuvant chemotherapy and adjuvant
radiation) for the index malignancy with

- No evidence of local or distant recurrent disease by physical examination, blood
tests (CBC, LFTs, Alk Phos), or symptom-directed imaging, per NCCN guidelines.

- Normal coagulation studies: PT and PTT ≤ 1.5 x upper limit of normal per
institutional laboratory range. For patients on therapeutic anti-coagulants,
medication must be clinically held peri-procedure per standard clinical management.

- Willing to undergo bone marrow aspiration and blood specimen collection per protocol
specifications

- Age 18 or over and able to give informed consent

- Patient has no evidence of meeting exclusion criteria for companion clinical trials,
which are listed below.

Exclusion Criteria:

- Concurrent enrollment on another investigational therapy

- Patients receiving chronic, high dose systemic treatment with corticosteroids defined
as: chronic use of cortisone >50mg; hydrocortisone >40mg, prednisone >10mg,
methylprednisone >8mg or dexamethasone >1.5mg; or another immunosuppressive agent.
Topical or inhaled corticosteroids are allowed.

- Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study such as:

- Symptomatic congestive heart failure of New York heart Association Class III or IV

- Unstable angina pectoris, myocardial infarction within 6 months of start of study
drug, serious uncontrolled cardiac arrhythmia or any other clinically significant
cardiac disease

- Severely impaired lung function with a previously documented spirometry and DLCO that
is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest
on room air

- Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

- Active (acute or chronic) or uncontrolled severe infections

- Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
hepatitis

- A known history of HIV seropositivity as reported by the patient

- Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small
bowel resection)

- Patients with an active, bleeding diathesis

- Female patients who are pregnant or breast feeding. Women of childbearing potential
must have a negative urine or serum pregnancy test.

- Patients who have received prior treatment with an mTOR inhibitor (sirolimus,
temsirolimus, everolimus).

- Patients with a known hypersensitivity to Everolimus or other rapamycins (sirolimus,
temsirolimus) or to its excipients

- A detailed assessment of Hepatitis B/C medical history and risk factors must be done
at screening for all patients. HBV DNA and HCV RNA PCR testing are required at
screening for all patients with a positive medical history based on risk factors
and/or confirmation of prior HBV/HCV infection.