Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score
Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score
The purpose of this study is to see whether adding everolimus to hormone treatment before
 breast surgery will increase the chances of shrinking the breast cancer in those patients
 with hormone-responsive breast cancer and a lower Oncotype DX® Recurrence Score ( 25 or
 less), compared to prior experience with hormone therapy alone. Everolimus is a drug
 currently approved for use by the United States Food and Drug administration (FDA) for the
 treatment of patients with advanced or metastatic kidney or breast cancer. Everolimus is
 considered investigational for non-metastatic breast cancer patients.
This is a single arm open-labeled neoadjuvant phase II clinical trial evaluating everolimus
 in combination with an aromatase inhibitor in postmenopausal women with hormone receptor
 positive/HER2 negative breast cancers with low and intermediate risk (< 25) Recurrence Scores
 by Oncotype Dx.
Inclusion Criteria:

 -  Patients must have a histologically confirmed diagnosis of hormone receptor positive,
 HER2 negative invasive breast carcinoma.

 -  Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP
 2010 guidelines as either ER or PR ≥ 1% positive nuclear staining by
 immunohistochemistry. Estrogen and/or progesterone receptor results by Oncotype Dx
 will not be accepted.

 -  Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by
 IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and
 must not be positive (must be a ratio of < 2), but otherwise FISH/CISH is not required
 if IHC is 0 or 1+ by institutional standards.

 -  Patients must not have had prior ipsilateral breast-conserving surgery or total
 mastectomy and be eligible for neoadjuvant treatment.

 -  Clinical Stage II-IIIC (T2-4 N0-3 M0) by mammogram, ultrasound or MRI

 -  Baseline Oncotpye Dx recurrence score < 25.

 -  Staging studies with a CT scan of the chest and abdomen and bone scan, or a PET/CT is
 required for clinical stage III, and are considered optional for stage II breast
 cancers.

 -  Patients with multifocal, multicentric and synchronous bilateral breast cancers are
 allowed:

 -  Multifocal disease is defined as more than one invasive cancer < 2 cm from the
 largest lesion within the same breast quadrant.

 -  Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the
 largest lesion within the same breast quadrant or more than one lesion in
 different quadrants.

 -  Synchronous bilateral disease is defined as invasive breast cancer in both
 breasts, diagnosed within 30 days of each other.

 -  In patients with multicentric or bilateral invasive breast cancers, all sampled
 lesions must be hormone receptor-positive and HER2-negative. Any lesion measuring
 > 1 cm must have an Oncotype Dx and the score must be < 25. Lesions less than 1
 cm in size are not required to have an Oncotype Dx. One lesion (typically the
 largest) should be designated as the target lesion for which clinical and
 radiographic response to the neoadjuvant therapy will be judged.

 -  Patients with a hormone receptor-positive, HER2-negative invasive cancer that
 meets study criteria may have ductal carcinoma in situ in another quadrant of the
 same breast or in the contralateral breast even if the DCIS is hormone
 receptor-negative.

 -  Patients must have adequate bone marrow function, as defined by peripheral granulocyte
 count of ≥ 1,500/mL, hemoglobin ≥ 9 g/dL and a platelet count ≥ 100,000/ mL within 28
 days prior to registration.

 -  Patients must have adequate hepatic function obtained within 28 days prior to
 registration and documented by all of the following:

 -  Bilirubin ≤ 1.5 mg/dL (or ≤ 3.0 mg/dL if due to Gilbert's Syndrome)

 -  ALT and AST ≤ 1.5 x Institutional Upper Limit of Normal (IULN)

 -  Alkaline phosphatase ≤ 1.5 x IULN

 -  Patients must have adequate renal function with serum creatinine level ≤ IULN within
 28 days prior to registration.

 -  Patients must have a fasting cholesterol ≤ 300 mg/dl OR ≤7.75 mmol/L and triglycerides
 ≤ 2.5 x IULN obtained within 28 days prior to registration. Patients may be on lipid
 lowering agents to reach these values.

 -  Patients must have a ECOG performance status of 0-2.

 -  Patients must be able to take oral medications.

 -  Postmenopausal women (women are considered post-menopausal and not of child-bearing
 potential if they are > 18 years of age and have had 12 months of natural
 (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate,
 history of vasomotor symptoms or biochemically postmenopausal by estradiol and FSH
 levels) prior to enrollment, or have had surgical bilateral oophorectomy (with or
 without hysterectomy) prior to registration. Medical ovarian suppression with LHRH
 agonists to render a patient postmenopausal will not be acceptable.

 16. Patients or their legally authorized representative must be informed of the
 investigational nature of this study and must sign and give written informed consent
 prior to any screening procedures in accordance with institutional and federal
 guidelines.

 Exclusion Criteria:

 -  Patients must not have inflammatory breast cancer (T4d) and must not have metastatic
 breast cancer (Stage IV disease).

 -  Patients must not have prior exposure to mTOR inhibitors (e.g. rapamycin, everolimus,
 sirolimus, temsirolimus, deforolimus).

 -  Patients must not have prior treatment with any investigational drug within the
 preceding 28 days and must not be planning to receive any other investigational drug
 for the duration of the study.

 -  Patient may not have any impairment of gastrointestinal function or gastrointestinal
 disease that may significantly alter the absorption of the drug (e.g. ulcerative
 disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small
 bowel resection).

 -  Uncontrolled diabetes mellitus as defined by HbA1c >8% within 28 days prior to
 registration despite adequate therapy.

 -  Patients who have any severe and/or uncontrolled cardiac disease within ≤ 6 months
 prior to start of everolimus, including: unstable angina pectoris, Symptomatic
 congestive heart failure of New York heart Association Class III or IV, myocardial
 infarction, serious uncontrolled cardiac arrhythmia, or any other clinically
 significant cardiac disease

 -  Patients must not have an organ allograft or other history of immune compromise.

 -  Patients must not be receiving chronic, systemic treatment with corticosteroids or
 other immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

 -  Patients must not have a known history of HIV seropositivity

 -  Patients must not have a known diagnosis of hepatitis B or C. Patients with the
 following risk factors must have hepatitis screening pre-treatment:

 -  Blood transfusions prior to 1990

 -  Current or prior IV drug users

 -  Current or prior dialysis

 -  Household contact with a hepatitis B or C patient

 -  Current or prior high-risk sexual activity

 -  History of jaundice.

 -  Patients must not have any known uncontrolled underlying pulmonary disease or severely
 impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation
 88% or less at rest on room air),

 -  Active (acute or chronic) or uncontrolled severe infection.

 -  Patients who have received live attenuated vaccines within 1 week of start of
 Everolimus, or have plans to receive such vaccination while on protocol treatment.
 Patient should also avoid close contact with others who have received live attenuated
 vaccines. Examples of live attenuated vaccines include intranasal influenza, measles,
 mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines;

 -  Patients who are currently part of or have participated in any clinical investigation
 with an investigational drug within 1 month prior to dosing;

 -  Patients must not have taken within 14 days prior to registration , be taking, nor
 plan to take while on protocol treatment, strong CYP3A4 inhibitors, and/or CYP3A4
 inducers.

 -  Patients with active bleeding diathesis.