Aromatase Inhibitor and Durvalumab in Postmenopausal Breast Cancer

Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Postmenopausal, defined as meeting criteria per protocol.
* Clinical T2-T4c, any N, MO by American Joint Committee on Cancer staging, 8th edition, with the goal being definitive surgery after completion of neoadjuvant therapy. Tumor is palpable and its size can be measured bidimensionally by tape, ruler or caliper technique. Largest tumor diameter over 2.0 cm.
* Pathologic confirmation of invasive breast cancer that is estrogen receptor (ER) positive as defined in the protocol.
* Invasive breast cancer is Human Epidermal Growth Factor Receptor 2 (HER2) negative as defined in the protocol protocol.
* Documentation of mammogram and ultrasound \[including ductal carcinoma in situ (DCIS) and invasive cancer\] of the diseased breast performed within 60 days prior to enrollment. Mammograms for the unaffected contralateral breast is required within 12 months prior to enrollment.
* Adequate organ and marrow function, as defined in the protocol.
* Participants must be willing to undergo a research biopsy at baseline and after one cycle of treatment and to provide tissue obtained at surgery for biomarker and correlative studies.
* Participants must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
* If taking herbal or natural remedies that may have immune modulatory effects, participants must be willing to discontinue use prior to first dose of durvalumab.
* Body weight over 30 kg.

Exclusion Criteria:

* Participation in another clinical study with an investigational product during the last 4 weeks.
* Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow up period of an interventional study.
* Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema).
* An excisional biopsy of this breast cancer. Hormone replacement therapy of any type, megestrol acetate, or raloxifene within one week prior to registration.
* Surgical axillary staging procedure prior to study entry. Note: Fine needle aspiration (FNA) or core needle biopsy of axillary node is permitted.
* Treatment for this cancer including surgery, radiation therapy, chemotherapy, biotherapy, hormonal therapy or investigational agent prior to study entry.
* Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
* History of another primary malignancy except for malignancy treated with curative intent and with no known active disease ≥ 5 years or adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease or adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ.
* History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral ductal carcinoma in situ (DCIS) treated with radiotherapy or endocrine therapy or contralateral invasive breast cancer at any time.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection); systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid; or steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). Some exceptions apply.
* History of primary immunodeficiency.
* History of allogeneic organ transplant.
* Known allergy or history of hypersensitivity to durvalumab, or any excipient.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, , or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
* Known active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved hepatitis B infection are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for hepatitis C RNA. Note: This is applied only to patients with known infection. Screening tests for TB, hepatitis B and C, or HIV are not required.
* Receipt of live attenuated vaccination within 30 days prior to receiving durvalumab. Note: Patients, if enrolled, should not receive live vaccine while receiving durvalumab and up to 30 days after the last dose of durvalumab.
* Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
* Participants with uncontrolled seizures.
* Participants with multi-centric breast cancer (defined as more than one lesion is invasive breast cancer in the same breast separated by ≥ 2 cm of normal breast tissue).
* Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product.