PD-1 +/- IL-4 Inhibition in ER+ Breast Cancer

Inclusion Criteria:

1. Female patients with newly diagnosed histologically confirmed primary invasive breast cancer currently not undergoing any treatment while awaiting surgery.
2. Invasive ductal or lobular carcinoma, invasive carcinoma Not Otherwise Specified (NOS)
3. ER+ breast cancer (1-10%\*) of any size. ER positive tumor defined ≥1% positively staining cells by immunohistochemistry, according to the current American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines.
4. The participant is eligible for surgery within the next 4-6 weeks.
5. HER2/neu must be negative by immunohistochemistry (IHC) defined as IHC 0 or 1+ or fluorescence in situ hybridization (FISH) or other ISH methods with a ratio of \< 2 according to current ASCO (American Society of Clinical Oncology)/CAP guidelines.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
7. Age ≥18 years.
8. The participant (or legally acceptable representative if applicable) is able to provide written informed consent for the study.

Exclusion Criteria:

1. Known or suspected breast cancer metastasized to distant organ (lung, liver, bone, brain, abdomen)
2. Prior therapy with any chemotherapy or endocrine for breast cancer or other cancers within last 3 months
3. Pre-dominant histology other than invasive ductal or lobular carcinoma or invasive carcinoma NOS.
4. Patients with an active infection or an absolute neutrophil count \< 1.5 x 10\^9/L.

6\. Patients with pre-existing renal impairment, Creatinine clearance calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of less than 50 mL/min/1.73m2.

7\. Known or current history of pneumonitis or interstitial lung disease (e.g., idiopathic pulmonary fibrosis) or pneumonia in past month 8. Has known HIV or active Hepatitis B (e.g., HBV detected by PCR, presence of HBsAg surface antigen and/or Anti-HBc core antigen) or active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). Presence of Anti-HBs alone suggesting immunity to Hepatis B is eligible.

9\. Any serious known immediate or delayed hypersensitivity reaction(s) to dupilumab and or cemiplimab.

10\. Concurrent medical condition requiring the use of systemic immunosuppressive medications, or systemic corticosteroids at doses of greater than 10 mg Prednisone-equivalent. Topical steroids and other localized corticosteroids are permitted. Patients who have received acute, low-dose, systemic immunosuppressant medications equivalent to ≤ 10mg of prednisone within the 7 days prior to study entry (small dose of dexamethasone for nausea, short course for upper respiratory tract infection etc.) may be enrolled in the study. Use of steroids as prophylactic treatment for subjects with contrast allergies to diagnostic imaging contrast dyes will be permitted.

11\. Concurrent use or planned use of any forbidden medications within 4 weeks prior to study drug administration, which include chemotherapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control cancers), other biologic therapy, investigational therapy, or hormonal therapy.

12\. Confirmed pregnancy (by pregnancy test) if patient is of childbearing age or breast feeding.

13\. Subjects with signs/symptoms suggestive of COVID-19 and confirmed positive COVID-19 test.

14\. Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (see Appendix) 15. Any underlying medical condition that, in the Principal Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events, or renders the patient ineligible to be on study.