HER2 and HER3-Directed Dendritic Cell Vaccine for the Treatment of Early Stage Triple Negative or Hormone Receptor Low Breast Cancer, The DecipHER Trial

Inclusion Criteria

• A diagnosis of HER2-negative breast cancer * Note: HER2- breast is defined by tumor tissue absence of HER2 overexpression and or tumor HER2 amplification. The lack of HER2 overexpression by immunohistochemistry (IHC) is defined as 0 or 1+, whereas overexpression is defined as 3+. In the event of equivocal IHC, 2+, the tumor must be gene-nonamplified by fluorescence in situ hybridization (FISH)/dual in situ hybridization (DISH) performed upon the primary tumor (ratio < 2 and HER2 copy number < 4 define HER2- disease) * Note: HER2 testing with alternative in situ hybridization chromosome-7 probe may be performed if standard IHC and FISH show equivocal results, in accordance with standard of care
• Diagnosis of HR negative or HR low positive tumor * Note: Estrogen receptor (ER) and progesterone receptor (PR) expression negativity is defined as less than 1% of tumor cells nuclei positive by immunohistochemistry in the sample on testing. HR low positive is defined as: estrogen receptor (ER) and progesterone receptor (PR) expression positivity is defined equal to or less than 20% of tumor cells nuclei positive by immunohistochemistry in the sample on testing
• Clinical stage T1c, nodal stage N1-N2 or stage T2-4, nodal stage N0-N2 breast cancer. * Note: as defined by the American Join Committee on Cancer (AJCC) TNM Stating System for Breast Cancer * Note: patients must have breast tumor able to be visualized on ultrasound and amenable to direct injection * Note: patients with bilateral synchronous breast cancer are allowed * Note: patients with recurrent tumors are allowed as long as they had not received prior treatment with paclitaxel/carboplatin (TC) followed doxorubicin hydrochloride/cyclophosphamide (AC) in the past
• Participant must be medically and surgically appropriate to undergo neoadjuvant chemotherapy regimen followed by standard of care local therapy as determined by their treating physician
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count (ANC) >= 1500/uL (within 14 days of registration)
• Platelets >= 75000/uL (within 14 days of registration)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be < 3.0 mg/dL (within 14 days of registration)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 14 days of registration)
• Creatinine =< 1.5 x institutional ULN (within 14 days of registration)
• Left ventricular ejection fraction above institutional lower limit of normal (by echocardiogram or multigated acquisition [MUGA] scan)
• Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. Effective methods of contraception must be used throughout the study and for 5 months following the last dose. To show that women do not have childbearing potential, postmenopausal women must be amenorrheic for at least 12 months naturally (and not because of/following chemotherapy) or patients must be surgically sterile
• Ability to understand and the willingness to sign a written informed consent agreement prior to study registration

Exclusion Criteria

• Patients who received prior anthracycline-based chemotherapy for the treatment of any cancer
• Patients with inflammatory breast cancer
• Patients must not be receiving any other investigational agents or active antineoplastic therapies
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune-suppressive treatment, including chronic prolonged systemic corticosteroid use (defined as corticosteroid use lasting one month or more)
• Female patients who are pregnant or nursing
• No other prior malignancy is allowed, except for the following: * adequately treated basal-cell or squamous-cell skin cancer, * in situ cervical cancer, * or any other cancer from which the patient has been disease free for at least 3 years
• History of testing positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
• History of positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection
• Patients who have received a live attenuated vaccine =< 30 days prior to registration
• Unable to comply with the treatment schedule and study procedures for any reason
• Previously treated with breast cancer-directed vaccine therapies in prior 3 months
• Previously treated with any form HER2- or HER3-primed DC1 therapy