Grouping Immune-modulation With Cryoablation (LOGIC) for Breast Cancers

Summary Points: 1. High Risk Breast Cancers: Triple negative cancer is considered high risk due to high rate of local and systemic failure. Newer innovative treatment strategies are needed to improve systemic control of disease and survival. 2. Immune system modulation: is an emerging modality in cancer treatment. Tumor antigens can stimulate T cells to identify and destroy cancer cells. Cancers express "altered self" antigens that tend to induce weaker responses than the "foreign" antigens expressed by infectious agents. Thus, immune stimulants and adjuvant approaches have been explored widely. Opportunities to develop effective cancer vaccines may benefit from seminal recent advances in understanding how immunosuppressive barricades are erected by tumors to mediate immune escape. This concept is precisely applicable to triple negative breast cancer due to their antigenicity. Checkpoint inhibitors are an attractive method for treatment of high-risk breast cancers. However, to leverage the efficacy of checkpoint inhibition, approaches are needed to enhance delivery of cancer antigens to the T cells. 3. Cryoablation: offers an efficacious and safe method to enhance tumor antigen presentation to the immune cells while destroying the primary tumor. This ablation method is superior by virtue of antigen preservation in situ despite toxicity to the tumor cell. Impact of cryoablation in enhancing immunological responses in tumor microenvironment are well established; however, cryoablation can also cause tumor antigen tolerance via non-specific stimulation of T cells. 4. Rationale for combining cryoablation and checkpoint inhibitors: Since checkpoint inhibitors curtail the tolerance developed by tumor antigens, and cryoablation enhances antigen presentation and T cell recruitment, it is intuitive that combination of these two approaches presents an ideal opportunity to leverage the benefits of both approaches while curtailing the limitations of either. Therefore, the investigators hypothesize in this study that their combination will improve the response rate and the degree of response.

Sex

Female

Minimum age

18 Years

Maximum age

90 Years

Inclusion Criteria:

* Females
* Stage I/II Cancer
* Age range 18 - 90 years
* Diagnoses: Invasive carcinoma, ER -, PR-, HER2- (triple negative)
* Radiology findings: Unifocal disease visible on ultrasound

Exclusion Criteria:

* Additional primary cancer
* Inflammatory breast cancer
* History of autoimmune disease
* History of chronic immunosuppression
* Prior immunotherapy
* Recent vaccination (within 4 wks.)
* Prior radiation therapy
* Prior investigational agent therapy within last 1 year
* Pregnancy at the time of diagnosis and/ or treatment
* Breast feeding