# Cryoablation and Intratumoral Immunotherapy for Breast Cancer: A Future Path to Cost-Effective De-Escalation for Larger Tumors, Lymph Nodes and Metastatic Disease

## TL;DR

This paper reviews how combining cryoablation with intratumoral immunotherapy could offer a safer, cheaper treatment for larger breast tumors and metastatic disease.

## Contribution

The paper proposes a novel combination of cryoablation and intratumoral immunotherapy for de-escalating breast cancer treatment in larger tumors.

## Key findings

- Cryoablation is currently limited to small breast tumors due to risks of metastasis.
- Intratumoral immunotherapy may reduce side effects and improve outcomes when combined with cryoablation.
- Multi-probe cryoablation could provide better local control for larger breast tumors.

## Abstract

This review explores cryoablation as a promising, cost-effective option to de-escalate surgical treatment in breast cancer. Regrettably, its use is currently limited to small tumors under 1.5 cm in select patients, as larger tumors pose a greater risk of metastatic spread. Adjunctive therapies such as hormone therapy, radiation, and chemotherapy are still required for regional and systemic control but come with significant side effects and morbidities. Intravenous immunotherapy also has high associated morbidities. Direct tumor injections (intratumoral) of immunotherapy drugs may help reduce these risks. This review summarizes current evidence suggesting that strategically placed cryoablation probes combined with intratumoral immunotherapy may enhance treatment effectiveness, potentially offering improved protection against metastatic disease while reducing the complications and costs associated with traditional cancer therapies.

Cryoablation is a promising, cost-effective option to de-escalate surgical breast cancer morbidity, but presently is only suggested for breast cancers < 1.5 cm, in select candidates. Breast cancer cryoablation is not a reliably covered procedure by insurance and is mainly guided by ultrasound (US), using a single cryoprobe. Yet, cryoablation is an accepted treatment option for various malignancies, including those of the kidney, liver and lung, utilizing a predominantly CT-guided, multi-probe approach using crucial cytotoxic isotherms for thorough tumor coverage. Cryoablation thus continues to find new clinical utility and is rapidly advancing on multiple fronts, similar to immunotherapy. Clinical concerns of expanding cryoablation to breast tumors > 1.5 cm is more related to the greater risk of metastatic spread to local lymph nodes and beyond. Combined adjuvant treatment, such as radiation and/or chemotherapy, are currently used for regional and systemic breast cancer control, but have significant associated morbidities. US/CT-guided multi-probe large-volume breast cryoablation is presented as a thorough local control option for select patients. Intratumoral chemotherapy by direct tumor injection has been shown to be safe and is currently being tested with immunotherapy drugs and exhibits much lower morbidity. Cryoablation combined with intratumoral immunotherapy is presented to show robust systemic immune response and the potential to provide additional protection from regional and/or metastatic disease spread while de-escalating the morbidities from current adjuvant treatments for larger breast cancers. While further clinical trials are needed, it is essential to pursue safe and effective breast cancer treatments that offer the potential for cost-efficiency and therapeutic de-escalation across a wide spectrum of breast cancer cases.