New research in early detection and prevention of breast cancer with immunotherapy

Author: Sasha Stanton, M.D., Ph.D., principal investigator, Cancer Immunoprevention Laboratory, Earle A. Chiles Research Institute; medical oncologist, Providence Cancer Institute

Routine mammography has contributed to earlier diagnosis of breast cancer and increased diagnosis of ductal carcinoma in situ (DCIS). Detecting cancer at a stage when it can be cured has led to better outcomes in many patients with breast cancer.

Mammography also has dramatically increased the identification of pre-invasive breast cancer and other tumors associated with a higher lifetime risk of breast cancer. These include DCIS, lobular carcinoma in situ, and atypical hyperplasia. Current standard-of-care for these cancers is aggressive treatment with surgery or radiation. With improved detection, better understanding of these lesions and better prevention therapies are needed.

Vaccine development for breast cancer treatment and prevention
The Cancer Immunoprevention Laboratory at Providence Cancer Institute is focused on developing immune therapies to treat pre-invasive disease and prevent breast cancer.

As tumors develop into invasive breast cancer, we have found concurrent changes in the immune system provide insight into the tumor immune response. One recent, exciting development by our team is that changes in the blood may allow for early identification of breast tumors based on changes in the immune system.

Our team also is developing vaccines with the dual purpose of treating pre-invasive malignancies and preventing development of invasive cancer. We identified 12 proteins that are overexpressed in pre-invasive and invasive disease. These proteins can be used as antigens – pieces of protein recognized by the immune system that can allow a person to develop an immune response against the tumor. As reported in NPJ Breast Cancer, we found that women diagnosed with DCIS or invasive breast cancer had increased antibodies to six of these proteins, demonstrating that their immune systems already recognized these overexpressed proteins. 

The important role of antibodies in disease detection
We also found that a panel of six of these antibodies can identify women with invasive breast cancer or DCIS, and aid in predicting an increased risk of developing breast cancer over a patient’s lifetime. These antibodies were derived from the serum of:

  • 43 women with no known breast abnormalities
  • 12 women who had a mammogram with hyperplasia
  • 36 women with fibroadenoma on mammogram
  • 59 women with DCIS on mammogram
  • 37 women with invasive breast cancer of any stage

These antibodies were increased in 87% of women with DCIS samples (range 78 to 97%, p<0.0001 Figure 1) and 87% of serum samples from women with invasive breast cancer (range 76 to 98%, p<0.0001). 

The antibody panel also could identify 98% of patients with fibroadenoma (range 96% to 100% p<0.0001) and 94% of women with hyperplasia (86% to 100%, p<0.0001). Therefore, these antibodies can identify breast disease early in tumor development through a blood test. 

Future directions
We now plan to study if that blood test can help improve early detection when used in conjunction with mammography. We are validating these findings with an independent collection of patient samples across all the breast cancer subtypes, such as hormone receptor positive, HER2 positive and DCIS. If this panel is validated, we will evaluate if it can identify more aggressive breast lesions. We also plan to conduct clinical studies to test whether the antibody panel can improve mammogram sensitivity. We hope our research will make a meaningful impact for patients with breast cancer by preventing the morbidity and mortality associated with invasive disease.

Figure 1: Six antigens can identify women with DCIS as compared to healthy volunteers.  Compared to healthy volunteers (n=43), six antigens could identify women with DCIS (n=59) with AUC 0.87 (95% CI 0.78 to 0.97 p<0.0001)

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