Clinical Perspectives

The Latest Advances in Breast Cancer Therapeutics: CDK-Inhibitors to Cellular Immunotherapy

March 30, 2022

Czerniecki Clinicalupdate

From new rapid MRI screening technologies to cancer vaccines, breast cancer prevention and therapeutics continue to improve. Breast cancer develops in about 1 in 8 women, comprising 30% of female cancer cases annually. As the only National Cancer Institute-designated Comprehensive Cancer Center based in Florida, Moffitt Cancer Center is at the forefront of cancer treatment and research.

The Latest Breast Cancer Therapies

New therapeutics target breast tumors using their cellular receptor subtype. Breast tumor receptors fall into 3 main categories: hormone-receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+), and triple-negative (TN).

The HR+ subtype includes estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) cancers, and accounts for approximately 75% of all breast cancer cases. HER2+ cancer arises from an overexpression of the HER2 receptor protein. TN cancer indicates an absence of estrogen, progesterone and HER2 receptors.

One new therapeutic, cyclin-dependent kinase (CDK) inhibitors, stops cancer cell growth in its tracks. "The most exciting changes in the field of hormone-receptor-positive breast cancers have been CDK,” says Brian Czerniecki, MD, PhD, chair of the Department of Breast Oncology at Moffitt. "They’ve dramatically improved survival in patients with metastatic hormone receptor-positive breast cancer in the order of months to years."

The inhibition of kinase activity ultimately blocks cell-cycle progression, thereby preventing cancer cell growth. In combination with anti-estrogen therapies, CDK-inhibitors prove very successful.

portrait of blockquote author

"Antibody therapies and targeted therapies against HER2+ cancers have dramatically improved. This tumor used to have one of the worst survival rates in breast cancer, period. Today, it’s one of the best."

- Brian Czerniecki, MD, PhD

After researchers identified mutations in breast cancer cell growth regulation, therapeutics focusing on antibody function surfaced. New antibody treatments improve survival rates by targeting the mutated cells and receptors involved in the cell growth process.

"I think once we identify more antibodies against some of these mutated proteins, it may be possible to create CAR T cells," suggests Dr. Czerniecki.

Perhaps the most notable progress occurred in HER2+ cancer treatments. "Antibody therapies and targeted therapies against HER2+ cancers have dramatically improved," says Dr. Czerniecki. "This tumor used to have one of the worst survival rates in breast cancer, period. Today, it’s one of the best."

Advances in Cellular Immunotherapy

Moffitt sees significant results using cellular immunotherapy, or adoptive cell therapy. This innovative treatment employs a patient’s own immune system to fight cancer using a dendritic cell vaccine.

The treatment combines vaccine and cell therapy technology. When given peptides or portions of tumor antigens, dendritic cell vaccines prompt the development of natural vaccine immunity. Dendritic cells also work to activate other parts of the immune system. 

"We’re injecting HER2-pulsed dendritic cells made from the patient back into their breast tumor before chemotherapy. By injecting them into the tumor itself, we unlock and activate a whole set of other immune parameters," Dr. Czerniecki explains. "It drives a wild immune response in their breast and helps the Herceptin® and Perjeta® antibodies actually create more complete responses."

Researcher studying breast cancer vaccine

A HER3-Specific Cancer Vaccine

Researchers at Moffitt successfully created a new vaccine specific to human epidermal growth factor receptor 3 (HER3) in a preclinical model. Published in Cancer Immunology Research, the study aimed to take advantage of the immune system’s own ability to target HER3.

The researchers assessed HER3-peptide stimulated dendritic cell vaccines as both a preventive and therapeutic strategy. Compared to controls, vaccinated mice that later received breast cancer or melanoma cell injections exhibited delayed tumor growth and prolonged survival. When injected into existing breast and melanoma tumors, the vaccine again delayed tumor growth and increased survival rates. The results maintained even against a model of drug-resistant breast cancer.

After confirming the vaccine triggered the immune response, the investigators identified the exact source of activation. In both healthy and breast cancer patients, they found 9 short peptide sequences on the HER3 protein that generates a CD4+ T cell immune response. Notably, these sequences apply to a broad patient population.

Several cancers involve overexpression of HER3, including breast, bladder, lung adenocarcinoma, prostate, and stomach. HER3+ has also been associated with poor survival rates in melanoma and pancreatic cancer.

"Developing HER3-specific cellular immunotherapy can be a novel and efficient treatment strategy for multiple cancer types to improve patient prognosis and survival," says Dr. Czerniecki.

Moffitt is a site for several cancer clinical trials studying HER2+ and TN cancers, leptomeningeal disease, brain metastases, and more.

If you’d like to refer a patient to Moffitt Cancer Center, complete our online form or contact a physician liaison for assistance. As part of our efforts to shorten referral times as much as possible, online referrals are typically responded to within 24 - 48 hours.