We live in a time in which many of us are very familiar with breast cancer – what it is, and what it can do. One in eight women in the U.S. is diagnosed with breast cancer. Going by the statistics alone, most of us probably know at least one person affected by it, personally.

While we see and recognize the pink ribbons and the flood of pink merchandise during Breast Cancer Awareness Month, are we aware of the current research to treat those affected? Can most of us name one treatment other than chemotherapy or radiation, to treat breast cancer? Fortunately for many, the Department of Defense Congressionally Directed Medical Research Program, Breast Cancer Research Program has supported the advancement of several promising therapeutics to treat and help find a cure for breast cancer.

Far too often, we think of research as a never-ending laboratory study; however, the unique method by which the CDMRP manages these research programs actually leads to products in the hands of the physician and in the lives of patients. The CDMRP partners with scientists and consumers in a collaborative process to ultimately find cures for a variety of diseases and illnesses.

"Using the two-tiered review process we are able to fund the most relevant medical research," said Col. Wanda Salzer, director of CDMRP. "The current portfolio of breast cancer research is helping to provide effective treatments for those facing the disease."

The BCRP has seen success regarding the therapeutics developed to treat breast cancer. These U.S. Food and Drug Administration-approved treatments should serve as proof that the established process effectively works to support the critical mission of ultimately ending breast cancer.

Dr. Gayle Vaday, BCRP program manager, has supported the CDMRP for over 11 years.

"The DOD BCRP is committed to funding research that will lead to breakthroughs in breast cancer treatments that are more effective, less toxic and save lives," said Vaday. "This program has supported the development of therapeutics that are now a part of standard-of-care treatment regimens, and many more therapeutics are in the clinical pipeline."

The BCRP has helped to fund the development of four FDA-approved therapeutics currently used to treat patients with breast cancer. The BCRP also provided funding for a study that led to a change in clinical practice for patients with breast cancer taking the hormone therapy tamoxifen. These are described below:

Herceptin®
Herceptin® (trastuzumab) is an antibody that targets the human epidermal growth factor receptor 2. HER2-positive breast cancer accounts for approximately 25 percent of all breast cancers. The BCRP was instrumental in supporting the preliminary studies needed to test the efficacy of Herceptin®, which later led to clinical trials and ultimately FDA approval. Herceptin® revolutionized breast cancer treatment and the field of targeted therapeutics. Herceptin® is now part of standard-of-care treatment regimens for HER2+ early-stage and metastatic breast cancers.

IBRANCE® [Pfizer]
IBRANCE® (palbociclib) is a drug that that inhibits the cyclin-dependent kinases which play a key role in the uncontrolled cell proliferation that is a hallmark of cancer. The BCRP funded preliminary laboratory studies that tested whether IBRANCE® could kill cancer cells, and the results led to IBRANCE® advancing to clinical trials. On February 3, 2015, the FDA granted accelerated approval to IBRANCE®, in combination with letrozole, for the treatment of estrogen receptor-positive, HER2-negative advanced breast cancer as initial endocrine based therapy in postmenopausal women. On March 31, 2017, the FDA granted regular approval to IBRANCE® for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women. An international clinical trial (PALOMA-2) demonstrated progression-free survival, 24.8 months in the IBRANCE® plus letrozole arm compared to 14.5 months in the placebo plus letrozole arm. Reference: N Engl J Med. 2016. 17:375(20):1925-1936.

KISQALI® [Novartis]
KISQALI® (ribociclib) is also a drug that inhibits the cyclin-dependent kinases which are key regulators of uncontrolled cancer growth. The BCRP funded preliminary laboratory studies that tested the ability of KISQALI® to kill cancer cells, and the findings later led to clinical trials. On March 13, 2017, the FDA approved KISQALI® in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Results from a Phase III clinical trial demonstrated significantly longer progression-free survival in the KISQALI® plus letrozole group (63 percent) compared to the placebo plus letrozole group (42.2 percent). Reference: N Engl J Med. 2016. 375(18):1738-1748.

Verzenio™ [Eli Lilly and Company]
Verzenio (abemaciclib) is a treatment for patients with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer which has progressed after taking hormone therapy. The BCRP funded preliminary laboratory studies that tested the ability of Verzenio™ to kill cancer cells, and the findings later led to clinical trials. Verzenio™ was approved by the FDA on September 28, 2017, to be given as a combination with the endocrine therapy fulvestrant, or as a standalone treatment for patients previously given endocrine and chemotherapy.

ATLAS (Adjuvant Tamoxifen Longer Against Shorter)
The ATLAS clinical trial resulted in a change in clinical practice for tamoxifen treatment. In the worldwide ATLAS trial, 12,894 women with early estrogen receptor-positive breast cancer who had completed the standard five years of treatment were randomly selected to continue tamoxifen for 10 years or to stop at five years. On May 27, 2014, the American Society of Clinical Oncology published new guidelines on adjuvant hormonal therapy that recommended all women diagnosed with hormone receptor-positive breast cancer be offered the option of taking hormonal therapy for 10 years, which demonstrated a further reduction in recurrence and mortality, especially after year 10. Reference: Lancet. 2013. 381:9869:805-816.

Along with these currently approved treatments, a number of other therapeutics are currently undergoing clinical testing in individuals with breast cancer. The BCRP either supported preclinical work leading to development of these products, or the BCRP is currently funding the clinical trial. These treatments are in various phases of clinical trials and may become the next breakthrough in breast cancer.

• TRC105 antibody
• VRP-HER2 vaccine
• 89Zr-trastuzumab HER2 radiotracer
• Pembrolizumab
• Tremelimumab and MED14736
• Meclofenamate
• Mesothelin CAR T cell therapy
• Temozolomide
• Talazoparib
• Mammoglobin cDNA vaccine
• PLX 3397 and eribulin
• Enzalutamide +/- Fulvestrant
• MM-302 anti-HER2 antibody
• D-1MT IDO inhibitor
• GM-CSF vaccine + cyclophosphamide + trastuzumab
• HER2 bi-armed T cells
• P10s-PADRE vaccine
• FdCyd
• Aromatase + Src Inhibitors
• Folate Receptor Alpha vaccine
• FASN inhibitor TVB-2640
• HER2 peptide vaccine
• NeuVax™
• Neoadjuvant T-DM1 + Pertuzumab vs. TCHP
• Aspirin

Unless you are a scientist, researcher or someone in the industry, these names are perhaps just words. To the patients that are faced with this disease, these words provide hope. These are the names of possible treatments to restore health and bring back quality of life to an affected individual and their family.

Not only does the BCRP-supported research have promise to deliver therapeutics that provide lifesaving treatments, with the high numbers of active duty Service Members and military family members who are affected by this disease, it also demonstrates the key role the DOD has played in the fight against breast cancer.