Haleemah Atobiloye, M.A., she/hers, BCAction Program Manager
Breast Cancer Action has a particular perspective on the concept of “pills for prevention” of breast cancer, and while engaged in the research to update the factsheet we provide, my curiosity was piqued. I wanted to hear what Dr. Melinda Telli, Associate Professor at Stanford University School of Medicine, had to say in her presentation, Recent advances in triple negative breast cancer at SABCS this year.
Dr. Tilli provided an overview of the recent advances, ongoing research efforts, drug approvals, and clinical trials in the treatment landscape for triple-negative breast cancer (TNBC). The presentation began with a case study to highlight what was described as “a remarkable evolution of TNBC treatments.” Dr. Tilli told us the story of a patient who was a 33-year-old mother, breastfeeding her second daughter, when she was diagnosed with TNBC. Her tumor was locally advanced and she was found to have a germline BRCA mutation. After being diagnosed, the treatment plan began with neoadjuvant (preoperative) therapy with an anthracycline and taxane-based regimen, followed by surgery, and subsequent platinum-based adjuvant therapy. The treatment plan followed the standard treatment protocols based on emerging data that existed at that time. And in case you were wondering like I was, the patient is living well and is now 50 years old.
The classification of breast cancer subtypes, including the identification of TNBC, was notably discussed in the work by Perou and Sørlie, who, in 2000, described intrinsic subtypes of breast cancer based on gene expression profiling. This laid the foundation for subsequent research that led to the identification and recognition of TNBC cancer as a distinct subtype. Dr. Tilli noted that the term “triple-negative breast cancer” entered the breast cancer lexicon around 2005, and is defined as a specific type of breast cancer characterized by the absence of two receptors—estrogen receptor (ER) and progesterone receptor (PR), and the protein HER2. Unlike other breast cancer subtypes, TNBC does not respond to hormonal therapies or drugs targeting HER2. TNBC tends to be more aggressive, grows quickly, and is commonly diagnosed in younger women, those of African ancestry, and individuals with BRCA1 mutations. With ongoing research and clinical trials leading to the development and approval of targeted therapies, immune checkpoint inhibitors, and other technological advancements, TNBC treatment approaches have steadily been evolving since the mid-2000s.
The following are key points Dr. Tilli highlighted as recent developments in the TNBC treatment space:
Immune Checkpoint Inhibitors
Dr. Tilli discussed Pembrolizumab (Keytruda) in the context of its use as an immune checkpoint inhibitor in the treatment of TNBC. Pembrolizumab is an immunotherapy drug that uses monoclonal antibodies that may help the body’s immune system attack cancer cells and interfere with their ability to grow and spread. Pembrolizumab targets the PD-1 (Programmed Cell Death Protein 1) pathway and has shown significant clinical impact in various areas of oncology, including breast cancer.
The speaker went on to mention the Keynote 355 trial, a randomized phase three trial evaluating Pembrolizumab combined with chemotherapy in the first-line treatment of metastatic TNBC. In this trial, patients with untreated, locally recurrent or metastatic TNBC were randomized to receive chemotherapy with Pembrolizumab or chemotherapy with a placebo. The study demonstrated that, for a subgroup of patients with PD-L1 positive tumors, the addition of Pembrolizumab improved progression-free survival and overall survival, making it a first-line standard for certain patients with metastatic TNBC.
Furthermore, Dr. Tilli noted that Pembrolizumab became the first checkpoint inhibitor to be indicated for the treatment of early-stage TNBC based on the results of the Keynote 522 trial. This indicates a significant advancement in the use of immunotherapy for both advanced and early-stage TNBC.
The presenter also highlighted future directions for immune checkpoint inhibitors for early-stage TNBC. She highlighted ongoing and upcoming clinical trials, including the OptimICE-PCR trial from Alliance A012103, which aims to investigate the role of adjuvant use of an immune checkpoint inhibitor in patients with TNBC who achieve a pathologic complete response to neoadjuvant therapy. The speaker also mentions that they are eagerly awaiting the results of the SWOG 1418 trial, another randomized Phase III clinical trial designed to evaluate the efficacy and safety of Pembrolizumab as adjuvant therapy for people living with TNBC.
After this session, I wanted to check if treatment with Immune Checkpoint Inhibitors answer BCAction’s critical questions:
In continuing the discussion on the advancements in the treatment landscape for both early and advanced TNBC, the speaker noted:
Chemotherapy combinations mean using more than one chemotherapy drug at the same time or in a specific order to treat cancer. The goal of this is to improve the effectiveness of treatment by attacking cancer cells in different ways, making it harder for them to survive. The following are updates regarding chemotherapy combinations:
One of the points Dr. Tilli emphasized toward the end, is that researchers in this field are working on identifying better biomarkers for both treatment benefit and toxicity, which is important in creating personalized medicine, which should have better treatment outcomes.
When in the process of making a treatment choice, in addition to discussing treatment options with your healthcare provider, it’s helpful to ask and get answers to the following:
Choosing your most suitable treatment plan should be based on a combination of your personal needs and values, and evidence-based science