Posted on January 11, 2024

Haleemah Atobiloye, M.A., she/hers, BCAction Program Manager 

Recent “Advances” in Triple Negative Breast Cancer

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: 

  1. Does the Pembrolizumab + chemotherapy treatment extend overall survival?  Yes, in certain cases of TNBC, according to the information provided during this session. Pembrolizumab treatment has been associated with an extension of overall survival in TNBC. Dr. Tilli mentions that in the Keynote 355 trial, which I explained the details above, 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 both progression-free survival and overall survival. The exact duration of overall survival associated with Pembrolizumab treatment in the TNBC was NOT stated. The term “overall survival” in this context refers to the length of time from the start of treatment until death caused by TNBC. 
  2. Does Pembrolizumab + chemotherapy treatment improve quality of life? There was no definite ‘yes’ or ‘no’ answers as to whether or not the Pembrolizumab + Chemotherapy treatment improved the quality of life for people living with TNBC. There were also no specific details about the toxicity or adverse effects associated with Pembrolizumab + chemotherapy treatment at this presentation. The discussion focused mostly on the clinical efficacy and benefits of Pembrolizumab in the treatment of TNBC, particularly in improving progression-free survival and overall survival.
  3. Does the Pembrolizumab + Chemotherapy treatment cost less than TNBC treatments that are already available?  The cost of this treatment was not mentioned in this presentation. According to this 2023 published research paper, the price of treatment with Pembrolizumab + chemotherapy is estimated to be approximately $235,918 per person for each year of treatment. 

Targeted Therapies 

In continuing the discussion on the advancements in the treatment landscape for both early and advanced TNBC, the speaker noted:  

  • The introduction of antibody drug conjugates (ADCs) into the treatment landscape for advanced TNBC. The first ADC mentioned is Sacituzumab Govitecan (Sacituzumab Jofa T Can), which targets the epithelial trop-2 antigen. This monoclonal antibody is linked to the SN-38, a topoisomerase I inhibitor. According to the researcher, the drug demonstrated clear benefits in terms of progression-free and overall survival in the phase three ASCENT trial for heavily pre-treated patients, leading to its FDA approval in April 2021. Additionally, the speaker mentioned another ADC, Trastuzumab Deruxtecan, showing improved progression-free and overall survival, particularly for pre-treated advanced HER2+ breast cancer, which may include triple-negative disease. 
  • The speaker mentioned that PARP inhibitors, specifically Olaparib and Talazoparib, have shown positive results in the treatment of advanced TNBC, particularly for patients with germline BRCA mutations. PARP inhibitors are a class of drugs that interfere with the activity of poly(ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair. By inhibiting PARP, these drugs prevent cancer cells, particularly those with BRCA mutations or other DNA repair deficiencies, from repairing their damaged DNA effectively. These PARP inhibitors were demonstrated to improve progression-free survival, and there was no explicit mention whether the PARP inhibitors improved overall survival. 
  • There was no mention of the toxicity of either antibody drug conjugates (ADCs) or PARP inhibitors. This means the harmful side effects or adverse reactions that can occur as a result of these treatments were not discussed. 

Chemotherapy Combinations 

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: 

  • Platinum-based regimens, such as carboplatin, in neoadjuvant settings, have shown improvements in pathologic complete response rates. 
  • Non-anthracycline, taxane, and platinum-based regimens for early-stage TNBC are being evaluated.

Personalized Approaches 

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: 

  1. Does the treatment extend my overall survival? And if so, for how long?  
  2. How will the treatment impact my quality of life? 
  3. How toxic is the treatment? What are the side effects or adverse reactions that can occur? 
  4. What is the cost of this treatment? 

Choosing your most suitable treatment plan should be based on a combination of your personal needs and values, and evidence-based science