As part of the operation “Pink October"implemented at the Pasteur Institute of Lille aimed at raising public awareness about the breast cancer and to highlight fundamental research, we met with Professors Chann LAGADEC and Robert-Alain TOILLON, two researchers from the Lille Oncological Institute (ONCOLille) working in the "Heterogeneity, plasticity and resistance to cancer therapies" team (CANTHER laboratory), and specializing in triple negative breast cancer.
Professor Robert-Alain TOILLON: Professor at the University of Lille and Professor Chann LAGADEC: research fellow at INSERM in the team " Heterogeneity, plasticity, and resistance to cancer therapies » (CANTHER laboratory), at the Lille Oncology Institute (ONCOLille).
What is triple-negative breast cancer and why is it particularly aggressive?
Triple-negative breast cancer is a subtype of breast cancer which does not possess three receptors commonly found on breast cancer cells: the estrogen receptor, the progesterone receptor, and the HER2 receptor. These receptors are targeted by some existing therapies, but their absence in triple-negative cancers makes the latter more difficult to treat with current targeted therapies.
This type of cancer is considered the most aggressive. It generally affects the young women In contrast to older patients (over 75 years old), it is characterized by increased mortality compared to other types of breast cancer. Its prognosis is often poor due to the lack of effective targeted therapies, leading patients to undergo treatment. conventional chemotherapiesThe 5-year survival rate for triple-negative cancers is approximately 85-88%, while it is 90-93% for hormone-dependent or HER2-positive cancers.
What are the main challenges associated with triple-negative breast cancer, particularly with regard to metastases?
One of the challenges with breast cancer, and in particular triple-negative breast cancers, is their high propensity to metastasize and the difficulty of treat these metastasesThe progression is even more unfavorable and the prognosis grim when metastases are present. Patient management is much more effective when the tumor is still localized in the breast, most often a surgical procedure which remains limited and safe, accompanied by effective adjuvant treatments that vary depending on the patient. Triple-negative breast cancers tend to metastasize to vital organs such as the brain, liver, and lungs. For example, when a brain metastasis is diagnosed in triple-negative breast cancer, the median survival (Editor's note: the time after diagnosis or the start of treatment during which half of those with cancer are still alive) is only 6 months.
Understanding the mechanisms of development of these metastases is crucial. Research is being conducted to understand why and how certain cancer cells They detach from the primary tumor, circulate in the blood, cross barriers such as the blood-brain barrier for the brain, and settle in a new environment to form a new tumor. It is also important to identify the factors which attract them towards specific organs, this is called “homing”.
A promising area of research is the development of computer programs based on the analysis of primary tumors to predict the risk of brain metastases. Researchers are working to isolate different cell populations and identify predictive markers in the primary tumor.
How do researchers approach the complexity of brain metastases from triple-negative breast cancer?
Researchers are addressing this issue by developing new study models, such as the individual monitoring of cancer cells, to understand what drives one cell among others to metastasize. They focus on understanding the mechanisms underlying brain metastases.
For example, some work focuses on the study of specific growth factors, such as “Nerve Growth Factor,” which is produced in the brain and could attract cancer cells, explaining why they choose the brain as a site for metastasis. Other research focuses on the plasticity of tumor cellsThat is, their ability to adapt to very different new environments (from the breast to the brain) and to interact with host cells in the target organ. Co-culture models and preclinical models are used to visualize and understand these interactions.
The ultimate goal is to better understand these mechanisms to be able to isolate the particularities of metastatic cancer cells, in order to target them with new therapies, whether therapeutic antibodies or new drugs.
What are the hopes and advances in the early detection of metastasis risks?
A promising area of research is the development of computer programs based on the analysis of primary tumors to predict the risk of brain metastases. Researchers are working to isolate different cell populations and identify predictive markers in the primary tumor.
The idea is to be able to determine, from a biopsy or analysis of the surgically removed tumor, whether a patient has a high risk of developing brain metastases. If a risk is identified, patient monitoring would be intensified, for example, with more frequent scans (every 3 or 6 months). The goal is to detect and remove any small metastases as early as possible, which can significantly improve the prognosis.
This approach is part of personalized medicineallowing patient monitoring to be adapted according to their risk profile: lighter monitoring for those without identified risk factors and intensified monitoring for those at risk.
Does breast cancer research have implications beyond this specific disease?
Yes, fundamental research conducted on breast cancer, and more specifically on mechanisms such as the action of growth factors or cellular plasticityThis has much broader implications. The fundamental mechanisms discovered can be found in other pathologies.
For example, research on "Nerve Growth Factor" and its receptors may have implications for immunology, allergology, or even Alzheimer's diseaseFurthermore, other types of tumors that metastasize to the brain or whose growth factors are involved could also benefit from these discoveries. It is therefore crucial to emphasize that basic research, although it may seem slow, is essential because it lays the groundwork for therapeutic advances in a multitude of diseases.
What are the risk factors and essential preventive measures against breast cancer?
The primary risk factor for breast cancer is ageHowever, many other factors are involved, making multifactorial diseaseSome breast cancers can be prevented through a healthy lifestyle. For example, alcohol and tobacco increase the risk, as does obesity. endocrine disruptors are also suspected of playing a role in hormone-dependent cancers.
Screening is a key message to convey: in France, screening is free for all women between 50 and 74 years old. However, only one in two women participates. The earlier breast cancer is detected, the greater the chances of recovery. This is why emphasizing the importance of screening is a top priority in awareness campaigns like Breast Cancer Awareness Month (October).
Why, despite the scale of breast cancer, have we not yet found a “single treatment”?
There is not just one “breast cancer” but “breast cancers”, which are very diversifiedResearchers have already identified several classes (hormone-dependent, HER2-positive, triple-negative), and it is likely that there are still others to be characterized in more detail. Each subtype has different genetic, molecular, and behavioral characteristics, requiring specific therapeutic approaches.
In addition, many factors Several factors influence the development and progression of cancer: the tumor microenvironment, the patient's immune system, vascularization, diet, age, and environmental factors such as pollution or pesticide exposure. This multifactorial nature makes the discovery of a single treatment extremely complex.
Research aims to characterize these differences in order to develop increasingly personalized therapies. A treatment that is effective for one type of breast cancer will not necessarily be effective for another, hence the need to continue basic research to understand these complexities.
What is the importance of basic and applied research in the fight against cancer, and what is the specific nature of the French healthcare system?
La fondamental research is essential to understand the complex mechanisms of cancersuch as the development of metastases or the action of growth factors. Only by isolating and characterizing the specific features of cancer cells can we hope to develop truly effective long-term targeted therapies. Without this deep understanding, drug development risks being ineffective and wasting precious time.
La Applied researchShe, for her part, uses this knowledge to to develop concrete treatments and medicationsThis includes work on therapies targeting specific receptors or understanding why some treatments fail. This approach is often carried out in international collaboration.
Regarding the French healthcare system, it offers an unparalleled opportunity: free care and treatment coverage, regardless of the patient's socioeconomic status or financial means. Unlike some countries, such as the United States, where the choice of treatment can be dictated by the patient's ability to pay (with some treatments costing up to €80,000 per year for certain subtypes of breast cancer), in France, the most effective treatment is administered, irrespective of its cost. This equal access to care is a precious advantage.
Key points to remember about triple-negative breast cancer (TNBC)
- Definition: Breast cancer that does not express the estrogen receptor, the progesterone receptor, or HER2 (hence “triple negative”).
- Features: The most aggressive type of breast cancer, often affects young women, has a higher mortality rate compared to other types, and represents 15 to 20% of breast cancers.
- Prognosis and treatments: Poor prognosis, few effective targeted therapies (e.g., Trodelvy, limited efficacy). The main treatment is conventional chemotherapy. Five-year survival is around 80% (compared to 92-93% for other types).
- Metastases: The main problem is that TNBCs tend to metastasize to crucial organs (brain, liver, lungs, bones). Life expectancy drops drastically after the detection of metastases (median survival of 6 months for brain metastases).
- Genetics: It resembles cancers linked to BRCA1/BRCA2 mutations, which often affect young women and are genetic in origin. Genetic testing is performed if there is a close family history.
- Prevention: Some avoidable risk factors (alcohol, tobacco, obesity, endocrine disruptors) can influence the risk of breast cancer, including potentially triple negative.
