Triple negative breast cancers: expanding the frontiers of the struggle

The diagnostic progress made in recent years has enabled us to diagnose several different types of breast cancer. For the most common ones - hormone-dependent breast cancers and “HER+” cancers - there are now very effective targeted therapies. 15% of patients have what's known as “triple negative” breast cancer, meaning that there is no known marker at the surface of cancer cells that is liable to respond to a known targeted therapy. “The women affected are often younger than average,” points out Prof Martine Piccart, an international specialist in breast cancer. “In some cases, it is a hereditary form of breast cancer, with a genetic mutation (of the BRCA1 or BRCA2 genes).”

“When the doctor told me I had triple-negative breast cancer, I thought ‘Great, that means no hormone therapy,’” recalls Mélanie, a former patient at Institut Curie, treated in 2011 at the age of 33. “But when I saw my doctor’s face I soon understood that it was not necessarily good news!” Indeed, around half of triple-negative breast cancers respond well to classic chemotherapy treatment, the other half are likely to develop resistance, which makes this cancer much more difficult to treat. The relapse rate is also quite high during the two years after the end of treatment.

“The urgent issue today is to find treatments that work for these women,” explains Prof Piccart. “There is hope, and a large number of protocols today focus on these tumors, especially in immunotherapy.” In order to succeed, researchers must first know more and understand more about triple-negative tumors. “Institut Curie has two major assets for developing this type of research,” explains Martine Piccart. It treats very many patients suffering from breast cancer and therefore has a large number of tumor samples to study. Institut Curie also has extraordinary laboratories for studying the mechanisms of the immune system and what the cancer cell does to thwart them. It may play a pioneering roles in the establishment of an ambitious research protocol, to answer very important questions, such as which is the best chemotherapy to offer? Who needs immunotherapy in addition? Why don’t these treatments work for everyone?”

The researcher Fatima Mechta-Grigoriou, head of the “Stress and cancer” Inserm/Institut Curie laboratory, has been trying for several years to answer these questions. “When I joined Institut Curie in 2005, and thanks to the proximity to physicians, I started to become interested in triple-negative breast cancers,” explains Fatima. “My team’s work helped to develop several promising leads.” Among its most recent projects, her team has “discovered a population of cells that prevents immunotherapy from being effective. By identifying the patients in whom these cells are present, we can then target these cells to prevent then from acting. Immunotherapy therefore becomes effective,” concludes Fatima. Another priority for Prof Piccart: “To identity “triple-negative” patients for whom immunotherapy will provide no benefit, since chemotherapy alone leads to recovery. And here there is a real lack of research, since the pharmaceutical industry is clearly not interested, as this would involve fewer treatments. And here again it is academic research, and institutions such as Institut Curie, that can make a difference.”

Mélanie, a former patient: “Today I’m feeling great”

Summer 2011. Mélanie, 33 years old and a young mother, discovered a lump in her breast. She had recently given birth and did not become concerned straight away. After a few weeks she decided to see a doctor. Mammogram, biopsy... and then the bombshell dropped: it was cancer. “I didn’t panic, I thought that it had to be at an early stage and that it simply needed to be removed. After an Internet search I made an appointment at Institut Curie, at the René-Huguenin site. I wanted to see the experts. When the doctor talked to me about triple-negative, he did not go into detail. It was when I searched the Internet that the 2nd tsunami hit: it was the cancer with the poorest prognosis.”

But Mélanie is a fighter. Following the PET scan that confirmed there were no metastases, her mind cleared, and she resolve to beat it. The first weeks were reason for optimism: the tumors regressed considerably and doctors were talking about tumorectomy rather than mastectomy. “What a relief! I’m aware that I’m luckier than many young women treated at the same time as me.” Once treatment is over, “of course we never say it’s over, there is always a high risk of relapse, especially during the first two years. So for a certain time we exist with the sword of Damocles hanging over our head. We call the doctor at the slightest symptom, and leave the hospital relieved after a battery of tests! Today, six years later, I feel great. Of course I’ve lost the carefree attitude of my youth, but I feel like I’ve been to war and won!”