Breast Cancer : understanding its origins to better cure it

“Where does my breast cancer come from, why me, why now?”: these are some questions that breast cancer patients legitimately ask.

With over 60,000 new cases a year in France, breast cancer remains the leading cancer for women and the number one cause of death from cancer.

In the laboratories at Institut Curie,researchers are studying the biological, genetic and epigenetic mechanisms acting at the time the tumor forms and then develops. The very tough challenge is to block the mechanisms as early as possible. Deciphering the complexity of these phenomena requires multi-disciplinary research, cutting-edge technologies and innovative work that Institut Curie scientists are doing on the front lines to provide answers for patients as well as future therapeutic solutions.

In terms of medical care everything is done to support the women, from the announcement of the diagnosis to the post-cancer period, and they are offered dedicated consultations (announcement, pyscho-oncology) to help them face the situation.

Institut Curie, the leading European center for breast cancer, treats over 7,000 breast cancer patients each year, 3,000 of them new patients.

This is what makes Institut Curie special: researchers are closely involved in the issues of the physicians, and thus those of the patients. The question of the origin of cancer motivates them every day. Understanding the very first events in the origin of cancer is absolutely crucial since the issues and the outlook are very important in terms of prevention and very early diagnosis, even before the appearance of clinical signs of the disease, but also therapeutic treatment for our patients.

Explains Prof. Alain Puisieux, Director of the Institut Curie Research Center

Understanding in order to develop the treatments of the future

Identifying the origin of cancer in each patient is crucial for Institut Curie. It is a vital step for implementing prevention, early diagnosis, adapting treatments and continuing to optimize chances of recovery.

A variety of exogenic and endogenic factors are constantly damaging our genome throughout our life. Although our body continuously repairs our DNA, anomalies do occur. For breast cancer some factors have been identified such as prolonged exposure to estrogen in connection with early puberty and late menopause; taking hormone replacements for longer than 10 years; obesity after menopause; alcohol; and lastly the impact of aging on our cells. The development of a mammary cell becomes uncontrolled and breast cancer occurs.

There is a wide variety of different breast cancers with different characteristics in terms of genetics, epigenetics and their micro-environment; these characteristics influence their aggressiveness and their response to treatments.

Explains Prof. Alain Puisieux.

This variety is connected to the fact that development of cancer is a dynamic process at the root of great architectural complexity, with cancerous cells that evolve gradually due to the occurrence of new mutations and the acquisition of exacerbated cellular plasticity, enabling them to change identity in response to the stress they are subject to. The teams at Institut Curie strive to understand these phenomena from the earliest stages in development of a cancer. Achieving better understanding of these phenomena helps us identify new points of vulnerability in cancer cells, paving the way for new ways to intervene, and innovative therapies, especially for breast cancer with poor prognosis.

Examining the origin and diversity of breast cancers to tailor treatments is the goal of Dr. Céline Vallot, team leader and CNRS research director, whose work focuses on the role of epigenetics in the occurrence of triple negative breast cancer and the adaptation of tumor cells to cancer-fighting treatments.

With my colleagues at Institut Curie, we are seeking to establish epigenetic ID cards for each of the cells, individually, in a tumor. This involves establishing the characteristics not of the DNA sequence itself, but of the alterations around this sequence that influence gene expression.

Explains Dr. Céline Vallot.

To achieve this, we examine the tumor cells of the mammary gland from a single-cell perspective. Using this extreme precision method, at the earliest stages we identify the epigenetic profiles responsible for their plasticity, meaning their transformation from healthy cells to cancerous cells. Ultimately some epigenetic alterations could enable us to develop new diagnostic tools, or identify relevant new therapeutic targets for treating triple negative breast cancer.

Almost half of breast and ovarian cancers are connected to deficiencies in the biological systems that repair DNA breaks. Researchers reveal a hitherto unknown DNA repair mechanism involving a protein, PolꝊ, which is able to act during cell division.

Along with my team at Institut Curie, we are examining the mechanisms that the cell puts in place to repair its DNA, enabling cancer cells to survive. It is by understanding such mechanisms that we can build new options to thwart cancer. Our discoveries on the role and functioning of polymerase theta in maintaining integrity of the genome gives us hope for new therapeutic strategies against cancer, particularly breast and ovarian cancer.

Explains Dr. Raphaël Ceccaldi, Inserm researcher and team leader at Institut Curie.

Oncogenetics: supporting women at high risk

One of the internationally recognized areas of expertise of Institut Curie, is oncogenetics, meaning the detection, monitoring and treatment of women at high risk of developing breast cancer of hereditary origin.

5 to 10% of breast cancers diagnosed are due to a genetic predisposition. Research has revealed several genes that predispose to breast cancer, whose mutated forms, passed on in certain families, give a high risk of developing breast cancer to the women carrying them. At Institut Curie,we continue research into predisposition genes and in parallel we see 2,500 women in consultation each year, and carry out 4,200 predisposition tests, 1,700 of which are for consultations from other establishments.

Explains Prof. Dominique Stoppa-Lyonnet, physician and Professor of Genetics at Université Paris-Cité.

Remaining close to patients at all stages of care

The Institut Curie teams support women at all stages, including diagnosis, treatment (surgery, radiotherapy, medical treatments, clinical trials), reconstruction, psychological support, treatment of side effects, pain management, prevention, appropriate exercise, nutrition, post-cancer and return to work.

Explains Prof. Steven Le Gouill, director of the Hospital Group at Institut Curie.

More than 1,400 medical professionals and health professionals are there to support women with breast cancer on Institut Curie’s two hospital sites.

The announcement of the diagnosis is a moment of turmoil for each patient. What has caused their cancer? Why them? Why now? These are some of the first questions they ask themselves and they ask us in consultation.

Explains Prof. Le Gouill.

Support for patients from the moment of the announcement is a priority

Institut Curie’s teams remain close to our patients, particularly in the Supportive care department (DISSPO), which offers consultations for treating women wishing to have increased psychological support. A pioneering diagnosis announcement system was introduced at Institut Curie in 2005.

Nurses are at the heart of the diagnosis announcement. We offer adapted support to patients as their navigate their treatment. Our specially trained health professionals intervene after a medical consultation during which the diagnosis has been announced and a treatment plan proposed. The announcement of a cancer diagnosis then of a treatment plan lead to a flood of questions while the patient is often anxious or overcome with emotion

Explains Prof. Le Gouill.

This meeting is chance to talk with the nurse, who listens attentively and adopts an appropriate attitude. It is a time to check that patients have understood the diagnosis and to answer their questions. At the same time as ensuring that the patient understands, the nurses assess their needs in terms of supportive care, and offer an appointment with the social worker, dietician, psychologist, geriatrician or addiction specialist if appropriate.