A CNIO group contributes to identifying which breast lesions will progress to cancer, thus helping avoid overtreatment

• “In other words, a very high number of women are being unnecessarily treated,” explains CNIO researcher Eva González-Suárez. “But at the moment there’s no way to avoid it”.
• Her new study, published in Nature Communications, identifies a marker that discriminates precancerous breast lesions that will develop into tumours
• The study also reveals that breast cancers originate in certain cells that the authors refer to as ‘infidel’

A discovery by the Transformation and Metastasis Group of the Spanish National Cancer Research Centre (CNIO) opens a path towards identifying precancerous breast lesions that will develop into tumours. This study, led by Eva González-Suárez, is published in the journal Nature Communications.

The research has focused on the role of the RANK protein, whose involvement in the genesis of breast tumours was also discovered by González-Suárez in 2010 at the Bellvitge Biomedical Research Institute (IDIBELL), where she still heads a clinical research line.

There are two types of cells in breast tissue: luminal cells, which produce milk, and basal cells, which are contractile and allow that milk to be ejected. Several studies suggested that breast tumours originate exclusively in a subpopulation of luminal cells, known as luminal progenitors.

The study now being published, with Jaime Redondo-Pedraza as first author, reveals, however, that tumours start in a different type of cells, referred to as infidel cells by the authors, and which derive from basal cells.

 The ‘traitorous’ cells where cancer begins

The new research shows that the expression of the RANK protein in basal cells causes them to lose their identity and become new cells that are neither clearly basal nor luminal, but rather hybrid, sharing characteristics from both types. These are the infidel cells.

All types of breast tumours would begin in these ‘traitorous’ cells, including luminal tumours, which express hormone receptors (+), as well as triple negative tumours that do not express them (-).

“What we know now is that basal cells in the breast can give rise to all types of tumours,” explains Eva González. “We could say that a defined cell identity protects against the appearance of tumours. However, when cells lose their initial identity and become these hybrid or infidel cells, regardless of their origin, that’s when cancer arises.”

Genetic signature in lesions that will progress to cancer

The group has developed a genetic signature that detects these infidel cells at the origin of precancerous lesions, identifying which of these cells will evolve into invasive tumours.

After identifying the genetic signature in mice, Eva González-Suarez’s group tested this new marker on a cohort of human precancerous breast lesions and confirmed that it can identify which lesions will indeed develop into cancer.

“A common diagnosis in breast medicine is ductal carcinoma in situ, which is considered a precancerous lesion, and it was previously impossible to know whether it would progress to cancer,” says González-Suárez. “As we haven’t been able to tell for sure so far, all women diagnosed with these lesions are treated as if it were already cancer. In other words, a very high number of women are being over-treated.”

Diagnoses of these precancerous lesions have increased thanks to screening programmes and the improvement of imaging techniques, to the point that, at this current moment in time, 20% of all cancer diagnoses are these precancerous lesions that are not actually cancer. Among them, only 30% will develop into cancer, but the inability to know which ones has led to the vast majority to be treated as cancer.

The genetic signature identified by Eva González’s group could detect which precancerous lesions will evolve into invasive tumours, that is, into cancer.

“Now we still need to confirm the signature with an independent cohort, and refine it to be able to use it in clinical practice to identify which lesions will indeed develop into invasive cancer,” González states.

About the National Cancer Research Centre (CNIO)

The National Cancer Research Centre (CNIO) is a public research centre under the Department of Science, Innovation and Universities. It is the largest cancer research centre in Spain and one of the most important in Europe. It includes around five hundred scientists, along with support staff, who are working to improve the prevention, diagnosis and treatment of cancer.