Why are some cancers more aggressive than others? This was the question explored by a number of doctors and other research scientists at the Institut Curie when they studied the biological profile of a form of breast cancer.
The results were astounding: tumour aggressiveness seems to be determined from the very first tumour cells and the biological diversity observed in invasive cancers already exists in localised forms.
These results could make it possible to define subpopulations of localised cancers and adapt the treatment according to the associated risks.
But with this work published in the Clinical Cancer Research issue of 1st April, the question remains of the origin of tumour cell aggressiveness: if it does not arise from biological modifications formerly acquired by tumour cells, how is the invasive capacity triggered off?
There is not one breast cancer: there are many sorts, and treatment differs according to the state of evolution, location and cells from which it is propagated.
15% to 20% of them are in situ canicular breast tumours: this localised cancer develops to the detriment of the epithelial cells of the galactophoric ducts, which convey the milk produced by the mammary gland. If it is not diagnosed in time, an in situ canicular breast carcinoma can invade the neighbouring tissues. Invasive canicular cancers represent 80% of all cases of invasive breast cancer.
Dr Anne Vincent-Salomon(1), a doctor/researcher at the Institut Curie working under Dr Olivier Delattre(2), Director of the "Genetics and biology of cancers" Inserm 830 Unit at the Institut Curie, has studied the biological profile of in situ canicular breast cancers. This work would not have been possible without the collaboration of the surgeons, anatomopathologists and radiotherapists of the Institut Curie Breast Cancer Unit headed by Dr Brigitte Sigal, nor without the help of biologists and biocomputer scientists from the Inserm/Institut Curie "Genetics and biology of cancers " Unit.
Drs Anne Vincent-Salomon and Olivier Delattre analysed the phenotype and genetic profile of 57 in situ canicular breast tumours, together with the gene expression – the transcriptome(3) – of 26 of these tumours. Now, these profiles at the localised stage are very similar to those observed with invasive in situ canicular breast cancers. Diversity, and in particular the invasive power of breast cancers, thus exists in the early stages.
Cancers characterised, for example, by a mutation of the TP53 gene or overexpression of HER2 receptors possess this alteration right from the first phases of their development. The classification – basal-like, luminal or ERBB2 (see inset on "breast cancers") – adopted to define invasive breast cancers and their treatment more clearly could thus be used with localised forms as well.
Another conclusion drawn from the work: since they are present from the very beginning of development, TP53 mutations or expression modifications in HER2 receptors are not those that trigger off the invasion of the cancers. Likewise for the alterations in the development genes that appear right at the start of the tumour's evolution. So how does a tumour acquire an aggressive character? If it does not arise from successive genetic modifications within tumour cells, could it be that a tumour's evolution depends on the genetic context in which it takes place?
Are there genetic specificities peculiar to the patient that influence the evolution of tumours? Maybe not everything is contained in the tumour cells alone…
Forms of breast cancer
There are many forms of breast cancer, depending on the stage of evolution, the location and the cells from which it is propagated.
The mammary glands are mainly composed of lobules, where milk is produced, and ducts serving to convey it. The initial phases of breast cancers develop from epithelial cells in the ducts or lobules.
While the cancer cells remain confined in the ducts or lobules, cancers are known as "in situ". With the increased use of screening through mammograms, nearly 20% of breast cancers are now diagnosed at this stage, compared with 2% previously.
On the other hand, once the cancer cells have broken through the membrane of the ducts or lobules (known as the "basal membrane"), and are present in the neighbouring tissues, the cancer is infiltrating. Cancer cells can then start to propagate in the glands under the arm (axillary glands) and possibly spread throughout the body.
There are also other less common forms of invasive cancer: mucinous carcinoma, micropapillary cancer, tubulous carcinoma, and some very rare forms such as medullary breast cancer.
(1) Dr Anne Vincent-Salomon is an anatomopathologist in the Tumour Biology Department at the Institut Curie. She undertook this work during her thesis carried out notably by means of an Inserm INTERFACE contract enabling her to devote her time to research while another doctor replaced her.
(2) Dr Olivier Delattre is the Inserm Research Director at the Institut Curie.
(3) The transcriptome is all the ARN messengers, the molecules serving as matrix for the synthesis of proteins from the expression of part of the genome of a cell tissue or type of cell.
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