Breast cancers What if their invasive power were "latent" from the

1 April 2008
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Breast cancers
What if their invasive power were "latent" from the
beginning of their development?
Why are some cancers more aggressive than others? This was the question explored by a number of
doctors and Inserm 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 (see inset on "breast cancers").
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-Salomon1, a doctor/researcher at the Institut Curie working under Dr Olivier Delattre2, 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 transcriptome3 – 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…
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.
1
Find out more
about breast cancers
In 2005, the number of new cases of breast cancer in France was estimated at 50,000 by the Institut
National de Veille Sanitaire health watchdog. This is the most common form of cancer with women.
Furthermore, half the cases of additional cancers in women arising over the last 25 years are attributed to it.
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.
Their classification
At present, doctors diagnose cancer and classify it morphologically from the analysis of certain criteria:
histological type, the size of the tumour, possible glandular invasion, analysis of the presence of hormonal
receptors (oestrogens and/or progesterone), and overexpression of the HER2 protein. These parameters
then make it possible to decide on the treatment best suited to the patient.
Recently this classification was fine-tuned, thanks to the emergence of genomic analyses and their
application in clinics. They now make it possible to distinguish “luminal”, "basal-like" and "HER2+" types,
generally according to the coupled expression of certain proteins, mainly receptors with oestrogens and
HER2.
Reference
"Integrated Genomics and Transcriptomic Analyses of Ductal Carcinoma In situ of the Breast"
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2,3
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Anne Vincent-Salomon , Carlo Lucchesi , Nadège Gruel , Virginie Raynal , Gaëlle Pierron , Rémi Goudefroye ,
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4
5
4
1
1,6
Fabien Reyal , François Radvanyi , Rémy Salmon , Jean-Paul Thiery , Xavier Sastre-Garau , Brigitte Sigal-Zafrani ,
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1,2
Alain Fourquet , Olivier Delattre for the Senology unit of the Institut Curie
1
2
3
4
Tumour Biology Department, Institut Curie,
Inserm Unit 830, Transfer Department, Institut Curie, UMR144 CNRS/Institut
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6
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Curie, Surgery Department, Institut Curie, Head of the Senology unit of the Institut Curie, Radiotherapy department, Institut
Curie.
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Clin. Cancer. Research, vol. 14, p. 1956-1965, 1 April 2008
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