Half of all breast cancers are diagnosed between the ages of 50 and 69, 20% before the age of 50 and 10% before the age of 40 (source ARCAGY). A precise diagnosis of breast cancer cannot be made on the basis of medical imaging alone. A biopsy is required to gain access to the suspect tissue and its cells, to determine whether they are benign or tumoral. This examination will be carried out by a radiologist who, under local anaesthetic, will take a tissue sample using a needle. This tissue sample will be taken from the area that appeared suspicious during mammography, ultrasound or clinical examination. The sample is then processed using a variety of dyes and reagents. In an anatomopathology laboratory. It will then be examined under a microscope by an anatomopathologist, who specializes in the analysis of organs, tissues and cells. It will take between a week and ten days before the results seen under the microscope are returned by the doctor. The doctor will first determine the nature of the cells observed. They may correspond to a non-invasive cancer, i.e. one that is confined to the immediate area where it started, and has not invaded adjacent tissues or other organs. These non-invasive cancers account for 15-20% of all breast cancers.
Non-invasive breast cancers, also known as “carcinoma in situ”, are cancers at an early stage. There are two different types :
Ductal carcinomas in situ (80-90% of non-invasive cancers) and lobular carcinomas in situ (10-15% of non-invasive cancers). The former are almost always discovered in post-menopausal women during mammography. On the images, the radiologist observes microcalcifications in almost 70% of cases. These ductal carcinomas in situ remain confined to the galactophore ducts, the ducts that carry milk from the glands that produce it to the nipple. The prognosis for these cancers is excellent, but they must be treated because, left untreated, they tend to progress to an invasive form.
Lobular carcinomas in situ are often discovered incidentally in pre-menopausal women, during a biopsy. These carcinomas remain confined to the milk-producing lobules. 70% of patients with lobular carcinoma in situ will not develop invasive cancer. Patients with this type of cancer will benefit from regular surveillance and a biopsy at the slightest doubt.
By examining the tissue sample, the pathologist can also make a diagnosis of invasive cancer. These cancers tend to invade surrounding tissues and may metastasize. As with non-invasive cancers, there are two main types of invasive cancer, depending on their origin:
Ductal carcinomas originate in the milk ducts and account for 80% of invasive cancers;
Lobular carcinomas start in the lobules and represent 10% of invasive cancers.
Rarer forms of invasive breast cancer include medullary and mucinous cancers.
On the tissue sample, the pathologist will study the level of expression of the Ki67 molecule, an excellent marker of cell proliferation. The higher Ki67 is, the more tumor cells proliferate.
He will also study the presence or absence of three important molecules which, when present on the surface of tumor cells, promote their multiplication: estrogen receptors (ER), progesterone receptors (PR) and epidermal growth factor 2 receptors (HER2). The results of this study are very important, as they will condition cancer treatment.
For the management of invasive breast cancer, a distinction is made between five subtypes of cancer that will be treated differently depending on the expression of hormone receptors ER and PR, HER2 and the proliferation marker ki67.
Anatomopathologists can also study the expression of the PD-L1 control point on the surface of tumour cells.
The PD-L1 checkpoint is used by cancer cells to suppress the immune system. High PD-L1 expression is indicative of a good response to immunotherapy.
To be complete, the diagnosis of breast cancer may require further analysis in a molecular biology laboratory.
In such a laboratory, mutations that may occur in genes are studied.
In the case of breast cancer, the mutations that will be particularly studied are those affecting the BRCA1 and BRCA2 genes. Other genes such as PIK3CA, GAT3, MAP3K1 or CDH1 are frequently mutated, and may also be studied to select a possible treatment targeting one of these genes.
