Breast cancer

The breast cancer is a Cancer developing starting from the units which produce milk, the units ducto-lobulaires of the Sein, primarily at the Femme (let us recall that the man has to him also an atrophied center). The Cancer of the center is a malignant Tumeur which touches the Glande mammaire. The malignant cells multiply in a disordered way until creating a tumor which attacks the neighbouring healthy fabrics. This tumor can propagate cancer cells in all the organization: it is said whereas it “metastasis”.

Epidemiology

The risk increases to a significant degree with the age between 30 and 60 years; it is homogeneous between 60 and 80 years; the Middle Age of the diagnosis is at 61 years.

There exist certain predisposing genetic factors, as well as hormonal factors.

Its incidence however significantly lowered (of approximately a little less than 9%) with the the United States since 2003, which would correspond to a less use of the substitute hormonal treatments of the Ménopause.

Breast cancer in France

breast cancer caused approximately 11 000 died in 1997, is 17,8 deaths for 100 000 inhabitants and 7,5 % of cancer deaths.
In the year 2000, one diagnosed 41 485 new breast cancers in France.
It is the first cause of mortality among gynaecological cancers of the women in the developed countries.
Less than 10% of breast cancers occurs before 40 years, 25% occur before 50 years, about half before 65 years.
breast cancer touches on average a woman on eleven.
In France, almost 10% of the women develop a breast cancer. 75% of the new detected cases are women of more than 50 years and this number is in continuous increase: 35.000 in 1995, 42.000 in 2001.
This increase is explained by many factors:

the ageing of the population, the frequency of cancer increases with the age;
the generalization of the tracking which makes it possible to diagnose more cancers and earlier. However, the diagnostic tracking of cancers of very slow evolution which would probably not have been diagnosed, nor even treated (one speaks then about Surdiagnostic);
modification of the lifestyle. Obesity is for example a risk factor of cancer of center;
the use of the substitute treatment hormonal of the Menopause. The impact of this treatment on the increase in breast cancer is recognized in the United States and very probable in France.

In the world

In 2002, one evaluated meadows of 1,1 million new cases, with more than 400.000 deaths which had with breast cancer. Nearly four million women develop a breast cancer (Boyle and Ferley, 2004). Because of the Surdiagnostic S, the Histological frequency of the examinations S conclusive with a " cancer" center depends especially on the intensity of tracking. Mortality decrease appreciably since the Nineties in the developed countries. It continues to grow in the other country.

Risk factors

It is primarily about a cancer of the woman. It is rare at the man (less than one breast cancer out of 100) but is more serious, the diagnosis being often later.

Breast cancers with genetic predispositions

5 to 10% of diagnosed breast cancers are breast cancers with genetic predispositions, that is to say between 2000 and 4000 people each year and person in charge of 550 to 1000 deaths in France.

Characteristics

Generally this type of breast cancer appears at a woman without particular health issue. Very seldom the woman is carrying a known genetic disease. Let us recall however that breast cancer reached certain men, but these cases are rather rare.

Several signs can make think of a breast cancer with predisposition Génétique

young Âge of the patient (average 43 years instead of 60 years in the nontransmissible forms)
Several cases in the family;
Cancer occurring on the level of the two centres in a successive or simultaneous way;
Appearance of the second cancer on the level of the ovary;
Standard histological medullary of cancer.

Mode of transmission

The Mode of transmission is of type Autosomique dominating; it is about the transmission of a abnormal Gène said “transferred”. The presence of only one change of gene exposes this woman at the risk of 80% to have a cancer of center instead of 10% in the absence of change.

The risk incurred by the women of a family where exists an abnormal gene depends on the fact that they or not inherited it. If they do not have gene, their risk is the same one as that of the other women, whereas if they inherited gene, they will have between 70% to 80% of risk to have indeed breast cancer.

The problem is similar for the cancer risks of the ovaries or the Côlon. In certain families one can observe the whole of these cancers among women in hot line (grandmother, mother, girl) or at close relationships (aunt, sister, German cousin). These cancers occur in general in the first part of their life.

A genetic Examen can then bring the proof of this very high risk, and all the relationships must be the subject of a followed monitoring. However, the tests of search for a transferred gene cannot bring certainty that if they are positive.

This very specialized act should be required only for the families whose women present probably a Hérédité genetic description by a consultation of Oncogénétique which will establish the Family tree of this family.

Genes in question

Two Gène S are identified:

BRCA1 on the chromosome 17. More than 500 changes or variations of sequence were already described.
BRCA2 on the chromosome 13. More than 100 different changes were counted.

Only part of the changes of these genes increase the risk factor of cancer. The changes of BRCA2 (1 woman over 1460) are found more frequently than the changes of BRCA1 (1 woman over 1960). These changes involve, in addition to on cancer risk of the center, one on cancer risk of the ovary.

The evolution of cancers carrying change on BRCA1 is variable according to the studies: more serious for some or of gravity similar to carrying changes on BCRA2 or not carrying changes.

The genetic Council

Any woman can, if she wishes it, profit from a genetic consultation whose objective is to determine the hereditary cancer risk. If the genetic risk of predisposition is higher than 25% one proposes with these patients a molecular diagnosis. This molecular research is particularly predictive if one knows the change in a relative already reached of a breast cancer with genetic predisposition.

Monitoring of the women at the high risk

The women at the risk of predisposition genetic or carrying a change, are followed by clinical monitoring every 6 months as of the 20 years age and by annual mammography as of the 30 years age.

Hyperoestrogenemy

Breast cancer is a hormono-dependant cancer: the factors increasing the rate of estrogen are thus at the risk.

Not-fruitfulness or late Fruitfulness

The women who did not have children, or who had their first pregnancy tardily (after 30 years) have a risk appreciably increased to develop a breast cancer, compared to those having had at least a child before 30 years.

Obesity

Obesity, by share the increase in the quantity of greasy fabric, increases the rate of blood estrogen.

Menopause late, Ménarche S early

Irradiations of the thorax

This risk is today in the process of disappearance and becomes exceptional, however it had been highlighted among many women having undergone radioscopies at the time where the pulmonary Tuberculosis was very widespread.

This risk had been found also among Japanese women who had been irradiated with amounts not mortals during the nuclear explosions of Hiroshima and of Nagasaki.

Mastopathies

It is a not very precise term indicating any disease of the center. One in general holds it for benign anomalies which can lend to confusion with a tumor and for this reason justify a taking away (Biopsie) allowing to identify them precisely. Some can support a later Cancer and justify a regular monitoring.

A dense aspect with the mammography, especially if it is extended, would increase the risk very appreciably to develop a breast cancer.

Tracking

It is possible to detect a breast cancer when it is still of very small size (less than one centimetre diameter) thanks to the Mammographie carried out within the framework of a regular follow-up. This monitoring will make it possible to increase the chances of cure, while profiting from less heavy treatments and less traumatisants that the Chimiothérapie and the surgery " mutilante" or ablation. Breast cancer is most frequent of female cancers. It is today the leading cause of mortality per cancer at the woman.

Between 50 and 74 years, age where the women are exposed to this type of cancer, it is advised to make a Mammographie every two years: it is an effective examination of tracking.

The objective of the Dépistage organized breast cancer is to reduce the Mortalité by breast cancer.

This tracking exposes to the risk of Surdiagnostic. correspondent with false-positive: the woman is regarded as carrying a breast cancer whereas it is not it, thus exposing it to a treatment not justified with all the side effects and the risks which follow. The benefit of this tracking must thus be carefully supported. It is highlighted in particular by a Méta-analyzes a significant reduction of mortality in the event of tracking. These results are however criticized.

The current proposal to regularly make a mammography with all the women from 50 to 75 years in France rests in particular on a report/ratio of experts worked out in 2001-2 by the department of Evaluation of technologies of the National agency of evaluation and accreditation of the care. The announced objective of this report/ratio included the recall of the French recommendations into force. The report/ratio concluded that the inefficiency of the mammography of tracking not being proven, the usual recommendations had to be maintained for tracking of breast cancer.

In France, the programs of Dépistage organized breast cancer propose with all the women, starting from around fifty and up to 74 years, a free examination mammographic every two years. A structure of departmental management or inter-secondary road sends to all the women from 50 to 74 years included an invitation for the mammography every two years. The structure can send an invitation on request (General doctor or gynecologist or of the woman itself). It must be carried out by an accredited radiologist, member of the network specialized in the Dépistage set up at the level of the departments.

On-diagnosis

Before the Menopause, the systematic Dépistage was not the proof of its effectiveness because the tiny suspect anomalies are frequent. The disadvantages seem in this case to override the advantages, except for the women at the risks.

In addition, according to a Swedish study , published at the beginning of 2006, the systematic tracking of breast cancer would lead to a Surdiagnostic and useless treatments or which could have waited, which would be the case in about 10% of the cases. The study consisted in measuring in 2001 the rate of breast cancer among women having taken part in the test between 1976 and 1986 and who did not continue tracking after their 74 years - age limit defined by the program - and to compare it with the reference group. This study reveals 10% of breast cancer in more among the women having profited from systematic tracking, whereas twenty-five years after the beginning of the test, the total rate of breast cancer should have been similar in the two groups - the rate of death into 2001 of the women of more than 80 years being similar in the rates groups (60%).

Several assumptions are already advanced: error of diagnosis or existence of cancers with slow evolution which do not become symptomatic within the framework of a normal life expectancy. According to the comment of the study, made by professors Henri Moller and Elisabeth Davies: “The risk to have a breast cancer for a woman is of 8% during her life; the risk to die of a breast cancer is of 2,5%. The tracking of 250 women makes it possible to prevent a cancer death of the center but can also lead to surdiagnostiquer 2 cancers (...) the woman whose death is avoided takes all the benefit of tracking, whereas the two surdiagnostiquées women pay part of its price, while wrongly becoming patients reached of cancer and under treatment. But we do not have the means of predicting which are these three women. ”

However, according to the department of the chronic diseases of the French Institute of health monitoring, these analyzes should in the future make it possible to make tracking even more powerful with as drank to identify cancers which will evolve/move of those which will remain latent, but without calling into question the benefit of tracking itself.

Diagnosis

Private clinic

The palpation of the center belongs to the annual gynaecological examination that practice any woman at the beginning of the sexual activity should make. Because of their anatomical situation, the centres are easy to palpate, all the more when they are of average volume or small.

At the time of palpation, suspicion is done starting from the discovery of a nodule, which one can approximately detect by palpation from 1 cm diameter. The irregularity can not be painful, but any recent anomaly must particularly draw the attention of the patient and her doctor.

Among the irregularities, that the patient can supervise itself:

a small cavity or a wrinkle digging the surface of the center with an aspect “orange skin”;
a deformation of the Nipple, retracting it towards the interior;
an eczematous aspect of the nipple which becomes red, croûteux or eroded;
a flow mamelonaire, especially if it is bloody or noirâtre.

The observation of the one of these signs must bring to a doctor visit very quickly. However, only the doctor will be able to consider examinations complementary necessary, because all these signs do not meet cancers only in the case of. A nodule can be of benign nature:

when it is of solid consistency, it can act of a Adénofibrome which developed in the gland mammaire;
when it is of liquid nature, it can act of a Kyste.

Mammography

The doctor can decide to make confirm its first diagnosis by a Mammographie. The echography is a complementary examination which can help to locate the anomaly to facilitate a taking away or to recognize if it is about a liquid cyst, but it can never replace the mammography. The mammography, practiced regularly and within the framework of the programs of Tracking, makes it possible to diagnose the disease at a sufficiently early stage so that the treatment is most preserving possible and at the same time effective.

Confirmation of the diagnosis

If the whole of the examinations still does not make it possible to make sure of a good diagnosis and so doubts persist, it is then necessary to consider a taking away carried out generally by a large needle (trocart) under local anesthesia without hospitalization. The taking away, or Biopsy, is often carried out under guide of echography or radiology; one then speaks about échoguidée biopsy and stereotaxic biopsy of the center. The diagnosis of certainty will be made by the anatomo-pathological study of the taken sample.

Various types of breast cancer

The anatomopathologic study shows the existence of various types of breast cancer. According to the the World Health Organization, table below watch the histological classification of breast cancers used in all the anti-cancer centers.

There exists as for any epithelial tumor of the in situ cancers. The most frequent variety of breast cancer is that of the canal type .

In situ Carcinome

Canal

Lobulaire

Infiltrating Carcinome

Canal

Lobulaire

5% of breast cancers
Recherche of the Récepteur S in Estrogène S is positive in 90% of the cases

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Assessment of extension

The search for metastasis S is fundamental in the strategy of the treatment of breast cancer. But in spite of the many studies carried out or the thorough knowledge of certain explorations, there does not exist currently any validated strategy of systematic search for metastasis in breast cancer. The search for metastasis will be done only according to the old one of the patient, the interrogation and the clinical examination:

Size of the tumor
Mobility of the tumor compared to the inflammatory muscle
Character of the tumor
Presence of the suspect to the clinical examination of hollows axillaire or known ganglia claviculaire

Treatments

As for all cancers, it rests ideally on the surgical ablation of the tumor, which allows in same time to make the diagnosis of certainty of it. The following problem is to make the assessment of extension : presence or not of ganglia reached, presence or absence of metastasis.

However the mutilation mammaire corresponds also in general for the women to a psychological and social mutilation, the centres being one of the symbols of femininity among strongest. Certain women can live this mutilation like a negation of their femininity and thus of their personality.

There also exists of other treatments like the Chimiothérapie, the Radiothérapie and the Hormonothérapie, which in certain cases can be used to obtain a reduction in the tumor in precondition of an surgical operation. The effectiveness and the risks of each type of treatment depend on the type of cancer, its extension and the ground.

Surgery

Ablation of the tumor

There exist three types of surgery of the center: the Tumorectomie (ablation of the tumor), the segmentectomy (ablation of part of the center) and the Mastectomie (ablation of the totality of the center).
Whenever the tumor is dealt with sufficiently early, tiny surgery (preserving surgery) is possible. Sometimes it is necessary to remove the totality of the center. A surgery reconstructrice can be made in same time or secondarily.

Clearing out axillaire

This technique consists of the ablation of the ganglia being in the hollow axillaire (on the level of the armpit). This operation has many side effects owing to the fact that this ablation destabilizes the lymphatic network, being able to lead to the appearance of a Lymphœdème (large arm). It is with an aim of decreasing these side effects that the technique of the ganglion sentinel was installation.

Technique of the ganglion sentinel

The ganglion sentinel is the first ganglion receiving the lymphatic drainage of a tumor.

The technique of the ganglion sentinel aims at the identification of this ganglion by injection of a dye and/or a radioactive colloid, and its Exérèse to make a anatomopathologic study. In the assumption of responsibility of breast cancer, its interest is to avoid a clearing out axillaire (exérèse of the near total of the ganglia of the area which generates considerable after-effects) in the patients which do not have a ganglionic attack. This could concern up to 70% of the patients presenting a tumor of less than 3 cm. This technique makes it possible to focus the histopathologic analysis on a small number of ganglia.

In the context of the generalized tracking of breast cancer, the tumors of small size with a risk of ganglionic invasion weak will be more frequently diagnosed. The technique of the ganglion sentinel will thus be addressed particularly to these patients. She is regarded today as validated. Many American teams and Frenchwomen use it already and the publications on this subject are very numerous.

Radiotherapy

The Radiothérapie reduces mortality by breast cancer but it requires an irreproachable technique in order to reduce the irradiation of healthy fabrics being able to involve a surmortality by cardiovascular pathology. One distinguishes the radiotherapies on the bearing center from those on the ganglionic surfaces.

In the event of preserving surgery, a radiotherapy must always be realized because it decreases the risk of local repetition significantly. The radiotherapy will be all the more important as the woman is young.
In the event of total ablation of the center, the radiotherapy is indicated, in certain cases, to decrease the risk of local repetition.
the irradiation of the ganglionic chains is function of the localization of the tumor and the result of the anatomo-pathological examination of the ganglia.

Chemotherapy

The Chimiothérapie consists in managing anti-cancer drugs in intravenous perfusion, with a fixed interval, in general every 3 weeks. The number of cures of auxiliary Chimiothérapie (chemotherapy carried out after the surgery) for breast cancer is between 4 and 6. The advantages of auxiliary chemotherapies compared to the surgical treatment without chemotherapy are a significant reduction of mortality and a less rate of repetition. In the event of ganglionic attack axillaire, the diagram associating 3 cycles of chemotherapy with anthracycline (Farmorubicine°) and cyclophosphamide (Endoxan°) then 3 cycles with docetaxel (Taxotere°) is currently the reference. For cancers without ganglionic invasion axillaire, the search for factors of bad forecast which can explain an unfavourable evolution (high histological rank, not of hormonal receivers, cuts tumoral higher than 15 even 10 mm for some,…) allows to also pose the indication of an auxiliary chemotherapy. Breast cancers which surexpriment Her2 in an important way (this relates to approximately 25% of cancers mammaires, often of bad forecast, since Her2 - or CerbB2 - is the membrane receiver making it possible to activate one of the ways of the increased proliferation cellular) find with trastuzumab (Herceptin°), a monoclonal antibody blocking this receiver. Added to auxiliary chemotherapy, Herceptin° in perfusion every 21 days, for 12 months, involves an important improvement of the survival of the patients.

In the event of advanced or inflammatory tumor, it is sometimes necessary to begin the treatment by a chemotherapy (néo-auxiliary Chimiothérapie) to decrease the tumoral size and to possibly allow a surgery conservatrice.
Néo-auxiliary chemotherapies are also practiced in order to limit the size of the exérèse: a tumorectomy is sometimes sufficient when a mastectomy with auxiliary chemotherapy was initially envisaged.
In this last indication, whereas total mortality, the time of aggravation of the disease and the rate of remote repetition are not different compared to auxiliary chemotherapy, the loco-regional repetitions would be more frequent. There currently does not exist protocol of néo-auxiliary chemotherapy of reference.

Its disadvantages: general tiredness, nauseas and vomiting, fall temporary of the hair. However they vary according to the products used and are better and better controlled.

Among the various products used, some really proved reliable within the framework of the auxiliary Traitement of breast cancer and constitute a protocol of reference, but with the time of other products arrive on the market and are the subject of studies.

Hormonothérapie

Approximately two thirds of breast cancers present to surface cancer cells hormonal receivers. At the woman, the estrogens stimulate the cancerous proliferation via these receivers. In breast cancer the treatment hormonal will act either by decreasing the rate of estrogens in the blood and thus the stimulation of the receivers hormonal (castration, anti-aromatases), or by blocking the receiver hormonal (Anti-estrogens).

The various types of hormonal treatments are the ovarienne suppression, the anti-estrogens, the antiones and the progestatifs.

Ovarienne suppression

surgical, by laparotomy or radic coelioscopy
, by carrying out 12 to 16 Gray into 4 to 8 fractions on small a pelvis, after having located the position of the ovaries by echography;
medical, by using the agonists of the LH-RH

LEUPTORELINE Enantone LP 3.75 Mg/4 sem
GOSERELINE Zoladex 3.6 Mg 4 sem
Note: decapeptyl does not have AMM in breast cancer

anti-estrogens

TAMOXIFENE 20 mg/j

Mechanism: antagonist partial of the receivers oestradiol
Precaution: to make examination endometer 1/an, to control hepatic function and triglycerides, to proportion plasmatic oestradiol and to add LHRH if increased, effective contraception (teratogenic).

FLUVESTRANT 250 Mg IM every 28 days

Mechanism: antagonist of the receivers to the estrogen without action partial agonist.

The use of tamoxifene is beneficial if there exist receivers with estrogenes on the level of the tumor whatever the age of the patient. The optimal duration of application of the auxiliary Hormonothérapie by tamoxifene is 5 years to the amount of 20 mg/j. The use of tamoxifene reduces the risk of repetition of 8% and that of death of 5%.
A Castration (surgical or by radiotherapy) of the woman is sometimes necessary if the patient is not ménopausée. This technique of castration is less and less used and replaced by a medicamentous castration.

Anti-aromatases

LETROZOLE 2.5 mg/j Femara

Mechanism: Inhibiters of the aromatases not stéroïdiennes
Precaution: osseous density, dyslipidemy

ANASTROZOLE 1 Mg Arimidex

Mechanism: Inhibiters of the aromatases not stéroïdiennes
Precaution: osseous density, dyslipidemy

EXEMESTANE 25 Mg Aromasine

Mechanism: inhibiter of the aromatase stréroïdien
Precaution: osseous density, dyslipidemy

Since 2004, new molecules can be proposed to the ménopausées women. They are the inhibiters of the Aromatase. The two most evaluated molecules are the Anastrozole and the Letrozole. Their profile of toxicity is different from tamoxifene. The administration of these 2 molecules makes it possible to reduce the relapses after surgery of breast cancer, without benefit when with total survival (versus tamoxifene).

Therapeutic strategy

There exists a great number of treatments available for breast cancer. Each situation must be individualized and treated in an optimal way.

Breast cancer localized

Metastatic breast cancer

Monitoring of an operated woman of a breast cancer

After the head end, it is essential that the patient is followed regularly.

The multiplication of the examinations is not necessary, but the annual Mammographie becomes essential, especially in the event of preserving surgery. According to the case, it could be associated with other definite complementary examinations according to each case.

Even a breast cancer treated in an optimal way can repeat locally or remote (metastasis). The repetition can occur of the years after the head end, from where interest to maintain the monitoring.

Psychological effects of a breast cancer

Cancers

To learn that one has a cancer is very difficult to assume, so much this new was regarded a long time as that from an imminent death. In addition the auxiliary hospitalization, surgical operation and treatments change the life of the patient radically. It is thus essential to bring to the patients an adapted psychological support.

In France, the association of Psycho-oncology studies how to help the cancer patients as well as possible, which passes in general by the participation in groups of patients who live the same tests.

Breast cancer

The treatments of breast cancer increasingly effective and being médiatisés as such, the psychological effects on the patients are often less heavy than before.

However breast cancers diagnosed tardily are often very mutilating. This mutilation mammaire corresponds in general for the women to a psychological and social mutilation. The center being one of the strongest symbols of the Femininity, certain women can live this mutilation like a negation of their femininity and thus of their personality.

Within this framework, the surgery réparatice is advised in connection with a psychological assumption of responsibility.

Sources, notes and references

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