breast cancer

Breast cancer

Breast cancer is a malignant tumor of the mammary gland. In other words, it is a cancer which develops in the cell units whose function is to secrete milk, units ducto-lobular breast, mainly women. 8 out of 10 breast cancers occur after 50 years

5-10% of these cancers have a hereditary genetic origin; 85 to 90% of cases (form so-called sporadic or inhabitants) have environmental or unknown origins. A significant proportion of the sporadic breast cancers is induced by taking hormones, estrogen and progesterone in contraceptives or treatments for menopause. Risk factors include alcohol, sugar, dairy, hydrogenated fats, obesity, lack of physical activity. Late first pregnancy and the lack of breastfeeding would also promote cancer.

The treatment will appeal according to protocols to the surgery, radiotherapy, chemotherapy, the combination of these treatments can be completed with hormone therapy.

Epidemiology
The risk increases significantly with the age between 30 and 60 years; It is then homogeneous between 60 and 80 years old; the average age of diagnosis is 61 years old.

There are some factors genetic predisposing, as well as hormonal factors.

It is worth noting that the incidence has declined significantly (by a little less than 9%) to the United States since 20031 and also in France2, which would correspond to a lower use of substitutive hormone treatments for menopause.
In 2002, it was estimated nearly 1.1 million new cases, with more than 400,000 deaths from breast cancer. The impact seems to increase steadily with more than 1.6 million new cases in 2010 and 425 000 deaths3. Nearly four million women develop cancer third4 [ref. inadequate]. The frequency of histological examinations finding a 'cancer' of breast especially depends on the intensity of screening (see overdiagnosis). Mortality decreases significantly since the 1990s in developed countries. It continues to grow in other countries.

The breast in France
The France is part of the country where the incidence of breast cancer is very high on a plan mondial5, 6, and where the incidence rate of breast cancer increased as fast (+ 2.4 per 100,000 women per year) over the period 1980-2005, with a decline in this rate between 2000 and 20 05 (+ 2.1 per 100,000 women per year) 7.

Breast cancer has caused about 11 000 deaths annually in the years 20008,9, the mortality is stable (11 201 deaths in 2005) 10.
One in eight women is affected by France11 breast cancer.
It represents more than one new case of cancer on 3 (36.7% in 2008) on the set of new cancers, at the femme12.
In the early 2000s, are diagnosed each year about 50 000 new cancers of the sein9.
In 2005, this number was 49 814, which corresponds to a rate of incidence among the highest in Europe. This rate has increased in France by 2.4% on average per year for 25 years (from 1980 to 2005) 7.
Less than 10% of breast cancers occur before age 40, 25% occur before age 50, almost half by 65.
Almost 10% of women develop breast cancer. 75% of the new cases detected involving women more of 50 years and this number is constantly growing: 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 age;
the generalization of the screening to diagnose more cancers and earlier. Indeed, screening diagnostic also of very slow-growing cancers that would have probably not been treated, nor even diagnosed (called overdiagnosis);
changes in lifestyle. Obesity, alcool13 intake and tobacco 14, most common in women in recent decades, are also risk factors;
use of substitutive hormone treatments for menopause. The impact of this treatment on the increase of breast cancer is recognized in the United States and very likely in France [ref. necessary].
Cancer is part of one of the three cancers for which survival has increased since the survival rate went from 80% to 87% in the early 2000s according to a joint report of the Institute of health monitoring, network Francim of cancer registers the national cancer Institute and the Hospital of Lyon15.

The breast in East Asia

The breast in China

Women in China, breast cancer is the most common, and the leading cause of cancer deaths. Breast cancer mortality has increased in recent years. Data from the second and third national surveys by retrospective survey of causes of death in China believe that breast cancer mortality has increased between 1990-1992 and 2004-2005 3.84 per 100 000 to 5.09 per 100,000. In 2008, approximately 169 000 new cases of breast cancer were diagnosed, and it was the most frequently diagnosed type of cancer in Chinese women. During this same year, breast cancer mortality was 5.7 per 100,000, resulting in about 44 900 deces16.

The Japan breast cancer

According to a study published in 2009, the incidence of breast cancer is historically much lower in Japan than in Western countries; between 1998-2002 in Osaka are a rate of 32.0 per 100 000 women, that compares with a rate of 105.6 per 100,000 Caucasian in Hawaii women and 107.5 per 100,000 Japanese women in Hawaii. The author notes the higher consumption of soy-based foods to the Japan that in Western countries and its effects on rates of cancer of the breast to the 17 countries.

Risk factors

Sporadic cancers (non-familiaux)

5-10% of breast cancers diagnosed are cancers of the breast to predispositions genetiques18, 19. Non-familiaux cancers are the remaining 90 to 95%.

Possible mechanisms

Of many molecules or molecules cocktails seem to trigger or promote breast cancer; regarding the mechanisms in question:

An inhibition of the DNA damage response system could be involved in half of the cancers of the breast, especially for those who are initiated or facilitated by the hormones used for hormonal treatment of menopause.

A protein (Akt1) is sur-exprimée in 50% of sporadic breast cancers. She could therefore predispose to breast cancer and/or be involved by other processes (environmental and not genetic). Activation of AKT1 actually lead to inhibition by sequestration of the BRCA1 protein in the cytoplasm; However, if this protein can no longer penetrate and circulate in the nucleus, DNA is more fixed (as in the absence of gene BRCA1 in the case of many hereditary cancers). AKT1 is also activated by the hormones that is suspected of causing cancer of the breast (in a chronic way in women following a long hormone estrogen). In this case, the non-mutated BRCA1 gene may be disturbed, with as consequence an increased risk of cancer of the sein20, 21.

Similarly another protein; "protein-kinase CK2" (enzyme important for epithelial cell plasticity), seems to be involved in the progression of these cancers22; the alteration in the activity of this protein is accompanied by a transformation of epithelial cells into cancer cells (mobile and source of metastases). Normally, this protein seems to prevent the cellular mechanism says "Epithelial-to-Mesenchymal Transition" (EMT; process of evolution of the epithelial cells to a State mesenchymal and mobility, with a resistance to some anticancereux22). This enzyme combines two elements; a "catalytic subunit" (CK2α) and of a "regulatory subunit" (CK2β). A malfunction of the CK2β subunit, allowing the EMT seems involved in the production of metastases for this type of cancer22.

Hormonal causes (hyperoestrogenemie)

Breast cancer is often a hormone-dependent cancers: factors increasing the rate of estrogen are therefore at risk. Schematically, the risk of breast cancer increases with the number of menstrual cycles, whether they are artificial (pill oestrogen) or naturels23.

The hormone replacement therapy for menopause significantly increases the risk of cancer of the sein24.

Early puberty and late menopause are acting by increase in the number of menstrual cycles and therefore rates of estrogen. The factors of precocious puberty are: childhood obesity, the increase in the consumption of animal protein (meat, milk), consumption of sugary drinks, exposure to the disruptive endocriniens25.

Non-fecondite or late fertility

Women who have not had children, or who have had their first pregnancy late (after 30 years) have a significantly increased risk of developing breast cancer, compared with those having at least one child before 30 years. These are indeed the cycles prior to the first term pregnancy that seem the most dangerous for the breast. Pregnancy protects breast by the mammary cells changing in the direction of greater differentiation. Differentiated cells are less sensitive to carcinogens in particular hormone. Pregnancy is like a vaccine to estrogen. More this first pregnancy occurs early, better it agit26, 27.

Pollutants and other endocrine disruptors

The Endocrine Society, in a statement written by experts internationaux28, stresses the parallelism between the increase in the incidence of cancer of the breast for the last 50 years and the proliferation of synthetic chemicals with one estrogenic or carcinogenic action. These countless products (the best known being the, DDT, Bisphenol A and dioxins), variety of sources (pesticides, chemical industry, plastics and plasticizers, fuels and other ubiquitous chemicals in) the environment), are a source of major concern for endocrinologists. Thus, the girls have been very exposed in utero in the 1960s to DDT have a fourfold increase in the risk of breast cancer according to a study published mid-201529. Diet plays a majeur30 role.

The Endocrine Society issued a series of recommendations designed to

increase the understanding of the effects of endocrine disrupters (including by basic research and clinical studies);

to invoke the precautionary principle;

promote individual involvement and that of learned societies to publicize the problem;

make legislative changes.

Synergy between cancer and obesity or overweight

For poorly understood reasons, obesity increases the risk of cancer of the breast, and particularly rapid proliferation of this cancer31. This has been demonstrated in vivo as vitro; Thus, when tumor cells (murine or human) are cocultivées with mature adipocytes, these increase the invasive capacity of cancer. In General, obesity would double the risk of developing cancer of the sein32. 

Obesity, due to the increase in the amount of fatty tissue, increases the rate of blood estrogen via activation of an enzyme called aromatase. In fact, it transformed type androgen into estrogen hormones. This persists after menopause; A study showed the increased risk of cancer of the breast in postmenopausal women based on their poids33 decision-making.

Of fat cells grown with cells present a modified phenotype in terms of defatting, and a decrease in markers of fat cells associated with an abnormal active characterized by an overexpression of proteases, including the metalloproteinase-11, and inflammatory cytokines (Interleukin-6 (IL-6) or it-1β 34.) 

Conversely, tumor cells of breast cancer affect fat cells (adipocytes) of the breast. These secrete including inflammatory factors including Interleukin 6 (which in-vitro alone is enough to make metastasiques of cancer cells) 34. This may explain why obesity increases the risk of metastasis and rapid dissemination of this cancer. Remains to understand the determinants of dialogues between cancer cells and adipocytes35, and larger tumors and/or involving a contribution of lymph nodes present higher levels of IL-6 in the tumor surrounding the adipocytes34. 

Peritumoraux adipocytes present a modified phenotype and biological features specific enough to be named fat cells associated with cancer (or CAA for Cancer-associated fat cells) 34.

Animal fatty acids, saturated fatty acids and trans

He showed that the consumption of animal fats and fatty acids trans (that fit in the composition many preparations of food industry) were risque32 factors. This relationship between the level of animal fat intake and breast cancer has been known for longtemps36, 37. The influence of polyunsaturated fat is less evidente38

A (Inserm-Gustave-Roussy, 1995-1998) study showed that the risk of breast cancer increases close to 50% among women with high blood acid trans fats, products that may be present in processed foods such as breads and cookies industrialists, pastries, cakes, chips, pasta with pizza39.

Dairy products

Several scientific studies hold milk as risk factor for hormone-dependent cancers such as prostate, ovaries and of the sein40, 41. The increased risk is linked to the increase in the rate of IGF - 1 in blood, itself strongly correlated with consumption of lait42. The link seems well established in phase pre-menopause43 and also seems consistent with the absence of cancer in the population of Laron syndrome, which produces no IGF - 1. The IGF - 1 concentration varies widely depending on the type of milk (cow, goat, sheep) 44, if he is reduced to 45, or the breeding of ruminants (bovine somatotropin) mode. However, other studies establish a protective role related to the content of the milk in vitamin D and calcium46, 47.

Alcohol and tobacco

The increase of the risk and the frequency of breast cancer is at least partly due to the increase of women's alcohol consumption;

Many studies have shown that alcohol consumption (whatever it is; wine, beer or liquor hard) increases the risk of breast cancer. This risk is increased on average by 30% for three glasses of alcohol by jour13. Meta-analyses have confirmed the role of alcohol in the Genesis or the facilitation of the breast cancer. A study estimated that the risk had been overestimated, but she has been refuted by a meta-analysis based on 98 studies case-control and prospectives13.

The risk is growing by 10% per 10 g of extra alcohol consumed on average by jour13 with different genetic sensitivities according to individuals, some sub-populations exposed to other carcinogenic risk can also be more sensibles13. Other factors aggravate indeed this risk: having more than 50 years, be post-menopausal, be affected by benign breast disease, a tumor involving estrogen and/or tumors progress/invasives13 receivers.

This risk doubles in case of chronic alcohol consumption (in women with a normal body mass index (BMI < 25), while obesity is another factor often cited).

The consequences of alcohol as factor or co-factor carcinogen on the breast could be fast enough, because statistics show that the impact of recent consumption is more significant than that of anciennes13 consumption.

There is a correlation between smoking and the onset of this cancer48.

Lack of vitamin D

Vitamin D and its analogues pharmaceutical have anti-proliferation and pro-differenciation effects. It has importance for the prevention and treatment of cancers in general. Notably, it can limit excessive production of estrogen, by acting on the aromatase49.

Breast cancer is often associated with low vitamin D levels (deficiency or deficiency in 78% of cases according to a study of 145 patientes50). An excess of mortality from cancer (including breast cancer) among African Americans is attributed to their pigmentation, which blocks most ultraviolet rays than necessary at these latitudes and hinders the production of vitamin D in a way marquee51. A French study of evolution over 10 years by 68 000 women confirmed the importance of the link between vitamin D deficiency and occurrence of breast cancer. Analysis of the index of exposure to the UV rays these women showed that only those who were most exposed to UV were getting sufficient protection against breast cancer so that food intake has a measurable impact. for all others, INSERM team concludes that, the longer you live to the North, it is difficult to reach this threshold of vitamin D protect the sein52 cancer.

Mastopathies

It is an imprecise term for any disease of the breast. Reserved generally for benign abnormalities that may be confused with a tumor and to justify a sample (biopsy) to identify them precisely. Some may encourage subsequent cancer and warrant regular monitoring.

A dense aspect to mammography, especially if it is extended, would significantly increase the risk of developing cancer of the sein53.

Other

Historically, it had been highlighted in women who have had many pictures at the time where pulmonary tuberculosis was widespread. This risk was also found among Japanese women who had been irradiated for nonlethal doses during nuclear explosions of Hiroshima or Nagasaki. It is essentially at the beginning of the twenty-first century of cases of chest radiotherapy in the treatment of certain cancers - Hodgkin's disease in particular - in young women in whom the risk of breast cancer increases substantiellement54. Some new forms of radiological examinations, such as the coronary scanner, can lead to a sufficient irradiation to increase the risk of cancer of the breast of the decades after the completion of the examen55.

Night work could increase the risk of cancer of the sein56, 57. This risk has been recognized legally in the Denmark and subject of compensation financieres58.

Breastfeeding acts as a protector against cancer of the sein59, including by developing ovaries sleep and decrease in the number of cycles.

The voluntary interruption of pregnancy does not increase the risk of cancer of the sein60

In men

1 percent of the breast cancers is developed by a man. At equal stage, the prognosis is identical. Nevertheless, the mammary gland in humans is very small, the diagnosis is often late, it is has so many more cancers detected at a point changed, accompanied by a skin involvement or deep plans (T4) 61. The risk of getting breast cancer is increased in men with a family of breast cancer history, particularly when there is a mutation of the BRCA1 and BRCA2 genes.

Factor size prenatal

In rich countries (no not there studies on this point elsewhere), larger than average at birth is correlated with a future risk of breast cancer. Fetal exposure to certain hormones involved in growth could be involved (to be confirmed). 5 percent of the breast cancers of women born in developed countries would be directly concernes62.

Family cancers

5-10% of breast cancers diagnosed died of cancers of the breast to predispositions genetiques18, 19, either between 2,000 and 4,000 people each year, 550 to 1,000, in France. In 2008, ten genes were associated with an increased risk of breast cancer. Nine are related to the system of response to DNA damage. The tenth code a protein that inhibits the action of the enzyme AKT1 (enzyme which inhibition also plays a role in non genetic cancers). Two of these ten genes (so-called BRCA1 and BRCA2) are to them solely responsible for half of these cancers to genetic predisposition, or 2.5 to 5 percent of all breast cancers.

Features

Most often, this type of breast cancer appears in a woman without any particular health problems. Very rarely, the woman is a carrier of a genetic disease known.

Several signs may suggest a genetic predisposition to breast cancer:

Young (average age 43 years instead of 60 in non-communicable forms);

Family history of breast cancer;

Cancers occurring at the level of both breasts in a successive or simultaneous way;

Appearance of a second level of ovarian cancer;

Medullary histological type of cancer.

Mode of transmission

It is autosomal dominant type. In a woman, the presence of a single gene mutation puts at risk by 80% to have breast (instead of 10% in the absence of mutation).

The risk for women coming from a family where there is an abnormal gene depends on whether they have inherited or not. If the inherited gene is not abnormal, the risk is similar to that of other women; If the gene is mutated, they will have between 70 to 80 percent chance of having breast cancer. The problem is similar to the ovaries and colon cancer risk. In some families, we can observe these cancers in the direct line (grandmother, mother, daughter) or close relatives (aunt, sister, cousin). These cancers occur generally in the first part of their life.

A genetic test can highlight this risk, but a search of a gene test brings certainty that if it is positive (in this case, all the relatives should be monitored). This very specialized Act must be requested only for families whose women likely have an heredity risk, highlighted by a genetics consultation which will establish the family tree of this family.

Genes involved

Two genes are identified:

BRCA1 on chromosome 17. More than 500 mutations or variations of sequence have already been described.

BRCA2 on chromosome 13. More than 100 different mutations have been identified.

Only a portion of all these mutations increase the risk factor for cancer. Mutations of the BRCA2 (1 woman in 1460) are found more frequently than mutations of BRCA1 (1 woman in 1960). In addition to the excess risk of breast cancer, these mutations cause a higher risk of ovarian cancer.

The probability of developing cancer of the breast in a carrier of a mutation of BRCA1 is about 65% before the age of 70 (45% to the carriers of a mutation in the BRCA2) 63.

The evolution of mutation in BRCA1 carriers cancers is still poorly known: worsening according to certains64, for others, gravity similar to carriers of mutations on BCRA2 or non-porteuse of mutations65.

These mutations prevalence remains low in patients with breast cancer (less than 4% for BRCA1, even if it is double among the Jewish ashkenazes66).

Genetic counseling

In some countries, any woman wishing it may be a genetic consultation to determine her risk of hereditary cancer. If the probability of genetic predisposition is greater than 25%, proposed a molecular diagnosis in these patients. This molecular research is particularly predictive if we know the mutation in a parent already with breast cancer to genetic predisposition.

Surveillance of women at high risk

Women at risk of carriers of a mutation or genetic predisposition are followed by teams of clinical monitoring every 6 months at the age of 20 years and annual mammogram at the age of 30 years [where?]. Among the factors increasing the risk, are the existence of a ductal carcinoma in-situ, considered a precancerous form, and carcinoma lobular in situ, more benign but can evolve into cancer in 20 to 30% of cases identifies67.

Screening

Detect and treat tumors when they are very small (less than a centimeter in diameter) is possible thanks to mammograms and regular follow-up. This reduces the risk of mortality, and allows treatment less heavy and less traumatic than chemotherapy, "mutilating" surgery (ablation). It's between 50 and 74 years that women are most vulnerable to this type of cancer. A mammography every two years allows effective screening, but that puts at risk of surdiagnostic68 corresponding to a false positive: the woman is considered to be carrier of breast cancer while it is not, the Exhibitor so no treatment justified with all the side effects and risks that ensue. The benefit of this screening must therefore be carefully supported. According to a meta-analysis of 2003, a significant reduction in mortality in the case of screening can be highlighted in some cases; the same meta-analysis reported however two other competing studies showing a lack of signficative69. However, the existence of a risk reduction is critiquee70.

In France, an inter-departementale or departmental management structure sends to all women aged 50 to 75 an invitation for a "free" mammogram (financial support to 100% by social security) every two years. The invitation can be sent on request of the practitioner, gynecologist or the woman herself. The visit must be made at a certified radiologist, Member of network specialized in screening put in place at the level of departments. This strategy is based on an expert report prepared by the Department of technology assessment of the national agency of evaluation and accreditation of care in 2001-2. The announced goal of the report included the recall of French recommendations into effect. The report concluded that the ineffectiveness of the mammography screening is unproven, maintain the recommendations in use for the detection of breast cancer.

An associated with mammography ultrasound can detect a greater number of cancer but is associated with a number more important false positives (biopsy refute the diagnosis of cancer) 71. The place of examination in the screening strategy remains to evaluate.

Imaging by magnetic resonance (MRI) would also be a promising review with a sensitivity higher than that of the mammographie72.

In 2015, a Danish research team has developed a blood test to detect cancer and even to predict if the person develop one within 2-5 years to come. The technique to measure some metabolites present in the blood and the metabolic profile of the plasma sanguin73.

Self-examination was a technique of testing very in vogue in the years 1980-1990, but still recommended not having the evidence of his efficacite74.

Beyond 75 years, the value of routine screening is not demonstrated. It seems to be between 70 and 75 ans75. For 50 years, the interest is debatable, but not less proved by the mortalite76, 77.

Overdiagnosis

Before menopause, the routine screening did not evidence of its effectiveness because minimal suspicious abnormalities are frequent. The disadvantages in this case seem to outweigh the benefits, except for women at risk.

The risk of screening is a wrong diagnosis and result in unjustified support, with a cost and a risk as a result. It's called overdiagnosis. As part of breast cancer, mammography may result in a significant rate of overdiagnosis. This proportion could go a case dix78 a case on quatre79, or even a case on deux80. The relationship between the number of lives saved and the number of women with an overdiagnosis (partially reflecting the so-called risk/benefit of a review report) can vary so 1 in 2 to 1 in 10.

The explanation of these over-diagnosis is not unequivocal: misinterpretation of documents, cancers of evolution very slow or even spontaneous regression of some tumors malignes81.

However, according to the Department of chronic diseases of the Institute french Health Watch, these analyses are expected in the future to make screening more efficient with as purpose to identify cancers that will change who will remain latent, without calling into question the benefit of screening itself.

Diagnosis

Clinic

Palpation of the breast is the first review. Due to their anatomical location, the breasts are easy to palpate, especially when they are of medium or small volume. It is recommended that patients realize this review themselves routinely at the end of the rules.

During palpation, the suspicion is based on the discovery of a nodule, that can be detected by palpation from 1 cm in diameter approximately. The irregularity may not be painful, but any recent anomaly must particularly attract the attention of the patient and his doctor.

Among the irregularities, that the patient can watch itself:

a dimple or a wrinkle digging the surface of the breast with an "orange peel" appearance

a deformation of the nipple, retracting it inwards;

apportioning part of the nipple that turns red, crouteux or eroded;

a nipple discharge, especially if it is bloody or blackish.

Finding one of these signs should lead to a medical consultation very quickly. However, only the doctor can determine the necessary complementary examinations, because all these signs meet not only in the case of cancers. A nodule may be benign in nature:

When it is of solid consistency, it may be a fibroadenoma, which developed in the mammary gland;

When it is fluid, it may be a cyst.

Mammography

The doctor may decide to confirm his initial diagnosis by a mammogram. Ultrasound is a further examination that can help locate the anomaly to facilitate a levy or to recognize whether it is a fluid cyst, but it can never replace the mammogram. Mammography, practiced regularly and as part of screening programs, allows to diagnose the disease early enough to make the more conservative treatment possible and at the same time effective. Indeed as long as the size of the tumor is less than 1-2cm, the chances of recovery are close to 100% 82.

Review by infrared thermography

The use of thermography infrarouge83, 84, 85, for the detection, is a review with fewer side effects (no radiation), with a better sensibilite86, 87, 88, less false positives and earlier than mammography detection. The cost of the thermography would also be significantly lower than that of mammography, whose annual budget is 250 million Euros89. Thermography is however, in 2017, almost not used in France90, 91.

Confirmation of the diagnosis

If all examinations does not always ensure a proper diagnosis and if doubts persist, it is then necessary to consider a levy directed most often by a large needle (trocar) under local anesthesia without hospitalization . The removal, or biopsy, is often performed under guidance of ultrasound or Radiology; This is called guided biopsy and stereotactic breast biopsy. The diagnosis of certainty will be the anatomopathological study of the sample taken.

Extension assessment

The research of metastases is fundamental in the strategy of treatment of breast cancer. But, despite many studies or in-depth knowledge of certain explorations, there is currently no validated strategy of systematic research of metastasis in breast cancer.

Currently, most of the recommendations offer an assessment of the extension with a chest x-ray, a liver ultrasound and a bone scan. For very small tumors, this balance may be optional. In contrast, for advanced tumors (tumors inflammatory, multifocal, important ganglionic invasion), initial metastatic risk is high and can justify a further check with CT scan (CT) body and a Breast MRI.

The size of the tumor, the existence of metastatic Lymphadenopathy, the existence of a breach of the skin or chest wall or distant metastases can establish a clinical classification of breast cancers.

Different types of cancer and carcinoma of the breast

WHO classification

The pathological study shows the existence of different types of breast cancer. According to the World Health Organization, the table below shows the histological classification of breast cancers used in all cancer centers.

There are as for any epithelial tumor cancers in situ. The most common variety of breast cancer is ductal type.

Inflammatory cancer

The sein93 inflammatory cancer is a rare form of breast cancer (1-4%) that develops quickly in a few days or a few weeks. It spreads by lymphatic route quickly without having the time to form a tumour. The blockage of the lymphatic vessels by cancer cells is at the origin of a local inflammation of the breast of varied significance. The diagnosis of breast abscess is often referred to initially as imaging (mammography and ultrasound) is often negative. Any persistence of a more or less painful redness of the breast requires to do biopsies, which only will argue the disease. The treatment is based primarily on chemotherapy which recent advances allow healing in many cases.

Histological and molecular classification

Research on cancers of the breast, there are mainly four types of breast cancer according to their morphology and the presence of three markers molecular: that of the receiver to the estrogen (ER), and overexpression of the progesterone (PR) receiver, and the marker HER2, the latter being a receptor EGFR 94. The resulting four classes are:

Basal: ER-/ PR-/ HER2-HER2-overexpressing: ER-/ PR-/ HER2 + Luminal A: + ER / PR + / HER2 Luminal B: + ER / PR + / HER.

The name of types basal and luminal comes from the resemblance of the epithelial tissue tumours breast normal correspondents. In general, types cancers basal and overexpressing HER2 were a bad clinical prognosis.

Studies based on the use of DNA in a systematic way in cohorts of patients were also able to isolate different gene expression signatures 95: thus the type luminal breast cancers tend to express the genes and proteins GATA3, KRT19 then those of basal conversely do not express these but between other ETS1 and CD44.

Treatments

As with all cancers, it is based ideally (from the medical point of view) on the surgical removal of the tumor, which allows at the same time to make the diagnosis of certainty. The next problem is to take stock of extension: presence or not of lymph nodes affected, presence or absence of metastasis.

However, the breast mutilation also corresponds in general for women to a mutilation, psychological and social, breasts are a symbol of femininity among the strongest. Some women may live this mutilation as a negation of their femininity and so their personality.

There are also other treatments like chemotherapy, radiation and hormone therapy, which in some cases can be used to obtain a reduction of the tumor prior to surgery. The effectiveness and risks of each treatment type depend on the type of cancer, its extension and the ground.

Therapeutic strategy

Many breast cancer treatments exist, but always to individualize for optimal treatment. Thus the Genomic analysis of breast cancers would appear a cinquantaine96 of different types of cancer of the breast, including each type, or group, would be likely to targeted therapy particuliere97.

For breast cancer located: the treatment almost always has a curative purpose. It is based on four therapeutic weapons are surgery, chemotherapy, radiation therapy and hormone therapy. Surgery is the essential step in the cure of cancer of the breast, other treatments usually designed only to reduce the risk of relapse. They will be so marked if this risk is important and if the supposed benefit of the treatment is enough, because all these treatments have side effects. The benefit expected must therefore be weighed against the risk of complication.

For metastatic breast cancer: at this stage of evolution, it is very rare to be able to offer a cure. But modern treatments can often extend the survival of several years. It is impossible to detail here the various possible therapeutic strategies because these are dependent on many factors. The treatment of metastatic breast cancer based on chemotherapy and hormone therapy. A surgical treatment or radiotherapy for metastatic sites may be considered either in a goal of healing when all sites are accessible to treatment (e.g.: liver or spinal metastases unique) in a palliative purpose (ex.): irradiation of a painful bone metastasis).

There are a number of genetic markers that are correlated with the prognosis of cancer of the sein98, 99, 100 and who can therefore potentially guide treatment.

Molecular markers of severity and prognosis of breast cancer also exist. The (MT) metallothioneines are un101. They bind easily to some metals are encoded by at least 10 genes MT functional that are associated with the proliferation of breast cancer cells, particularly cancers invasive ductal breast. This makes MT a biomarker for prognosis for the detectable breast by immunohistochimie102, 103, 104, 105. More MT expressed in the more serious breast cancers is the cancer106, 107.

Some treatments (alkylating or tamoxifene108) can be inhibited by an overexpression of metallothioneines (for example in a patient who was a victim of poisoning by heavy metals)

Surgery

Removal of the tumor

Drawing representing a mastectomy, national cancer Institute.

There are three types of breast surgery: Lumpectomy (removal of the tumor), the segmentectomie (removal of part of the breast) and mastectomy (removal of the whole breast). 

In cases where the tumor is supported early enough, a minimal surgery (conservative surgery) is possible. Sometimes, you should remove the entire breast. Reconstructive Surgery may be made at the same time or secondarily.

Illustration of the Reconstructive Breast Surgery: recovery of part of the abdominal muscles (restus abdominus) to reconstruct the breast, axillary

This technique is removal of lymph nodes in the Axilla (at the level of the armpit). This operation has many side effects that this ablation destabilizes the lymphatic network, which may lead to the appearance of lymphedema (muscle). This is in order to decrease these side effects that the Sentinel node technique has been implemented.

Technique of the Sentinel lymph node

In a tumor, the Sentinel lymph node is the first to receive lymphatic drainage.

The Sentinel lymph node is identified by the injection of a dye, accompanied or not of a radioactive colloid. He is then removed to allow a pathological study. If the studied lymph node is healthy, this technique allows not to use an axillary (withdrawal from almost all of the lymph nodes in the region), resulting in significant damage. It can be applied to patients with a tumor making less than 3 centimeters, and affect up to 70% of elles109.

This technique is validated, with an error rate less than 10% 110.

Monitoring after operation

After the initial treatment, it is essential that the patient be followed regularly.

The multiplication of examinations is not necessary, but annual bilateral mammography is essential, especially in the case of conservative surgery. According to the case, it may be associated with other complementary tests based on each case.

Even a treated optimally breast cancer can recur locally or remotely (metastasis). The recurrence may occur years after initial treatment, where the interest of maintaining surveillance.

Radiotherapy

She reduced the mortality rate of this cancer, but requires a flawless technique to reduce the irradiation of healthy tissue that can lead to an excess mortality from cardiovascular disease. There are radiation on the breast of the lymph node areas. In case of conservative surgery, radiation therapy must always be carried out because it significantly decreases the risk of recurrence locale111. Radiotherapy will be all the more important that the woman is young. In case of total breast removal, radiotherapy is indicated, in some cases, to reduce the risk of local recurrence. Irradiation of the ganglion chains is dependent on the location of the tumor and the result of the histopathology examination of lymph.

Long term side effects

The risk of mortality secondary to radiotherapy, compared to that of cardiovascular mortality seems to increase in the third decade after treatment, according to a study of the follow-up of more than 500 000 femmes112.

A European study on the risks to the fetus as part of radiotherapy or chemotherapy for cancer treatment has shown that the fetus whose mother would have been treated during pregnancy would no more heart defect that a child who is not expose113.

To identify the risks of breast fibrosis induced by radiotherapy, a test was developed by Inserm to measure the radio-induced lymphocyte apoptosis "taux (TALRI) ". " The higher the rate of TALRI and there is more risk of fibrosis of breast faible114.

Chemotherapy

It is to administer anti-cancer drugs, at fixed intervals, usually every 3 weeks. The number of courses of chemotherapy adjuvant (completed chemotherapy after surgery) for breast cancer is between 4 and 6. The benefits of chemotherapy adjuvant compared to surgical treatment without chemo are a significant reduction in mortality and a lower recidivism rate. Axillary ganglionic infringement scheme combining 3 cycles of chemotherapy with anthracycline (Farmorubicine °) and cyclophosphamide (Endoxan °) then 3 cycles with docetaxel (Taxotere °) is currently the reference. For cancers without axillary ganglionic swamping, research of bad prognosis factors which may explain an unfavorable evolution (high histological grade of hormone receptors, tumor size greater than 15 or even 10 mm for) some...) can ask also the indication of adjuvant chemotherapy.

If the tumor is advanced or inflammatory, it is sometimes necessary to begin treatment with chemotherapy (chemotherapy neo-adjuvante) to reduce the tumor size and possibly allow a conservative surgery.

Neo-adjuvantes chemotherapy are also practiced in order to limit the size of the resection: a Lumpectomy is sometimes sufficient when was initially scheduled for a mastectomy with adjuvant chemotherapy.

This last indication, while overall mortality, the period of exacerbation of the disease and distant recurrence rate are not different from chemotherapy adjuvant, loco-regional recurrence would be more frequent. There is no reference currently neo-adjuvante chemotherapy Protocol.

Cons: fatigue General, nausea and vomiting, temporary hair fall. They vary according to the products used, and are better and better controlled.

Number of products have been proven in the adjuvant treatment of breast cancer and have a reference Protocol, but other products onto the market or are the subject of studies.

Targeted therapies

Trastuzumab has upset the support of many patients. Other drugs are being evaluated. These molecules are often characterized by a good tolerance, however these are particularly expensive products.

Trastuzumab

The breast cancers that overexpress the gene Her2 significantly (this concerns approximately 25% of breast cancers, often poor prognosis, since Her2 - or CerbB2 - is the membrane receptor to activate one of the routes of proliferation increased cell) are with trastuzumab (Herceptin °), a monoclonal antibody blocking this receptor. Herceptin was first used in palliative situation. In this context, Herceptin allowed, on average doubling time of survival of these patients. Added to chemotherapy adjuvant, Herceptin ° in infusion every 21 days, 12 months, reduced by half the risk of relapse in patients HER2 + and about one-third the mortalite115.

Since November 2017, the Ontruzant, Biosimilar of trastuzumab, is holder of the first authorization to market issued by the European Commission, thus allowing its distribution in the European Union as well as in Norway, in Iceland and the Liechtenstein116, 117.

Bevacizumab

In 2007, bevacizumab (Avastin) is used in the breast cancer metastatic (authorisation on the french market in 2007, in first-line metastatic). It is an antibody monoclonal anti VEGF, issued in infusion. It binds selectively on this growth factor and thus blocks the neo-angiogenesis. Associated with paclitaxel, this treatment double response time (time until disease progression) 118. On the other hand, there is no increase in survival time.

However, in France, in May 2011, the health authority concludes: "in view of the low gain free survival and the lack of improvement in overall survival with the association bevacizumab/taxane versus taxane, the interest of the addition of bevacizumab. paclitaxel is now less well established. This interest is limited to negative patients with HER2 receptors, estrogens and progesterone. ' 119.

Lapatinib

Lapatinib (Tyverb), given in oral treatment, is an intracellular inhibitor of the activity of tyrosine kinase receptors HER2 and HER1 (EGFR). For patients overexpressing HER2, tumour growing under herceptin and having already received anthracyclines and taxanes, capecitabine lapatinib association double response compared to the capecitabine alone time, without benefit on survival globale120. The AMM was obtained in 2008.

Hormone therapy

In about two thirds of cancers of the breast, cancer cells have Hormone receptors in excess. The tumor is then called hormone sensitive because estrogens stimulate cancer proliferation through these receptors. In breast cancer hormone treatment will act either by decreasing the rate of estrogen in the blood and so stimulation of hormone receptors (castration, anti-aromatases), either by blocking Hormone receptors (anti-oestrogenes).

Ovarian suppression

surgical laparotomy or laparoscopy

headscarves, realizing 12 to 16 Gray in 4 to 8 fractions on a small pelvis, after spotting the position of the ovaries by ultrasound;

medical, most often using the LH - RH agonists

Leuprorelin, Enantone LP 3.75 mg / 4 weeks

Goserelin, Zoladex 3.6 mg / 4 weeks

Note: Decapeptyl doesn't have the AMM in breast cancer.

Antiestrogens

Tamoxifen 20 mg j−1

Mechanism: partial antagonist of estradiol receptors

Caution: do review endometrium 1/year, monitor liver function and triglycerides, assay plasma estradiol and add if increased LHRH, effective contraception (teratogenic).

Fulvestrant 250 mg IM every 28 days

Mechanism: antagonist of partial agonist action without estrogen receptors.

The use of tamoxifen is beneficial if there are receptors to oestrogens at the level of the tumor regardless of the age of the patient. The optimal duration of adjuvant tamoxifen by HT is 5 years at the dose of 20 mg j−1. The use of tamoxifen reduced the risk of recurrence of 8% and 5% death.

Anti-aromatases

Main article: aromatase inhibitor.

Since 2004, new molecules can be proposed to postmenopausal women. These are aromatase inhibitors. The two most valued molecules are the anastrozole and letrozole. Their toxicity profile is different from the tamoxifene121. The administration of these two molecules can reduce relapses after breast cancer surgery, without benefit for overall survival (versus tamoxifen).

Letrozole, Femara 2.5 mg j−1

Mechanism: non steroidal aromatase inhibitor

Caution: bone density, Dyslipidemia

Anastrozole Arimidex 1 mg

Mechanism: Non steroidal aromatase inhibitors

Caution: bone density, Dyslipidemia

Exemestane AROMASIN 25 mg

Mechanism: steroidal aromatase inhibitor

Caution: bone density, Dyslipidemia

Prevention: how to reduce the risk

Knowing that breast cancer is a hormonal disease, any action or treatment to reduce the duration and intensity of exposure to estrogens or endocrine disruptors mimicking these estrogens is supposed to be theoretically efficient.

Actions or events decreasing the risk

Several types of actions can be carried out in order to reduce the risk of breast cancer.

Gynecological choice

Risk factors have a common denominator: the increase in women's hormonal imprinting: direct for hormonal treatment of menopause, the oestroprogestatives, the increase in the number of menstrual cycles pill (small number of) pregnancies or short durations of breastfeeding), or indirect through the increased activity of the enzyme aromatase in the fat for alcohol, being overweight, lack of physical activity. Thus, a primary prevention of breast cancer could be proposed, involving a change in the mode of vie122

The choice of contraceptive pill

It's focus on pills that do not contain any estrogen blocking the ovarienne123 activity.

A first pregnancy at a young age

The decrease in the age of first pregnancy allows to decrease the risk of breast cancer because cycles between puberty and the first term pregnancy seem most dangerous from the point of vue124. The first term pregnancy would be such a vaccine against cancer via a differentiation of fabrics making them less vulnerable to the hormones. Pregnancy is like a vaccine to estrogen. More this first pregnancy occurs early, better it is.

Extended breastfeeding

Extended breastfeeding baby (because putting the ovaries 'dormant') reduces the risk. According to the WCRF report, breastfeeding brings a profit regardless of the time of development of cancer (pre-or post-menopause) 125.

Avoid the hormone therapy in menopause (HRT)

"The hormonal menopause treatment is now considered a risk factor for breast cancer, especially when taken for more than 5 years" reports Le Figaro in 2008125.

Choice of lifestyle

Weight loss

Obesity and overweight increase the risk of breast cancer. Professor Pierre Kerbrat (centre Eugène Marquis, Rennes) was estimated in 2008 that the fight against women's obesity would avoid 13 000 new cases of cancer of the breast annually in Union europeenne125.

Physical exercise

According to Professor Kerbrat, the practice of 30 minutes of physical activity 5 days a week, would reduce from 30% to 40% the number of new cases. The protective effect is both the fight against obesity and the action of the exercise on the hormonales125 secretions. American studies also showed its preventive effect against a recurrence of the maladie125.

The reduction of alcohol consumption

The risk of breast cancer increases with the intake alcool13. Moderate alcohol consumption increases the risk of 20% to 30%. Specifically, the risk increases of 10% when daily alcohol consumption increases by 10 g of alcohol (or a glass) 125.

Food choices

They would reduce the risk.

Conducted questionnaires with 334 850 women aged 35 to 70 years and included in the cohort EPIC (European Prospective Investigation into Cancer and Nutrition) 126 (follow-up duration: 11.5 years), a study dated April 2013 shows that there is no link between consumption of flavonoids and Lignans (of Phytoestrogens) and the risk of breast cancer that we take into account or not the menopausal status and the status of hormonaux127 receptors.

Acids trans fats

Fatty acids trans in the blood increase the risk of cancer of the breast in women by up to 50%. Fatty acids trans are used in processed foods such as breads and industrial cookies, pastries, cakes, chips, pasta to pizza industriels39.

Green tea or soya could have protective virtues (which would explain the fact that in Europe 1 out of 12 women develop this cancer, against one for 80 to the Japan where these foods are very consumed) [ref. necessary].

After the onset of breast cancer, doubling the consumption of fruit and vegetables does not decrease the risk of recidive128.

We test in 2008 omega 3 supplementation in order to see if it improves the chimiotherapie129.

Other

Not taking hormone treatments would reduce the risk of cancer of the sein2.

Treatment of type SERMs (tamoxifen, raloxifene) would reduce the risque130. However, these drugs have significant side effects (increase in the number of Embolic disease for two molecules, of cancer of the endometrium for tamoxifen) and their place is at determiner131.

Preventative surgery "»

Preventive surgical treatments have been suggested for women with a family history of breast cancer with mutation on the BRCA1 or BRCA2 genes. These women, the breast cancer risk varies between 40 and 85% before the age of 80. Surgical proposals are either the removal of both breasts with or without bilateral oophorectomy, the only bilateral oophorectomy.

If preventive bilateral mastectomy, the risk of developing breast cancer within five years goes to 2% instead of 30% of women not operated. The oophorectomy without mastectomy reduced by half the risk of breast cancer in the next 10 to 15 years.

Psychological aspects

Learn we have cancer can be very difficult to take, so this new has long been considered one of imminent death. In addition, hospitalization, surgery and adjuvant treatments change deeply the patient's life. It is essential to bring the sick adapted psychological support, what is happening in general through participation in groups of patients who live the same events.

However, the late diagnosed breast cancers are often very disfiguring. This breast mutilation is generally for women a psychological and social mutilation. The breast is one of the strongest symbols of femininity, some women can live this mutilation as a negation of their femininity and so their personality.

The relationship is often affected by the disease. In the period following treatment, sometimes the patient or his or her spouse to express negative emotions, such as complaints. This type of situation should be taken seriously by professionals, because it is can be associated with psychological disorders such as depression. According to Nicolas Favez, Sarah Ciro Notari, Tania Antonini and Linda Charvoz132, this type of situation is likely to appear from the early stages of the disease, and even when the medical prognosis is optimistic. In this context, reconstructive surgery can be proposed, with psychological support.

Breast cancer is therefore not only a medical problem. It affects the life, the body and self-confidence. When a woman receives the 'breast cancer' verdict, she left the doctor's office, the scared, with many questions about what will now be his life. How to talk about this to his family? How to deal with the fall of hair and eyebrows? How leaving home and confront the gaze of others? How to continue to take care of her children? Can have? Will she lose her job? What happens to his relationship with the man of her life? So many questions, few possibilities of dialogue, a lot of taboos. Often women are retreating on the disease and this is bad even for the success of the therapy.

Much more needs to be done to properly communicate with patients and their families but also to concretely improve the medical care provided to women and their quality of life in general.

Bibliographic tracks

Testimony

The psychologist, Maryse Vaillant tells in his story a year singular with my breast cancer (Albin Michel, 2008) his battle against the disease, after his cancer diagnosis, her mastectomy, and his reflections on femininity after this operation: This cancer, which took me a breast has not lessened the woman I am. I wouldn't have bothered me to this disease. But when I think about it, I have gained a deep enjoyment of life. I come more alive - and even more women. »