Breast cancer

breast cancer, also known as breast cancer or cancer of the mammary glands, is a malignant proliferation of epithelial cells that They line the mammary ducts or lobules. It is a clonal disease; where an individual cell, product of a series of somatic or germline mutations, acquires the ability to divide without control or order, causing it to reproduce until it forms a tumor. The resulting tumor, which begins as a mild abnormality, becomes severe, invades neighboring tissues, and eventually spreads to other parts of the body. Untreated cancer causes death.

There are two main types of breast cancer. Infiltrating ductal carcinoma, which begins in the ducts that carry milk from the breast to the nipple, is by far the most common (approximately 80% of cases). In second place is infiltrating lobular carcinoma (10–12% of cases), which begins in parts of the breast called lobules, which produce breast milk. The other types of breast cancer together do not exceed 10% of the cases.

The main risk factors for breast cancer include being a woman (although it can also occur in men), older age, early menstruation, older age at first delivery, or never having given birth, family history of breast cancer, the fact of consuming hormones such as estrogen and progesterone. Recent studies show the association of breast cancer with the overproduction of zonulin in the intestine and the consequent increase in intestinal permeability. Among 5 In 10% of cases, breast cancer is caused by inherited genetic mutations.

To detect breast cancer, different tests are used such as mammography, breast ultrasound with high-resolution transducers (ultrasound), or magnetic resonance imaging. The diagnosis of breast cancer can only be definitive by means of a breast biopsy.

Of all breast carcinomas, less than 1% occur in males. International Breast Cancer Day is celebrated on October 19, its objective is to raise awareness among the general population about the importance of this disease in the industrialized world.

History

Breast cancer is one of the cancer tumors that has been known since ancient times. The oldest description of cancer (although without using the term "cancer") comes from Egypt, from 1600 BC. c. approximately.

The Edwin Smith Papyrus describes 8 cases of cancer tumors or ulcers that were treated with cauterization, using a tool called the "fire fork. The letter says about the disease: "There is no treatment" when the tumor is bleeding, hard and infiltrating. At least one case described is of a man. Descriptions are also made in ancient Egypt and in the Ebers papyrus. Hippocrates later describes several cases and points out that patients with extensive and deep cancer should not be treated because they live longer. In his work Diseases of women, Hippocrates paid attention to advanced karkinoma of the breast.

The physician Galen was the first to use the term "cancer", from the Latin cancrum, because of the association with crabs. Galen's ideas were different from those of Hippocrates and the Egyptians. Aulus Cornelius Celsus in the I century and Galen in the II referred to the removal of breast tumors and the use of cautery for breast surgery. Celsus believed that reckless intervention on cancer could be harmful and exasperate the tumor. It is attributed to Leonidas of Alexandria, Greek doctor, the first recorded surgical procedure for breast cancer, antecedent of the modern mastectomy. With this, he distanced himself from the treatments or medications commonly used until then, such as lukewarm baths or castor oil, among others. In addition, Leonidas noted nipple retraction as a sign of malignancy for a breast tumor. In the VI century, Aetius of Amida pointed out the possibility that satellite swellings coexist in the axillary hollow in breast cancer. In the VII century, the surgeon Byzantine Paul of Aegina sought to perfect the technique of removing breast cancer by scraping the lymph nodes from the armpit.

For centuries doctors have described similar cases, all leading to a sad conclusion. It was not until medical science achieved a greater understanding of the circulatory system in the 17th century that happy advances were made. In this century it was possible to determine the relationship between breast cancer and axillary lymph nodes. The French surgeon Jean Louis Petit (1674-1750), with his removal of the lymph nodes, and later the surgeon Alfredo Velpeau (1795-1867), paved the way for modern mastectomy. Alfredo Velpeau is the author of the most important in this matter of his time: Treatise on Diseases of the Breast and Mammary Region. His path of understanding and advancement was followed by William Stewart Halsted who invented the operation known as " Halsted's radical mastectomy, a popular procedure until the late 1970s.

Epidemiology

For several decades, breast cancer has increased remarkably around the world, especially in Western countries. And this growth continues, despite the fact that there are better diagnostic instruments, various early detection programs, better treatments and greater knowledge of risk factors.

Breast cancer is the most common malignancy in Western women and the leading cause of cancer death in women in Europe, the United States, Australia and some Latin American countries.

As of 2006, this condition occupies the first place in mortality due to neoplasia in women over 25 years of age, displacing cervical cancer, causing nearly five hundred thousand deaths each year, of which 70% occur in developing countries, although the risk of dying is higher among women living in poor countries, due to less access to health services for early detection, treatment and control. In 2010, the standardized mortality rate was 18.7 per hundred thousand women aged 25 and over, which represents an increase of 49.5% in the last 20 years.

Breast cancer accounts for 31% of all cancers in women worldwide. Approximately 43% of all cases registered in the world in 1997 correspond to developing countries. The incidence is increasing in Latin America and in other regions where the risk is intermediate (Uruguay, Canada, Brazil, Argentina, Puerto Rico and Colombia) and low (Ecuador, Costa Rica and Peru).

Based on a statistical analysis of the most recent year for which data exist in each country, there are five countries where the annual mortality per 10,000 women is higher: Uruguay (46.4), Trinidad and Tobago (37.2), Canada (35.1), Argentina (35.2), and the United States (34.9).

Frequency of breast cancer in Latin America (data)

Country Year assessed Prevalence Mortality Argentina 2008 74 20.1 Brazil 2008 42.3 12.3 Chile 2000 - 2008 40.1 13 Colombia 2008 31.2 10 Costa Rica 2008 37.88 (1999-2000); 42.9 (2008) 10.76(1999-2000); 12.2 (2008) Cuba 2008 38.5 15.5 Ecuador 2008 30.8 10.1 Spain 1978-1992, 2008 61 (2008) 21.61 (1978-1992); 12.9 (2008) Haiti 2002, 2008 23.9 (2008) 4.4 (2002); 10.6 (2008) Mexico 2008 27.2 9 (years 1990); 10.1 (2008) Paraguay 2008 29.2 11,6 Peru 2008 34 10.8 Uruguay 2008 90.7 24.3 Venezuela 2008 42.5 13.7

Classification

In medicine, breast cancer is known as breast carcinoma. It is a malignant neoplasm that has its origin in the accelerated and uncontrolled proliferation of cells that line, in 90% of cases, the interior of the ducts that, during lactation, carry milk from the glandular acini, where it is produced, to the lactiferous ducts, located behind the areola and the nipple, where it accumulates waiting to go outside. This breast cancer is known as ductal carcinoma. In the remaining 10% of cases, the cancer originates from the glandular acini themselves and is called lobular carcinoma. Ductal carcinoma can extend into the interior of the ductal lumen and invade the interior of the acini in what is known as the phenomenon of lobular cancerization.

Breast cancer has been classified on the basis of different schemes.

Etiology

According to the origin, there are three generic types of breast cancer:

• Sporadic: No family history. It would be between 70 and 80 per cent of cases.
• Family: with family history, but not attributable to the mutation of a single gene, but to the contribution of many genes (multigenic or multifactorial tolerance). 15-20%.
• Hereditary: attributed to germline mutations of a single gene (monogenic tolerance). It would only be between 5-10%. Within these, 40% is due to mutations in BRCA1 and BRCA2 (Breast Cancer susceptibility gen/protein)

Staging

The TNM staging system for breast cancer is based on the size of the tumor (T), whether the tumor has spread to the lymph nodes (N), in the armpits, or still has not spread, and whether the tumor has metastasized (M) (i.e., has spread to a more distant region of the body). Larger, nodally spreading, and metastatic tumors have higher staging numbers. and a worse prognosis.

Primary staging includes:

• Stadium 0: is a pre-maligna disease or with positive markers (sometimes called CDIS: ductal carcinoma in situ). It would be the time when the cell has recently become carcinogenic, but it has not yet broken the basal membrane.
• Stage 1: Cancer cells have already passed the basal membrane, but the tumor does not exceed 2 cm in size.
• Stage 2: similar to stage 1 but the tumor is already more than 2 cm, but not more than 5 cm since it has not yet spread to the lymph nodes.
• Stage 3: Within this stage different classifications are given depending on the size of the tumor mass and whether the lymph nodes are affected or not.

Stages 1-3 are defined as the 'beginnings' of cancer and are potentially curable because in many cases they are operable.

• Stage 4 is defined as advanced stage cancer and/or metastatic cancer because the cancer has spread to other organs of the body. This type of cancer most frequently metastatizes in bones, lungs, liver, or brain and has a poor prognosis.

Pathology

Most breast cancers derive from the ducto-lobular unit. Cancer cells derived from other tissues are considered rare in breast cancer. The term "Carcinoma in situ" refers to the type of cancer that is confined to the lumen of the ducts or glandular lobules, without invading neighboring tissues. For its part, invasive carcinoma it proliferates excessively until it breaks the so-called basement membrane and spreads infiltrating the tissues that surround the mammary ducts and lobules, thus penetrating the surrounding tissue. Cells that divide more rapidly have a worse prognosis. One way to measure the growth of tumor cells is with the presence of the Ki67 protein, which indicates that the cell is in the S phase of its development and also indicates its susceptibility to certain treatments.

Prognostic factors

Classics

• Status of lymph nodes: if they were contaminated it would be a sign of a bad prognosis.
• Tumor size: in general a large tumor is usually linked to a poor prognosis, although it is not always so, since in reality it is more important to invade.
• Proliferative state: to greater proliferation worse prognosis. This parameter can be studied using histological analysis (with hematoxylin staining and eosin (HE), by immunohistological analysis (Ki67) or FACS analysis (in which phase S cells are studied)
• Histological grade: a combination of several factors such as the structure of tubules (more or less defined), the proliferative state (% of mythotic cells) and nuclear pleomorphism (number, form and size of nuclei and nucleolos) is taken into account in determining this. There are two systems to classify breast cancer according to histologic grade: the SBR system Scarff-Bloom-Richardson (USA) and the Nottingham (Europe) system that is nothing but the SBR modified by Elston and Ellis. The difference between both systems would be the limits of each parameter between each grade.

Sensitivity to receptors

All cells have receptors on their surface, in their cytoplasm, and in the cell nucleus. Certain chemical messengers such as hormones bind to these receptors and this causes changes in the cell. In breast cancer there are three receptors that are used as tumor markers: estrogen receptor (ER), progesterone receptor (PR) and the HER2/neu oncogene. Cells that have altered expression of any of these receptors are given a positive sign and a negative sign if it does not occur. Those cells that do not over-express any of these receptors are called basal or triple negative. All of these receptors are identified by immunohistochemistry and molecular genetics.

• (ER+/PR+) positive cancer for estrogen receptors and progesterone: around 70% of breast cancers are sensitive to estrogens, which means that estrogen makes the breast cancerous tumor grow. Breast cancer ER+ may be treated with adjuvant therapy by medications that block activation of estrogen receptors (SERMs), such as tamoxifen, or with aromatase inhibitors (Ais), such as anastrol. This type of therapy is combined with surgery and may go or not, followed by a chemotherapy treatment.^{[chuckles]required]}

• About 30% of patients with breast cancer have what is known as positive breast cancer for HER2. HER2 refers to an oncogen that helps cells grow, divide and repair themselves. When cells have too many copies of this gene, cells (including cancers) multiply more quickly. Experts think that women with positive breast cancer for HER2 have a more aggressive disease, have greater resistance to conventional chemotherapy treatments and a higher risk of recurrence than those who do not have this type of cancer. However, HER2+ breast cancer responds to medicines such as monoclonal antibody, trastuzumab—in combination with conventional chemotherapy—and this has significantly improved the prognosis.

The receptor status is used to divide breast cancer into four molecular classes:

• Subtype basal-epithelial (or basocellular): characterized by the absence or minimum expression of estrogen receptor (RE) and HER2 (negative gut), high expression of cytokerats 5/6 and 17 (mioepiteliales), laminine, and protein 7 of binding to fatty acids. Unlike other subtypes, this group of tumors has high frequency (82 %) of TP53 mutations (in thyrosine) and p53 protein expression (TP53 works as a control point (checkpoint) in the cell cycle triggering responses to DNA damage, including repair and apoptosis. The basal-type tumors receive this name because of their genomic expression profile similar to that of a normal basal cell epithelium and normal mioepiteliar cells. It also shares histologic characteristics with the basal epitheliare cells of the normal breast, and shows a high proliferative rate, central necrosis and infiltrative margin, as well as low estroma, frequent apoptotic cells and lymphocytic entromal response, similar to those also observed in the carcinomas that appear in female mutation carriers in the BRCA1 gene.
• HER2+ subtype: absence or minimum expression of RE, high expression of HER2. The expression profile reveals not only increased copies of HER2/neu RNAm, but also an increase in transcription of other adjacent genes that are amplified in this segment of DNA, such as GRB7.
• Luminous A: characterized by the high expression of RE, protein 3 binding to GATA, protein binding to box-X, factor 3, nuclear factor 3 hepatocyte alpha and LIV-1 regulated by estrogen. It shares features with the luminal epithelial cells that develop from the inner layer of lining of the breast duct.
• Luminal B and C: low to moderate expression of specific luminar profile genes including those of RE group.

Lastly, recipient status has become a critical assessment of all breast cancers, as it determines the adequacy of use of specific treatments, for example, tamoxifen and/or trastuzumab. These treatments are now some of the most effective adjuvant treatments for breast cancer. In contrast, triple-negative (ie, nonreceptor-positive) breast cancer is now thought to be indicative of a poor prognosis.

Gene Expression Profile

The biological heterogeneity of breast cancer has implications for prognosis and therapeutic decision-making. A new approach in the classification of breast cancer through the analysis of the expression of multiple genes in an individual tumor will help to obtain better classifications for tumors (by knowing their origin better) and thus improve the prognostic capacity and thus choose a more personalized and effective treatment.

New microarray technologies such as microarrays make it possible to simultaneously detect and quantify the expression of numerous genes, since they allow the simultaneous study of a large battery of genes.

DNA chips are able to distinguish normal cells from breast cancer cells, finding differences in hundreds of genes, although the significance of most of these differences is unknown. Several screening tests are commercially available, but the evidence for their value is limited. The Oncotype DX brand is the only test supported by Level II evidence, which has not been approved by the US Food and Drug Administration (FDA), but is endorsed by the American Society of Clinical Oncology. The MammaPrint brand has been approved by the FDA, but is only supported by level III evidence. Two other tests have level III tests: Theros and MapQuant Dx.

Risk factors

Today, breast cancer, like other forms of cancer, is considered the result of DNA damage. This damage comes from many known or hypothesized factors (such as exposure to ionizing radiation). Some factors such as estrogen exposure lead to an increased mutation rate, while other factors such as the BRCA1, BRCA2, and p53 oncogenes cause decreased repair of damaged cells.

Humans are not the only mammals capable of developing breast cancer. Dogs, cats, and some types of mice, mainly house mice, are susceptible to developing breast cancer, which is suspected to be caused by insertional mutagenesis. Mouse Mammary Cancer Virus Randomization (MMTV). The suspicion of the existence of a viral origin of breast cancer is controversial, and the idea is not widely accepted due to the lack of definitive or direct evidence. There is much more research on the diagnosis and treatment of cancer than on its root cause.

Age

The risk of developing breast cancer increases with age, but breast cancer tends to be more aggressive when it occurs in younger women. Most cases of advanced breast cancer are found in women over the age of 50 years. Women are 100 times more likely to get breast cancer than men.

For a woman who lives past the age of 90, the chance of getting breast cancer in her lifetime is 12.5%, or 1 in 8.

One type of breast cancer that occurs and is especially aggressive and disproportionate in young women is inflammatory breast cancer. It is usually discovered at stage III or stage IV. It is also characteristic because it normally does not present with a mass, therefore it is not detected with mammography or ultrasound. It presents with the signs and symptoms of mastitis.

Genetic mutations

Approximately 5 % of patients with breast cancer (represented in red) "hered" a peculiar form of genes that make it susceptible to the disease.

Although external factors more often predispose a woman to breast cancer, a small percentage carry a hereditary predisposition to the disease.

Two genes, BRCA1 and BRCA2, have been linked to a rare familial form of breast cancer. Women whose families carry mutations in these genes are at increased risk of developing breast cancer. Not all people who inherit mutations in these genes will develop breast cancer. Together with the p53 oncogene mutation characteristic of Li-Fraumeni syndrome, these mutations would determine approximately 40% of hereditary breast cancer cases (5-10% of the total), suggesting that the rest of the cases are sporadic. It has recently been found that when the BRCA1 gene appears in combination with the BRCA2 gene in the same person, it increases their risk of breast cancer by up to 87%.

Other genetic changes associated with certain clinical data of breast cancer have been verified, so they are not only used as molecular markers, but also as prognostic and predictive factors. For example, mutations in the TP53 gene are usually associated with high levels of the Ki67 biomarker, luminal B tumors, and high histological grade. This type of mutation is usually linked to resistance to treatment with aromatase inhibitors, a very important fact when choosing an appropriate treatment for the patient. In the same way, an important mutation at a predictive level (positive for Ais therapy) in luminal breast cancer, although not very abundant, would be the one concerning GATA3. In addition, for luminal A type cancers, with a low proliferation index (Ki67), mutations have been detected in the MAP3K1 and MAP4K2 genes (target of the former) that would be associated with a good prognosis and that would explain, due to their targets (ERK or JNK) insensitivity due to loss of signaling or accumulation of mutations.

Other genetic changes that increase the risk of breast cancer include PTEN gene mutations (Cowden syndrome), STK11 (Peutz-Jeghers syndrome) and CDH1 mutated in 50.5% of lobular tumors (Cadherin-E); its frequency and increased risk for breast cancer is not yet exactly known. In more than 50% of cases, the gene associated with inherited breast cancer is unknown. Compared to countries with an all-white population, the prevalence of these mutations in the Latin American population is possibly lower.

Through the sequencing of 560 genomes of breast cancer patients, five new cancer genes (MED23, FOXP1, MLLT4, XBP1, and ZFP36L1) were identified for which the evidence was previously absent or equivocal, or for which the mutations indicate that the gene acts in breast cancer in a recessive rather than a dominant manner.

Hormones

Exogenous estrogens, especially those used in hormone replacement therapy together with genetic predisposition, are the most important factors in the development of breast cancer. Many women take this type of therapy to reduce the symptoms of menopause. A slightly increased risk of breast cancer has also been described in women taking oral contraceptives.

Factors associated with female hormones and increased frequency of breast cancer include early sexual maturity (before age 12), menopause after age 50, nulliparity, and first full-term pregnancy achieved after the age of 30 or 35. On the other hand, if the first menstruation occurs after the age of 12, menopause is before the age of 50, or the first pregnancy occurs before the 10-20 years following the first menstruation, the risk of breast cancer is less.

There are definitive conclusions on an association between abortion performed in the first trimester of pregnancy and the subsequent risk of breast cancer.

Epidemiological studies have suggested that a diet high in phytoestrogens, which are polyphenolic compounds similar to estradiol and present in plants such as soybeans, cereals, and 300 other vegetables and legumes, may be associated with a lower incidence of breast cancer, however, scientific studies continue to yield contradictory conclusions.

Increased intestinal permeability

Illness of the wall of the intestine with increased permeability. The two most powerful factors that cause it are certain intestinal bacteria and gluten, both in celiacs and in non-Celiacs. This allows the uncontrolled passage of substances to the bloodstream, with the consequent possible development of cancers (both intestinal and other organs), autoimmune diseases, inflammatory, infections or allergies.

Recent discoveries have shown the association between breast cancer and an excess production of zonulin in the intestine.

The main function of zonulin is to regulate the flow of molecules between the intestine and the bloodstream, loosening the tight junctions between cells (the "pores" of the intestine) to allow the passage of nutrients and block the passage of nutrients. passage of macromolecules, incompletely digested nutrient fragments, toxins and microorganisms from the proximal intestine.

When there is an overproduction of zonulin, the tight junctions of the intestinal wall open excessively (intestinal permeability increases), the intestine loses its protective barrier capacity and substances pass into the bloodstream that should not pass. This can cause, both in the intestine and in other organs and depending on the genetic predisposition of each person, the development of cancers, autoimmune and inflammatory diseases. In most cases, the increase in intestinal permeability appears before the disease and triggers the multi-organ process that causes the development of systemic diseases, such as cancer.

The two most potent factors that cause the release of zonulin and the consequent increase in intestinal permeability are certain intestinal bacteria and gliadin (the main toxic fraction of gluten), regardless of genetic predisposition, that is, both in celiac patients as in non-celiacs. Other possible causes are prematurity, radiation exposure, and chemotherapy.

The discovery of the role of intestinal permeability in the development of these diseases upsets traditional theories and suggests that these processes can be stopped if the interaction between genes and triggering environmental factors is prevented, through the restoration of function of the zonulin-dependent intestinal barrier.

Others

According to a researcher named Kelly where he published in Science magazine, he explains that in general white women are more likely to get breast cancer. However, although there is a risk of losing ability to have children (mainly due to the fact that chemotherapy and radiotherapy can destroy reproductive tissues), there are currently different means of fertility preservation, which are available in health centers to prevent this problem.

It has been suggested that air pollution, chemicals in deodorant, underwire bras, and breast implants increase the risk of breast cancer, however there is no scientific basis yet to confirm that these factors increase the risk.

Women who took diethylstilbestrol (DES) to prevent miscarriage may have an increased risk of breast cancer after age 40. This drug was given to women between the 1940s and 1960s.

Obesity has been associated with breast cancer, although this link is controversial. The theory is that obese women produce more estrogen, which may stimulate the development of this cancer.

If a patient received radiation therapy as a child or young adult to treat cancer of the chest area, there is an increased risk of developing breast cancer. The younger you were when you started radiation, the greater the risk, especially if the radiation therapy was given when the woman's breasts were developing.

The influence of liquor on breast cancer risk is discussed. However, it should be emphasized that women who do not have any known risk factors can develop breast cancer, so the absence of risk factors should not cause a false sense of security.

Gum disease has also been associated with an increased risk of postmenopausal breast cancer, particularly among ex-smokers who quit within the past 20 years.

Permanent or long-term nulliparity are risk factors for breast cancer. For example, a meta-analysis of 8 population-based studies in the Nordic countries found that never giving birth is associated with a 30% increased risk of breast cancer, compared with women who have given birth. light; In addition, the risk is reduced by approximately 16% for every 2 deliveries carried out. Women who had their first birth after the age of 35 had a 40% higher risk compared with those who had their first birth before the age of 20. Breastfeeding, on the other hand, is a factor that reduces risk in the breast cancer without estrogen receptors (ER-).

Clinical picture

The main reason for consultation in relation to a woman's breasts is the detection of a mass or tumor. Approximately 90% of all breast masses are caused by benign lesions. Those that are soft and elastic masses are generally associated with a fibroadenoma in women between 20 and 30 years of age and cysts in women between 30 and 40 years of age. Malignant breast masses are characterized by being solitary, not very noticeable, hard and painful on palpation.

Another frequent manifestation is breast pain. Such mastalgia is rarely associated with breast cancer and is often related to fibrocystic changes in premenopausal women. Postmenopausal women taking estrogen replacement therapy may also complain of breast pain caused by fibrocystic changes. The pain of these fibrocystic disorders is often accompanied by small diffuse lumps in the breasts.

Early breast cancer usually causes no symptoms; which is why regular breast exams are important. As the cancer grows, symptoms may include redness, swelling, and retraction of the skin or nipple with holes or puckering that looks like orange peel. Another common problem is nipple discharge. The discharge from a breast carcinoma is usually spontaneous, bloody, associated with a mass, and located in a single duct in one of the breasts. In some cases, the discharge from the nipple may be clear to yellowish or greenish in color and look like pus.

Breast lumps or lumps in the armpits that are hard, have irregular edges, and are usually painless. Change in the size, shape, or texture of the breasts or nipple. Men can also develop breast cancer, and symptoms include breast lumpiness, as well as breast pain and tenderness.

Symptoms of advanced breast cancer may include:

• Bulto in the chest
• Increase in the size of lymph nodes (adenopathies) in the armpit
• Changes in size, skin texture or breast color
• Redness of the skin
• Training of depressions or wrinkles
• Changes or secretion by nipple
• Rest
• Traction of the nipple to one side or change of direction
• Bone pain.
• Pain or discomfort in the breasts.
• Skin ulcers.
• Swelling of an arm (close to the breast with cancer).
• Weight loss.

It must be emphasized that breast cancer can manifest as an asymptomatic tumor and that when there is already skin retraction it is an advanced cancer, so when detecting a mass, the patient should seek professional help and request an exact diagnosis based on studies and not on clinical assumption.

Diagnosis

The breast exam should be performed in an upright position, sitting and lying down with the woman's hands behind her head. The breasts should be inspected for differences in size, skin or nipple retraction, prominent venous patterns, and signs of inflammation. The flat surface of the fingertips should be used to palpate the breast tissue against the chest wall. The axillary and supraclavicular areas should be checked for nodules. The nipple should be gently compressed to check for discharge.

Mammogram

The widespread use of mammography has been effective, reducing the mortality rate from breast cancer by up to 30%. Mammography is the best screening method for early lesions available. The survival rate for women with breast cancer is dramatically increased when diagnosed at an early stage, with early detection having a 10-year survival of up to 98%. Unfortunately, only 60% of cancers are diagnosed. in a localized phase. So regular mammography should be accompanied by a regular physical breast exam to improve that percentage.

Yearly mammography is recommended for asymptomatic women over age 40. It is known as screening mammography and uses a two-view protocol, usually one of them in a medial lateral oblique direction and the craniocaudal projection, that is, from top to bottom. Mammography in symptomatic women or those with high risk factors is known as diagnostic mammography and therefore they generally use more than two projections per image.

Screening in women between the ages of 50 and 75 significantly decreases the mortality rate from breast cancer. Screening in women between 40 and 49 years of age is controversial, due to a lower incidence of the disease in this age group and the denser breasts, which decreases the sensitivity of mammography. Several studies show a significant reduction in mortality rates in women of this age group who received mammograms, while other studies did not show benefits in this group. In the cases of people with dense breasts, it is important to perform additional tests to rule out false negatives: Octava Pink test, ultrasound and/or MRI.

There is a chance of getting false positives with mammograms. Women ages 40-69 have a 30% chance of false positives on their mammogram over a 10-year period. These false positives lead to additional tests, follow-up and biopsies, increased costs and unnecessary anxiety, the psychological consequences of which can persist even after a final benign result.^{[citation needed]} The frequency of false positives is higher for younger women because most masses in their breasts are usually benign.

Ultrasound

Ultrasound screening is useful in differentiating between solid and cystic breast masses or tumors, especially when a palpable mass is not well visualized on a mammogram. Ultrasound is especially useful in young women with dense breast tissue with a mass palpable that is not visible on a mammogram. Ultrasound should not be used in routine check-ups, especially since microcalcifications are not visualized and detection of carcinomas is negligible with ultrasound.

Eighth Pink

This is a method in which the diagnosis of breast cancer is made by means of a blood test in which the antibodies compatible with the development of breast cancer are detected. It is a non-invasive test (a blood test) in which serum is separated from the blood. Once the serum is separated, the antibodies found in the serum are analyzed.

The immunological processes that cause the production of autoantibodies are due to the presence of altered proteins in cancer cells and that cause an immune response. Alterations are due to mutations, inappropriate degradation, overexpression, and/or release of proteins from damaged tissue. Octava Pink is based on this technique as part of routine clinical use and does not present any risks for the patient, only taking a peripheral blood sample.

In a very recent trial, 1009 serum samples were used (397 from women with breast cancer and 612 from healthy women). 721 samples were used to adjust the test, and the 288 were used to check the reliability of the test. OctavaPink recognized 81 of the 120 samples from women with breast cancer as diseased, and 165 of the 168 samples as healthy. These data provide a sensitivity of 68% and a specificity of 98%.

This test is recommended in groups of people at risk: People with dense breasts, people at high risk of familial cancer or who have tested positive for a pathogenic mutation in a BRCA gene, people who cannot have a mammogram.

This test is contraindicated in people who have had treatments with any type of immunosuppressants, are undergoing cancer treatment or have ever been diagnosed with breast cancer, as they are all situations in which antibody levels may be altered outside of normal so the test result may be incorrect.

High-field MRI

High-field MRI is an additional and complementary method to detect and diagnose breast cancer and should be used in high-risk women, it can be used to detect or confirm the presence of cancer and assess its extent. Like other tests, it should be used in people at high risk of familial breast cancer. Although it is not a common screening tool due to its high cost and because it generates many false positives, it is commonly used in women who have already been diagnosed.

The Blue Box

The Blue Box is a device capable of detecting breast cancer biomarkers by performing a chemical analysis of a urine sample and sending the result to the cloud where an algorithm based on Artificial Intelligence (AI) is executed, which produces a diagnosis that can be consulted in real time and stored through a mobile application.

The device has been developed by Judit Giró, a Spanish biochemical engineer, using two prototypes, the first carried out in collaboration with the Hospital Universitari Sant Joan de Reus and the second at the University of California at Irvine, which has a rate of classification of 95% and incorporates Artificial Intelligence (AI) and on which he continues to investigate in order to reach the stage of clinical trials in the future and continue training him with the aim of detecting cancer in early stages.

Treatment

Treatment for breast cancer depends on the stage of the cancer and the person's age, and may include:

• Surgery. There are several surgical procedures depending on tumor size and lymph node involvement.

1. Tumorectomy or lumpectomy: it consists of the removal of the tumor mass with an adequate tissue margin.
2. Quadratectomy: involves the removal of a breast quadrant with the tumor; it may be accompanied or not by ganglion vaciation, that is, of the removal of the axillary lymph nodes.
3. Simple mastectomy: consists of removal of the breast with the tumor, including nipple, areola and skin, as well as one or more axillary lymph nodes. It does not remove any of the muscles below the chest. It can be hygienic in advanced tumors, for palliative purposes.
4. Modified radical mastectomy: breast resection is made with axillary vaciation. A negative pressure drainage system is left.

• Intravenous or oral medications or chemotherapy or intratecal chemotherapy (medications introduced in the spinal cord with a needle, in the area called subaracnoid space)
• Radiation therapy
• Biological therapy
• Adjuvant therapy
• Hormonotherapy An antagonist of estrogens such as Tamophoden is used.
• Medicines to prevent and treat nausea and other side effects of treatment.
• Psychotherapy

Forecast

5-year overall survival was 59.9%. Women with clinical stage I were found to have the highest survival (82%), followed by those with stages IIB (70.4%), IIA (65.3%), IIIB (47.5%), IIIA (44.2%) and finally those with stage IV (15%). The effect of greater metastatic infiltration was notorious in women with blood-borne metastases, who showed the lowest survival (21.4%). Women who received chemotherapy and radiotherapy had the lowest survival (52%) although this difference was not significant. In women who did not have persistent breast cancer, survival was 72.3%, unlike those who did present it, in which a survival of 12.6% was identified.

Due to various public outreach campaigns, most women in the United States know that cardiovascular disease is the leading cause of death. However, the problem they fear most is breast cancer, despite the fact that the 1990s have decreased death rates from this neoplasm. Although many older women get breast cancer, they die from other causes. Only a minority of women know that lung cancer is the leading cause of cancer death in women. Such misconceptions are unfortunate because they perpetuate the scant attention paid to modifiable risk factors such as dyslipidemia, hypertension, or smoking.

Social impact

«The social representations of a disease are determinants of cultural behaviors with respect to it, in which a complex set of scientific and popular knowledge, the scale of values and other cultural elements, such as beliefs, that determine the general reaction of society and the particular reaction of each individual to a disease". Due to the social environment in which man develops, perhaps it can be said that no disease is merely biological or merely social. But due to the particular organ that is affected by this disease, and also affected in the treatment, breast cancer is a latent example of how a biologically less aggressive and invasive disease than many others can become one of the most feared.

The breast constitutes an organ of feminine aesthetics and is, in addition, a modified sebaceous gland that is involved in breastfeeding. Therefore, the breast is not just another organ, but more than an organ, it is part of feminine identity; Expressed in another way, when humanized, the breast becomes the breast. For women, their breasts fulfill an aesthetic function for themselves before for others. "If the only function of the female breast were lactation, as it happens In the rest of mammals, their diseases would undoubtedly have much less importance than they do."

Breast cancer has strong social representations since women fear "abandonment by their partner, involving the affective and sexual world and deteriorating their self-esteem, because this cancer compromises organs that are especially erogenous and attractive to them", to which is added the destabilization of the life project, which gives rise to a definitive turn in relationships and lifestyle, and drastic changes in the world of work and society.

In Colombia, a study was carried out in which it is stated that, faced with the diagnosis, the patients «express fear of being judged for not preventing and, in turn, of receiving a confirmatory diagnosis of the disease (...). Additionally, they imagine the procedures as painful. In short, the representations of breast cancer in the women in the study were quite gloomy and denoted enormous fear of loss, mutilation, pain, and death."