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Apoptosis or programmed cell death. In this process, cells self-destruct without triggering inflammatory reactions or leaving tissue scars. Apoptosis is therefore considered a natural physiological death, resulting in a mechanism for eliminating unwanted, damaged or unknown cells and playing a protective role against possible diseases.

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It is the process by which mammary tumor tissues are able to proliferate, grow and acquire invasive and migratory properties. This facilitates neoplastic dissemination to other locations.

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Metastatic breast cancer occurs when cancer cells break away from the original tumor and travel through the bloodstream or lymphatic system, settling and growing in distant areas. Although it spreads, it is still named after the area where it started, such as "metastatic breast cancer" rather than "lung cancer" if it spread to the lungs.

Metastatic breast cancer can affect several areas, but most often spreads to the bones, liver, lungs and brain.

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Breast cancer consists of an abnormal and disorderly growth of the cells of this tissue and sometimes forms a lump, also called a tumor. Tumors can be benign or malignant; the difference is that the former are formed by cells of normal appearance, and lack the ability to invade surrounding tissues and spread to other parts of the body; malignant tumors are formed by cells of abnormal appearance, capable of invading nearby tissues and spread to other parts of the body.

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According to the International Agency for Research on Cancer (IARC), an estimated 2.3 million new cases of breast cancer were diagnosed worldwide in 2020, making it the most common cancer in women globally.

Although men represent a significant minority of breast cancer cases, they are still an affected population. It is estimated that about 1% of all breast cancer cases occur in men.

In the United States, more women are diagnosed with breast cancer than any other type of cancer; the disease accounts for 1 in 3 new cases of female cancer per year.

Since the mid-2000s, invasive breast cancer in women has increased by approximately half a percentage point each year.

Currently, there are more than 4 million women who have been diagnosed or are living with breast cancer in the United States.

In 2020, an estimated 684,996 women worldwide died of breast cancer.

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For Colombia, breast cancer is the leading cancer in the country, with 13 376 new cases in 2018 (incidence rate of 63.9 cases per 100 000 women over 15 years of age) and is the leading cause of cancer death in women with a rate of 17.2 deaths per 100 000 inhabitants

In Colombia, mortality from breast cancer is on the rise; about 12% of deaths in women are directly attributable to this type of malignant neoplasm.

Since the end of the last century, its increase at the national level has been over 35%; the mortality rate between 1997 and 2018 went from 8 to 11.2 deaths per hundred thousand.

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The pathophysiology of breast cancer: It involves a series of complex events that lead to the uncontrolled growth of breast cells.

Breast cancer begins with a genetic mutation in normal breast cells, which triggers their uncontrolled proliferation and tumor formation. To maintain its growth, the tumor needs a constant supply of blood and nutrients, leading to angiogenesis. Over time, cancer cells can invade nearby tissues and spread to other parts of the body, a process known as metastasis. In addition to cell proliferation, breast cancer involves a complex interaction between tumor cells and their surrounding environment. As the cancer progresses, tumor cells may become more resistant to conventional therapy, such as chemotherapy or radiation therapy.

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BENIGN AND MALIGNANT PATHOLOGIES OF THE MAMMARY GLAND, THEIR EPIDEMIOLOGY AND ASSOCIATED RISK FACTORS.

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BENIGN AND MALIGNANT PATHOLOGIES OF THE MAMMARY GLAND, THEIR EPIDEMIOLOGY AND ASSOCIATED RISK FACTORS.

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Cell checkpoints: Cell cycle checkpoints are control mechanisms that regulate the proper progression of the cell cycle and detect and repair DNA damage. However, in breast cancer, these checkpoints can be disrupted, allowing damaged or mutated cells to continue dividing. For example, the p53 protein is an important regulator of the cell cycle checkpoint that induces apoptosis (programmed cell death) in cells with DNA damage, but its mutation or inactivation can allow abnormal cells to survive.

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Alterations in the cell cycle: Breast cancer involves an interruption in the normal cell cycle, where cells go through different phases, such as the synthesis phase (S), the growth phase (G1), the DNA duplication phase (G2) and the cell division phase (M). Genetic mutations can affect cell cycle regulatory genes, such as oncogenes (which promote cell division) and tumor suppressor genes (which inhibit cell division). These alterations can lead to uncontrolled cell proliferation and tumor formation.

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Tumor markers: Tumor markers are substances produced by tumor cells or in response to their presence. In breast cancer, tumor markers can be proteins, antigens or nucleic acids that are detected in blood, urine or tumor tissues and are used for diagnosis, prognosis and treatment monitoring. For example, estrogen receptor (ER), progesterone receptor (PR), and human epithelial growth factor receptor 2 (HER2/neu) are commonly used markers in breast cancer staging and management.

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Regulation of cell division: The cell cycle is a highly regulated process that controls cell division and proliferation. Normal cells go through an orderly cell cycle, which includes phases of growth, DNA duplication and cell division. However, in breast cancer, this regulated process is disrupted, leading to uncontrolled cell proliferation.

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Genetic mutations: Genetic mutations affecting cell cycle regulatory genes can trigger the development of breast cancer. For example, mutations in oncogenes can promote excessive cell division, while mutations in tumor suppressor genes can inhibit mechanisms that curb abnormal cell proliferation.

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Altered cellular checkpoints: Cell cycle checkpoints, such as the damaged DNA checkpoint, are mechanisms that ensure that cells only progress through the cell cycle if they are in the right condition. However, in breast cancer, these checkpoints may be altered, allowing damaged cells to continue dividing and accumulating more mutations.

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Targeted therapy: Understanding the cell cycle in breast cancer is crucial for the development of targeted therapies. For example, some breast cancer treatments, such as CDK4/6 inhibitors, work by blocking key proteins involved in cell cycle regulation, which helps to slow cell proliferation.

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G1/S checkpoint checkpoint: This checkpoint regulates the cell's decision to enter the synthesis (S) phase of the cell cycle, where DNA is duplicated. In breast cancer, cells can develop mutations that deregulate the regulatory genes of this checkpoint, such as the tumor suppressor gene p53. Loss of p53 function can allow cells with DNA damage to continue dividing, which contributes to cancer progression.

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G2/M checkpoint checkpoint: This checkpoint assesses whether DNA has replicated correctly before the cell enters mitosis (M) phase and divides. Alterations in regulatory proteins at this checkpoint, such as CDC25 and cyclin-dependent kinase 1 (CDK1), can lead to premature entry into M phase and contribute to genomic instability and breast cancer progression.

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Mitosis checkpoint checkpoint: During mitosis, several checkpoints are activated to ensure that chromosomes segregate correctly into daughter cells. Alterations in regulatory proteins at these checkpoints, such as the protein kinase BUBR1, can lead to errors in chromosome segregation and the generation of aneuploid cells, which have an abnormal number of chromosomes and are common in breast cancer.

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DNA damage checkpoint checkpoint: This checkpoint detects and responds to DNA damage induced by internal and external factors, such as ultraviolet radiation or chemical agents. Breast cancer cells can develop mechanisms to bypass this checkpoint, allowing the proliferation of DNA-damaged cells and contributing to tumor progression.

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Hormone receptors: These markers include estrogen receptors (ER) and progesterone receptors (PR). Positivity for these receptors indicates that breast cancer cells are sensitive to the female hormones estrogen and progesterone. Hormone receptor expression can influence treatment options and breast cancer prognosis.

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Her2/neu (also known as HER2): HER2 is a cell growth receptor that is overexpressed in approximately 20% of breast cancers. Overexpression of HER2 can lead to uncontrolled cell growth and more aggressive disease. HER2 detection is important in determining eligibility for targeted therapies, such as trastuzumab (Herceptin).

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Ki-67: Ki-67 is a protein that is expressed during all phases of the cell cycle, except for the G0 phase, and is used as a marker of cell proliferation. Ki-67 levels can provide information on the proliferation rate of cancer cells and help predict treatment response and prognosis.

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P53: The p53 protein is a tumor suppressor that regulates DNA damage response and apoptosis (programmed cell death). Mutations in the TP53 gene, which encodes the p53 protein, are common in breast cancer and may be associated with a worse prognosis and inferior response to treatment.

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Genetic and molecular markers: Several genetic and molecular markers have been identified in breast cancer that can provide prognostic and predictive information. Examples include the PAM50 gene expression profile, which classifies breast tumors into molecular subtypes, and mutations in genes such as BRCA1 and BRCA2, which are associated with an increased risk of hereditary breast cancer.

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FIBROADENOMAS: Solid tumors composed of glandular tissue and fibrous tissue, common in young women. They are usually mobile, with well-defined borders and are not usually painful.

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FIBROADENOMAS: Solid tumors composed of glandular tissue and fibrous tissue, common in young women. They are usually mobile, with well-defined borders and are not usually painful.

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BREAST CYSTS: Fluid-filled pockets that can form in the breast tissue. They are often benign and may be palpable as soft, rounded masses.

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BREAST CYSTS: Fluid-filled pockets that can form in the breast tissue. They are often benign and may be palpable as soft, rounded masses.

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FIBROSKYSTIC CHANGES: A condition characterized by benign changes in breast tissue, including cysts, fibrous tissue, and changes in the milk ducts. May cause breast pain or tenderness.

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FIBROSKYSTIC CHANGES: A condition characterized by benign changes in breast tissue, including cysts, fibrous tissue, and changes in the milk ducts. May cause breast pain or tenderness.

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ADENOSIS: Increase in the amount of glandular tissue in the breast, often associated with small cysts and changes in the surrounding tissues.

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ADENOSIS: Increase in the amount of glandular tissue in the breast, often associated with small cysts and changes in the surrounding tissues.

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DUCTAL AND LOBULAR HYPERPLASIA: Increased number of cells in the ducts or lobules of the breast, respectively. It may be a benign finding but is considered a risk factor for breast cancer.

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DUCTAL AND LOBULAR HYPERPLASIA: Increased number of cells in the ducts or lobules of the breast, respectively. It may be a benign finding but is considered a risk factor for breast cancer.

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MASTITIS: Inflammation of the breast, usually due to a bacterial infection in the milk ducts. May cause redness, swelling and pain in the affected breast.

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MASTITIS: Inflammation of the breast, usually due to a bacterial infection in the milk ducts. May cause redness, swelling and pain in the affected breast.

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Non-modifiable factors:

- Sex

- Age

- Genetic mutations (Hereditary risk)

- Personal history

- Family history

- Dense breast tissue

- Chest X-ray

- Endogenous hormonal factors

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Modifiable factors:

Dietary factors

- Physical exercise

- Obesity

- Alcohol

- Tobacco

- Reproductive history

- Exogenous hormonal factors

- Ionizing radiation

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Areas of the country with the highest CA breast cancer rates

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Areas of the country with the highest CA breast cancer rates

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Cali and Bucaramanga, only in the latter has there been a decrease in the mortality rate, specifically since 2001, falling from 17 to 10.8 per 100,000 inhabitants in 2010.

In Cali, incidence trends showed a steady increase from the middle of the last century until 2007, reaching a maximum of 48 new cases per 100,000 inhabitants, but has stagnated in the last four years measured, remaining at 43.3 per 100,000 inhabitants between 2008 and 2016.

In women, breast cancer ranked first in mortality. In the geographic pattern of breast cancer mortality, three regions of the country with a higher risk are identified, corresponding to the Andean region and some pockets of the Caribbean and Orinoco regions. In these regions, in most cases, the high risk was observed in capital cities such as: Cali, Barranquilla, Santa Marta, Bucaramanga, Cúcuta, among others. At the departmental level in Atlántico, followed by Quindío, Valle del Cauca, Arauca and Risaralda, and to a lesser degree in Caldas, San Andrés y Providencia, Bogotá and Antioquia.

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Risk factors that Colombians have for breast CA

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Risk factors that Colombians have for breast CA

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Advanced age.

Family history of breast cancer.

Inherited genetic mutations, such as variants in the BRCA1 and BRCA2 genes.

Obesity and unhealthy diet.

Use of hormone therapy.

Alcohol consumption.

Lack of physical activity.

Exposure to certain chemicals and environmental pollutants.

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Focus on Prevention and Early Detection:

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Focus on Prevention and Early Detection:

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Perform breast self-examination every month as a women's self-care practice.

Efforts are underway to improve access to health services, education on healthy lifestyles and early detection programs throughout the country.

Practice clinical breast examination every year for all women starting at age 40 as part of a woman's physical examination.

Perform mammography every two years, for women between 50 and 69 years of age, or earlier according to medical criteria.

Health authorities and non-governmental organizations often offer awareness campaigns and early detection programs, especially targeting vulnerable populations.

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1. Lumps: One of the most common signs of breast cancer is the presence of a lump or nodule that can be felt during self-examination or detected by imaging tests such as mammography or ultrasound.

2. Skin changes: This may include redness, swelling, thickening of the skin or changes in texture, such as dimpling or orange peel-like wrinkling.

3. Nipple changes: This may include nipple retraction (when the nipple turns inward), changes in the size or shape of the nipple, nipple discharge other than breast milk, or persistent nipple or breast pain.

4. Pain: Breast cancer does not always cause pain, but some women may experience pain in the breast or surrounding area.