Breast Cancer
Disease Details
Family Health Simplified
- Description
- Breast cancer is a malignant tumor that originates in the cells of the breast tissue, commonly affecting women but also occurring in men.
- Type
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Breast cancer can be broadly categorized into several types, including ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), triple-negative breast cancer (TNBC), and HER2-positive breast cancer, among others.
In terms of genetic transmission, most breast cancers are sporadic, meaning they are not caused by inherited genetic mutations but rather by acquired mutations. However, some breast cancers are hereditary and are linked to inherited genetic mutations. The most well-known genetic mutations associated with hereditary breast cancer are BRCA1 and BRCA2. These mutations significantly increase the risk of developing breast cancer and are transmitted in an autosomal dominant pattern. This means a person needs only one copy of the mutated gene from either parent to have an increased risk of developing the disease. - Signs And Symptoms
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Most people with breast cancer have no symptoms at the time of diagnosis; their tumor is detected by a breast cancer screening test. For those who do have symptoms, a new lump in the breast is most common. Most breast lumps are not breast cancer, though lumps that are painless, hard, and with irregular edges are more likely to be cancerous. Other symptoms include swelling or pain in the breast; dimpling, thickening, redness, or dryness of the breast skin; and pain, or inversion of the nipple. Some may experience unusual discharge from the breasts, or swelling of the lymph nodes under the arms or along the collar bone.Some less common forms of breast cancer cause distinctive symptoms. Up to 3% of people with breast cancer have Paget's disease of the breast, with eczema-like red, scaly irritation on the nipple and areola. There may also be discharge from the nipple. Approximately half the women diagnosed with Paget's disease of the breast also have a lump in the breast.Inflammatory breast cancer is a rare (only seen in less than 5% of breast cancer diagnosis) yet aggressive form of breast cancer characterized by the swollen, red areas formed on the top of the breast. The visual effects of inflammatory breast cancer is a result of a blockage of lymph vessels by cancer cells. This type of breast cancer is seen in more commonly diagnosed in younger ages, obese women and African American women. As inflammatory breast cancer does not present as a lump there can sometimes be a delay in diagnosis.In rare cases, what initially appears as a fibroadenoma (hard, movable non-cancerous lump) could in fact be a phyllodes tumour. Phyllodes tumours are formed within the stroma (connective tissue) of the breast and contain glandular as well as stromal tissue. Phyllodes tumours are not staged in the usual sense; they are classified on the basis of their appearance under the microscope as benign, borderline or malignant.Advanced breast tumors can spread (metastasize) beyond the breast. The symptoms caused by metastatic breast cancer will depend on the location of metastasis. Common sites of metastasis include bone, liver, lung, and brain. When cancer has reached such an invasive state, it is categorized as a stage 4 cancer, cancers of this state are often fatal. Common symptoms of stage 4 cancer include unexplained weight loss, bone and joint pain, jaundice and neurological symptoms. These symptoms are called non-specific symptoms because they could be manifestations of many other illnesses. Rarely breast cancer can spread to exceedingly uncommon sites such as peripancreatic lymph nodes causing biliary obstruction leading to diagnostic difficulties.
Most symptoms of breast disorders, including most lumps, do not turn out to represent underlying breast cancer. Less than 20% of lumps, for example, are cancerous, and benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. - Prognosis
- Breast cancer prognosis depends on various factors including the stage at diagnosis, tumor size, lymph node involvement, hormone receptor status, HER2 status, and patient’s overall health. Early-stage breast cancer generally has a more favorable prognosis. Advances in treatment have improved survival rates, with five-year survival rates for localized breast cancer exceeding 90%. Early detection through screening and personalized treatment plans play critical roles in improving outcomes.
- Onset
- Onset: Breast cancer can occur at any age but is most commonly diagnosed in women over the age of 50. However, it can also affect younger women and, in rare cases, men. Early detection through screening is crucial for effective treatment.
- Prevalence
- Breast cancer is one of the most common cancers worldwide. It primarily affects women, but men can also develop the disease. The prevalence of breast cancer varies significantly by region, with higher rates generally reported in more developed countries. For example, in the United States, approximately 1 in 8 women (about 12%) will develop invasive breast cancer over the course of their lifetime.
- Epidemiology
- Breast cancer is the most-common invasive cancer in women, accounting for 30% of cancer cases in women. Along with lung cancer, breast cancer is the most commonly diagnosed cancer, with 2.09 million cases each in 2018. Breast cancer affects 1 in 7 (14%) of women worldwide. (The most common form of cancer is non-invasive non-melanoma skin cancer; non-invasive cancers are generally easily cured, cause very few deaths, and are routinely excluded from cancer statistics.) In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women and 6.0% of all cancer deaths for men and women together). Lung cancer, the second most-common cause of cancer-related deaths in women, caused 12.8% of cancer deaths in women (18.2% of all cancer deaths for men and women together).The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows: 18 in Eastern Asia, 22 in South Central Asia and sub-Saharan Africa, 26 in South-Eastern Asia, 26, 28 in North Africa and Western Asia, 42 in South and Central America, 42, 49 in Eastern Europe, 56 in Southern Europe, 73 in Northern Europe, 74 in Oceania, 78 in Western Europe, and 90 in North America. Metastatic breast cancer affects between 19% (United States) and 50% (parts of Africa) of women with breast cancer.The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles. Breast cancer is strongly related to age with only 5% of all breast cancers occurring in women under 40 years old. There were more than 41,000 newly diagnosed cases of breast cancer registered in England in 2011, around 80% of these cases were in women age 50 or older. Based on U.S. statistics in 2015 there were 2.8 million women affected by breast cancer. In the United States, the age-adjusted incidence of breast cancer per 100,000 women rose from around 102 cases per year in the 1970s to around 141 in the late-1990s, and has since fallen, holding steady around 125 since 2003. However, age-adjusted deaths from breast cancer per 100,000 women only rose slightly from 31.4 in 1975 to 33.2 in 1989 and have since declined steadily to 20.5 in 2014.
- Intractability
- Breast cancer is not considered intractable. There are various treatment options available, including surgery, radiation therapy, chemotherapy, hormone therapy, and targeted therapies. The effectiveness of treatment depends on factors such as the stage of the cancer, its type, and the patient's overall health. Early detection and advances in medical treatments have significantly improved prognosis and survival rates.
- Disease Severity
- Breast cancer severity can vary widely. It is often categorized by stages, from 0 (non-invasive) to IV (metastatic). Early stages (0-II) generally have a better prognosis and more treatment options. Stages III-IV indicate more advanced disease with potentially more serious outcomes. Early detection and treatment are crucial. Nan refers to "Not a Number" and is not applicable in this context.
- Healthcare Professionals
- Disease Ontology ID - DOID:1612
- Pathophysiology
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Breast cancer, like other cancers, occurs because of an interaction between an environmental (external) factor and a genetically susceptible host. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when they lose their ability to stop dividing, to attach to other cells, to stay where they belong, and to die at the proper time.
Normal cells will self-destruct (programmed cell death) when they are no longer needed. Until then, cells are protected from programmed death by several protein clusters and pathways. One of the protective pathways is the PI3K/AKT pathway; another is the RAS/MEK/ERK pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of self-destructing when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the PTEN protein turns off the PI3K/AKT pathway when the cell is ready for programmed cell death. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not self-destruct.Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure. Additionally, G-protein coupled estrogen receptors have been associated with various cancers of the female reproductive system including breast cancer.Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth. In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.In the United States, 10 to 20 percent of women with breast cancer or ovarian cancer have a first- or second-degree relative with one of these diseases. Men with breast cancer have an even higher likelihood. The familial tendency to develop these cancers is called hereditary breast–ovarian cancer syndrome. The best known of these, the BRCA mutations, confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. Some mutations associated with cancer, such as p53, BRCA1 and BRCA2, occur in mechanisms to correct errors in DNA. These mutations are either inherited or acquired after birth. Presumably, they allow further mutations, which allow uncontrolled division, lack of attachment, and metastasis to distant organs. However, there is strong evidence of residual risk variation that goes well beyond hereditary BRCA gene mutations between carrier families. This is caused by unobserved risk factors. This implicates environmental and other causes as triggers for breast cancers. The inherited mutation in BRCA1 or BRCA2 genes can interfere with repair of DNA cross links and DNA double strand breaks (known functions of the encoded protein). These carcinogens cause DNA damage such as DNA cross links and double strand breaks that often require repairs by pathways containing BRCA1 and BRCA2. However, mutations in BRCA genes account for only 2 to 3 percent of all breast cancers. Levin et al. say that cancer may not be inevitable for all carriers of BRCA1 and BRCA2 mutations. About half of hereditary breast–ovarian cancer syndromes involve unknown genes. Furthermore, certain latent viruses, may decrease the expression of the BRCA1 gene and increase the risk of breast tumours.GATA-3 directly controls the expression of estrogen receptor (ER) and other genes associated with epithelial differentiation, and the loss of GATA-3 leads to loss of differentiation and poor prognosis due to cancer cell invasion and metastasis. - Carrier Status
- Carrier status for breast cancer often refers to individuals who carry genetic mutations that increase their risk of developing breast cancer. Key genes associated with breast cancer risk include BRCA1 and BRCA2. Mutations in these genes are inherited and significantly raise the likelihood of breast cancer and other cancers. Genetic testing can identify carrier status for these mutations. If you carry such a mutation, it is important to discuss risk management and preventive measures with a healthcare professional.
- Mechanism
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Breast cancer primarily develops due to genetic mutations and epigenetic changes that lead to uncontrolled cell growth in breast tissue. The following are key molecular mechanisms involved:
1. **Genetic Mutations**:
- **BRCA1 and BRCA2**: Mutations in these tumor suppressor genes significantly increase the risk for breast cancer by impairing DNA repair mechanisms.
- **TP53**: Mutations in this gene, which encodes the p53 protein, result in the loss of cell cycle control and apoptosis, enabling cancer progression.
- **PIK3CA**: Mutations in this gene lead to activation of the PI3K/AKT pathway, promoting cell survival and growth.
2. **Hormone Receptors**:
- **Estrogen Receptor (ER)** and **Progesterone Receptor (PR)**: The presence of these receptors on cancer cells allows them to grow in response to hormones. ER-positive tumors are often driven by estrogen signaling.
- **Human Epidermal Growth Factor Receptor 2 (HER2/neu)**: Overexpression of HER2 accelerates cell division and is associated with aggressive tumor behavior.
3. **Epigenetic Changes**:
- **DNA Methylation**: Abnormal methylation patterns can silence tumor suppressor genes.
- **Histone Modification**: Alterations in histone proteins can influence gene expression, facilitating cancerous changes.
4. **Cell Signaling Pathways**:
- **MAPK/ERK Pathway**: Dysregulation of this pathway can contribute to uncontrolled proliferation.
- **Notch, Wnt, and Hedgehog Pathways**: Abnormal activation of these developmental pathways can also promote cancer.
Understanding these mechanisms is crucial for developing targeted therapies to treat various subtypes of breast cancer. - Treatment
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Breast cancer treatment typically involves a combination of approaches based on the type and stage of the cancer. Common treatments include:
1. **Surgery**:
- Lumpectomy: Removal of the tumor and a small margin of surrounding tissue.
- Mastectomy: Removal of one or both breasts, partially or completely.
2. **Radiation Therapy**:
- Uses high-energy waves to kill cancer cells or keep them from growing.
3. **Chemotherapy**:
- Uses drugs to destroy cancer cells, often systemic (affecting the whole body).
4. **Hormone Therapy**:
- Blocks cancer cells from getting the hormones they need to grow, typically used in hormone receptor-positive breast cancers.
5. **Targeted Therapy**:
- Focuses on specific molecules involved in cancer growth, such as HER2-positive breast cancer treatments.
6. **Immunotherapy**:
- Uses the body’s immune system to fight cancer.
The choice of treatment depends on various factors, including the cancer's type, stage, and patient-specific factors like overall health and preferences. Treatment plans are often tailored to the individual case. - Compassionate Use Treatment
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Compassionate use treatment for breast cancer refers to the provision of investigational drugs outside of clinical trials for patients with serious or life-threatening conditions when no comparable alternative therapy options exist. Access to such treatments is tightly regulated and typically requires approval from medical authorities.
Off-label treatments involve the use of FDA-approved drugs for an unapproved indication. In breast cancer, this might include the use of medications initially approved for different cancers or other conditions but have shown efficacy in treating certain types of breast cancer based on emerging research or clinician experience.
Experimental treatments are therapies currently being studied in clinical trials but not yet approved for general use. These can include new drugs, combinations of drugs, novel drug delivery systems, or innovative treatments such as immunotherapies, targeted therapies, or gene therapies. Participation in clinical trials is the primary way patients can access these experimental treatments. - Lifestyle Recommendations
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Lifestyle recommendations for breast cancer prevention and management include:
1. **Healthy diet**: Consume a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Limit processed foods and red meats.
2. **Regular physical activity**: Aim for at least 150 minutes of moderate aerobic activity or 75 minutes of vigorous activity weekly, combined with strength training exercises.
3. **Maintain a healthy weight**: Being overweight or obese increases the risk of breast cancer, especially after menopause.
4. **Limit alcohol consumption**: Alcohol intake should be minimized, ideally to one drink per day or less.
5. **Avoid smoking**: Do not smoke, and avoid exposure to secondhand smoke.
6. **Breastfeeding**: Breastfeeding, if possible, can lower the risk of breast cancer.
7. **Regular screenings**: Follow guidelines for mammograms and other breast cancer screenings based on your age and risk factors.
8. **Medication and preventive surgery**: For those at high risk, discuss with a healthcare provider the potential benefits of medications or preventive surgery.
Implementing these lifestyle changes can help reduce the risk of developing breast cancer and improve overall health. - Medication
- The selective estrogen receptor modulators reduce the risk of breast cancer but increase the risk of thromboembolism and endometrial cancer. There is no overall change in the risk of death. They are thus not recommended for the prevention of breast cancer in women at average risk but it is recommended they be offered for those at high risk and over the age of 35. The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications. Aromatase inhibitors (such as exemestane and anastrozole) may be more effective than selective estrogen receptor modulators (such as tamoxifen) at reducing breast cancer risk and they are not associated with an increased risk of endometrial cancer and thromboembolism.Medications used after and in addition to surgery are called adjuvant therapy. Chemotherapy or other types of therapy prior to surgery are called neoadjuvant therapy. Aspirin may reduce mortality from breast cancer when used with other treatments.There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone-blocking agents, chemotherapy, and monoclonal antibodies.
- Repurposable Drugs
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There are several drugs originally approved for other conditions that have shown potential for repurposing in the treatment of breast cancer. Some examples include:
1. **Metformin**: Originally used to treat type 2 diabetes, metformin has been studied for its potential anti-cancer properties, particularly in breast cancer, due to its effects on cellular metabolism and growth pathways.
2. **Aspirin**: Commonly used as an anti-inflammatory and blood thinner, aspirin has been investigated for its role in reducing the risk of breast cancer recurrence, attributed to its anti-inflammatory and anti-proliferative effects.
3. **Statins**: Cholesterol-lowering drugs, statins, have been explored for their potential to inhibit cancer cell growth and metastasis in breast cancer through their effects on cholesterol synthesis pathways.
4. **Beta-blockers**: Typically prescribed for cardiovascular conditions, beta-blockers have shown promise in potentially improving survival outcomes in breast cancer patients by reducing stress hormone effects on cancer progression.
However, more research and clinical trials are needed to fully understand the efficacy and safety of these repurposed drugs in treating breast cancer. - Metabolites
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Breast cancer is associated with various metabolic alterations. Some key metabolites involved in breast cancer include:
1. **Lactate**: Increased levels due to the Warburg effect, where cancer cells preferentially use glycolysis for energy production even in the presence of oxygen.
2. **Glutamine**: Often utilized for the synthesis of nucleotides, amino acids, and other macromolecules essential for rapidly proliferating cancer cells.
3. **Choline-containing compounds**: Elevated in breast cancer tissues and associated with membrane synthesis and turnover.
4. **Glycine**: Involved in the synthesis of proteins and nucleic acids, often upregulated in cancer cells.
5. **Hydroxybutyrate**: Sometimes elevated, its role in cancer metabolism is still under investigation.
These metabolic changes are part of the complex biochemical network that supports breast cancer development and progression. - Nutraceuticals
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Nutraceuticals are products derived from food sources that provide additional health benefits beyond basic nutritional value. In the context of breast cancer, certain nutraceuticals have been studied for their potential supportive roles:
1. **Curcumin**: Found in turmeric, it may have anti-inflammatory and anti-cancer properties.
2. **Green Tea Extract (EGCG)**: Contains antioxidants that might inhibit cancer cell growth.
3. **Omega-3 Fatty Acids**: Present in fish oil, they may reduce inflammation and possibly slow the growth of cancer cells.
4. **Resveratrol**: Found in red grapes, it has shown potential anti-cancer effects.
It's essential to consult with healthcare professionals before using nutraceuticals as part of cancer treatment, as they should complement, not replace, conventional therapies. - Peptides
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In breast cancer research and treatment, peptides and nanotechnology have shown promising advancements:
1. **Peptides**: Peptides are short chains of amino acids that can play various roles in cancer therapy. They can be used as targeting agents, drugs, or vaccines.
- **Targeting peptides**: These can bind specifically to cancer cells, facilitating targeted drug delivery.
- **Therapeutic peptides**: Some peptides can induce cancer cell death or inhibit cancer growth processes.
- **Peptide vaccines**: These can stimulate the immune system to recognize and attack breast cancer cells.
2. **Nanotechnology**: This involves the use of nanoparticles to improve the diagnosis, imaging, and treatment of breast cancer.
- **Drug delivery**: Nanoparticles can deliver chemotherapy drugs directly to tumor cells, reducing side effects and improving drug efficacy.
- **Imaging**: Nanoparticles can enhance the contrast in imaging techniques like MRI and PET scans, aiding in the early detection and monitoring of breast cancer.
- **Theranostics**: This combines therapeutic and diagnostic capabilities in one system, allowing for targeted treatment and real-time monitoring.
The integration of peptides and nanotechnology in breast cancer research aims to create more effective and less toxic treatment options.