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breast cancer
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{{Short description|Cancer that originates in mammary glands}}{{cs1 config|name-list-style=vanc|display-authors=6}}{{pp-pc}}{{Use American English|date=March 2024}}{{Use dmy dates|date=June 2021}}- the content below is remote from Wikipedia
- it has been imported raw for GetWiki
| factoids |
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Signs and symptoms
(File:En Breast cancer illustrations.png|thumb|Common symptoms of breast cancer|alt=Cartoons of breasts with a lump, skin dimpling, red fluid leaking from the nipple, or changes in the appearance of the skin or nipple)Most people with breast cancer have no symptoms at the time of diagnosis; their tumor is detected by a breast cancer screening test.{{sfn|Hayes|Lippman|2022|loc=“Evaluation of Breast Masses“}} 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.WEB,www.cancer.org/cancer/types/breast-cancer/screening-tests-and-early-detection/breast-cancer-signs-and-symptoms.html, 25 March 2024, Breast Cancer Signs and Symptoms, American Cancer Society, 14 January 2022, 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 5% of people with breast cancer have inflammatory breast cancer, where cancer cells block the lymph vessels of one breast, causing the breast to substantially swell and redden over three to six months.WEB,www.cancer.org/cancer/types/breast-cancer/about/types-of-breast-cancer/inflammatory-breast-cancer.html, 28 March 2024, Inflammatory Breast Cancer, American Cancer Society, 1 March 2023, 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.WEB,www.cancerresearchuk.org/about-cancer/breast-cancer/types/pagets-disease-breast, 25 March 2024, Paget’s disease of the breast, Cancer Research UK, 20 June 2023, Advanced tumors can spread (metastasize) beyond the breast, most commonly to the bones, liver, lungs, and brain.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Fig. 9: Common Metastatic Sites in Breast Cancer“}} Bone metastases can cause swelling, progressive bone pain, and weakening of the bones that leads to fractures.WEB,www.bcrf.org/blog/metastatic-breast-cancer-symptoms-treatment/, 3 May 2024, Metastatic Breast Cancer: Symptoms, Treatment, Research, 27 February 2024, Breast Cancer Research Foundation, Liver metastases can cause abdominal pain, nausea, vomiting, and skin problems – rash, itchy skin, or yellowing of the skin (jaundice). Those with lung metastases experience chest pain, shortness of breath, and regular coughing. Metastases in the brain can cause persistent headache, seizures, nausea, vomiting, and disruptions to the affected person’s speech, vision, memory, and regular behavior.Screening
(File:MammographyinprocessGraphic.jpg|thumb|Cartoon of a mammogram, with the breast to be imaged pressed between two plates.)Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to diagnose breast tumors early when treatments are more successful. The most common screening test for breast cancer is low-dose X-ray imaging of the breast, called mammography.WEB,www.cancer.gov/types/breast/patient/breast-screening-pdq, 5 January 2024, National Cancer Institute, Breast Cancer Screening PDQ – Patient Version, 26 June 2023, Each breast is pressed between two plates and imaged. Tumors can appear unusually dense within the breast, distort the shape of surrounding tissue, or cause small dense flecks called microcalcifications.WEB,www.komen.org/breast-cancer/screening/mammography/mammogram-images/, 5 January 2024, Findings on a Mammogram and Mammogram Results, Susan G. Komen Foundation, 30 November 2022, Radiologists generally report mammogram results on a standardized scale – the six-point Breast Imaging-Reporting and Data System (BI-RADS) is the most common globally – where a higher number corresponds to a greater risk of a cancerous tumor.{{sfn|Nielsen|Narayan|2023|loc=“Interpretation of a Mammogram“}}{{sfn|Metaxa|Healy|O’Keeffe|2019|loc=“Introduction“}}A mammogram also reveals breast density; dense breast tissue appears opaque on a mammogram and can obscure tumors.WEB,www.cancer.org/cancer/types/breast-cancer/screening-tests-and-early-detection/mammograms/understanding-your-mammogram-report.html, 8 January 2024, American Cancer Society, Understanding Your Mammogram Report, 14 January 2022, WEB,www.cancer.org/cancer/types/breast-cancer/screening-tests-and-early-detection/mammograms/breast-density-and-your-mammogram-report.html, 8 January 2024, American Cancer Society, Breast Density and Your Mammogram Report, 28 March 2023, BI-RADS categorizes breast density into four categories. Mammography can detect around 90% of breast tumors in the least dense breasts (called “fatty” breasts), but just 60% in the most dense breasts (called “extremely dense“).{{sfn|Nielsen|Narayan|2023|loc=“Implications of Breast Density“}} Women with particularly dense breasts can instead be screened by ultrasound, magnetic resonance imaging (MRI), or tomosynthesis, all of which more sensitively detect breast tumors.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Screening“}}File:Mammo breast cancer wArrows.jpg|thumb|MammogramsMammogramsRegular screening mammography reduces breast cancer deaths by at least 20%.{{sfn|Loibl|Poortmans|Morrow|Denkert|2021|loc=“Screening“}} Most medical guidelines recommend annual screening mammograms for women aged 50–70.{{sfn|Hayes|Lippman|2022|loc=“Screening for Breast Cancer“}} Screening also reduces breast cancer mortality in women aged 40–49, and some guidelines recommend annual screening in this age group as well.{{sfn|Hayes|Lippman|2022|loc=“Screening for Breast Cancer“}}{{sfn|Rahman|Helvie|2022|loc=“Table 1“}} For women at high risk for developing breast cancer, most guidelines recommend adding MRI screening to mammography, to increase the chance of detecting potentially dangerous tumors.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Screening“}} Regularly feeling one’s own breasts for lumps or other abnormalities, called breast self-examination, does not reduce a person’s chance of dying from breast cancer.WEB,www.cancer.gov/types/breast/hp/breast-screening-pdq, 10 January 2024, National Cancer Institute, Breast Cancer Screening (PDQ) - Health Professional Version, 7 June 2023, Clinical breast exams, where a health professional feels the breasts for abnormalities, are common;{{sfn|Menes|Coster|Coster|Shenhar-Tsarfaty|2021|loc=“Abstract“}} whether they reduce the risk of dying from breast cancer is not known. Regular breast cancer screening is commonplace in most wealthy nations, but remains uncommon in the world’s poorer countries.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Screening“}}Diagnosis
(File:Needle Breast Biopsy.png|thumb|upright=0.8|Needle breast biopsy)Those who have a suspected tumor from a mammogram or physical exam first undergo additional imaging – typically a second “diagnostic” mammogram and ultrasound – to confirm its presence and location.{{sfn|Hayes|Lippman|2022|loc=“Evaluation of Breast Masses“}} A biopsy is then taken of the suspected tumor. Breast biopsy is typically done by core needle biopsy, with a hollow needle used to collect tissue from the area of interest.WEB,www.nationalbreastcancer.org/breast-cancer-biopsy/, 10 January 2024, Breast Biopsy, National Breast Cancer Foundation, Suspected tumors that appear to be filled with fluid are often instead sampled by fine-needle aspiration.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Diagnostic Work-Up“}} Around 10–20% of breast biopsies are positive for cancer.{{sfn|Hayes|Lippman|2022|loc=“Pathologic Findings of the Breast“}} Most biopsied breast masses are instead caused by fibrocystic breast changes, a term that encompasses the benign growth of small pockets of fluid, cell growth, or fibrous tissue.{{sfn|Hayes|Lippman|2022|loc=“Pathologic Findings of the Breast“}}File:Invasive Ductal Carcinoma 40x.jpg|High-grade invasive ductal carcinoma, with minimal tubule formation, marked pleomorphism, and prominent mitoses, 40x fieldFile:Mamma-CA.jpg|F-18 FDG PET/CT: A breast cancer metastasis to the right scapulaClassification
Breast cancers are classified by several grading systems, each of which assess a tumor characteristic that impacts a person’s prognosis. First, a tumor is classified by the tissue it arises from, or the appearance of the tumor tissue under a microscope. Most breast cancers (85%) are ductal carcinoma – derived from the lining of the mammary ducts. 10% are lobular carcinoma – derived from the mammary lobes – or mixed ductal/lobular carcinoma.{{sfn|Hayes|Lippman|2022|loc=“Invasive Breast Cancers“}} Rarer types include mucinous carcinoma (around 2.5% of cases; surrounded by mucin), tubular carcinoma (1.5%; full of small tubes of epithelial cells), medullary carcinoma (1%; resembling “medullary” or middle-layer tissue), and papillary carcinoma (1%; covered in finger-like growths).{{sfn|Hayes|Lippman|2022|loc=“Invasive Breast Cancers“}} Oftentimes a biopsy reveals cells that are cancerous but have not yet spread beyond their original location. This condition, called carcinoma in situ, is often considered “precancerous” rather than a dangerous cancer itself.{{sfn|Hayes|Lippman|2022|loc=“Noninvasive Breast Neoplasms“}} Those with ductal carcinoma in situ (in the mammary ducts) are at increased risk for developing true invasive breast cancer – around a third develop breast cancer within five years.{{sfn|Hayes|Lippman|2022|loc=“Noninvasive Breast Neoplasms“}} Lobular carcinoma in situ (in the mammary lobes) rarely causes a noticeable lump, and is often found incidentally during a biopsy for another reason. It is commonly spread throughout both breasts. Those with lobular carcinoma in situ also have an increased risk of developing breast cancer – around 1% develop breast cancer each year. However, their risk of dying of breast cancer is no higher than the rest of the population.{{sfn|Hayes|Lippman|2022|loc=“Noninvasive Breast Neoplasms“}}Invasive tumor tissue is assigned a grade based on how distinct it appears from healthy breast.WEB,www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-grades.html, 13 February 2024, American Caner Society, Breast Cancer Grade, 8 November 2021, Breast tumors are graded based on three features: the proportion of cancer cells that form tubules, the appearance of the cell nucleus, and how many cells are actively replicating.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Histologic Grade“}} Each feature is scored on a three-point scale, with a higher score indicating less healthy looking tissue. A grade is assigned based on the sum of the three scores. Combined scores of 3, 4, or 5 represent grade 1, a slower-growing cancer. Scores of 6 or 7 represent grade 2. Scores of 8 or 9 represent grade 3, a faster-growing, more aggressive cancer.In addition to grading, tumor biopsy samples are tested by immunohistochemistry to determine if the tissue contains the proteins estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2).{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Theranostic Biomarkers“}} Tumors containing either ER or PR are called “hormone receptor-positive” and can be treated with hormone therapies.WEB,www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-hormone-receptor-status.html, 20 February 2024, Breast Cancer Hormone Receptor Status, American Cancer Society, 8 November 2021, Around 15 to 20% of tumors contain HER2; these can be treated with HER2-targeted therapies.WEB,www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html, 20 February 2024, Breast Cancer HER2 Status, American Cancer Society, 25 August 2022, The remainder that do not contain ER, PR, or HER2 are called “triple-negative” tumors, and tend to grow more quickly than other breast cancer types.After the tumor is evaluated, the breast cancer case is staged using the American Joint Committee on Cancer and Union for International Cancer Control’s TNM staging system.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Lymph node status and pathological stage“}} Scores are assigned based on characteristics of the tumor (T), lymph nodes (N), and any metastases (M).{{sfn|AJCC Staging Manual|2017|loc=“Rules for Classification“}} T scores are determine by the size and extent of the tumor. Tumors less than 20 millimeters (mm) across are designated T1. Tumors 20–50 mm across are T2. A tumor greater than 50 mm across is T3. Tumors that extend to the chest wall or to the skin are designated T4.{{sfn|AJCC Staging Manual|2017|loc=“Primary Tumor (T)“}} N scores are based on whether the cancer has spread to nearby lymph nodes. N0 indicates no spread to the lymph nodes. N1 is for tumors that have spread to the closest axillary lymph nodes (called “level I” and “level II” axillary lymph nodes, in the armpit). N2 is for spread to the intramammary lymph nodes (on the other side of the breast, near the chest center), or for axillary lymph nodes that appear attached to each other or to the tissue around them (a sign of more severely affected tissue).{{sfn|AJCC Staging Manual|2017|loc=“Regional Lymph Nodes – Clinical“}} N3 designates tumors that have spread to the highest axillary lymph nodes (called “level 3” axillary lymph nodes, above the armpit near the shoulder), to the supraclavicular lymph nodes (along the neck), or to both the axillary and intramammary lymph nodes.{{sfn|AJCC Staging Manual|2017|loc=“Regional Lymph Nodes – Clinical“}} The M score is binary: M0 indicates no evidence metastases; M1 indicates metastases have been detected.{{sfn|AJCC Staging Manual|2017|loc=“Distant Metastasis (M)“}}TNM scores are then combined with tumor grades and ER/PR/HER2 status to calculate a cancer case’s “prognostic stage group”. Stage groups range from I (best prognosis) to IV (worst prognosis), with groups I, II, and III further divided into subgroups IA, IB, IIA, IIB, IIIA, IIIB, and IIIC. In general, tumors of higher T and N scores and higher grades are assigned higher stage groups. Tumors that are ER, PR, and HER2 positive are slightly lower stage group than those that are negative. Tumors that have metastasized are stage IV, regardless of the other scored characteristics.{{sfn|AJCC Staging Manual|2017|loc=“AJCC Prognostic Stage Groups“}}File:Diagram showing stage T1 breast cancer CRUK 244.svg|Stage T1 breast cancerFile:Diagram showing stage T2 breast cancer CRUK 252.svg|Stage T2 breast cancerFile:Diagram showing stage T3 breast cancer CRUK 259.svg|Stage T3 breast cancerFile:Stage 4 of Breast Cancer.jpg|Metastatic or stage 4 breast cancerManagement
The management of breast cancer depends on the affected person’s health, the cancer case’s molecular characteristics, and how far the tumor has spread at the time of diagnosis.Local tumors
File:Mastectomie 02.jpg|thumb|Chest after right breast mastectomymastectomyThose whose tumors have not spread beyond the breast often undergo surgery to remove the tumor and some surrounding breast tissue.{{sfn|Hayes|Lippman|2022|loc=“Local (Primary) Treatments“}} The surgery method is typically chosen to spare as much healthy breast tissue as possible, removing just the tumor (lumpectomy) or a larger part of the breast (partial mastectomy). Those with large or multiple tumors, high genetic risk of subsequent cancers, or who are unable to receive radiation therapy may instead opt for full removal of the affected breast(s) (full mastectomy).{{sfn|Hayes|Lippman|2022|loc=“Local (Primary) Treatments“}} To reduce the risk of cancer spreading, women will often have the nearest lymph node removed in a procedure called sentinel lymph node biopsy. Dye is injected near the tumor site, and several hours later the lymph node it accumulates in is removed.{{sfn|Hayes|Lippman|2022|loc=“Evaluation and Treatment of the Axillary Lymph Nodes“}} After surgery, many undergo radiotherapy to decrease the chance of cancer recurrence.{{sfn|Hayes|Lippman|2022|loc=“Local (Primary) Treatments“}} Those who had lumpectomies receive radiation to the whole breast.WEB,www.cancer.org/cancer/types/breast-cancer/treatment/radiation-for-breast-cancer.html, 12 April 2024, Radiation for Breast Cancer, American Cancer Society, 27 October 2021, Those who had a mastectomy and are at elevated risk of tumor spread – tumor greater than five centimeters wide, or cancerous cells in nearby lymph nodes – receive radiation to the mastectomy scar and chest wall.{{sfn|Hayes|Lippman|2022|loc=“Local (Primary) Treatments“}} If cancerous cells have spread to nearby lymph nodes, those lymph nodes will be irradiated as well. Radiation is typically given five days per week, for up to seven weeks. Radiotherapy for breast cancer is typically delivered via external beam radiotherapy, where a device focuses radiation beams onto the targeted parts of the body. Instead, some undergo brachytherapy, where radioactive material is placed into a device inserted at the surgical site the tumor was removed from. Fresh radioactive material is added twice a day for five days, then the device is removed. Surgery plus radiation typically eliminates a person’s breast tumor. Less than 5% of those treated have their breast tumor grow back.{{sfn|Hayes|Lippman|2022|loc=“Local (Primary) Treatments“}} After surgery and radiation, the breast can be surgically reconstructed, either by adding a breast implant or transferring excess tissue from another part of the body.{{sfn|Hayes|Lippman|2022|loc=“Local (Primary) Treatments“}} Chemotherapy reduces the chance of cancer recurring in the next ten years by around a third. However, 1-2% of those on chemotherapy experience life-threatening or permanent side effects. To balance these benefits and risks, chemotherapy is typically offered to those with a higher risk of cancer recurrence. There is no established risk cutoff for offering chemotherapy; determining who should receive chemotherapy is controversial.{{sfn|Hayes|Lippman|2022|loc=“Prognostic and Predictive Variables“}} Chemotherapy drugs are typically given in two- to three-week cycles, with periods of drug treatment interspersed with rest periods to recover from the therapies’ side effects.WEB,www.cancer.org/cancer/types/breast-cancer/treatment/chemotherapy-for-breast-cancer.html, 15 April 2024, Chemotherapy for Breast Cancer, American Cancer Society, 27 October 2021, Four to six cycles are given in total.{{sfn|Hayes|Lippman|2022|loc=“Chemotherapy“}} Many classes of chemotherapeutic agents are effective for breast cancer treatment, including the DNA alkylating drugs (cyclophosphamide), anthracyclines (doxorubicin and epirubicin), antimetabolites (fluorouracil, capecitabine, and methotrexate), taxanes (docetaxel and paclitaxel), and platinum-based chemotherapies (cisplatin and carboplatin).{{sfn|Hayes|Lippman|2022|loc=“Chemotherapy“}} Chemotherapies from different classes are typically given in combination, with particular chemotherapy drugs selected based on the affected person’s health and the different chemotherapeutics’ side effects.{{sfn|Hayes|Lippman|2022|loc=“Chemotherapy“}} Anthrocyclines and cyclophosphamide cause leukemia in up to 1% of those treated. Anthrocyclines also cause congestive heart failure in around 1% of people treated. Taxanes cause peripheral neuropathy, which is permanent in up to 5% of those treated.{{sfn|Hayes|Lippman|2022|loc=“Chemotherapy Toxicities“}} The same chemotherapy agents can be given before surgery – called neoadjuvant therapy – to shrink tumors, making them easier to safely remove.{{sfn|Hayes|Lippman|2022|loc=“Neoadjuvant Chemotherapy“}}For those whose tumors are HER2-positive, adding the HER2-targeted antibody trastuzumab to chemotherapy reduces the chance of cancer recurrence and death by at least a third.{{sfn|Hayes|Lippman|2022|loc=“Predictive Factors“}}{{sfn|Hayes|Lippman|2022|loc=“Anti-HER2 Therapy“}} Trastuzumab is given weekly or every three weeks for twelve months.{{sfn|Hayes|Lippman|2022|loc=“Anti-HER2 Therapy“}} Adding a second HER2-targeted antibody, pertuzumab slightly enhances treatment efficacy.{{sfn|Hayes|Lippman|2022|loc=“Anti-HER2 Therapy“}} In rare cases, trastuzumab can disrupt heart function, and so it is typically not given in conjunction with anthrocyclines, which can also damage the heart.{{sfn|Hayes|Lippman|2022|loc=“Anti-HER2 Therapy“}}After their chemotherapy course, those whose tumors are ER-positive or PR-positive benefit from endocrine therapy, which reduces the levels of estrogens and progesterones that hormone receptor-positive breast cancers require to survive.WEB,www.cancer.org/cancer/types/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html, 16 April 2024, Hormone Therapy for Breast Cancer, American Cancer Society, 31 January 2024, Tamoxifen treatment blocks the ER in the breast and some other tissues, and reduces the risk of breast cancer death by around 40% over the next ten years.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Systemic Therapy“}}{{sfn|Hayes|Lippman|2022|loc=“Endocrine Therapy“}} Chemically blocking estrogen production with GnRH-targeted drugs (goserelin, leuprolide, or triptorelin) and aromatase inhibitors (anastrozole, letrozole, or exemestane) slightly improves survival, but has more severe side effects.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Systemic Therapy“}}{{sfn|Hayes|Lippman|2022|loc=“Endocrine Therapy“}} Side effects of estrogen depletion include hot flashes, vaginal discomfort, and muscle and joint pain.{{sfn|Hayes|Lippman|2022|loc=“Endocrine Therapy“}} Endocrine therapy is typically recommended for at least five years after surgery and chemotherapy, and is sometimes continued for 10 years or longer.{{sfn|Hayes|Lippman|2022|loc=“Endocrine Therapy“}}{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Systemic Therapy“}}Metastatic disease
For around 1 in 5 people treated for localized breast cancer, their tumors eventually spread to distant body sites – most commonly the nearby bones (67% of cases), liver (41%), lungs (37%), brain (13%), and peritoneum (10%).{{sfn|Hayes|Lippman|2022|loc=“Diagnostic Considerations“}}{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=“Fig. 9: Common Metastatic Sites in Breast Cancer“}} Those with metastatic disease can receive further chemotherapy, typically starting with capecitabine, an anthracycline, or a taxane. As one chemotherapy drug fails to control the cancer, another is started. In addition to the chemotherapeutic drugs used for localized cancer, gemcitabine, vinorelbine, etoposide, and epothilones are sometimes effective.{{sfn|Hayes|Lippman|2022|loc=“Systemic Treatments for Metastatic Breast Cancer“}} Those with bone metastases benefit from regular infusion of the bone-strengthening agents denosumab and the bisphosphonates; infusion every three months reduces the chance of bone pain, fractures, and bone hypercalcemia.{{sfn|Hayes|Lippman|2022|loc=“Bone-Modifying Agents“}}Up to 70% of those with ER-positive metastatic breast cancer benefit from additional endocrine therapy. Therapy options include those used in localized cancer, plus toremifene and fulvestrant, often used in combination with CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib). When one endocrine therapy fails, most will benefit from transitioning to a second one. Some respond to a third sequential therapy as well.{{sfn|Hayes|Lippman|2022|loc=“Systemic Treatments for Metastatic Breast Cancer“}} Adding an mTOR inhibitor, everolimus, can further slow the tumors’ progression.{{sfn|Hayes|Lippman|2022|loc=“Systemic Treatments for Metastatic Breast Cancer“}}Those with HER2-positive metastatic disease can benefit from continued use of trastuzumab, alone, in combination with pertuzumab, or in combination with chemotherapy. Those whose tumors continue to progress on trastuzumab benefit from HER2-targeted antibody drug conjugates (HER2 antibodies linked to chemotherapy drugs) trastuzumab emtansine or trastuzumab deruxtecan. The HER2-targeted antibody margetuximab can also prolong survival, as can HER2 inhibitors lapatinib, neratinib, or tucatinib.{{sfn|Hayes|Lippman|2022|loc=“Systemic Treatments for Metastatic Breast Cancer“}}Certain therapies are targeted at those whose tumors have particular gene mutations: Alpelisib or capivasertib for those with mutations activating the protein PIK3CA.{{sfn|Hayes|Lippman|2022|loc=“Systemic Treatments for Metastatic Breast Cancer“}} PARP inhibitors (olaparib and talazoparib) for those with mutations that inactivate BRCA1 or BRCA2.{{sfn|Hayes|Lippman|2022|loc=“Systemic Treatments for Metastatic Breast Cancer“}} The immune checkpoint inhibitor antibody atezolizumab for those whose tumors express PD-L1.{{sfn|Hayes|Lippman|2022|loc=“Systemic Treatments for Metastatic Breast Cancer“}}WEB,www.cancer.org/cancer/types/breast-cancer/treatment/treatment-of-breast-cancer-by-stage/treatment-of-stage-iv-advanced-breast-cancer.html, 18 April 2024, Treatment of Stage IV (Metastatic) Breast Cancer, American Cancer Society, 28 November 2023, And the similar immunotherapy pembrolizumab for those whose tumors have mutations in various DNA repair pathways.Supportive care
(File:Breast reconstruction 15.jpg|thumb|Breasts after double mastectomy followed by nipple-sparing reconstruction with implants)Many breast cancer therapies have side effects that can be alleviated with appropriate supportive care. Chemotherapy causes hair loss, nausea, and vomiting in nearly everyone who receives it. Antiemetic drugs can alleviate nausea and vomiting; cooling the scalp with a cold cap during chemotherapy treatments may reduce hair loss.{{sfn|Hayes|Lippman|2022|loc=“Chemotherapy Toxicities“}} Many complain of cognitive issues during chemotherapy treatment. These usually resolve within a few months of the end of chemotherapy treatment.{{sfn|Hayes|Lippman|2022|loc=“Chemotherapy Toxicities“}} Those on endocrine therapy often experience hot flashes, muscle and joint pain, and vaginal dryness/discomfort that can lead to issues having sex. Around half of women have their hot flashes alleviated by taking antidepressants; pain can be treated with physical therapy and nonsteroidal anti-inflammatory drugs; counseling and use of personal lubricants can improve sexual issues.{{sfn|Hayes|Lippman|2022|loc=“Endocrine Therapy“}}{{sfn|Hayes|Lippman|2022|loc=“Breast Cancer Survivorship Issues“}} In women with non-metastatic breast cancer, psychological interventions such as cognitive behavioral therapy can have positive effects on outcomes such as cognitive impairment, anxiety, depression and mood disturbance, and can also improve the quality of life.JOURNAL, Jassim GA, Doherty S, Whitford DL, Khashan AS, January 2023, Psychological interventions for women with non-metastatic breast cancer, The Cochrane Database of Systematic Reviews, 2023, 1, CD008729, 10.1002/14651858.CD008729.pub3, 36628983, 9832339, JOURNAL, Lange, M., Joly, F., Vardy, J, Ahles, T., Dubois, M., Tron, L., Winocur, G., De Ruiter, M.B., Castel, H., 2019, Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors,linkinghub.elsevier.com/retrieve/pii/S092375342032562X, Annals of Oncology, en, 30, 12, 1925–1940, 10.1093/annonc/mdz410, 8109411, 31617564, JOURNAL, Janelsins, Michelle C., Kesler, Shelli R., Ahles, Tim A., Morrow, Gary R., 2014, Prevalence, mechanisms, and management of cancer-related cognitive impairment, International Review of Psychiatry, en, 26, 1, 102–113, 10.3109/09540261.2013.864260, 0954-0261, 4084673, 24716504, Physical activity interventions, yoga and meditation may also have beneficial effects on health related quality of life, cognitive impairment, anxiety, fitness and physical activity in women with breast cancer following adjuvant therapy.JOURNAL, Lahart IM, Metsios GS, Nevill AM, Carmichael AR, Physical activity for women with breast cancer after adjuvant therapy, The Cochrane Database of Systematic Reviews, 1, CD011292, January 2018, 1, 29376559, 6491330, 10.1002/14651858.cd011292.pub2, JOURNAL, Biegler, Kelly A., Alejandro Chaoul, M., Cohen, Lorenzo, 2009, Cancer, cognitive impairment, and meditation,www.tandfonline.com/doi/full/10.1080/02841860802415535, Acta Oncologica, en, 48, 1, 18–26, 10.1080/02841860802415535, 0284-186X,Prognosis
Breast cancer prognosis is most impacted by the tumor size and the extent of its spread to other tissues. The histological grade and type of cancer also impact prognosis. Tumors with histological grade 1 have better prognoses; those graded 3 have worse prognoses. The relatively rare tumors with tubular, mucinous, or medullary growth tend to have better prognoses.{{sfn|Hayes|Lippman|2022|loc=“Prognostic Factors“}}The higher the stage at diagnosis, the poorer the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behavior (grading). {| class=“wikitable floatright” style="text-align:center”- Stage 1 cancers (and DCIS, LCIS) have an excellent prognosis and are generally treated with lumpectomy and sometimes radiation.WEB,www.stopcancerfund.org/wp/wp-content/uploads/2009/12/booklet04bc.pdf, Surgery Choices for Women with Early Stage Breast Cancer, National Cancer Institute and the National Research Center for Women & Families, August 2004,www.stopcancerfund.org/wp/wp-content/uploads/2009/12/booklet04bc.pdf," title="web.archive.org/web/20130813054115www.stopcancerfund.org/wp/wp-content/uploads/2009/12/booklet04bc.pdf,">web.archive.org/web/20130813054115www.stopcancerfund.org/wp/wp-content/uploads/2009/12/booklet04bc.pdf, 13 August 2013,
- Stage 2 and 3 cancers with a progressively poorer prognosis and greater risk of recurrence are generally treated with surgery (lumpectomy or mastectomy with or without lymph node removal), chemotherapy (plus trastuzumab for HER2+ cancers) and sometimes radiation (particularly following large cancers, multiple positive nodes or lumpectomy).{{medical citation needed|date=May 2018}}
Risk factors
Hormonal
Up to 80% of the variation in breast cancer frequency across countries is due to differences in reproductive history that impact a woman’s levels of female sex hormones (estrogens).{{sfn|Hayes|Lippman|2022|loc=“Clinical, Hormonal, and other Nongenetic Risk Factors“}} Women who begin menstruating earlier (before age 12) or who have their first pregnancy later (after age 35) are at increased risk of developing breast cancer.{{sfn|Hayes|Lippman|2022|loc=“Clinical, Hormonal, and other Nongenetic Risk Factors“}} Those who lack functioning ovaries, breastfeed their children, or experience early menopause have reduced breast cancer risk.{{sfn|Hayes|Lippman|2022|loc=“Clinical, Hormonal, and other Nongenetic Risk Factors“}}Hormone replacement therapy (HRT) to treat menopause is associated with only a small increased risk of breast cancer.JOURNAL, Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence, Lancet, 394, 10204, 1159–1168, September 2019, 31474332, 6891893, 10.1016/S0140-6736(19)31709-X, Collaborative Group on Hormonal Factors in Breast Cancer, JOURNAL, 20 December 2021, Risk of breast cancer with HRT depends on therapy type and duration,evidence.nihr.ac.uk/alert/risk-of-breast-cancer-with-hrt-depends-therapy-type-and-duration/, NIHR Evidence, National Institute for Health and Care Research, 10.3310/alert_48575, 26 October 2023, 26 October 2023,web.archive.org/web/20231026104418/https://evidence.nihr.ac.uk/alert/risk-of-breast-cancer-with-hrt-depends-therapy-type-and-duration/, live, JOURNAL, Vinogradova Y, Coupland C, Hippisley-Cox J, Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases, BMJ, 371, m3873, October 2020, 33115755, 7592147, 10.1136/bmj.m3873, The level of risk also depends on the type of HRT, the duration of the treatment and the age of the person. Estrogen-only HRT, taken by people who had a hysterectomy, comes with an extremely low level of breast cancer risk. The most commonly taken combined HRT (estrogen and progestogen) is linked to a small risk of breast cancer. This risk is lower for women in their 50s and higher for older women. The risk increases with the duration of HRT. When HRT is taken for a year or less, there is no increased risk of breast cancer. HRT taken for more than five years comes with an increased risk but the risk reduces after the therapy is stopped.In the 1980s, the abortion–breast cancer hypothesis posited that induced abortion increased the risk of developing breast cancer.JOURNAL, Russo J, Russo IH, Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumor incidence, The American Journal of Pathology, 100, 2, 497–512, August 1980, 6773421, 1903536, In contrast, abortion is associated with increased risk of carcinomas of the breast. The explanation for these epidemiologic findings is not known, but the parallelism between the DMBA-induced rat mammary carcinoma model and the human situation is striking. ... Abortion would interrupt this process, leaving in the gland undifferentiated structures like those observed in the rat mammary gland, which could render the gland again susceptible to carcinogenesis., This hypothesis was the subject of extensive scientific inquiry, which concluded that neither miscarriages nor abortions are associated with a heightened risk for breast cancer.JOURNAL, Beral V, Bull D, Doll R, Peto R, Reeves G, Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83?000 women with breast cancer from 16 countries, Lancet, 363, 9414, 1007–16, March 2004, 15051280, 10.1016/S0140-6736(04)15835-2, 20751083, The use of hormonal birth control does not cause breast cancer for most women;JOURNAL, Kanadys W, BaraÅ„ska A, Malm M, BÅ‚aszczuk A, Polz-Dacewicz M, Janiszewska M, JÄ™drych M, April 2021, Use of Oral Contraceptives as a Potential Risk Factor for Breast Cancer: A Systematic Review and Meta-Analysis of Case-Control Studies Up to 2010, International Journal of Environmental Research and Public Health, 18, 9, 4638, 10.3390/ijerph18094638, 8123798, 33925599, free, if it has an effect, it is small (on the order of 0.01% per user–year), temporary, and offset by the users’ significantly reduced risk of ovarian and endometrial cancers.JOURNAL, Chelmow D, Pearlman MD, Young A, Bozzuto L, Dayaratna S, Jeudy M, Kremer ME, Scott DM, O’Hara JS, June 2020, Executive Summary of the Early-Onset Breast Cancer Evidence Review Conference, Obstetrics and Gynecology, 135, 6, 1457–1478, 10.1097/AOG.0000000000003889, 7253192, 32459439, Among those with a family history of breast cancer, use of modern oral contraceptives does not appear to affect the risk of breast cancer.JOURNAL, Gaffield ME, Culwell KR, Ravi A, October 2009, Oral contraceptives and family history of breast cancer, Contraception, 80, 4, 372–380, 10.1016/j.contraception.2009.04.010, 19751860,Lifestyle
{{See also|Alcohol and breast cancer|Risk factors for breast cancer}}File:NIH standard drink comparison.jpg|upright=1.2|alt=Diagram of different sizes, showing how big a single serving of alcohol is for different types of alcoholic beverages|thumb|All types of alcoholic beveragealcoholic beverage{{Image frame
| caption=Drinking alcohol, even at low levels, increases the risk of breast cancer{{legend|red| Additional risk from drinkingJOURNAL, Bagnardi V, Rota M, Botteri E, Tramacere I, Islami F, Fedirko V, Scotti L, Jenab M, Turati F, Pasquali E, Pelucchi C, Galeone C, Bellocco R, Negri E, Corrao G, Boffetta P, La Vecchia C, Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis, British Journal of Cancer, 112, 3, 580–593, February 2015, 25422909, 4453639, 10.1038/bjc.2014.579, }}
{{legend|pink| Original breast cancer risk ({{=}}100%)}}
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}}Drinking alcoholic beverages increases the risk of breast cancer, even among very light drinkers (women drinking less than half of one alcoholic drink per day).JOURNAL, Choi YJ, Myung SK, Lee JH, Light Alcohol Drinking and Risk of Cancer: A Meta-Analysis of Cohort Studies, Cancer Research and Treatment, 50, 2, 474–487, April 2018, 28546524, 5912140, 10.4143/crt.2017.094, The risk is highest among heavy drinkers.JOURNAL, Shield KD, Soerjomataram I, Rehm J, Alcohol Use and Breast Cancer: A Critical Review, Alcoholism: Clinical and Experimental Research, 40, 6, 1166–1181, June 2016, 27130687, 10.1111/acer.13071, All levels of evidence showed a risk relationship between alcohol consumption and the risk of breast cancer, even at low levels of consumption., Globally, about one in ten cases of breast cancer is caused by women drinking alcoholic beverages. Alcohol use is among the most common modifiable risk factors.JOURNAL, McDonald JA, Goyal A, Terry MB, Alcohol Intake and Breast Cancer Risk: Weighing the Overall Evidence, Current Breast Cancer Reports, 5, 3, 208–221, September 2013, 24265860, 3832299, 10.1007/s12609-013-0114-z, Obesity and diabetes increase the risk of breast cancer. A high body mass index (BMI) causes 7% of breast cancers while diabetes is responsible for 2%.JOURNAL, 5 October 2023, Why we need to understand breast cancer risk,evidence.nihr.ac.uk/collection/breast-cancer-risk-why-we-need-to-understand-it/, NIHR Evidence, Plain English summary, National Institute for Health and Care Research, 10.3310/nihrevidence_60242, 263690185, 26 October 2023, 26 October 2023,web.archive.org/web/20231026071852/https://evidence.nihr.ac.uk/collection/breast-cancer-risk-why-we-need-to-understand-it/, live, JOURNAL, Pearson-Stuttard J, Zhou B, Kontis V, Bentham J, Gunter MJ, Ezzati M, Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment, The Lancet. Diabetes & Endocrinology, 6, 6, e6–e15, June 2018, 29803268, 5982644, 10.1016/S2213-8587(18)30150-5, At the same time the correlation between obesity and breast cancer is not at all linear. Studies show that those who rapidly gain weight in adulthood are at higher risk than those who have been overweight since childhood. Likewise, excess fat in the midriff seems to induce a higher risk than excess weight carried in the lower body.WEB, Lifestyle-related Breast Cancer Risk Factors,www.cancer.org/cancer/breast-cancer/risk-and-prevention/lifestyle-related-breast-cancer-risk-factors.html, American Cancer Society, 18 April 2018, 27 July 2020,web.archive.org/web/20200727075717/https://www.cancer.org/cancer/breast-cancer/risk-and-prevention/lifestyle-related-breast-cancer-risk-factors.html, live, Dietary factors that may increase risk include a high-fat dietJOURNAL, Blackburn GL, Wang KA, Dietary fat reduction and breast cancer outcome: results from the Women’s Intervention Nutrition Study (WINS), The American Journal of Clinical Nutrition, 86, 3, s878-81, September 2007, 18265482, 10.1093/ajcn/86.3.878S, free, and obesity-related high cholesterol levels.WEB, BBC News,news.bbc.co.uk/1/hi/health/5171838.stm, Weight link to breast cancer risk, 12 July 2006,news.bbc.co.uk/1/hi/health/5171838.stm," title="web.archive.org/web/20070313141518news.bbc.co.uk/1/hi/health/5171838.stm,">web.archive.org/web/20070313141518news.bbc.co.uk/1/hi/health/5171838.stm, 13 March 2007, JOURNAL, Kaiser J, Cancer. Cholesterol forges link between obesity and breast cancer, Science, 342, 6162, 1028, November 2013, 24288308, 10.1126/science.342.6162.1028, Dietary iodine deficiency may also play a role in the development of breast cancer.JOURNAL, Aceves C, Anguiano B, Delgado G, Is iodine a gatekeeper of the integrity of the mammary gland?, Journal of Mammary Gland Biology and Neoplasia, 10, 2, 189–96, April 2005, 16025225, 10.1007/s10911-005-5401-5, 16838840, Smoking tobacco appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the risk.JOURNAL, Johnson KC, Miller AB, Collishaw NE, Palmer JR, Hammond SK, Salmon AG, Cantor KP, Miller MD, Boyd NF, Millar J, Turcotte F, Active smoking and secondhand smoke increase breast cancer risk: the report of the Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk (2009), Tobacco Control, 20, 1, e2, January 2011, 21148114, 10.1136/tc.2010.035931, 448229, In those who are long-term smokers, the relative risk is increased by 35% to 50%.A lack of physical activity has been linked to about 10% of cases.JOURNAL, Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT, Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy, Lancet, 380, 9838, 219–29, July 2012, 22818936, 3645500, 10.1016/S0140-6736(12)61031-9, Sitting regularly for prolonged periods is associated with higher mortality from breast cancer. The risk is not negated by regular exercise, though it is lowered.JOURNAL, Biswas A, Oh PI, Faulkner GE, Bajaj RR, Silver MA, Mitchell MS, Alter DA, Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis, Annals of Internal Medicine, 162, 2, 123–32, January 2015, 25599350, 10.7326/M14-1651, 7256176, Actions to prevent breast cancer include not drinking alcoholic beverages, maintaining a healthy body composition, avoiding smoking and eating healthy food. Combining all of these (leading the healthiest possible lifestyle) would make almost a quarter of breast cancer cases worldwide preventable.JOURNAL, Zhang YB, Pan XF, Chen J, Cao A, Zhang YG, Xia L, Wang J, Li H, Liu G, Pan A, Combined lifestyle factors, incident cancer, and cancer mortality: a systematic review and meta-analysis of prospective cohort studies, British Journal of Cancer, 122, 7, 1085–1093, March 2020, 32037402, 7109112, 10.1038/s41416-020-0741-x, The remaining three-quarters of breast cancer cases cannot be prevented through lifestyle changes.Other risk factors include radiationWEB, American Cancer Society, 2005, Breast Cancer Facts & Figures 2005–2006,www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf, 26 April 2007,www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf," title="web.archive.org/web/20070613192148www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf,">web.archive.org/web/20070613192148www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf, 13 June 2007, and circadian disruptions related to shift-workJOURNAL, Wang XS, Armstrong ME, Cairns BJ, Key TJ, Travis RC, Shift work and chronic disease: the epidemiological evidence, Occupational Medicine, 61, 2, 78–89, March 2011, 21355031, 3045028, 10.1093/occmed/kqr001, and routine late-night eating.JOURNAL, Marinac CR, Nelson SH, Breen CI, Hartman SJ, Natarajan L, Pierce JP, Flatt SW, Sears DD, Patterson RE, Prolonged Nightly Fasting and Breast Cancer Prognosis, JAMA Oncology, 2, 8, 1049–55, August 2016, 27032109, 4982776, 10.1001/jamaoncol.2016.0164, A number of chemicals have also been linked, including polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and organic solvents.JOURNAL, Brody JG, Rudel RA, Michels KB, Moysich KB, Bernstein L, Attfield KR, Gray S, Environmental pollutants, diet, physical activity, body size, and breast cancer: where do we stand in research to identify opportunities for prevention?, Cancer, 109, 12 Suppl, 2627–34, June 2007, 17503444, 10.1002/cncr.22656, 34880415, Although the radiation from mammography is a low dose, it is estimated that yearly screening from 40 to 80 years of age will cause approximately 225 cases of fatal breast cancer per million women screened.JOURNAL, Hendrick RE, Radiation doses and cancer risks from breast imaging studies, Radiology, 257, 1, 246–53, October 2010, 20736332, 10.1148/radiol.10100570, free, |xAxisTitle=Maximum drinks per day
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Genetics
Around 10% of those with breast cancer have a family history of the disease or genetic factors that put them at higher risk.{{sfn|Loibl|Poortmans|Morrow|Denkert|2021|loc=“Epidemiology and risk factors“}} Women who have had a first-degree relative (mother or sister) diagnosed with breast cancer are at a 30–50% increased risk of being diagnosed with breast cancer themselves.{{sfn|Hayes|Lippman|2022|loc=“Inherited germline susceptibility factors“}} In those with zero, one or two affected relatives, the risk of breast cancer before the age of 80 is 7.8%, 13.3%, and 21.1% with a subsequent mortality from the disease of 2.3%, 4.2%, and 7.6% respectively.JOURNAL, Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease, Lancet, 358, 9291, 1389–99, October 2001, 11705483, 10.1016/S0140-6736(01)06524-2, Collaborative Group on Hormonal Factors in Breast Cancer, 24278814, Women with certain genetic variants are at higher risk of developing breast cancer. The most well known are variants of the BRCA genes BRCA1 and BRCA2.{{sfn|Hayes|Lippman|2022|loc=“Inherited germline susceptibility factors“}} Women with pathogenic variants in either gene have around a 70% chance of developing breast cancer in their lifetime, as well as an approximately 33% chance of developing ovarian cancer.{{sfn|Loibl|Poortmans|Morrow|Denkert|2021|loc=“Epidemiology and risk factors“}}{{sfn|Hayes|Lippman|2022|loc=“Inherited germline susceptibility factors“}} Pathogenic variants in PALB2 – a gene whose product directly interacts with that of BRCA2 – also increase breast cancer risk; a woman with such a variant has around a 50% increased risk of developing breast cancer.{{sfn|Loibl|Poortmans|Morrow|Denkert|2021|loc=“Epidemiology and risk factors“}} Variants in other tumor suppressor genes can also increase one’s risk of developing breast cancer, namely p53 (causes Li–Fraumeni syndrome), PTEN (causes Cowden syndrome), and PALB1.{{sfn|Hayes|Lippman|2022|loc=“Inherited germline susceptibility factors“}}Other genetic predispositions include the density of the breast tissue and hormonal levels. Women with dense breast tissue are more likely to get tumors and are less likely to be diagnosed with breast cancer – because the dense tissue makes tumors less visible on mammograms. Furthermore, women with naturally high estrogen and progesterone levels are also at higher risk for tumor development.WEB, CDC – What Are the Risk Factors for Breast Cancer?,www.cdc.gov/cancer/breast/basic_info/risk_factors.htm, www.cdc.gov, 14 December 2018, 29 April 2019, 13 August 2020,web.archive.org/web/20200813064946/https://www.cdc.gov/cancer/breast/basic_info/risk_factors.htm, live, JOURNAL, Tian JM, Ran B, Zhang CL, Yan DM, Li XH, Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression, Brazilian Journal of Medical and Biological Research, 51, 3, 1–7, January 2018, 29513878, 5912097, 10.1590/1414-431X20175612,www.popline.org/node/328955, 29 April 2019, 14 May 2017,www.popline.org/node/328955," title="web.archive.org/web/20170514183905www.popline.org/node/328955,">web.archive.org/web/20170514183905www.popline.org/node/328955,Medical conditions
Breast changes like atypical ductal hyperplasiaWEB,www.cancer.gov/cancertopics/understanding-breast-changes/page6#F8, Understanding Breast Changes – National Cancer Institute,www.cancer.gov/cancertopics/understanding-breast-changes/page6," title="web.archive.org/web/20100527185336www.cancer.gov/cancertopics/understanding-breast-changes/page6,">web.archive.org/web/20100527185336www.cancer.gov/cancertopics/understanding-breast-changes/page6, 27 May 2010, and lobular carcinoma in situ,WEB,www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page6, Breast Cancer Treatment, National Cancer Institute, live,www.cancer.gov/cancertopics/pdq/treatment/breast/healthprofessional/page6," title="web.archive.org/web/20150425224841www.cancer.gov/cancertopics/pdq/treatment/breast/healthprofessional/page6,">web.archive.org/web/20150425224841www.cancer.gov/cancertopics/pdq/treatment/breast/healthprofessional/page6, 25 April 2015, January 1980, JOURNAL, Afonso N, Bouwman D, Lobular carcinoma in situ, European Journal of Cancer Prevention, 17, 4, 312–6, August 2008, 18562954, 10.1097/CEJ.0b013e3282f75e5d, 388045, found in benign breast conditions such as fibrocystic breast changes, are correlated with an increased breast cancer risk.Diabetes mellitus might also increase the risk of breast cancer.JOURNAL, Anothaisintawee T, Wiratkapun C, Lerdsitthichai P, Kasamesup V, Wongwaisayawan S, Srinakarin J, Hirunpat S, Woodtichartpreecha P, Boonlikit S, Teerawattananon Y, Thakkinstian A, Risk factors of breast cancer: a systematic review and meta-analysis, Asia-Pacific Journal of Public Health, 25, 5, 368–87, September 2013, 23709491, 10.1177/1010539513488795, 206616972, Autoimmune diseases such as lupus erythematosus seem also to increase the risk for the acquisition of breast cancer.JOURNAL, Böhm I, Breast cancer in lupus, Breast, 20, 3, 288–90, June 2011, 21237645, 10.1016/j.breast.2010.12.005, free,Pathophysiology
{{See also|Carcinogenesis}}File:Lobules and ducts of the breast.jpg|thumb|Ducts and lobules are the main locations of breast cancers.]]File:Signal transduction pathways.svg|thumb|Overview of signal transduction pathways involved in programmed cell death. Mutations leading to loss of this ability can lead to cancer formation.]]The major causes of sporadic breast cancer are associated with hormone levels. Breast cancer is promoted by estrogen. This hormone activates the development of breast throughout puberty, menstrual cycles and pregnancy. The imbalance between estrogen and progesterone during the menstrual phases causes cell proliferation. Moreover, oxidative metabolites of estrogen can increase DNA damage and mutations. Repeated cycling and the impairment of repair process can transform a normal cell into pre-malignant and eventually malignant cell through mutation. During the pre-malignant stage, high proliferation of stromal cells can be activated by estrogen to support the development of breast cancer. During the ligand binding activation, the ER can regulate gene expression by interacting with estrogen response elements within the promotor of specific genes. The expression and activation of ER due to lack of estrogen can be stimulated by extracellular signals.JOURNAL, Williams C, Lin CY, Oestrogen receptors in breast cancer: basic mechanisms and clinical implications, ecancermedicalscience, 7, 370, November 2013, 24222786, 3816846, 10.3332/ecancer.2013.370, Interestingly, the ER directly binding with the several proteins, including growth factor receptors, can promote the expression of genes related to cell growth and survival.JOURNAL, Levin ER, Pietras RJ, Estrogen receptors outside the nucleus in breast cancer, Breast Cancer Research and Treatment, 108, 3, 351–361, April 2008, 17592774, 10.1007/s10549-007-9618-4, 11394158, 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.CONFERENCE, Lee A, Arteaga C, 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium, Sunday Morning Year-End Review, 14 December 2009,www.sabcs.org/Newsletter/Docs/SABCS_2009_Issue5.pdf,www.sabcs.org/Newsletter/Docs/SABCS_2009_Issue5.pdf," title="web.archive.org/web/20130813021816www.sabcs.org/Newsletter/Docs/SABCS_2009_Issue5.pdf,">web.archive.org/web/20130813021816www.sabcs.org/Newsletter/Docs/SABCS_2009_Issue5.pdf, 13 August 2013, Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.JOURNAL, Cavalieri E, Chakravarti D, Guttenplan J, Hart E, Ingle J, Jankowiak R, Muti P, Rogan E, Russo J, Santen R, Sutter T, Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1766, 1, 63–78, August 2006, 16675129, 10.1016/j.bbcan.2006.03.001, Additionally, G-protein coupled estrogen receptors have been associated with various cancers of the female reproductive system including breast cancer.JOURNAL, Filardo EJ, A role for G-protein coupled estrogen receptor (GPER) in estrogen-induced carcinogenesis: Dysregulated glandular homeostasis, survival and metastasis, The Journal of Steroid Biochemistry and Molecular Biology, 176, 38–48, February 2018, 28595943, 10.1016/j.jsbmb.2017.05.005, 19644829, Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.JOURNAL, Haslam SZ, Woodward TL, Host microenvironment in breast cancer development: epithelial-cell-stromal-cell interactions and steroid hormone action in normal and cancerous mammary gland, Breast Cancer Research, 5, 4, 208–15, June 2003, 12817994, 165024, 10.1186/bcr615, free, JOURNAL, Wiseman BS, Werb Z, Stromal effects on mammary gland development and breast cancer, Science, 296, 5570, 1046–9, May 2002, 12004111, 2788989, 10.1126/science.1067431, 2002Sci...296.1046W, In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.JOURNAL, Jardé T, Perrier S, Vasson MP, Caldefie-Chézet F, Molecular mechanisms of leptin and adiponectin in breast cancer, European Journal of Cancer, 47, 1, 33–43, January 2011, 20889333, 10.1016/j.ejca.2010.09.005, Some mutations associated with cancer, such as p53, BRCA1 and BRCA2, occur in mechanisms to correct errors in DNA. The inherited mutation in BRCA1 or BRCA2 genes can interfere with repair of DNA crosslinks and double-strand breaks (known functions of the encoded protein).JOURNAL, Patel KJ, Yu VP, Lee H, Corcoran A, Thistlethwaite FC, Evans MJ, Colledge WH, Friedman LS, Ponder BA, Venkitaraman AR, Involvement of Brca2 in DNA repair, Molecular Cell, 1, 3, 347–57, February 1998, 9660919, 10.1016/S1097-2765(00)80035-0, free, These carcinogens cause DNA damage such as DNA crosslinks and double-strand breaks that often require repairs by pathways containing BRCA1 and BRCA2.JOURNAL, Marietta C, Thompson LH, Lamerdin JE, Brooks PJ, Acetaldehyde stimulates FANCD2 monoubiquitination, H2AX phosphorylation, and BRCA1 phosphorylation in human cells in vitro: implications for alcohol-related carcinogenesis, Mutation Research, 664, 1–2, 77–83, May 2009, 19428384, 2807731, 10.1016/j.mrfmmm.2009.03.011, JOURNAL, Theruvathu JA, Jaruga P, Nath RG, Dizdaroglu M, Brooks PJ, Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine adducts from acetaldehyde, Nucleic Acids Research, 33, 11, 3513–20, 2005, 15972793, 1156964, 10.1093/nar/gki661, 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.JOURNAL, Kouros-Mehr H, Kim JW, Bechis SK, Werb Z, GATA-3 and the regulation of the mammary luminal cell fate, Current Opinion in Cell Biology, 20, 2, 164–70, April 2008, 18358709, 2397451, 10.1016/j.ceb.2008.02.003,Prevention
Lifestyle
Women can reduce their risk of breast cancer by maintaining a healthy weight, reducing alcohol use, increasing physical activity, and breastfeeding.WEB,www.cancer.org/cancer/breast-cancer/risk-and-prevention/lifestyle-related-breast-cancer-risk-factors.html, Lifestyle-related Breast Cancer Risk Factors, www.cancer.org, 18 April 2018, 27 July 2020,web.archive.org/web/20200727075717/https://www.cancer.org/cancer/breast-cancer/risk-and-prevention/lifestyle-related-breast-cancer-risk-factors.html, live, These modifications might prevent 38% of breast cancers in the US, 42% in the UK, 28% in Brazil, and 20% in China. The benefits with moderate exercise such as brisk walking are seen at all age groups including postmenopausal women.JOURNAL, Eliassen AH, Hankinson SE, Rosner B, Holmes MD, Willett WC, Physical activity and risk of breast cancer among postmenopausal women, Archives of Internal Medicine, 170, 19, 1758–64, October 2010, 20975025, 3142573, 10.1001/archinternmed.2010.363, High levels of physical activity reduce the risk of breast cancer by about 14%.JOURNAL, Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K, Veerman JL, Delwiche K, Iannarone ML, Moyer ML, Cercy K, Vos T, Murray CJ, Forouzanfar MH, Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013, BMJ, 354, i3857, August 2016, 27510511, 4979358, 10.1136/bmj.i3857, Strategies that encourage regular physical activity and reduce obesity could also have other benefits, such as reduced risks of cardiovascular disease and diabetes.JOURNAL, Hayes J, Richardson A, Frampton C, November 2013, Population attributable risks for modifiable lifestyle factors and breast cancer in New Zealand women, Internal Medicine Journal, 43, 11, 1198–204, 10.1111/imj.12256, 23910051, 23237732, A study that included data from 130,957 women of European ancestry found “strong evidence that greater levels of physical activity and less sedentary time are likely to reduce breast cancer risk, with results generally consistent across breast cancer subtypes”.NEWS, New study finds ‘strong evidence’ that exercise cuts breast cancer risk, en-GB, belfasttelegraph,www.belfasttelegraph.co.uk/news/uk/new-study-finds-strong-evidence-that-exercise-cuts-breast-cancer-risk-41967524.html, 2022-09-07, 0307-1235, 7 September 2022,web.archive.org/web/20220907045207/https://www.belfasttelegraph.co.uk/news/uk/new-study-finds-strong-evidence-that-exercise-cuts-breast-cancer-risk-41967524.html, live, The American Cancer Society and the American Society of Clinical Oncology advised in 2016 that people should eat a diet high in vegetables, fruits, whole grains, and legumes.JOURNAL, Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, Cannady RS, Pratt-Chapman ML, Edge SB, Jacobs LA, Hurria A, Marks LB, LaMonte SJ, Warner E, Lyman GH, Ganz PA, American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline, CA: A Cancer Journal for Clinicians, 66, 1, 43–73, January 2016, 26641959, 10.3322/caac.21319, free, 2027.42/136493, free, Eating foods rich in soluble fiber contributes to reducing breast cancer risk.JOURNAL, Farvid MS, Spence ND, Holmes MD, Barnett JB, Fiber consumption and breast cancer incidence: A systematic review and meta-analysis of prospective studies, Cancer, 126, 13, 3061–3075, July 2020, 32249416, 10.1002/cncr.32816, 214809009, free, JOURNAL, Farvid MS, Barnett JB, Spence ND, Fruit and vegetable consumption and incident breast cancer: a systematic review and meta-analysis of prospective studies, British Journal of Cancer, 125, 2, 284–298, July 2021, 34006925, 8292326, 10.1038/s41416-021-01373-2, High intake of citrus fruit has been associated with a 10% reduction in the risk of breast cancer.JOURNAL, Song JK, Bae JM, Citrus fruit intake and breast cancer risk: a quantitative systematic review, Journal of Breast Cancer, 16, 1, 72–6, March 2013, 23593085, 3625773, 10.4048/jbc.2013.16.1.72, Marine omega-3 polyunsaturated fatty acids appear to reduce the risk.JOURNAL, Zheng JS, Hu XJ, Zhao YM, Yang J, Li D, Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies, BMJ, 346, f3706, June 2013, 23814120, 10.1136/bmj.f3706, free, High consumption of soy-based foods may reduce risk.JOURNAL, Wu AH, Yu MC, Tseng CC, Pike MC, Epidemiology of soy exposures and breast cancer risk, British Journal of Cancer, 98, 1, 9–14, January 2008, 18182974, 2359677, 10.1038/sj.bjc.6604145,Preventive surgery
Removal of the breasts before breast cancer develops (called preventive mastectomy) reduces the risk of developing breast cancer by more than 95%.{{sfn|Hayes|Lippman|2022|loc=“Prevention of Breast Cancer“}} In women genetically predisposed to developing breast cancer, preventive mastectomy reduces their risk of dying from breast cancer.{{sfn|Hayes|Lippman|2022|loc=“Prevention of Breast Cancer“}} For those at normal risk, preventive mastectomy does not reduce their chance of dying, and so is generally not recommended.{{sfn|Hayes|Lippman|2022|loc=“Prevention of Breast Cancer“}} Removing the second breast in a person who has breast cancer (contralateral riskâ€reducing mastectomy or CRRM) may reduce the risk of cancer in the second breast, but it is not clear whether removing the second breast improves the chance of survival.JOURNAL, Carbine NE, Lostumbo L, Wallace J, Ko H, Risk-reducing mastectomy for the prevention of primary breast cancer, The Cochrane Database of Systematic Reviews, 4, CD002748, April 2018, 4, 29620792, 6494635, 10.1002/14651858.cd002748.pub4, An increasing number of women who test positive for faulty BRCA1 or BRCA2 genes choose to have risk-reducing surgery. The average waiting time for undergoing the procedure is two years, which is much longer than recommended.JOURNAL, 2021-12-07, Earlier decisions on breast and ovarian surgery reduce cancer in women at high risk,evidence.nihr.ac.uk/alert/earlier-decisions-breast-ovarian-surgery-reduce-risk-cancer/, NIHR Evidence, Plain English summary, en, National Institute for Health and Care Research, 10.3310/alert_48318, 263487127, 21 December 2022, 27 June 2022,web.archive.org/web/20220627135653/https://evidence.nihr.ac.uk/alert/earlier-decisions-breast-ovarian-surgery-reduce-risk-cancer/, live, JOURNAL, Marcinkute R, Woodward ER, Gandhi A, Howell S, Crosbie EJ, Wissely J, Harvey J, Highton L, Murphy J, Holland C, Edmondson R, Clayton R, Barr L, Harkness EF, Howell A, Lalloo F, Evans DG, Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers, Journal of Medical Genetics, 59, 2, 133–140, February 2022, 33568438, 10.1136/jmedgenet-2020-107356,jmg.bmj.com/lookup/doi/10.1136/jmedgenet-2020-107356, 21 December 2022, live, 231876899,web.archive.org/web/20230202082122/https://jmg.bmj.com/content/59/2/133, 2 February 2023,Medications
Selective estrogen receptor modulators (SERMs) 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.JOURNAL, Nelson HD, Smith ME, Griffin JC, Fu R, Use of medications to reduce risk for primary breast cancer: a systematic review for the U.S. Preventive Services Task Force, Annals of Internal Medicine, 158, 8, 604–14, April 2013, 23588749, 10.7326/0003-4819-158-8-201304160-00005, free, JOURNAL, Cuzick J, Sestak I, Bonanni B, Costantino JP, Cummings S, DeCensi A, Dowsett M, Forbes JF, Ford L, LaCroix AZ, Mershon J, Mitlak BH, Powles T, Veronesi U, Vogel V, Wickerham DL, Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data, Lancet, 381, 9880, 1827–34, May 2013, 23639488, 3671272, 10.1016/S0140-6736(13)60140-3, 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.JOURNAL, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Doubeni CA, Epling JW, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Tseng CW, Wong JB, Medication Use to Reduce Risk of Breast Cancer: US Preventive Services Task Force Recommendation Statement, JAMA, 322, 9, 857–867, September 2019, 31479144, 10.1001/jama.2019.11885, free, The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications.JOURNAL, Cuzick J, Sestak I, Bonanni B, Costantino JP, Cummings S, DeCensi A, Dowsett M, Forbes JF, Ford L, LaCroix AZ, Mershon J, Mitlak BH, Powles T, Veronesi U, Vogel V, Wickerham DL, Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data, Lancet, 381, 9880, 1827–34, May 2013, 23639488, 3671272, 10.1016/S0140-6736(13)60140-3, Aromatase inhibitors (such as exemestane and anastrozole) may be more effective than SERMs (such as tamoxifen) at reducing breast cancer risk and they are not associated with an increased risk of endometrial cancer and thromboembolism.JOURNAL, Mocellin S, Goodwin A, Pasquali S, Risk-reducing medications for primary breast cancer: a network meta-analysis, The Cochrane Database of Systematic Reviews, 2019, CD012191, April 2019, 4, 31032883, 6487387, 10.1002/14651858.cd012191.pub2,Epidemiology
(File:Breast cancer incidence by age.tif|thumb|upright=1.4|alt=Bar graph showing incidence increasing with age|Breast cancer incidence in women by age group)Breast cancer is the most common invasive cancer in women in most countries, accounting for 30% of cancer cases in women.{{sfn|Loibl|Poortmans|Morrow|Denkert|2021|loc=“Epidemiology and risk factors“}} In 2022, an estimated 2.3 million women were diagnosed with breast cancer, and 670,000 died of the disease.WEB,www.who.int/news-room/fact-sheets/detail/breast-cancer, 29 March 2024, Breast cancer, 12 March 2024, World Health Organization, The incidence of breast cancer is rising by around 3% per year, as populations in many countries are getting older.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=Demographics, incidence, and mortality}}Rates of breast cancer vary across the world, but generally correlate with wealth.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=Demographics, incidence, and mortality}} Around 1 in 12 women are diagnosed with breast cancer in wealthier countries, compared to 1 in 27 in lower income countries. Most of that difference is due to differences in menstrual and reproductive histories – women in wealthier countries tend to begin menstruating earlier and have children later, both factors that increase risk of developing breast cancer.{{sfn|Hayes|Lippman|2022|loc=Clinical, Hormonal, and Other Nongenetic Risk Factors}} People in lower income countries tend to have less access to breast cancer screening and treatments, and so breast cancer death rates tend to be higher.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc=Demographics, incidence, and mortality}} 1 in 71 women die of breast cancer in wealthy countries, while 1 in 48 die of the disease in lower income countries.Breast cancer predominantly affects women; less than 1% of those with breast cancer are men.{{sfn|Hayes|Lippman|2022|loc=Clinical, Hormonal, and Other Nongenetic Risk Factors}} Women can develop breast cancer as early as adolescence, but risk increases with age, and 75% of cases are in women over 50 years old.{{sfn|Hayes|Lippman|2022|loc=Clinical, Hormonal, and Other Nongenetic Risk Factors}}History
(File:Louis-Jacques Goussier Enzyklopädie Diderot Pl XXIX.jpg|thumb|Breast cancer surgery in 18th century)Because of its visibility, breast cancer was the form of cancer most often described in ancient documents.BOOK, Olson JS, Bathsheba’s breast: women, cancer & history, The Johns Hopkins University Press, 2002, 978-0-8018-6936-5, {{rp|9–13}} Because autopsies were rare, cancers of the internal organs were essentially invisible to ancient medicine. Breast cancer, however, could be felt through the skin, and in its advanced state often developed into fungating lesions: the tumor would become necrotic (die from the inside, causing the tumor to appear to break up) and ulcerate through the skin, weeping fetid, dark fluid.{{rp|9–13}}The oldest discovered evidence of breast cancer is from Egypt and dates back 4200 years, to the Sixth Dynasty.NEWS,in.reuters.com/article/egypt-antiquities-cancer-idINKBN0MK1ZW20150324, Oldest evidence of breast cancer found in Egyptian skeleton, 24 March 2015, 25 March 2015, live,in.reuters.com/article/2015/03/24/egypt-antiquities-cancer-idINKBN0MK1ZW20150324," title="web.archive.org/web/20150327023314in.reuters.com/article/2015/03/24/egypt-antiquities-cancer-idINKBN0MK1ZW20150324,">web.archive.org/web/20150327023314in.reuters.com/article/2015/03/24/egypt-antiquities-cancer-idINKBN0MK1ZW20150324, 27 March 2015, Reuters, The study of a woman’s remains from the necropolis of Qubbet el-Hawa showed the typical destructive damage due to metastatic spread. The Edwin Smith Papyrus describes eight cases of tumors or ulcers of the breast that were treated by cauterization. The writing says about the disease, “There is no treatment.“WEB, The History of Cancer, American Cancer Society, 25 March 2002,www.cancer.org/docroot/CRI/content/CRI_2_6x_the_history_of_cancer_72.asp?sitearea=CRI, 9 October 2006,www.cancer.org/docroot/CRI/content/CRI_2_6x_the_history_of_cancer_72.asp?sitearea=CRI," title="web.archive.org/web/20061009011530www.cancer.org/docroot/CRI/content/CRI_2_6x_the_history_of_cancer_72.asp?sitearea=CRI,">web.archive.org/web/20061009011530www.cancer.org/docroot/CRI/content/CRI_2_6x_the_history_of_cancer_72.asp?sitearea=CRI, 9 October 2006, For centuries, physicians described similar cases in their practices, with the same conclusion. Ancient medicine, from the time of the Greeks through the 17th century, was based on humoralism, and thus believed that breast cancer was generally caused by imbalances in the fundamental fluids that controlled the body, especially an excess of black bile.{{rp|32}} Alternatively it was seen as divine punishment.BOOK, Yalom M, A history of the breast, Alfred A. Knopf, New York, 1997, 234, 978-0-679-43459-7,archive.org/details/historyofbreast00yalo/page/234, Mastectomy for breast cancer was performed at least as early as AD 548, when it was proposed by the court physician Aetios of Amida to Theodora.{{rp|9–13}} It was not until doctors achieved greater understanding of the circulatory system in the 17th century that they could link breast cancer’s spread to the lymph nodes in the armpit. In the early 18th century the French surgeon Jean Louis Petit performed total mastectomies that included removing the axillary lymph nodes, as he recognized that this reduced recurrence.BOOK, Faguet G, The Conquest of Cancer: A Distant Goal, 2015, 978-94-017-9165-6, 24, Chapter 2: An Historical Overview: From Prehistory to WWII. From Medieval Europe to World War II, Springer, Petit’s work built on the methods of the surgeon Bernard Peyrilhe, who in the 17th century additionally removed the pectoral muscle underlying the breast, as he judged that this greatly improved the prognosis.BOOK, Kaartinen M, Breast cancer in the eighteenth century, 2013, Pickering & Chatto, London, 978-1-84893-364-4, 53, Chapter 2: “But Sad Resources”: Treating Cancer in the Eighteenth Century, But poor results and the considerable risk to the patient meant that physicians did not share the opinion of surgeons such as Nicolaes Tulp, who in the 17th century proclaimed “the sole remedy is a timely operation.” The eminent surgeon Richard Wiseman documented in the mid-17th century that following 12 mastectomies, two patients died during the operation, eight patients died shortly after the operation from progressive cancer and only two of the 12 patients were cured.BOOK, Breast Cancer, Winchester DJ, Winchester DP, Hudis CA, Norton L, PMPH-USA, 2006, 978-1-55009-272-1, {{rp|6}} Physicians were conservative in the treatment they prescribed in the early stages of breast cancer. Patients were treated with a mixture of detox purges, blood letting and traditional remedies that were supposed to lower acidity, such as the alkaline arsenic.BOOK, A short history of breast cancer, de Moulin D, Springer Science & Business Media, 2013, 978-94-017-0601-8, {{rp|24}}When in 1664 Anne of Austria was diagnosed with breast cancer, the initial treatment involved compresses saturated with hemlock juice. When the lumps increased the King’s physician commenced a treatment with arsenic ointments.{{rp|25}} The royal patient died 1666 in atrocious pain.{{rp|26}} Each failing treatment for breast cancer led to the search for new treatments, spurring a market in remedies that were advertised and sold by quacks, herbalists, chemists and apothecaries.BOOK, Pain and Emotion in Modern History, Boddice RG, Springer, 2014, 978-1-137-37243-7, 24, The lack of anesthesia and antiseptics made mastectomy a painful and dangerous ordeal. In the 18th century, a wide variety of anatomical discoveries were accompanied by new theories about the cause and growth of breast cancer. The investigative surgeon John Hunter claimed that neural fluid generated breast cancer. Other surgeons proposed that milk within the mammary ducts led to cancerous growths. Theories about trauma to the breast as cause for malignant changes in breast tissue were advanced. The discovery of breast lumps and swellings fueled controversies about hard tumors and whether lumps were benign stages of cancer. Medical opinion about necessary immediate treatment varied.{{rp|5}} The surgeon Benjamin Bell advocated removal of the entire breast, even when only a portion was affected.JOURNAL, Macintyre IM, Scientific surgeon of the Enlightenment or ‘plagiarist in everything’: a reappraisal of Benjamin Bell (1749–1806), The Journal of the Royal College of Physicians of Edinburgh, 41, 2, 174–81, June 2011, 21677925, 10.4997/JRCPE.2011.211, free, {{open access}}(File:William Stewart Halsted, Surgical papers Wellcome L0004968.jpg|thumb|Radical mastectomy, Halsted’s surgical papers)Breast cancer was uncommon until the 19th century, when improvements in sanitation and control of deadly infectious diseases resulted in dramatic increases in lifespan. Previously, most women had died too young to have developed breast cancer.BOOK, Aronowitz RA, Unnatural history: breast cancer and American society, Cambridge University Press, Cambridge, UK, 2007, 22–24, 978-0-521-82249-7,archive.org/details/unnaturalhistory00aron/page/22, In 1878, an article in Scientific American described historical treatment by pressure intended to induce local ischemia in cases when surgical removal were not possible.BOOK,books.google.com/books?id=p4o9AQAAIAAJ, Scientific American, “The Treatment of Cancer by Pressure”, 10 August 1878, Munn & Company, 86, en, William Stewart Halsted started performing radical mastectomies in 1882, helped greatly by advances in general surgical technology, such as aseptic technique and anesthesia. The Halsted radical mastectomy often involved removing both breasts, associated lymph nodes, and the underlying chest muscles. This often led to long-term pain and disability, but was seen as necessary to prevent the cancer from recurring.{{rp|102–106}} Before the advent of the Halsted radical mastectomy, 20-year survival rates were only 10%; Halsted’s surgery raised that rate to 50%.{{rp|1}}Breast cancer staging systems were developed in the 1920s and 1930s to determining the extent to which a cancer has developed by growing and spreading.{{rp|102–106}} The first case-controlled study on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 controls of the same background and lifestyle for the British Ministry of Health.BOOK, Morabia A, A History of Epidemiologic Methods and Concepts, Birkhauser, Boston, 2004, 301–302, 978-3-7643-6818-0,books.google.com/books?id=E-OZbEmPSTkC&pg=PA301, 31 December 2007, 14 January 2023,web.archive.org/web/20230114150424/https://books.google.com/books?id=E-OZbEmPSTkC&pg=PA301, live, Radical mastectomies remained the standard of care in the USA until the 1970s, but in Europe, breast-sparing procedures, often followed by radiation therapy, were generally adopted in the 1950s.{{rp|102–106}} In 1955 George Crile Jr. published Cancer and Common Sense arguing that cancer patients needed to understand available treatment options. Crile became a close friend of the environmentalist Rachel Carson, who had undergone a Halsted radical mastectomy in 1960 to treat her malign breast cancer.BOOK, Beyond Slash, Burn, and Poison: Transforming Breast Cancer Stories Into Action, Knopf-Newman MJ, Rutgers University Press, 2004, 978-0-8135-3471-8, {{rp|39–40}} The US oncologist Jerome Urban promoted super radical mastectomies, taking even more tissue, until 1963, when the ten-year survival rates proved equal to the less-damaging radical mastectomy.{{rp|102–106}} Carson died in 1964 and Crile went on to published a wide variety of articles, both in the popular press and in medical journals, challenging the widespread use of the Halsted radical mastectomy. In 1973 Crile published What Women Should Know About the Breast Cancer Controversy. When in 1974 Betty Ford was diagnosed with breast cancer, the options for treating breast cancer were openly discussed in the press.{{rp|58}} During the 1970s, a new understanding of metastasis led to perceiving cancer as a systemic illness as well as a localized one, and more sparing procedures were developed that proved equally effective.BOOK, Lacroix M, A Concise History of Breast Cancer, Nova Science Publishers, USA, 2011, 59–68, 978-1-61122-305-7, In the 1980s and 1990s, thousands of women who had successfully completed standard treatment then demanded and received high-dose bone marrow transplants, thinking this would lead to better long-term survival. However, it proved completely ineffective, and 15–20% of women died because of the brutal treatment.BOOK, Sulik GA, Pink Ribbon Blues: How Breast Cancer Culture Undermines Women’s Health,archive.org/details/pinkribbonbluesh0000suli, registration, Oxford University Press, USA, 2010, 978-0-19-974045-1, 535493589, {{rp|200–203}} The 1995 reports from the Nurses’ Health Study and the 2002 conclusions of the Women’s Health Initiative trial conclusively proved that HRT significantly increased the incidence of breast cancer.Society and culture
{{See also|Breast cancer awareness|List of people with breast cancer|Cultural differences in breast cancer diagnosis and treatment}}Before the 20th century, breast cancer was feared and discussed in hushed tones, as if it were shameful. As little could be safely done with primitive surgical techniques, women tended to suffer silently rather than seeking care.{{citation needed|date=June 2022}} When surgery advanced, and long-term survival rates improved, women began raising awareness of the disease and the possibility of successful treatment. The “Women’s Field Army”, run by the American Society for the Control of Cancer (later the American Cancer Society) during the 1930s and 1940s was one of the first organized campaigns. In 1952, the first peer-to-peer support group, called “Reach to Recovery”, began providing post-mastectomy, in-hospital visits from women who had survived breast cancer.{{rp|37–38}}The breast cancer movement of the 1980s and 1990s developed out of the larger feminist movements and women’s health movement of the 20th century.{{rp|4}} This series of political and educational campaigns, partly inspired by the politically and socially effective AIDS awareness campaigns, resulted in the widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in care.WEB,www.crcfl.net/content/view/history-of-breast-cancer-advocacy.html, History of Breast Cancer Advocacy, Riter B, Cancer Resource Center of the Finger Lakes, 29 June 2013,www.crcfl.net/content/view/history-of-breast-cancer-advocacy.html," title="web.archive.org/web/20130623074930www.crcfl.net/content/view/history-of-breast-cancer-advocacy.html,">web.archive.org/web/20130623074930www.crcfl.net/content/view/history-of-breast-cancer-advocacy.html, 23 June 2013,Pink ribbon
File:Pink ribbon.svg|upright=0.75|thumb|The pink ribbonpink ribbonA pink ribbon is the most prominent symbol of breast cancer awareness. Pink ribbons, which can be made inexpensively, are sometimes sold as fundraisers, much like poppies on Remembrance Day. They may be worn to honor those who have been diagnosed with breast cancer, or to identify products that the manufacturer would like to sell to consumers that are interested in breast cancer.{{rp|27–72}} In the 1990s, breast cancer awareness campaigns were launched by US-based corporations. As part of these cause-related marketing campaigns, corporations donated to a variety of breast cancer initiatives for every pink ribbon product that was purchased.BOOK, Klawiter M, The Biopolitics of Breast Cancer: Changing Cultures of Disease and Activism, University of Minnesota Press, 2008, 978-0-8166-5107-8, {{rp|132–133}} The Wall Street Journal noted that “the strong emotions provoked by breast cancer translate to a company’s bottom line”. While many US corporations donated to existing breast cancer initiatives, others such as Avon established their own breast cancer foundations on the back of pink ribbon products.{{rp|135–136}}Wearing or displaying a pink ribbon has been criticized by the opponents of this practice as a kind of slacktivism, because it has no practical positive effect. It has also been criticized as hypocrisy, because some people wear the pink ribbon to show good will towards women with breast cancer, but then oppose these women’s practical goals, like patient rights and anti-pollution legislation.{{rp|366–368}}WEB, Landeman A, 11 June 2008,www.prwatch.org/node/7436, Pinkwashing: Can Shopping Cure Breast Cancer?, Center for Media and Democracy, live,www.prwatch.org/node/7436," title="web.archive.org/web/20110605122507www.prwatch.org/node/7436,">web.archive.org/web/20110605122507www.prwatch.org/node/7436, 5 June 2011, Critics say that the feel-good nature of pink ribbons and pink consumption distracts society from the lack of progress on preventing and curing breast cancer.{{rp|365–366}} It is also criticized for reinforcing gender stereotypes and objectifying women and their breasts.{{rp|372–374}} Breast Cancer Action launched the “Think Before You Pink” campaign in 2002 against pinkwashing, to target businesses that have co-opted the pink campaign to promote products that cause breast cancer, such as alcoholic beverages.WEB,www.ctvnews.ca/breast-cancer-month-overshadowed-by-pinkwashing-1.561275, Breast cancer month overshadowed by ‘pinkwashing’,ottawa.ctv.ca/servlet/an/local/CTVNews/20101008/pinkwashing-pink-ribbon-101009/20101009/?hub=OttawaHome," title="web.archive.org/web/20101012151918ottawa.ctv.ca/servlet/an/local/CTVNews/20101008/pinkwashing-pink-ribbon-101009/20101009/?hub=OttawaHome,">web.archive.org/web/20101012151918ottawa.ctv.ca/servlet/an/local/CTVNews/20101008/pinkwashing-pink-ribbon-101009/20101009/?hub=OttawaHome, 12 October 2010, live, 9 October 2010, Mulholland A, ctvnews.ca,Breast cancer culture
In her 2006 book Pink Ribbons, Inc.: Breast Cancer and the Politics of Philanthropy Samantha King claimed that breast cancer has been transformed from a serious disease and individual tragedy to a market-driven industry of survivorship and corporate sales pitch.BOOK, King S, Pink ribbons, inc.: breast cancer and the politics of philanthropy, University of Minnesota Press, Minneapolis, 2006, 0-8166-4898-0, In 2010 Gayle Sulik argued that the primary purposes or goals of breast cancer culture are to maintain breast cancer’s dominance as the pre-eminent women’s health issue, to promote the appearance that society is doing something effective about breast cancer, and to sustain and expand the social, political, and financial power of breast cancer activists.{{rp|57}} In the same year Barbara Ehrenreich published an opinion piece in Harper’s Magazine, lamenting that in breast cancer culture, breast cancer therapy is viewed as a rite of passage rather than a disease. To fit into this mold, the woman with breast cancer needs to normalize and feminize her appearance, and minimize the disruption that her health issues cause anyone else. Anger, sadness, and negativity must be silenced. As with most cultural models, people who conform to the model are given social status, in this case as cancer survivors. Women who reject the model are shunned, punished and shamed. The culture is criticized for treating adult women like little girls, as evidenced by “baby” toys such as pink teddy bears given to adult women.NEWS, Ehrenreich B, Welcome to Cancerland, Harper’s Magazine, November 2001,www.barbaraehrenreich.com/cancerland.htm,barbaraehrenreich.com/cancerland.htm," title="web.archive.org/web/20101120135605barbaraehrenreich.com/cancerland.htm,">web.archive.org/web/20101120135605barbaraehrenreich.com/cancerland.htm, 20 November 2010,Emphasis
In 2009 the US science journalist Christie Aschwanden criticized that the emphasis on breast cancer screening may be harming women by subjecting them to unnecessary radiation, biopsies, and surgery. One-third of diagnosed breast cancers might recede on their own.NEWS, The Trouble with Mammograms, 17 August 2009, Aschwanden C, Los Angeles Times,articles.latimes.com/2009/aug/17/health/he-breast-overdiagnosis17, live,articles.latimes.com/2009/aug/17/health/he-breast-overdiagnosis17," title="web.archive.org/web/20101204073704articles.latimes.com/2009/aug/17/health/he-breast-overdiagnosis17,">web.archive.org/web/20101204073704articles.latimes.com/2009/aug/17/health/he-breast-overdiagnosis17, 4 December 2010, Screening mammography efficiently finds non-life-threatening, asymptomatic breast cancers and precancers, even while overlooking serious cancers. According to the cancer researcher H. Gilbert Welch, screening mammography has taken the “brain-dead approach that says the best test is the one that finds the most cancers” rather than the one that finds dangerous cancers.In 2002 it was noted that as a result of breast cancer’s high visibility, the statistical results can be misinterpreted, such as the claim that one in eight women will be diagnosed with breast cancer during their lives – a claim that depends on the unrealistic assumption that no woman will die of any other disease before the age of 95.{{rp|199–200}} By 2010 the breast cancer survival rate in Europe was 91% at one years and 65% at five years. In the USA the five-year survival rate for localized breast cancer was 96.8%, while in cases of metastases it was only 20.6%. Because the prognosis for breast cancer was at this stage relatively favorable, compared to the prognosis for other cancers, breast cancer as cause of death among women was 13.9% of all cancer deaths. The second most common cause of death from cancer in women was lung cancer, the most common cancer worldwide for men and women. The improved survival rate made breast cancer the most prevalent cancer in the world. In 2010 an estimated 3.6 million women worldwide have had a breast cancer diagnosis in the past five years, while only 1.4 million male or female survivors from lung cancer were alive.BOOK, Olopade OI, Falkson CI, Breast Cancer in Women of African Descent, Springer Science & Business Media, 2010, 5, 978-1-4020-3664-4,Health disparities in breast cancer
There are ethnic disparities in the mortality rates for breast cancer as well as in breast cancer treatment. Breast cancer is the most prevalent cancer affecting women of every ethnic group in the United States. Breast cancer incidence among black women aged 45 and older is higher than that of white women in the same age group. White women aged 60–84 have higher incidence rates of breast cancer than Black women. Despite this, Black women at every age are more likely to succumb to breast cancer.BOOK, Yedjou CG, Sims JN, Miele L, Noubissi F, Lowe L, Fonseca DD, Alo RA, Payton M, Tchounwou PB, Breast Cancer Metastasis and Drug Resistance, Health and Racial Disparity in Breast Cancer, Advances in Experimental Medicine and Biology, 1152, 31–49, 3 January 2020, 31456178, 6941147, 10.1007/978-3-030-20301-6_3, 978-3-030-20300-9,Special populations
Men
Breast cancer is relatively uncommon in men, but it can occur. Typically, a breast tumor appears as a lump in the breast. Men who develop gynecomastia (enlargement of the breast tissue due to hormone imbalance) are at increased risk, as are men with disease-associated variations in the BRCA2 gene, high exposure to estrogens, or men with Klinefelter syndrome (who have two copies of the X chromosome, and naturally high estrogen levels).{{sfn|Hayes|Lippman|2022|loc=“Male Breast Cancer“}} Treatment typically involves surgery, followed by radiation if needed. Around 90% men’s tumors are ER-positive, and are treated with endocrine therapy, typically tamoxifen.{{sfn|Hayes|Lippman|2022|loc=“Male Breast Cancer“}} The disease course and prognosis is similar to that in women of similar age with similar disease characteristics.{{sfn|Hayes|Lippman|2022|loc=“Male Breast Cancer“}}Pregnant women
Diagnosing breast cancer in pregnant women is often delayed as symptoms can be masked by pregnancy-related breast changes.{{sfn|Hayes|Lippman|2022|loc=“Breast Cancer in Pregnancy“}} The diagnostic path is the same as in non-pregnant women, except that radiography of the abdomen is avoided. Chemotherapy is avoided during the first trimester, but can be safely administered through the rest of the pregnancy term. anti-HER2 treatments and endocrine therapies are delayed until after delivery. These treatments given after delivery can cross into the breast milk, and so breast feeding is generally not possible. The prognosis for pregnant women with breast cancer is similar to non-pregnant women of similar age.{{sfn|Hayes|Lippman|2022|loc=“Breast Cancer in Pregnancy“}}Research
Treatments are being evaluated in clinical trials. This includes individual drugs, combinations of drugs, and surgical and radiation techniques Investigations include new types of targeted therapy,JOURNAL, Venur VA, Leone JP, Targeted Therapies for Brain Metastases from Breast Cancer, International Journal of Molecular Sciences, 17, 9, 1543, September 2016, 27649142, 5037817, 10.3390/ijms17091543, free, cancer vaccines, oncolytic virotherapy,JOURNAL, Suryawanshi YR, Zhang T, Essani K, Oncolytic viruses: emerging options for the treatment of breast cancer, Medical Oncology, 34, 3, 43, March 2017, 28185165, 10.1007/s12032-017-0899-0, 44562857, gene therapyJOURNAL, Obermiller PS, Tait DL, Holt JT, Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies, Breast Cancer Research, 2, 1, 28–31, 1999, 11250690, 521211, 10.1186/bcr26, free, JOURNAL, Roth JA, Swisher SG, Meyn RE, p53 tumor suppressor gene therapy for cancer, Oncology, 13, 10 Suppl 5, 148–54, October 1999, 10550840, and immunotherapy.JOURNAL, Yu LY, Tang J, Zhang CM, Zeng WJ, Yan H, Li MP, Chen XP, New Immunotherapy Strategies in Breast Cancer, International Journal of Environmental Research and Public Health, 14, 1, 68, January 2017, 28085094, 5295319, 10.3390/ijerph14010068, free, The latest research is reported annually at scientific meetings such as that of the American Society of Clinical Oncology, San Antonio Breast Cancer Symposium,San Antonio Breast Cancer Symposium {{webarchive|url=https://web.archive.org/web/20100516171511www.sabcs.org/EnduringMaterials/Index.asp |date=16 May 2010 }} Abstracts, newsletters, and other reports of the meeting. and the St. Gallen Oncology Conference in St. Gallen, Switzerland.JOURNAL, Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thürlimann B, Senn HJ, Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009, Annals of Oncology, 20, 8, 1319–29, August 2009, 19535820, 2720818, 10.1093/annonc/mdp322, These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.Fenretinide, a retinoid, is also being studied as a way to reduce the risk of breast cancer.NEWS,www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-new-research, What’s new in breast cancer research and treatment?, Cancer, 17 November 2015, live,www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-new-research," title="web.archive.org/web/20151112202807www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-new-research,">web.archive.org/web/20151112202807www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-new-research, 12 November 2015, NEWS,www.hindawi.com/journals/bmri/2012/172897/, Fenretinide (4-HPR): A Preventive Chance for Women at Genetic and Familial Risk?, hindawi, 17 November 2015, live,www.hindawi.com/journals/bmri/2012/172897/," title="web.archive.org/web/20151117181548www.hindawi.com/journals/bmri/2012/172897/,">web.archive.org/web/20151117181548www.hindawi.com/journals/bmri/2012/172897/, 17 November 2015, In particular, combinations of ribociclib plus endocrine therapy have been the subject of clinical trials.JOURNAL, Burris HA, Ribociclib for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, Expert Review of Anticancer Therapy, 18, 3, 201–213, March 2018, 29457921, 10.1080/14737140.2018.1435275, 3425945, A 2019 review found moderate certainty evidence that giving people antibiotics before breast cancer surgery helped to prevent surgical site infection (SSI). Further study is required to determine the most effective antibiotic protocol and use in women undergoing immediate breast reconstruction.JOURNAL, Gallagher M, Jones DJ, Bell-Syer SV, Prophylactic antibiotics to prevent surgical site infection after breast cancer surgery, The Cochrane Database of Systematic Reviews, 2019, CD005360, September 2019, 9, 31557310, 6953223, 10.1002/14651858.CD005360.pub5, Cochrane Wounds Group,Cryoablation
As of 2014 cryoablation is being studied to see if it could be a substitute for a lumpectomy in small cancers.JOURNAL, Sabel MS, Nonsurgical ablation of breast cancer: future options for small breast tumors, Surgical Oncology Clinics of North America, 23, 3, 593–608, July 2014, 24882353, 10.1016/j.soc.2014.03.009, There is tentative evidence in those with tumors less than 2 centimeters across. It may also be used in those in who surgery is not possible.JOURNAL, Roubidoux MA, Yang W, Stafford RJ, Image-guided ablation in breast cancer treatment, Techniques in Vascular and Interventional Radiology, 17, 1, 49–54, March 2014, 24636331, 10.1053/j.tvir.2013.12.008, 24372526, free, Another review states that cryoablation looks promising for early breast cancer of small size.JOURNAL, Fornage BD, Hwang RF, Current status of imaging-guided percutaneous ablation of breast cancer, AJR. American Journal of Roentgenology, 203, 2, 442–8, August 2014, 25055283, 10.2214/AJR.13.11600,Breast cancer cell lines
{{See also|List of breast cancer cell lines}}Part of the current knowledge on breast carcinomas is based on in vivo and in vitro studies performed with cell lines derived from breast cancers. These provide an unlimited source of homogenous self-replicating material, free of contaminating stromal cells, and often easily cultured in simple standard media. The first breast cancer cell line described, BT-20, was established in 1958. Since then, and despite sustained work in this area, the number of permanent lines obtained has been strikingly low (about 100). Indeed, attempts to culture breast cancer cell lines from primary tumors have been largely unsuccessful. This poor efficiency was often due to technical difficulties associated with the extraction of viable tumor cells from their surrounding stroma. Most of the available breast cancer cell lines issued from metastatic tumors, mainly from pleural effusions. Effusions provided generally large numbers of dissociated, viable tumor cells with little or no contamination by fibroblasts and other tumor stroma cells. Many of the currently used BCC lines were established in the late 1970s. A very few of them, namely MCF-7, T-47D, MDA-MB-231 and SK-BR-3, account for more than two-thirds of all abstracts reporting studies on mentioned breast cancer cell lines, as concluded from a Medline-based survey.Molecular markers
Metabolic markers
Clinically, the most useful metabolic markers in breast cancer are the estrogen and progesterone receptors that are used to predict response to hormone therapy. New or potentially new markers for breast cancer include BRCA1 and BRCA2JOURNAL, Duffy MJ, Biochemical markers in breast cancer: which ones are clinically useful?, Clinical Biochemistry, 34, 5, 347–52, July 2001, 11522269, 10.1016/s0009-9120(00)00201-0, to identify people at high risk of developing breast cancer, HER-2,{{medical citation needed|date=May 2018}} and SCD1, for predicting response to therapeutic regimens, and urokinase plasminogen activator, PA1-1 and SCD1 for assessing prognosis.{{medical citation needed|date=May 2018}}Other animals
- Mammary tumor for breast cancer in other animals
- Mouse models of breast cancer metastasis
See also
References
{{Reflist}}Works cited
- BOOK, Amin MB, Edge SB, Greene FL, et al, 48: Breast, AJCC Cancer Staging Manual, 2017, Springer Cham, 8, 978-3-319-40617-6, {{harvid, AJCC Staging Manual, 2017, }}
- JOURNAL, Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, Ruddy K, Tsang J, Cardoso F, Breast cancer, Nat Rev Dis Primers, 5, 1, 66, September 2019, 31548545, 10.1038/s41572-019-0111-2, 202718231,
- BOOK, Hayes DF, Lippman ME, 79: Breast Cancer, Harrison’s Principles of Internal Medicine, 21, McGraw Hill, 2022, Loscalzo J, Fauci A, Kasper D, et al, 978-1-264-26850-4,
- JOURNAL, Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G, Breast cancer, Lancet, 397, 10286, 1750–1769, May 2021, 33812473, 10.1016/S0140-6736(20)32381-3, 232485291,
- JOURNAL, Menes TS, Coster D, Coster D, Shenhar-Tsarfaty S, Contribution of clinical breast exam to cancer detection in women participating in a modern screening program, BMC Womens Health, 21, 1, 368, October 2021, 34666735, 10.1186/s12905-021-01507-x, free, 8524962,
- JOURNAL, Metaxa L, Healy NA, O’Keeffe SA, Breast microcalcifications: the UK RCR 5-point breast imaging system or BI-RADS; which is the better predictor of malignancy?, Br J Radiol, 92, 1103, 20190177, November 2019, 31365279, 6849664, 10.1259/bjr.20190177,
- JOURNAL, Nielsen S, Narayan AK, Breast Cancer Screening Modalities, Recommendations, and Novel Imaging Techniques, Surg Clin North Am, 103, 1, 63–82, February 2023, 36410354, 10.1016/j.suc.2022.08.004, 252990902,
- JOURNAL, Rahman WT, Helvie MA, Breast cancer screening in average and high-risk women, Best Pract Res Clin Obstet Gynaecol, 83, 3–14, September 2022, 34903436, 10.1016/j.bpobgyn.2021.11.007, 244447464,
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