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Breast cancer is a cancer that starts in the breast, usually in the inner lining of the milk ducts or lobules. There are different types of breast cancer, with different stages (spread), aggressiveness, and genetic makeup. Survival varies greatly depending on those factors; with best treatment, 10-year disease-free survival varies from 98% to 10%. Treatment includes surgery, drugs (hormone therapy and chemotherapy), and radiation.[1]

Worldwide, breast cancer is the second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted)[2] and the fifth most common cause of cancer death.[3] In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).[3] Breast cancer is about 100 times as frequent among women as among men, but survival rates are equal in both sexes.[4][5][6]

Some breast cancers require the hormones estrogen and progesterone to grow, and have receptors for those hormones. Those cancers are treated with drugs that interfere with those hormones, usually tamoxifen]], and with drugs that shut off the production of estrogen in the ovaries or elsewhere; this may damage the ovaries and end fertility. Low-risk, hormone-sensitive breast cancers may be treated with hormone therapy and radiation alone. Breast cancers without hormone receptors, or which have spread to the lymph nodes in the armpits, or which express certain genetic characteristics, are higher-risk, and are treated more aggressively. One standard regimen, popular in the U.S., is cyclophosphamide plus doxorubicin (Adriamycin), known as Chemotherapy regimens (CA); these drugs damage DNA in the cancer, but also in fast-growing normal cells where they cause serious side effects. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT; taxane attacks the microtubules in cancer cells. An equivalent treatment, popular in Europe, is cyclophosphamide, methotrexate, and fluorouracil (CMF).[7] Monoclonal antibodies, such as trastuzumab, are used for cancer cells that have the HER2 mutation. Radiation is usually added to the surgical bed to control cancer cells that were missed by the surgery, which usually extends survival, although radiation exposure to the heart may cause damage and heart failure in the following years.[8]

Signs and symptoms

The first symptom, or subjective sign, of breast cancer is typically a lump that feels different from the rest of the breast tissue. According to the The Merck Manual, more than 80% of breast cancer cases are discovered when the woman feels a lump.[9] According to the American Cancer Society, the first medical sign, or objective indication of breast cancer as detected by a physician, is discovered by mammogram. Lumps found in lymph nodes located in the armpits[9] can also indicate breast cancer.

Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.[9][10]

When breast cancer cells invade the dermal lymphatics—small lymph vessels in the skin of the breast—its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer (IBC). Symptoms of inflammatory breast cancer include pain, swelling, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange.[9]

Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes such as redness and mild flaking of the nipple skin. As Paget's advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's also have a lump in the breast.[11]

Occasionally, breast cancer presents as metastatic disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain.[12] Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are "non-specific", meaning they can also be manifestations of many other illnesses.[13]

Most symptoms of breast disorder do not turn out to represent underlying breast cancer. Benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. The appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.[14]

Causes

The primary risk factors that have been identified are sex,[15] age,[16] childbearing, hormones,[17] a high-fat diet,[18] alcohol intake,[19][20] obesity,[21] and environmental factors such as tobacco use, radiation[22], endocrine disruptors and shiftwork.[23]

Well established risk factors account for 47% of cases while 5% are attributable to hereditary syndromes.[24] In particular, carriers of the breast cancer susceptibility genes, BRCA1 and BRCA2, are at a 30-40% increased risk for breast and ovarian cancer, depending on in which portion of the protein the mutation occurs.[25]

  • Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting cancer in her other breast.
  • Family history: A woman's risk of breast cancer is higher if her mother, sister, or daughter had breast cancer. The risk is higher if her family member got breast cancer before age 40. Having other relatives with breast cancer (in either her mother's or father's family) may also increase a woman's risk.
  • Certain breast changes: Some women have cells in the breast that look abnormal under a microscope. Having certain types of abnormal cells (atypical hyperplasia and lobular carcinoma in situ [LCIS]) increases the risk of breast cancer.
  • Race: Breast cancer is diagnosed more often in Caucasian women than Latina, Asian, or African American women.
  • No physical activity: Women who are physically inactive throughout life may have an increased risk of breast cancer. Being active may help decrease risk.

Abortion has not been found to be a risk factor for breast cancer. The breast cancer abortion hypothesis however continues to be promoted by some pro-life groups.[26][27][28] Bras and tight fitting clothing has not been found to be related to breast cancer.[29]

Pathophysiology

Breast cancer, like other forms of cancer, is the outcome of multiple environmental and hereditary factors. Some of these factors include:

  1. Inherited defects in DNA repair genes, such as BRCA1, BRCA2[22] and TP53.[30]
  2. Lesions to DNA such as genetic mutations. Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.[31]
  3. Failure of immune surveillance, a theory in which the immune system removes malignant cells throughout one's life.[32]
  4. Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.

People in less-developed countries report lower incidence rates than in developed countries.

In the United States, 10 to 20 percent of patients with breast cancer and patients with ovarian cancer have a first- or second-degree relative with one of these diseases. Mutations in either of two major susceptibility genes, breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2), confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. However, mutations in these genes account for only 2 to 3 percent of all breast cancers.[33]

Screening

Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis. The assumption is that early detection will improve outcomes. A number of screening test have been employed including: clinical and self breast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging.

A clinical or self breast exam involves feeling the breast for breast lump or other abnormalities. Evidence however does not support its use.[34] Mammographic screening for breast cancer is also controversial. It uses x-rays to examine the breast for any uncharacteristic masses or lumps. The Cochrane collaboration in 2009 concluded that it is unclear whether screening does more good than harm.[35] Many national organizations however recommend it. If mammography is decided upon it should only be done every two years in women between the ages of 50 and 74.[36]

In women at high risk, such as those with a strong family history of cancer, additional testing may include genetic screening and / or magnetic resonance imaging. Genetic screening involves testing for mutations in the BRCA genes.

Diagnosis

While screening techniques discussed above are useful in determining the possibility of cancer, a further testing is necessary to confirm whether a lump detected on screening is cancer, as opposed to a benign alternative such as a simple cyst.

In a clinical setting, breast cancer is commonly diagnosed using a "triple test" of clinical breast examination (breast examination by a trained medical practitioner), mammography, and fine needle aspiration cytology. Both mammography and clinical breast exam, also used for screening, can indicate an approximate likelihood that a lump is cancer, and may also identify any other lesions. Fine Needle Aspiration and Cytology (FNAC), which may be done in a GP's office using local anaesthetic if required, involves attempting to extract a small portion of fluid from the lump. Clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, these three tools can be used to diagnose breast cancer with a good degree of accuracy.

Other options for biopsy include core biopsy, where a section of the breast lump is removed, and an excisional biopsy, where the entire lump is removed.

Management

The mainstay of breast cancer treatment is surgery. Adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor) is given when the tumor expresses estrogen receptors or progesterone receptors. Chemotherapy is given for more advanced stages of disease. Monoclonal antibodies are sometimes used, especially for HER2-positive tumors. Radiotherapy is given after surgery to the region of the tumor bed, to destroy microscopic tumors that may have escaped surgery. Treatments are constantly being evaluated in randomized, controlled trials, to evaluate and compare individual drugs, combinations of drugs, and surgical and radiation techniques. The latest research is reported annually at scientific meetings such as that of the American Society of Clinical Oncology, San Antonio Breast Cancer Symposium, and the St. Gallen Oncology Conference in St. Gallen, Switzerland.[37] These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.

In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests that predict breast cancer recurrence risk based on gene expression. In February 2007, the first breast cancer predictor test won formal approval from the Food and Drug Administration. This is a new gene test to help predict whether women with early-stage breast cancer will relapse in 5 or 10 years, this could help influence how aggressively the initial tumor is treated.[38]

Radiation therapy is also used to help destroy cancer cells that may linger after surgery. Radiation therapy can be delivered as external beam radiotherapy or as brachytherapy (internal radiotherapy). Radiation can reduce the risk of recurrence by 50-66% (1/2 - 2/3rds reduction of risk) when delivered in the correct dose.[39]

Prognosis

A prognosis is the medical team's "best guess" in how cancer will affect a patient. There are many prognostic factors associated with breast cancer: staging, tumor size and location, grade, whether disease is systemic (has metastasized, or traveled to other parts of the body), recurrence of the disease, and age of patient.

Stage is the most important, as it takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse 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 behaviour (grading). Size is not a factor in staging unless the cancer is invasive. Ductal Carcinoma in situ throughout the entire breast is stage zero.

Grading is based on how biopsied, cultured cells behave. The closer to normal cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used).

Younger women tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts are active with their cycles, they may be nursing infants, and may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biologic factors contributing to a higher risk of disease recurrence for younger women with breast cancer.[40]

The presence of estrogen and progesterone receptors in the cancer cell, while not prognostic, is important in guiding treatment. Those who do not test positive for these specific receptors will not respond to hormone therapy.

Likewise, HER2/neu status directs the course of treatment. Patients whose cancer cells are positive for HER2/neu have more aggressive disease and may be treated with trastuzumab, a monoclonal antibody that targets this protein.

Elevated CA15-3, in conjunction with alkaline phosphatase, was shown to increase chances of early recurrence in breast cancer.[41]

Psychological aspects

The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which provide a supportive environment to help patients cope and gain perspective from cancer survivors. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.

Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.[42]

On the other hand, a recent study conducted by researchers at the College of Public Health of the University of Georgia showed that older women may face a more difficult recovery from breast cancer than their younger counterparts.[43] As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.[43]

Society and culture

Pink ribbon

In the fall of 1991, Susan G. Komen for the Cure handed out pink ribbons to participants in its New York City race for breast cancer survivors.[44]

The widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in patient care have stemmed, in part, from the breast cancer advocacy movement.[45]

In the month of October, the National Breast Cancer Awareness Month is recognized by survivors, family and friends of survivors and/or victims of the disease.[46] A pink ribbon is worn to recognize the struggle that sufferers face when battling with the cancer.[47]

Pink for October is an initiative started by Matthew Oliphant, which asks that any sites willing to help make people aware of breast cancer, change their template or layout to include the color pink, so that when visitors view the site, they see that the majority of the site is pink. Then after reading a short amount of information about breast cancer, or being redirected to another site, they are aware of the disease itself.[48]

The patron saint of breast cancer is Agatha of Sicily.[49]

The pink and blue ribbon was designed in 1996 by Nancy Nick, President and Founder of the John W. Nick Foundation to bring awareness that "Men Get Breast Cancer Too!"[50]

In 2009 Out of the Shadow of Pink, A Man's Pink and the Brandon Greening Foundation for Breast Cancer in Men joined together to globally establish the third week of October as Male Breast Cancer Awareness Week[51]

Research

In 2008, the American College of Surgeons Oncology Group began a National Cancer Institute funded study to explore the success of cryoablation therapy in the treatment of Invasive Breast Carcinoma. The Visica 2TM Treatment System from Sanarus Technologies was chosen as the exclusive cryoablation treatment technology for the study, which is currently in Phase 2. [52]

In December 2009, researchers at the University of New South Wales found a link between so-called "high-risk" variants of human papillomavirus, (HPV) and two types of breast cancer.[53] (early-stage, noninvasive, (DCIS) and invasive, ductal carcinoma (IDC))

See also

References

  1. ↑ Merck Manual Online, Breast Cancer
  2. ↑ World Health Organization International Agency for Research on Cancer (June 2003). World Cancer Report. Retrieved on 2009-03-26.
  3. ↑ 3.0 3.1 World Health Organization (February 2006). Fact sheet No. 297: Cancer. Retrieved on 2009-03-26.
  4. ↑ Male Breast Cancer Treatment - National Cancer Institute. National Cancer Institute (2006). Retrieved on 2006-10-16.
  5. ↑ Breast Cancer in Men: Cancer Research UK. Cancer Research UK (2007). Retrieved on 2007-11-06.
  6. ↑ American Cancer Society (September 27, 2007). What Are the Key Statistics About Breast Cancer in Men?. Retrieved on 2008-02-03.
  7. ↑ Muss HB, Berry DA, Cirrincione CT, et al. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009 May 14;360(20):2055-65.
  8. ↑ Buchholz TA. N Engl J Med. 2009 Jan 1;360(1):63-70. Radiation therapy for early-stage breast cancer after breast-conserving surgery.
  9. ↑ 9.0 9.1 9.2 9.3 Merck Manual of Diagnosis and Therapy (February 2003). Breast Disorders: Cancer. Retrieved on 2008-02-05.
  10. ↑ eMedicine (August 23, 2006). Breast Cancer Evaluation. Retrieved on 2008-02-05.
  11. ↑ National Cancer Institute (June 27, 2005). Paget's Disease of the Nipple: Questions and Answers. Retrieved on 2008-02-06.
  12. ↑ Lacroix M (December 2006). "Significance, detection and markers of disseminated breast cancer cells". Endocrine-related Cancer 13 (4): 1033–67. doi:10.1677/ERC-06-0001. PMID 17158753. 
  13. ↑ National Cancer Institute (September 1, 2004). Metastatic Cancer: Questions and Answers. Retrieved on 2008-02-06.
  14. ↑ Merck Manual of Diagnosis and Therapy (February 2003). Breast Disorders: Introduction. Retrieved on 2008-02-05.
  15. ↑ Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN (July 2004). "Breast carcinoma in men: a population-based study". Cancer 101 (1): 51–7. doi:10.1002/cncr.20312. PMID 15221988. 
  16. ↑ Breast Cancer Risk Factors (2008-11-25). Retrieved on 2009-11-10.
  17. ↑ Yager JD; Davidson NE (2006). "Estrogen carcinogenesis in breast cancer". New Engl J Med 354 (3): 270–82. doi:10.1056/NEJMra050776. PMID 16421368. 
  18. ↑ Chlebowski RT, Blackburn GL, Thomson CA, et al. (December 2006). "Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study". Journal of the National Cancer Institute 98 (24): 1767–76. doi:10.1093/jnci/djj494. PMID 17179478. 
  19. ↑ Boffetta P, Hashibe M, La Vecchia C, Zatonski W, Rehm J (August 2006). "The burden of cancer attributable to alcohol drinking". International Journal of Cancer 119 (4): 884–7. doi:10.1002/ijc.21903. PMID 16557583. 
  20. ↑ [1]
  21. ↑ BBC report Weight link to breast cancer risk
  22. ↑ 22.0 22.1 American Cancer Society (2005). Breast Cancer Facts & Figures 2005-2006 (PDF). Retrieved on 2007-04-26.
  23. ↑ WHO international Agency for Research on Cancer Press Release No. 180, December 2007.
  24. ↑ Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN (November 1995). "Proportion of breast cancer cases in the United States explained by well-established risk factors". Journal of the National Cancer Institute 87 (22): 1681–5. doi:10.1093/jnci/87.22.1681. PMID 7473816. 
  25. ↑ Venkitaraman AR (January 2002). "Cancer susceptibility and the functions of BRCA1 and BRCA2". Cell 108 (2): 171–82. doi:10.1016/S0092-8674(02)00615-3. PMID 11832208. 
  26. ↑ WHO - Induced abortion does not increase breast cancer risk. who.int. Retrieved on 2007-12-24.
  27. ↑ ACS :: Can Having an Abortion Cause or Contribute to Breast Cancer?. cancer.org. Retrieved on 2008-03-31.
  28. ↑ Summary Report: Early Reproductive Events Workshop - National Cancer Institute. cancer.gov. Retrieved on 2007-11-04.
  29. ↑ Can Wearing a Bra Cause Breast Cancer?.
  30. ↑ Dunning AM, Healey CS, Pharoah PD, Teare MD, Ponder BA, Easton DF (1 October 1999). "A systematic review of genetic polymorphisms and breast cancer risk". Cancer Epidemiology, Biomarkers & Prevention 8 (10): 843–54. PMID 10548311. 
  31. ↑ Cavalieri E, Chakravarti D, Guttenplan J, et al. (August 2006). "Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention". Biochimica et Biophysica Acta 1766 (1): 63–78. doi:10.1016/j.bbcan.2006.03.001. PMID 16675129. 
  32. ↑ Farlex (2005). ">immunological surveillance The Free Dictionary: Immunological Surveilliance. Retrieved on 2008-02-10.
  33. ↑ Breast and Ovarian Cancer, Richard Wooster and Barbara L. Weber, New Engl J Medicine, 348:2339-2347, June 5, 2003. [Free Full Text
  34. ↑ Kösters JP, Gøtzsche PC (2003). "Regular self-examination or clinical examination for early detection of breast cancer". Cochrane Database Syst Rev (2): CD003373. doi:10.1002/14651858.CD003373. PMID 12804462. 
  35. ↑ Gøtzsche PC, Nielsen M (2009). "Screening for breast cancer with mammography". Cochrane Database Syst Rev (4): CD001877. doi:10.1002/14651858.CD001877.pub3. PMID 19821284. 
  36. ↑ Breast Cancer: Screening. United States Preventive Services Task Force.
  37. ↑ Annals of Oncology 2009 20(8):1319-1329; doi:10.1093/annonc/mdp322 Special article: Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009, A. Goldhirsch, J. N. Ingle, R. D. Gelber, et al. Review of latest research in breast cancer, as reported by expert panels at the St. Galen Oncology Conference, St. Galen, Switzerland. Free full text.
  38. ↑ "FDA Approves New Breast Cancer Test". Associated Press, February 6, 2007.
  39. ↑ Breastcancer.org Treatment Options
  40. ↑ Peppercorn J (2009). "Breast Cancer in Women Under 40". Oncology 23 (6). 
  41. ↑ Keshaviah A, Dellapasqua S, Rotmensz N, et al. (April 2007). "CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials". Annals of Oncology 18 (4): 701–8. doi:10.1093/annonc/mdl492. PMID 17237474. 
  42. ↑ Pritchard KI (2009). "Ovarian Suppression/Ablation in Premenopausal ER-Positive Breast Cancer Patients". Oncology 23 (1). 
  43. ↑ 43.0 43.1 Robb C, Haley WE, Balducci L, et al. (April 2007). "Impact of breast cancer survivorship on quality of life in older women". Critical Reviews in Oncology/hematology 62 (1): 84–91. doi:10.1016/j.critrevonc.2006.11.003. PMID 17188505. 
  44. ↑ http://ww5.komen.org/uploadedFiles/Content_Binaries/The_Pink_Ribbon_Story.pdf
  45. ↑ http://www.crcfl.net/content/view/history-of-breast-cancer-advocacy.html
  46. ↑ Breast Cancer Awareness Month. Retrieved on 2008-01-04.
  47. ↑ Pink Ribbon. Retrieved on 2008-01-04.
  48. ↑ Pink for October. Retrieved on 2008-01-04.
  49. ↑ Index of Saints. Catholic Forum. Retrieved on 2008-01-04.
  50. ↑ About Our Ribbon. Retrieved on 2008-09-17.</
  51. ↑ Male Breast Cancer Awareness Week Campaign. Retrieved on 2009-10-01.
  52. ↑ Cryoablation of Early Invasive Ductal Breast Cancer
  53. ↑ HPV Vaccine May Prevent Breast Cancer by Lillie Shockney, Yahoo! Health

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