Mammography

Mammography
Intervention

Mammography
ICD-10-PCS BH0
ICD-9-CM 87.37
MeSH D008327
OPS-301 code 3-10
MedlinePlus 003380

Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast, which is used as a diagnostic and screening tool. The goal of mammography is the early detection of breast cancer, typically through detection of characteristic masses and/or microcalcifications.

Like all X-rays, mammograms use doses of ionizing radiation to create images. These images are then analyzed for any abnormal findings. It is normal to use lower-energy X-rays, typically Mo (K-shell x-ray energies of 17.5 and 19.6 keV) and Rh (20.2 and 22.7 keV) than those used for radiography of bones. Ultrasound, ductography, positron emission mammography (PEM), and magnetic resonance imaging (MRI) are adjuncts to mammography. Ultrasound is typically used for further evaluation of masses found on mammography or palpable masses not seen on mammograms. Ductograms are still used in some institutions for evaluation of bloody nipple discharge when the mammogram is non-diagnostic. MRI can be useful for further evaluation of questionable findings as well as for screening pre-surgical evaluation in patients with known breast cancer to detect any additional lesions that might change the surgical approach, for instance from breast-conserving lumpectomy to mastectomy. Other procedures being investigated include tomosynthesis.

For the average woman, the U.S. Preventive Services Task Force recommended (2009) mammography every two years in women between the ages of 50 and 74.[1] The American College of Radiology and American Cancer Society recommend yearly screening mammography starting at age 40.[2] The Canadian Task Force on Preventive Health Care (2012) and the European Cancer Observatory (2011) recommends mammography every 2–3 years between 50 and 69.[3][4] These task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation.[5][6] Additionally, mammograms should not be done with any increased frequency in people undergoing breast surgery, including breast enlargement, mastopexy, and breast reducation.[7] The Cochrane Collaboration (2013) concluded that the trials with adequate randomisation did not find an effect of mammography screening on total cancer mortality, including breast cancer, after 10 years. The authors of this Cochrane review write: "If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings." The authors conclude that the time has come to re-assess whether universal mammography screening should be recommended for any age group.[8] They thus state that universal screening may not be reasonable.[9] The Nordic Cochrane Collection, which in 2012 reviews updated research to state that advances in diagnosis and treatment make mammography screening less effective today. They state screening is “no longer effective.” They conclude that “it therefore no longer seems reasonable to attend” for breast cancer screening at any age, and warn of misleading information on the internet.[9]

Mammography has a false-negative (missed cancer) rate of at least 10 percent. This is partly due to dense tissues obscuring the cancer and the fact that the appearance of cancer on mammograms has a large overlap with the appearance of normal tissues. A meta-analysis review of programs in countries with organized screening found 52% over-diagnosis.[9]

Risks and benefits

Normal (left) versus cancerous (right) mammography image.

The use of mammography as a screening tool for the detection of early breast cancer in otherwise healthy women without symptoms is controversial.[10][11][12]

Keen and Keen indicated that repeated mammography starting at age 50 saves about 1.8 lives over 15 years for every 1,000 women screened.[13] This result has to be seen against the negatives of errors in diagnosis, overtreatment, and radiation exposure. The Cochrane analysis of screening indicates that it is "not clear whether screening does more good than harm". According to their analysis one in 2,000 women will have her life prolonged by 10 years of screening, however, another 10 healthy women will undergo unnecessary breast cancer treatment. Additionally, 200 women will suffer from significant psychological stress due to false positive results.[14] Newman points out that screening mammography does not reduce death overall, but causes significant harm by inflicting cancer scare and unnecessary surgical interventions.[15] The Nordic Cochrane Collection notes that advances in diagnosis and treatment of breast cancer actually may make breast cancer screening no longer effective in decreasing deaths in breast cancer, and therefore no longer recommend routine screening for healthy women as the risks might outweigh the benefits.[9]

Often women are quite distressed to be called back for a diagnostic mammogram. Most of these recalls will be false positive results. Of every 1,000 U.S. women who are screened, about 7% will be called back for a diagnostic session (although some studies estimate the number closer to 10%–15%).[16] About 10 of these individuals will be referred for a biopsy; the remaining 60 are found to be of benign cause. Of the 10 referred for biopsy, about 3.5 will have a cancer and 6.5 will not. Of the 3.5 who have cancer, about 2 have a low stage cancer that will be essentially cured after treatment.

Mammography may also produce false negatives. Estimates of the numbers of cancers missed by mammography are usually around 20%.[17] Reasons for not seeing the cancer include observer error, but more frequently it is because the cancer is hidden by other dense tissue in the breast and even after retrospective review of the mammogram, the cancer cannot be seen. Furthermore, one form of breast cancer, lobular cancer, has a growth pattern that produces shadows on the mammogram which are indistinguishable from normal breast tissue.

Mortality

The Cochrane Collaboration states that the best quality evidence does not demonstrate a reduction in mortality generally or a reduction in mortality from all types of cancer from screening mammography.[14]

The Canadian Task Force found that for women aged 50–69, screening 720 women once every 2–3 years for 11 years would prevent 1 death from breast cancer. For women age 40-49, 2100 women would need to be screened at the same frequency and period to prevent 1 death from breast cancer.[18]

Women whose breast cancer was detected by screening mammography before the appearance of a lump or other symptoms commonly assume that the mammogram "saved their lives".[19] In practice, the vast majority of these women received no practical benefit from the mammogram. There are four categories of cancers found by mammography:

  1. cancers that are so easily treated that a later detection would have produced the same total cure (woman would have lived even without mammography);
  2. cancers so aggressive that even "early" detection is too late (woman dies despite detection by mammography);
  3. cancers that would have receded on their own or are so slow-growing that the woman would die of other causes before the cancer produces symptoms (mammography results in overdiagnosis and overtreatment of this class); and
  4. the small number of breast cancers that are detected by screening mammography and whose treatment outcome improves as a result of earlier detection.

Only between 3% and 13% of breast cancers detected by screening mammography will fall into this last category. Clinical trial data suggests that 1 woman per 1,000 healthy women screened over 10 years fall into this category as well.[20] Screening mammography produces no benefit to any of the remaining 87% to 97% of women.[19]

The probability of a woman falling in any of the above four categories differs based on age.[21][22] Applying age-based uplift modelling improves targeting.[23][24][25]

False positives

The goal of any screening procedure is to examine a large population of patients and find the small number most likely to have a serious condition. These patients are then referred for further, usually more invasive, testing. Thus a screening exam is not intended to be definitive: It is intended to have sufficient sensitivity to detect a useful proportion of cancers. The cost of higher sensitivity is a larger number of results that would be regarded as suspicious in patients without disease. This is true of mammography. The patients without disease who are called back for further testing from a screening session (about 7%) are sometimes referred to as "false positives". There is a trade-off between the number of patients with disease found, and the much larger number of patients without disease that must be re-screened.

Research shows[26] that false-positive mammograms may affect women's well-being and behavior. Some women who receive false-positive results may be more likely to return for routine screening or perform breast self-examinations more frequently. However, some women who receive false-positive results become anxious, worried and distressed about the possibility of having breast cancer, feelings that can last for many years.

False positives also mean greater expense, both for the individual woman, and for the screening program. Since follow-up screening is typically much more expensive than initial screening, more false positives that must receive follow-up means fewer woman may be screened for a given amount of money. Thus as sensitivity increases, a screening program will cost more, or be able to screen a smaller number of women.

Overdiagnosis

The central harm of mammographic breast cancer screening is overdiagnosis; the detection of abnormalities that meet the pathologic definition of cancer but will never progress to cause symptoms or death during a patient's lifetime. Dr. H. Gilbert Welch, a researcher at Dartmouth College, states that "in screen-detected breast and prostate cancer survivors are more likely to have been overdiagnosed than actually helped by the test."[20] Estimates of overdiagnosis associated with mammography have ranged from 1% to 54%.[27] In 2009, Peter C. Gotzsche and Karsten Juhl Jørgensen, reviewed the literature and found that one in three cases of breast cancer detected in a population offered mammographic screening is overdiagnosed.[28] In contrast, a 2012 panel convened by the national cancer director for England and Cancer Research UK concluded one in five cases of breast cancer diagnosed among women who have undergone breast cancer screening are overdiagnosed. This means an overdiagnosis rate of 129 women per 10,000 invited to screening.[29]

False negatives

At the same time, mammograms also have a rate of missed tumors, or "false negatives." Accurate data regarding the number of false negatives are very difficult to obtain, simply because mastectomies cannot be performed on every woman who has had a mammogram to determine the false negative rate accurately. Estimates of the false negative rate depend on close follow-up of a large number of patients for many years. This is difficult in practice, because many women do not return for regular mammography making it impossible to know if they ever developed a cancer. Dr. Samuel S. Epstein, in his book, The Politics of Cancer, claims that in women ages 40 to 49, one in four instances of cancer is missed at each mammography. Researchers have found that breast tissue is denser among younger women, making it difficult to detect tumors. For this reason, false negatives are twice as likely to occur in premenopausal mammograms (Prate). This is why the screening program in the UK does not start calling women for screening mammograms until the age of 50. Some work has been done on trying to automatically detect false negative mammograms.[30][31]

The importance of these missed cancers is not clear, particularly if the woman is getting yearly mammograms. Research on a closely related situation has shown that small cancers that are not acted upon immediately, but are observed over periods of even several years, will have good outcomes. A group of 3,184 women had mammograms which were formally classified as "probably benign." This classification is for patients who are not clearly normal but have some area of minor concern. This results, not in the patient being biopsied, but having early follow up mammography every six months for three years to guarantee no change. Of these 3,184 women, 17 (0.5%) did have cancers. Most importantly, when the diagnosis was finally made, they were all still stage 0 or 1, the earliest stages. Five years after treatment, none of these 17 women had evidence of recurrence. Thus, small early cancers, even though not acted on immediately, were still entirely curable (Sickles, Radiology, 179:463-468, 1991).

Other risks

The radiation exposure associated with mammography is a potential risk of screening. The risk of exposure appears to be greater in younger women. The largest study of radiation risk from mammography concluded that for women 40 years of age or older, the risk of radiation-induced breast cancer was minuscule, particularly compared with the potential benefit of mammographic screening, with a benefit-to-risk ratio of 48.5 lives saved for each life lost due to radiation exposure.[32] Organizations such as the National Cancer Institute and United States Preventive Task Force take such risks into account when formulating screening guidelines.[33]

The majority of health experts agree that the risk of breast cancer for asymptomatic women under 35 is not high enough to warrant the risk of radiation exposure. For this reason, and because the radiation sensitivity of the breast in women under 35 is possibly greater than in older women, most radiologists will not perform screening mammography in women under 40. However, if there is a significant risk of cancer in a particular patient (BRCA positive, very positive family history, palpable mass), mammography may still be important. Often, the radiologist will try to avoid mammography by using ultrasound or MRI imaging.

There is a body of evidence that clearly shows that there is overdiagnosis of cancer when women are screened. These cancers would never have affected these women in their lifetimes. An estimate of this overdiagnosis is 10 breast cancers diagnosed and unnecessarily treated per life saved when 2000 women are screened for 10 years.[14]

While screening between 40 and 50 is still controversial, the preponderance of the evidence indicates that there is some small benefit in terms of early detection. Currently, the American Cancer Society, the American College of Radiology, and the American Congress of Obstetricians and Gynecologists encourage annual mammograms beginning at age 40.[34][35][36] The National Cancer Institute encourages mammograms one to two years for women ages 40 to 49.[37] In contrast, the American College of Physicians, a large internist group, has recently encouraged individualized screening plans as opposed to wholesale biannual screening of women aged 40 to 49.[38] In 2009, the U.S. Preventive Services Task Force recommended that screening of those age 40 to 49 be based on individual's risk factors and values, and that screening should not be routine in this age group.[39] Their report says that the benefits of screenings before the age of 50 don't outweigh the risks.[40]

Procedure

Illustration of a mammogram
A mobile mammography unit in New Zealand

During the procedure, the breast is compressed using a dedicated mammography unit. Parallel-plate compression evens out the thickness of breast tissue to increase image quality by reducing the thickness of tissue that x-rays must penetrate, decreasing the amount of scattered radiation (scatter degrades image quality), reducing the required radiation dose, and holding the breast still (preventing motion blur). In screening mammography, both head-to-foot (craniocaudal, CC) view and angled side-view (mediolateral oblique, MLO) images of the breast are taken. Diagnostic mammography may include these and other views, including geometrically magnified and spot-compressed views of the particular area of concern. Deodorant, talcum powder or lotion may show up on the X-ray as calcium spots, and women are discouraged from applying these on the day of their exam. There are two types of mammogram studies: screening mammograms and diagnostic mammograms. Screening mammograms are performed yearly on a patient who presents with no symptoms and consists of only four standard X-ray images. Diagnostic mammograms are reserved for patients with breast symptoms, changes, or abnormal findings seen on their screening mammogram. Diagnostic mammograms are also performed on patients with breast implants, breast reductions, and patients with personal and/or family history of breast cancer.

Until some years ago, mammography was typically performed with screen-film cassettes. Now, mammography is undergoing transition to digital detectors, known as digital mammography or Full Field Digital Mammography (FFDM). The first FFDM system was approved by the FDA in the U.S. in 2000. This progress is some years later than in general radiology. This is due to several factors:

  1. the higher spatial resolution demands of mammography,
  2. significantly increased expense of the equipment,
  3. concern by the FDA that digital mammography equipment demonstrate that it is at least as good as screen-film mammography at detecting breast cancers without increasing breast dose or the number of women recalled for further evaluation.

As of March 1, 2010, 62% of facilities in the United States and its territories have at least one FFDM unit.[41] (The FDA includes computed radiography units in this figure.[42])

In order to encourage the use of mammograms as a screening measure for breast cancer, a number of hospitals, cancer centers and other healthcare groups have started mobile mammography vans to bring affordable, accessible and convenient mammograms to their communities. Many mobile mammography vans prioritize serving uninsured, low-income and/or non-English-speaking women who otherwise could not otherwise afford a mammogram or who are unaccustomed to seeing a doctor. Many offer free or low-cost mammograms to women who are uninsured and/or cannot afford a mammogram.[43]

Mammograms are either looked at by one (single reading) or two (double reading) trained professionals:[44] these film readers are generally radiologists, but may also be radiographers, radiotherapists or breast clinicians (non-radiologist physicians specialising in breast disease).[45] Double reading, which is standard practice in the UK but less common in the US, significantly improves the sensitivity and specificity of the procedure.[44] Clinical decision support systems may be used with digital mammography (or digitised images from analogue mammography[46]), but studies suggest these do not significantly improve performance or only provide a small improvement.[44][47]

Scoring

Mammogram results are often expressed in terms of the BI-RADS Assessment Category, often called a "BI-RADS score." The categories range from 0 (Incomplete) to 6 (Known biopsy – proven malignancy). In the UK mammograms are scored on a scale from 1-5 (1 = normal, 2 = benign, 3 = indeterminate, 4 = suspicious of malignancy, 5 = malignant). Evidence suggests that accounting for genetic risk factors improve breast cancer risk prediction.[48]

"Work-up" process

In the past several years, the "work-up" process has become quite formalized. It generally consists of screening mammography, diagnostic mammography, and biopsy when necessary, often performed via stereotactic core biopsy or ultrasound-guided core biopsy. After a screening mammogram, some women may have areas of concern which can't be resolved with only the information available from the screening mammogram. They would then be called back for a "diagnostic mammogram". This phrase essentially means a problem-solving mammogram. During this session, the radiologist will be monitoring each of the additional films as they are taken by a Radiographer. Depending on the nature of the finding, ultrasound may often be used at this point, as well.

Generally the cause of the unusual appearance is found to be benign. If the cause cannot be determined to be benign with sufficient certainty, a biopsy will be recommended. The biopsy procedure will be used to obtain actual tissue from the site for the pathologist to examine microscopically to determine the precise cause of the abnormality. In the past, biopsies were most frequently done in surgery, under local or general anesthesia. The majority are now done with needles using either ultrasound or mammographic guidance to be sure that the area of concern is the area that is biopsied. These core biopsies require only local anesthesia, similar to what would be given during a small dental procedure.

History

As a medical procedure that induces ionizing radiation, the origin of mammography can be traced to the discovery of x-rays by Wilhelm Röntgen in 1895. In the late 1950s Robert Egan at the University of Texas M.D. Anderson Cancer Center combined a technique of low kVp with high mA and single emulsion films to devise a method of screening mammography for the first time. He published these results in 1959 in a paper, and subsequently in a book in 1964 called Mammography.[49] The "Egan technique", as it became known, enabled physicians to detect calcification in breast tissue;[50] of the 245 breast cancers that were confirmed by biopsy among 1000 patients, Egan and his colleagues at M.D. Anderson were able to identify 238 cases by using his method, nineteen of which were in patients whose physical examinations had revealed no breast pathology. Usage of mammography as a screening technique spread clinically after a 1966 study demonstrating the impact of mammograms on mortality and treatment led by Philip Strax. This study, based in New York, was the first large-scale randomized controlled trial of mammography screening.[51][52]

Regulation

Mammography facilities in the United States and its territories (including military bases) are subject to the Mammography Quality Standards Act (MQSA). The act requires annual inspections and accreditation every 3 years through an FDA-approved body. Facilities found deficient during the inspection or accreditation process can be barred from performing mammograms until corrective action has been verified or, in extreme cases, can be required to notify past patients that their exams were sub-standard and should not be trusted.

At this time MQSA applies only to traditional mammography and not related scans such as breast ultrasound, stereotactic breast biospy, or breast MRI.

See also

References

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  2. ↑ "Breast Cancer Early Detection". cancer.org. 2013-09-17. Retrieved 29 July 2014.
  3. ↑ "Recommendations on screening for breast cancer in average-risk women aged 40–74 years". Retrieved 2013-02-21.
  4. ↑ http://eu-cancer.iarc.fr/cancer-13-breast-screening.html,en
  5. ↑ "Breast Cancer: Screening". United States Preventive Services Task Force.
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  43. ↑ , "Mobile Mammography Vans Can Bring Free and Low-Cost Mammograms to You," MyHealthCafe.com
  44. 1 2 3 Taylor P, Potts HW (2008). "Computer aids and human second reading as interventions in screening mammography: Two systematic reviews to compare effects on cancer detection and recall rate". European Journal of Cancer. 44 (6): 798–807. doi:10.1016/j.ejca.2008.02.016.
  45. ↑ Taylor P, Champness J, Given-Wilson R, Johnston K, Potts H (2005). "Impact of computer-aided detection prompts on the sensitivity and specificity of screening mammography" (PDF). Health Technology Assessment. 9: 6. doi:10.3310/hta9060.
  46. ↑ Taylor CG, Champness J, Reddy M, Taylor P, Potts HW, Given-Wilson R (2003). "Reproducibility of prompts in computer-aided detection (CAD) of breast cancer". Clinical Radiology. 58 (9): 733–8. doi:10.1016/S0009-9260(03)00231-9.
  47. ↑ Gilbert FJ, Astley SM, Gillan MGC, Agbaje OF, Wallis MG, James J, Boggis CRM, Duffy , Group CADET II (2008). "Single reading with computer-aided detection for screening mammography". New England Journal of Medicine. 359 (16): 1675–84. doi:10.1056/nejmoa0803545.
  48. ↑ Liu, Jie; Page, David; Nassif, Houssam; Shavlik, Jude; Peissig, Peggy; McCarty, Catherine; Onitilo, Adedayo A; Burnside, Elizabeth (2013). "Genetic Variants Improve Breast Cancer Risk Prediction on Mammograms". American Medical Informatics Association Symposium (AMIA). 2013: 876–885. PMID 24551380.
  49. ↑ Medich DC, Martel C. Medical Health Physics. Health Physics Society 2006 Summer School. Medical Physics Publishing. ISBN 1930524315 pp.25
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  51. ↑ http://www.iom.edu/~/media/Files/Activity%20Files/Disease/NCPF/ToSeeTodaywiththeEyesofTomorowAHistoryofScreeningMammography.pdf
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