Mammography/3D Mammography (Tomosynthesis):
What is it? Mammograms are low-dose x-rays of the breast.
Types of mammograms: A screening mammogram is performed at regular intervals to check for breast cancer in women who have no signs or symptoms of the disease. Screening mammograms have been used since the 1980s. A diagnostic mammogram is used to check for breast cancer when there is a sign or symptom of disease. A diagnostic mammogram is monitored by the radiologist at the time of the examination, but starts with the same images as a screening mammogram. Symptoms can include a lump, breast pain, nipple discharge or a change in the size or shape of the breast; however, these symptoms are often due to benign (noncancerous) conditions.
How mammography works: The breast is placed on the surface (detector) of the mammography system and briefly squeezed (compressed) while x-rays are taken. In a screening mammogram, x-rays of each breast are taken from two different positions to make sure the maximum amount of tissue is included. Sometimes additional images are needed to fully include all the breast tissue. The total examination takes about 10 minutes to complete although the compression lasts only seconds. Compression reduces the amount of radiation needed to penetrate the tissue and also spreads out the breast tissue to help produce clearer images. Compression also reduces motion which can blur the image and cause abnormalities to be missed.
What does cancer look like on a mammogram? Cancers may be seen as masses (like a ball, but usually with an irregular shape), areas of asymmetry that resemble normal tissue, calcifications (white specks), and/or areas of architectural distortion (imagine the puckering caused by pulling a thread in a piece of fabric). Many noncancerous (benign) conditions also produce masses and calcifications and normal tissue can appear as areas of asymmetry. Additional views, such as magnification views for calcifications, or ultrasound for masses can help distinguish benign from cancerous entities, but a needle biopsy is ultimately required for diagnosis of suspicious findings.
Benefits: Mammograms allow detection of 2 to 7 cancers for every thousand women screened. (see Summary of Cancer Detection Rates). Screening mammography is the only breast cancer screening technology that has been studied by multiple randomized controlled clinical trials evaluating deaths from breast cancer. Across those trials, mammography has been shown to reduce deaths due to breast cancer by 15-22%;i in actual practice, the observed reduction in deaths from breast cancer among women actually participating in mammography is 40-60%.ii,iii
Mammography recommendations: Mammography is the recommended first step in breast cancer screening for all women aged 40 years and older except those who are pregnant. In pregnant women, imaging is usually done only for diagnostic purposes, when symptoms are present, and ultrasound is usually the first imaging test performed. Some women at high risk may start screening with magnetic resonance imaging (MRI) by age 25 and mammographic screening by age 30.
Types of mammography are seen below (Figs. 1-2)
Mammograms can be:
1) Digital, 2-dimensional, known as a “Full Field Digital Mammogram” (FFDM), 2D mammogram or digital mammogram, uses a dedicated electronic detector system to computerize and display the x-ray information (Fig. 1).
Courtesy of Dr. Wendie Berg
Figure 1. Standard Digital Mammogram Images: Craniocaudal (CC, left) and mediolateral oblique (MLO, right) views of 48 year-old woman with palpable lump in upper outer left breast show heterogeneously dense tissue which may obscure small masses. The patient’s cancer, in the area marked by red arrows, is not well seen.
2) Digital Breast Tomosynthesis, also referred to as “3-Dimensional mammography” (3D mammography) or tomosynthesis, uses a dedicated electronic detector system to obtain multiple projection images which are “synthesized” by the computer to create thin slices of the breast (Fig. 2). While the images are not truly 3-dimensional, individual slices can be displayed for review by the radiologist.
Courtesy of Dr. Wendie Berg
Figure 2. Tomosynthesis Images. 1-mm slices from CC (left) and MLO (right) tomosynthesis from the same patient as in Fig. 1 (done in combination with the standard digital mammogram, i.e. during the same breast compression). The irregular mass due to invasive ductal carcinoma (in the area of the red ovals), is much better seen on the tomosynthesis(3D) slices than the 2D digital images.
In both 2D digital mammography and tomosynthesis exams, the x-rays are transmitted to high-resolution computer monitors with electronic tools that allow the images to be magnified or manipulated for more detailed evaluation. Digital images are stored in a computer system called a PACS (picture archive communication system). This allows the radiologist to retrieve previous exams for comparison from year to year and to manipulate the images for complete viewing.
How Does Tomosynthesis Work? A digital mammogram provides a 2-dimensional picture of the breast, which is a 3-dimensional object. The breast is composed of different structures, such as milk ducts, fat, connective tissues and blood vessels. These structures appear at different levels within the breasts and can overlap one another when viewed as a 2D image. Overlapping tissue can hide small breast cancers and in some cases make normal tissue appear abnormal. Tomosynthesis can help to reduce the confusion created by overlapping tissues.
Tomosynthesis utilizes specially-equipped digital (x-ray) mammography machines and acquires images at multiple angles. Like standard mammography, tomosynthesis utilizes a paddle to compress the breast to minimize any possible motion as well as minimize the amount of radiation needed to penetrate the breast tissue. The images are reconstructed as multiple thin slices which can be individually “scrolled through” to reduce tissue overlap (Figs.3a-3b).
Courtesy of Drs. Wendie and Jeremy Berg
Figure 3a. Tomosynthesis. For tomosynthesis, the breast is compressed as for a regular 2D mammogram and the x-ray tube moves in an arc over the breast. Multiple short-exposure “projection” images are obtained and used to create thin “slice” (often 1-mm thick) images of the breast (A, B and C bottom row), which reduces the overlap of tissues and can help show masses and architectural distortion (e.g. red mass in slice “B”). Figure3b. Image of Tomosynthesis System.
Benefits of Tomosynthesis: When added to standard digital mammography, tomosynthesis depicts an additional 1 to 2 cancers per thousand women screened in the first round of screening and this benefit appears to continue every year.iv
Tomosynthesis is interpreted together with a 2D mammogram (Fig. 4). When a 2D mammogram and tomosynthesis are performed together (in “combination mode”), the study results in about twice the radiation dose as from a 2D mammogram alone - and the dose is greater in thicker breasts. Many centers have the computer software needed to create a “synthetic” 2D mammogram from the same images used to create the tomosynthesis slices. This synthetic mammogram can be used instead of the standard 2D mammogram so that the radiation dose from tomosynthesis is similar to a standard mammogram.
Courtesy of Dr. Wendie Berg
Figure 4. Digital Mammography & Tomosynthesis (same patient as Figures 1-2), with palpable irregular mass seen on tomosynthesis (ovals) in area of asymmetry (arrows) that looks almost normal on the 2D mammogram.
While slightly better performance is observed with tomosynthesis than with standard 2D mammography in women of all breast densities, some cancers will still remain hidden by dense tissue. An analysis of over 170,000 tomosynthesis exams compared to over 270,000 2D mammograms showed an increase in cancer detection of 1.6 per 1000 in women with heterogeneously dense breasts but no improvement in cancer detection in extremely dense breasts.v Another large study of tomosynthesis showed an increase in cancer detection of more than 2.5 per 1000 women aged 40-49 with dense breasts.vi One studyiv showed there is a benefit to having tomosynthesis every year, with fewer cancers presenting as lumps in the interval between screens, though further validation of the approach is ongoing.
A very large NIH-funded multicenter trial (TMIST) is underway where women will have either 2D mammography alone (the control group), 2D plus tomosynthesis, or synthetic 2D plus tomosynthesis. The main endpoint of the study is to determine if using tomosynthesis reduces the rates of advanced cancers and interval cancers. These are surrogate measures to predict reduced rates of death from breast cancer, without having to follow large groups of women for decades. For more information, see Goals of TMIST on the cancer.gov website.
Importantly, compared to standard mammography, tomosynthesis reduces the number of false positive studies that require additional imaging or “callback” from screening to prove that no abnormality is present. This additional imaging beyond the screening study typically involves a “diagnostic mammogram” with additional mammographic views and/or ultrasound. About 95% of areas called back prove to be normal overlapping tissue or benign changes such as cysts. When tomosynthesis images show a mass, the spot compression or spot magnification views which are otherwise commonly performed can often be skipped, and the woman can usually just have ultrasound (see Fig.5).
Courtesy of Dr. Wendie Berg
Figure 5. Ultrasound. On same patient as in figures 1-2, ultrasound was performed directed to the palpable mass seen on tomosynthesis and shows an irregular hypoechoic (dark gray) complex cystic and solid mass, (arrows) compatible with cancer. US-guided core needle biopsy showed grade 2-3 invasive ductal cancer with associated DCIS.
Considerations: All mammograms utilize x-ray technology and dense tissue absorbs more x-rays than fatty tissue. Some breast tumors are hidden (masked) by overlying or surrounding dense breast tissue (Fig. 6). A cancer masked on a 2D mammogram could still be masked on tomosynthesis unless the cancer is at least partially surrounded by fatty tissue. Standard 2D mammography has been shown to miss about 50% of cancers present in women with dense breasts.vii-xii In one large clinical study of population-based screening, the addition of tomosynthesis to 2D mammography produced significant gains in sensitivity (52.1% for 2D mammography vs 70.5% for 2D mammography plus tomosynthesis) across all breast densities.xiii
Figure 6. Comparison of breast cancer visualization in a fatty breast versus a dense breast.
i Oeffinger KC, Fontham ET, Etzioni R, et al. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society. JAMA 2015; 314:1599-1614
ii Coldman A, Phillips N, Wilson C, et al. Pan-canadian study of mammography screening and mortality from breast cancer. J Natl Cancer Inst 2014; 106
iii Tabar L, Dean PB, Chen TH, et al. The incidence of fatal breast cancer measures the increased effectiveness of therapy in women participating in mammography screening. Cancer 2019; 125:515-523
iv McDonald ES, Oustimov A, Weinstein SP, et al. (2016). Effectiveness of Digital Breast Tomosynthesis Compared With Digital Mammography: OutcomesAnalysis From 3 Years of Breast Cancer Screening. JAMA Oncology.Jun1;2(6):737-43
v Rafferty EA, Durand MA, Conant EF, et al. (2016). Breast Cancer Screening Using Tomosynthesis and Digital Mammography in Dense and Nondense Breasts. JAMA. 315(16):1784-6
vi Conant EF, Barlow WE, Herschorn SD, et al. Association of Digital Breast Tomosynthesis vs Digital Mammography With Cancer Detection and Recall Rates by Age and Breast Denistiy. JAMA Oncol.Published onlineFeb. 28, 2019
vii Mandelson MT, Oestreicher N, Porter PL, et al. Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 2000; 92:1081-1087
viii Wanders JOP, Holland K, Karssemeijer N, et al. The effect of volumetric breast density on the risk of screen-detected and interval breast cancers: a cohort study. Breast Cancer Res 2017; 19:67
ix Destounis S, Johnston L, Highnam R, Arieno A, Morgan R, Chan A. Using Volumetric Breast Density to Quantify the Potential Masking Risk of Mammographic Density. AJR Am J Roentgenol 2017; 208:222-227
x Kerlikowske K, Scott CG, Mahmoudzadeh AP, et al. Automated and Clinical Breast Imaging Reporting and Data System Density Measures Predict Risk for Screen-Detected and Interval Cancers: A Case-Control Study. Ann Intern Med 2018; 168:757-765
xi Kolb TM, Lichy J, Newhouse JH. Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: An analysis of 27,825 patient evaluations. Radiology 2002; 225:165-175
xii Berg WA, Zhang Z, Lehrer D, et al. Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. JAMA 2012; 307:1394-1404
xiii Skaane P, Bandos AI, Niklason LT, et al. Digital Mammography versus Digital Mammography Plus Tomosynthesis in Breast Cancer Screening: The Oslo Tomosynthesis Screening Trial. Radiology 2019; 291:23-30