Mammograms and Dense Breasts
1. If a mammography report indicates the patient has heterogeneously dense or extremely dense tissue but is otherwise categorized as “negative” or “benign” what should be considered next?
Dense breasts are “normal.” In fact, 40% of women over age 40 have dense breasts. But dense breast tissue can hide cancer on a mammogram and can reduce the effectiveness of mammography screening. So a “normal,” “negative,” or “benign” mammogram result does not reliably exclude cancer in women with dense breasts. This is why, sometimes, a woman with dense breasts may have cancer detected soon after a “normal,” “negative,” or “benign” mammogram. This is known as an “interval cancer.” To find cancer in a woman with dense breasts, additional screening should be considered. See flow chart: Who Needs More Screening? (or, in Europe, European Screening Decision Support Tool).
2. A patient recently had a “normal” mammogram and has extremely dense breasts. She now feels a lump. What should you recommend?
It is important for any woman not to ignore a lump just because the recent mammogram was normal, and this is especially important if the breasts are dense. While cysts, other benign masses, and areas of normal tissue can present as lumps, malignant masses, especially those lacking calcifications, are frequently masked by dense breast tissue and a “normal,” “negative,” or “benign” mammogram does not mean that there is no cancer present. Tomosynthesis can help show some cancers not found with 2D-mammography, but ultrasound is the test of choice to evaluate palpable lumps and allows targeted assessment and correlation of the area being felt with findings on ultrasound. If there is a mass suspicious for cancer, the radiologist/technologist may also include ultrasound of the tissue in the axilla (under the arm) because the first place cancer will spread is to lymph nodes in the axilla. Cancers presenting because of symptoms prior to the next annual mammogram are called “interval cancers” and interval cancers are increasingly common with increasing breast density.
3. When should screening mammography begin and stop?
Based on randomized trials (invitation to screening) mammography, there is at least a 15% decrease in deaths due to breast cancer in women screened in their 40s and a 22% reduction in deaths among women screened from ages 50 to 74 [1]. In observational studies of women actually having mammographic screening, reduction in deaths due to breast cancer is closer to 40% [2, 3]. Based on these results, the American College of Radiology (ACR) recommends annual screening beginning at age 40 for women at average risk for breast cancer [4]. The European Society of Breast Imaging (EUSOBI) recommends biennial screening mammography for average-risk women aged 50–69 years; extension up to 73 or 75 years biennially and from 40–45 to 49 years, annually [5]. Breast cancer incidence peaks earlier, in the 40s, for African American, Asian, and Hispanic women [6], than for Caucasian women when the peak is in the early 50s. As such, it is especially important for African American, Asian, and Hispanic women to start screening by age 40. The age to stop screening should be based on a woman’s overall health status. Women with a life expectancy less than 5-7 years are unlikely to realize a benefit from screening mammography.
Women at high risk for breast cancer, because of known or suspected disease-causing variants (mutations) in BRCA or other genes such as P53, should begin screening earlier; American Cancer Society recommendations, as well as those of the European Society of Mastology (EUSOMA), include annual MRI [7, 8]: BRCA-1 carriers should begin by age 25, and BRCA-2 carriers by age 30. Women with a history of radiation therapy to the chest (e.g., for Hodgkin’s disease) before age 30 should begin screening with mammography and MRI at age 25, or 8 years after treatment, whichever is later. Emerging evidence suggests that for BRCA-1 carriers who have annual MRI, the benefit of mammography is relatively small before age 40 [9]. Once a woman has had breast cancer, she should have at least annual mammography; if she also has dense breasts and/or was diagnosed with breast cancer by the age of 50, the ACR recommends she consider annual MRI in addition to mammography [10].
For other women with a family history of breast cancer, it is important to consider many factors, including the age at diagnosis of family members. Several risk models have been developed. While all models can over- or underestimate risk in a given individual, the Tyrer-Cuzick model is the most consistently accurate and, as of September 2017, includes breast density as a risk factor. For women estimated to have a lifetime risk of breast cancer of 20% or more, annual MRI screening has been recommended in addition to mammography [7, 10].
References Cited
1. Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for breast cancer: An update for the U.S. Preventive Services Task Force. Ann Intern Med 2009; 151:727-737, W237-742
2. 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
3. Broeders M, Moss S, Nystrom L, et al. The impact of mammographic screening on breast cancer mortality in Europe: A review of observational studies. J Med Screen 2012; 19 Suppl 1:14-25
4. Monticciolo DL, Newell MS, Hendrick RE, et al. Breast cancer screening for average-risk women: Recommendations from the ACR Commission on Breast Imaging. J Am Coll Radiol 2017; 14:1137-1143
5. Sardanelli F, Aase HS, Alvarez M, et al. Position paper on screening for breast cancer by the European Society of Breast Imaging (EUSOBI) and 30 national breast radiology bodies from Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Israel, Lithuania, Moldova, The Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Spain, Sweden, Switzerland and Turkey. Eur Radiol 2017; 27:2737-2743
6. Stapleton SM, Oseni TO, Bababekov YJ, Hung YC, Chang DC. Race/ethnicity and age distribution of breast cancer diagnosis in the United States. JAMA Surg 2018; 153:594-595
7. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75-89
8. Sardanelli F, Boetes C, Borisch B, et al. Magnetic resonance imaging of the breast: Recommendations from the EUSOMA working group. Eur J Cancer 2010; 46:1296-1316
9. Heijnsdijk EA, Warner E, Gilbert FJ, et al. Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening-MRISC, MARIBS, and Canadian studies combined. Cancer Epidemiol Biomarkers Prev 2012; 21:1458-1468
10. Monticciolo DL, Newell MS, Moy L, Niell B, Monsees B, Sickles EA. Breast cancer screening in women at higher-than-average risk: Recommendations from the ACR. J Am Coll Radiol 2018; 15:408-414
4. Should mammography screening begin at age 40 or 50?
Women should begin screening at age 40. Though breast cancer is more common as women get older, it is still important to begin screening at 40 because:
- We screen for breast cancer to find it EARLY, when it is easier to treat and most survivable.
- Breast cancer is the number one cause of death in women aged 35 to 54 years.
- Deaths from breast cancer are reduced the most when screening starts at age 40. The most years of life are saved when screening starts at age 40.
- More than half of women in their 40s have dense breasts (heterogeneously dense or extremely dense). Dense breast tissue increases the risk for developing breast cancer and the consideration of additional screening after a mammogram.
- Women at “high risk” for breast cancer, most often because they have a disease-causing mutation (such as BRCA1 or BRCA2), should begin screening even younger – at least by age 30 and with the inclusion of an MRI.
WHAT ABOUT FALSE ALARMS (KNOWN AS “FALSE POSITIVES”)?
- About 10% of women having a screening mammogram will be called back (recalled) for extra testing or views. THIS IS NORMAL. Among women called back, 95% do not have cancer. If a needle biopsy is necessary, even that is a simple test not much different from a dental filling.
- The newer technique of 3D-mammography (also known as tomosynthesis), is better able to show cancer AND results in fewer callbacks for extra testing.
WHAT ABOUT SCREENING IN DENSE BREASTS?
- Younger women are more likely to have dense breast tissue that can hide cancer on mammography.
- In women who have breasts categorized as “dense” (heterogeneously dense or extremely dense), adding screening ultrasound after a mammogram can help find more breast cancers. However, ultrasound also finds areas/masses that are not cancer and increases the chance of needing a needle biopsy to determine if such areas/masses detected are cancerous or not.
IS IT COVERED?
- Under the Affordable Care Act, insurance carriers are required to cover the full cost of screening mammography. If the screening is performed by 3D mammography (tomosynthesis), the full cost might not be covered by some insurance companies in some states.
- Insurance coverage for additional screening tests, such as ultrasound or MRI, varies by state and by insurance company. Women should check with their insurance carriers to determine how additional tests will be covered. In women at high risk for breast cancer, most insurers will cover screening MRI (regardless of density) though a deductible/co-pay will typically apply, and pre-authorization may be needed.
- Diagnostic mammography is performed to evaluate abnormalities found on screening or when a woman has signs or symptoms of breast cancer. A deductible/co-pay will usually apply for diagnostic mammography.
5. What is “risk-based mammography screening” for women age 40-49? Is it safe?
The idea that only women at increased risk should be screened in their 40s is an example of “risk-based screening.”
Since breast cancer is less common in the 40s than in older women, there are fewer cancers to be found. At the same time, largely because it may be the first time a woman has mammography screening, and also because the breasts are more often dense, there are more false positives (callbacks for additional testing when no cancer is found) in women in their 40s. In risk-based screening, the goal is to reduce the number of women who are screened or the frequency of screening or both.
However, if mammography screening were limited to only women with family history of breast cancer and/or dense breasts, most studies suggest that the majority of women diagnosed with cancer in their 40s would not be screened.
Several studies have examined how many cancers occur in women who would not be screened by “risk-based screening.” In the study of Destounis et al [1], 61% of women diagnosed with cancer in their 40s had no family history of breast cancer. In the study of Price et al [2], only 24% of women diagnosed with breast cancer in their 40s had a very strong family history of breast cancer (first degree relative diagnosed by age 50 or two first-degree relatives diagnosed) or extremely dense breasts. Some family history of breast cancer (first-degree relative diagnosed at any age) or dense breast tissue (including heterogeneously dense breast tissue) was present in 79% of women diagnosed with breast cancer. Neal et al [3] found only 20% of women diagnosed with breast cancer in their 40s had a family history of breast cancer.
The ongoing WISDOM Study [4] (Women Informed to Screen Depending On Measures of risk) randomizes consenting women to “adaptive screening.” In women who accept randomization, screening will commence for a woman in her 40s only when she has 5-year risk at least as high as an average 50-year-old woman (1.3% 5-year risk of developing breast cancer) and screening would then be biennial for most women and annual for women with extremely dense breasts or other risks. Burnside et al [5] evaluated cancer yield if screening were limited to those women in their 40s who had at least the same 5-year risk of breast cancer as a woman of age 50. They found that only 13/50 (26%) of cancers occurred in women who would have been screened based on risk. If screening were limited to women over age 45, 34/50 (68%) of cancers diagnosed in women in their 40s would have been found on screening.
Importantly:
- Breast cancer is the number one cause of death in women aged 35 to 54 years.
- Mammography has been proven to reduce deaths due to breast cancer in women screened beginning at age 40.
- Treatment is less invasive for women diagnosed by screening, including women diagnosed in their 40s [6].
- 25% of all years of life lost to breast cancer occur in women diagnosed before the age of 45.
Thus, under any scenario of restricting mammography screening in the 40s to only those women at increased risk, the cancer-detection benefits of screening are reduced.
All U.S. national medical societies agree that breast cancer screening beginning at the age of 40 saves the most lives. For more information about screening guidelines by medical society, click here.
References Cited
1. Destounis SV, Arieno AL, Morgan RC, et al. Comparison of breast cancers diagnosed in screening patients in their 40s with and without family history of breast cancer in a community outpatient facility. AJR Am J Roentgenol 2014; 202:928-932
2. Price ER, Keedy AW, Gidwaney R, Sickles EA, Joe BN. The potential impact of risk-based screening mammography in women 40-49 years old. AJR Am J Roentgenol 2015; 205:1360-1364
3. Neal CH, Rahman WT, Joe AI, Noroozian M, Pinsky RW, Helvie MA. Harms of restrictive risk-based mammographic breast cancer screening. AJR Am J Roentgenol 2018; 210:228-234
4. Esserman LJ, Study W, Athena I. The WISDOM Study: Breaking the deadlock in the breast cancer screening debate. NPJ Breast Cancer 2017; 3:34
5. Burnside ES, Trentham-Dietz A, Shafer CM, et al. Age-based versus risk-based mammography screening in women 40-49 years old: A cross-sectional study. Radiology 2019:181651
6. Ahn S, Wooster M, Valente C, et al. Impact of screening mammography on treatment in women diagnosed with breast cancer. Ann Surg Oncol 2018; 25:2979-2986
6. Should women with dense breasts still have mammography screening?
Yes. Mammography is the first step in screening for most women. While additional screening may be recommended for women with dense breasts and/or high risk for developing breast cancer, there are still some cancers and precancerous changes that will show on a mammogram better than on ultrasound or MRI. Whenever possible, women with dense breasts should have digital mammography rather than film mammography, and preferably with DBT (tomosynthesis) due to slightly improved cancer detection using digital mammography [1]. About half of cancers seen on mammography have calcifications (white dots like salt crystals), and calcifications can be seen even in dense areas of the breast (Figure below). It is important to know that at least a few calcifications can be seen in nearly all breasts and that the vast majority of calcifications seen on a mammogram are not due to cancer. Some calcifications require special magnification mammography views to be adequately evaluated. A biopsy may be recommended for calcifications which are new or increasing and have a concerning appearance on magnification views. Even when a biopsy is recommended for calcifications, only about 1 in 4 or 5 are shown to be due to cancer. When there are no calcifications, some masses due to cancer can be seen in dense breasts because they distort (pucker) the tissue around them. Some masses due to cancer are seen in dense breasts because at least a portion of the mass is in an area where the breast is more fatty.
Women who are pregnant may want to defer screening mammography until after the pregnancy. (For women who are pregnant with a lump or other breast problem, diagnostic ultrasound is performed first, and mammography can be used safely and effectively performed if needed with abdominal shield protection.) For women who are breastfeeding, if they will only be nursing for a short time (3-5 months), they might defer screening mammography until 2-3 months after the baby is weaned. For those planning on breastfeeding 6 months or longer, mammography screening can be performed while nursing but probably best to schedule it after the first 3 months when the breasts are less likely to be engorged. Patients who are breastfeeding will almost certainly have dense breasts during that time.
Mammography Shows Some Early Breast Cancers Not Seen on Ultrasound. Magnification of mammographic images of heterogeneously dense breasts show new grouped calcifications (white specks like salt crystals within yellow circles). These are difficult or impossible to see with ultrasound. Most calcifications seen on mammograms are not due to cancer; however, biopsy showed these to be due to ductal carcinoma in situ (DCIS), a noninvasive cancerous change which, if left untreated, can progress to invasive breast cancer.
References Cited
1. Pisano ED, Gatsonis C, Hendrick E, et al. Diagnostic performance of digital versus film mammography for breast-cancer screening. N Engl J Med 2005; 353:1773-1783
7. Can a patient skip mammography and instead have a screening ultrasound?
Ultrasound should NOT be considered a replacement or substitute for mammography, as many breast cancers (about half of DCIS, seen most often as calcifications, and one in four to five invasive breast cancers) may only be depicted on mammography/tomosynthesis, even in women with dense breasts. Ultrasound screening should only be done as an adjunct to screening mammography in patients with dense breast tissue.
Women who refuse mammography based on concerns about radiation or other factors (for example, pain/discomfort from compression) should be counseled on the safety of mammography, the low risks of the radiation associated with mammography, and the success of mammography as a screening test. Many centers will not perform screening ultrasound without a screening mammogram/tomosynthesis.
However, in some uncommon situations, ultrasound may be performed as the primary test for screening if the center has the required expertise:
- The most common situation for using ultrasound as a primary screening tool would be in young patients (under age 30) who are at high risk for developing breast cancer but who are unable to have breast MRI due to pregnancy or other factors.
- Women for whom mammography cannot be performed for any reason may benefit from ultrasound screening, such as women over age 40 with disability impacting the ability to cooperate with mammographic positioning.
In women at elevated risk of breast cancer who cannot have MRI due to implanted devices, claustrophobia, allergy to contrast (gadolinium chelate), or body habitus precluding positioning, ultrasound screening can also be used as a supplement to mammography.
8. If a woman is a breast cancer survivor and has dense breasts, is mammography adequate screening?
Often not. Across all breast densities, compared to women without a history of breast cancer, mammography is less sensitive and interval cancer rates are higher in women who have had breast cancer [1]. Women diagnosed before the age of 50 or with dense breasts are especially likely to have subsequent breast cancer missed by screening mammography [2]. In these high-risk women, early detection of second breast cancers has been shown to improve survival [3], so there are guidelines recommending additional screening beyond mammography.
Tomosynthesis, or 3D mammography, improves cancer detection in most women (by 1-2 per 1000 screening examinations) compared to standard 2D mammography. In all women with dense breasts, however, tomosynthesis remains limited, as cancers that lack calcifications can be masked by overlying tissue. For women with dense breasts and prior breast cancer, the American College of Radiology now recommends [4] annual MRI in addition to either 2D or 3D mammography for the following women (provided the patient has not had bilateral mastectomy):
- All women with a personal history of breast cancer and dense breasts.
- Women with any breast density diagnosed with breast cancer by age 50.
Women with a personal history of breast cancer diagnosed after age 50 even with breasts that are not dense should strongly consider supplemental screening with MRI, especially if other risk factors are present.
If breast MRI is not possible, contrast-enhanced mammography (CEM) or molecular breast imaging (MBI) are other options. Ultrasound can be considered if these options are not possible.
What are the data?
Several supplemental screening methods improve detection of early, node-negative invasive breast cancers in women with a history of breast cancer. MRI will show the most cancers, even after combined mammography (and several studies also used ultrasound), at an average of 15 per 1000 examinations [5-11]. If MRI is not possible, contrast-enhanced mammography may be considered, which improves cancer detection in women who have undergone breast conservation over digital mammography (15 vs. 6 per 1000 examinations, respectively) [12]. If these options are not possible or not available, screening ultrasound can be added to annual mammography, though the added cancer detection (at 2-4 per 1000 examinations) is less than that achieved with MRI or CEM. Ultrasound is not indicated for screening women who have had screening MRI [13].
References Cited
- Houssami N, Abraham LA, Miglioretti DL, et al. Accuracy and outcomes of screening mammography in women with a personal history of early-stage breast cancer. JAMA 2011; 305:790-799
- Lowry KP, Braunstein LZ, Economopoulos KP, et al. Predictors of surveillance mammography outcomes in women with a personal history of breast cancer. Breast Cancer Res Treat 2018; 171:209-215
- Houssami N, Ciatto S, Martinelli F, Bonardi R, Duffy SW. Early detection of second breast cancers improves prognosis in breast cancer survivors. Ann Oncol. 2009; 20(9):1505-10
- Monticciolo DL, Newell MS, Moy L, Lee CS, Destounis SV. Breast cancer screening for women at higher-than-average risk: Updated recommendations from the ACR. J Am Coll Radiol2023; S1546-1440(23)00334-4
- 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(13):1394-404
- Giess CS, Poole PS, Chikarmane SA, Sippo DA, Birdwell RL. Screening Breast MRI in Patients Previously Treated for Breast Cancer: Diagnostic Yield for Cancer and Abnormal Interpretation Rate. Acad Radiol. 2015; 22(11):1331-7
- Gweon HM, Cho N, Han W, et al. Breast MR imaging screening in women with a history of breast conservation therapy. Radiology. 2014; 272(2):366-73
- Weinstock C, Campassi C, Goloubeva O, et al. Breast magnetic resonance imaging (MRI) surveillance in breast cancer survivors. SpringerPlus. 2015; 4:459
- Lehman CD, Lee JM, DeMartini WB, et al. Screening MRI in Women With a Personal History of Breast Cancer. J Natl Cancer Inst. 2016; 108(3)
- Nadler M, Al-Attar H, Warner E, et al. MRI surveillance for women with dense breasts and a previous breast cancer and/or high risk lesion. Breast. 2017; 34:77-82
- Vreemann S, Gubern-Merida A, Schlooz-Vries MS, et al. Influence of Risk Category and Screening Round on the Performance of an MR Imaging and Mammography Screening Program in Carriers of the BRCA Mutation and Other Women at Increased Risk. Radiology. 2018; 286(2):443-51
- Gluskin J, Rossi Saccarelli C, Avendano D, et al. Contrast-Enhanced Mammography for Screening Women after Breast Conserving Surgery. Cancers (Basel) 2020; 12:3495
- Berg WA. Data Do Not Support Semiannual Screening US after MRI, and Screening Mammography after MRI Has Limited Benefit. Radiology 2023; 307:e230932
9. Are a digital mammogram and a 3D mammogram (known as tomosynthesis) the same thing?
No, but they are different types of mammograms. Both involve computer-generated images. A standard 2D digital mammogram captures images from two different angles (or views). Tomosynthesis (3D) captures images from many different angles (projection images). The multiple images are then compiled by a computer and used to create thin “slice” images of a breast. A “3D” mammogram can be performed in addition to a standard 2D mammogram. Tomosynthesis uses x-rays that produce about the same radiation exposure to the breasts as a standard mammogram: if a patient has both 2D and 3D their breasts will receive nearly twice the amount of radiation as from a standard mammogram, though the combined dose is still within standard safety limits. A new technique that creates a 2D-like image from the projection images, i.e. a “synthetic” 2D image, is being used in many centers instead of the standard 2D mammogram. The total radiation dose from tomosynthesis with synthetic 2D images is similar to or slightly more than a standard 2D mammogram and varies with breast thickness and tissue density.
10. Is the mammography recall rate (or the false positive rate/false alarm rate) higher for women with dense breasts than in women with fatty breasts?
Yes. Women with dense breasts are about twice as likely to be called back for additional testing as are women with non-dense breasts, and the vast majority (about 95%) of callbacks will not show cancer [1, 2]. Thus, the denser the breast, the more likely a false positive (additional testing when no cancer is present) is to occur. Women with extremely dense breasts are about twice as likely to experience a false positive as are women with fatty breasts.
References Cited
1. McCarthy AM, Kontos D, Synnestvedt M, et al. Screening outcomes following implementation of digital breast tomosynthesis in a general-population screening program. J Natl Cancer Inst 2014; 106
2. Lehman CD, White E, Peacock S, Drucker MJ, Urban N. Effect of age and breast density on screening mammograms with false-positive findings. AJR Am J Roentgenol 1999; 173:1651-1655
11. Is annual screening more effective than biennial screening?
Yes. If a woman is going to participate in screening, annual screening is especially important for women in their 40s when cancers tend to be more biologically aggressive. Greater breast density also contributes to worse outcomes from screening mammography among women in their 40s [1, 2]. Biennial screening is nearly as effective as annual screening at reducing deaths due to breast cancer among women who are over the age of 50 (or postmenopausal).
References Cited
1. Hendrick RE, Helvie MA, Hardesty LA. Implications of CISNET modeling on number needed to screen and mortality reduction with digital mammography in women 40-49 years old. AJR Am J Roentgenol 2014; 203:1379-1381
2. Bailey SL, Sigal BM, Plevritis SK. A simulation model investigating the impact of tumor volume doubling time and mammographic tumor detectability on screening outcomes in women aged 40-49 years. J Natl Cancer Inst 2010; 102:1263-1271
12. Are there some cancers found by screening mammography that do not require treatment?
Probably, but it is difficult to determine this at the individual level, i.e. for a given patient. Some cancers are so indolent and slow-growing that they might not ever have been detected otherwise in a patient’s lifetime (“overdiagnosis”). While estimates of overdiagnosis vary, on average, of 11 breast cancers found with screening, 2 will be life saving, 1 will represent overdiagnosis, and 8 will be found earlier than they would have been without screening (with better prognosis) [1]. Some ductal carcinoma in situ found on the first screening examination represents overdiagnosis (estimated at 37% of such cases), but new findings on subsequent screens are uncommonly overdiagnosis (estimated at 4% of cancers on annual screens).
References Cited
1. Yen MF, Tabar L, Vitak B, Smith RA, Chen HH, Duffy SW. Quantifying the potential problem of overdiagnosis of ductal carcinoma in situ in breast cancer screening. Eur J Cancer 2003; 39:1746-1754