dense breasts-what to know-do-oct 2015 - pa breast cancer ... - dense breasts(1).pdftomosynthesis...
TRANSCRIPT
1
Dense Breasts: What to Know and What to Do
Wendie A. Berg, MD, PhD, FACR Professor of Radiology
Magee-Womens Hospital of UPMC University of Pittsburgh School of
Medicine [email protected]
Disclosures
n I am a radiologist specializing in breast imaging
n Hologic, General Electric Healthcare, Gamma Medica, Inc. provide equipment and research support to the institution
n Unpaid Chief Scientific Advisor to DenseBreast-info.org n Educational support from GE and Volpara
SCREENING
Basic Principles
n Early detection will alter the natural history n Reduce mortality n Earlier detection will allow more breast
conservation, less harmful treatments
n Healthy women will not be harmed n Test widely available, cost effective, well
tolerated
Survival by Invasive Tumor size at Detection
00.10.20.30.40.50.60.70.80.9
1
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16Time in years since diagnosis
Sur
viva
l pro
babi
lity
1-9 mm10-14 mm15-19 mm20-29 mm30-49 mm50+ mm
Mammo
CBE
Tabar Rad Clin NA 2000;38:625-652, via R. Edward Hendrick, PhD, U. Colorado
2
n Mammography is the only screening test for which randomized trials have been conducted
n Mammography has been shown to reduce deaths due to breast cancer
RCT Results in Women 50-74 Randomized
Trial Relative
Risk 95% Confidence
Interval HIP of NY 0.79 0.58 – 1.08 Malmo 0.83 0.66 - 1.04
Sw. 2 County 0.65 0.55 - 0.77 Gothenburg 0.91 0.61 - 1.36 Stockholm 0.70 0.46 - 1.07
Edinburgh 0.79 0.60 – 1.02 CNBSS-2 1.02 0.78 - 1.33
Combined 0.78 0.70 – 0.85 Combined results demonstrate a statistically significant 22% mortality reduction from “invitation to screening”
RandomizedTrial
Relative Risk
95% Confidence Interval
HIP of NY 0.77 0.52 – 1.13 Malmo 0.70 0.49 - 1.00
Sw. 2 County 0.93 0.63 - 1.37 Gothenburg 0.65 0.40 – 1.05 Stockholm 1.52 0.80 - 2.88 Edinburgh 0.75 0.48 - 1.18 CNBSS-1 0.97 0.74 - 1.27 Age Trial (GB) 0.83 0.66 – 1.04
RCT Results in Women 39-49
Combined 0.85 0.75 – 0.96 Nelson et al. meta-analysis released with the USPSTF guidelines demonstrated a statistically significant 15% mortality reduction
Tabar L et al Lancet 2003;361:1405-1410
Delay in Benefit of Screening
Life Expectancy
Walter LC and Covinsky KE. JAMA 2001;285:2570
10-Year Horizon
n Stop screening when life expectancy < 10 years n Healthiest quartile at age 85 n Comorbidities: Lowest quartile at age 70
n Applies to supplemental screening as well
3
Why isn’t screening more effective at reducing mortality?
n Nonparticipation n Diagnosed at young age before
screening would have commenced n Cancer not detected n Cancer has already spread at time of
detection
Webb ML et al Cancer 2013 n Invasive breast cancers Partners Health dx
1990-1999, followed through 2007, median 12.5 yrs, 609 breast cancer deaths
n Median age at dx of fatal cancer = 49 yrs n 118 (19.4%) deaths screen-detected ca n 60 (9.8%) from interval cancers (lumps) n 395 (64.9%) in women never screened
n 36 (5.9%) in women screened > 2 yr prior n 71% of deaths in women without regular
screening
Webb ML et al: Cancer 2013 epub 9-9-13
n Median age at diagnosis of fatal breast cancer is 49
n Women should participate in screening by age 40
n Improve efforts to identify high-risk women who may be diagnosed even earlier
Supplemental Screening
n At best, can reduce n 10% of breast cancer deaths due to interval cancers, palpable in the interval between screens
n Another ~20% of deaths by earlier detection of screen-detected cancers
Deaths
n 34% of all deaths in women screened are due to interval cancers n 60% of deaths if dx < age 40 n 47% of deaths 40-49 n 28% of deaths 50-59 n 26% of deaths 60-69 n 24% of deaths 70 or older
Webb ML et al: Cancer 2013 epub 9-9-13
4
Reasons for Mammographic Nondetection
n #1: Dense breasts n Benign appearing: seen and dismissed
n Asymmetries n Benign-appearing mass n Stable calcifications
n Overlooked n Calcifications, distortion
n Rapidly growing cancer, not present on prior mammogram
Reasons for Mammographic Nondetection
n #1: Dense breasts – Supplemental screen n Benign appearing: seen and dismissed
n Asymmetries n Benign-appearing mass - Feedback n Stable calcifications
n Overlooked – CAD n Calcifications, distortion
n Rapidly growing cancer, not present on prior mammogram – Screen more often
DENSE BREASTS
from www.oncologychannel.com
What is Breast Density?
n Dense tissue in a mammogram is comprised of ducts, glands and fibrous tissue
Courtesy Hologic Inc.
Breast Density
n Is determined on imaging: mammography or MRI, but also CT and ultrasound
n Not related to the way the breast feels
5
Tabar Classification
“Low Risk” Gram IT et al Eur J Radiol 1997;24:131-136
“High Risk”
BI-RADS® Density
n Visual n A. Almost entirely fatty n B. Scattered fibroglandular density n C. Heterogeneously dense which could
obscure detection of small masses n D. Extremely dense, which lowers the
sensitivity of mammography
A B C D
Volumetric Density vs. 2D Visual
100 BIRADS 1, 2, 3 and 4 from University of Virginia, courtesy Volpara, Inc.
Relative Risk
n Risk of developing breast cancer for women with that risk factor compared to risk for women without that risk factor
n Usually stated as risk with extremely dense vs. fatty breasts
6
1
0
2
3
4
5
6
1 1.2
2.2 2.4
3.4
5.3 6
5
4
3
2
1
0 0 None <10
% 10 – 25% 25 –
50% 50-75%
>75%
Rel
ativ
e R
isk!
Boyd, 1995 via J. Harvey, UVA
Interval Cancer
n Cancer diagnosed because of clinical symptoms in the interval between recommended screenings
n Worse prognosis and worse outcome
n ~Half of deaths in screened women who are diagnosed in their 40’s are due to interval cancers
Interval Cancers and Breast Density
Density Odds Ratio 95% CI* < 10% 1.0 -
10-24% 2.1 (0.9, 5.2)
25-49% 3.6 (1.5, 8.7)
50-74% 5.6 (2.1, 15.3)
≥ 75% 17.8 (4.8, 65.9)
Adjusted for age, BMI, parity, menarche, #childbirths, menopausal status, HRT use *p<0.001 Boyd NF, et al. NEJM 2007;356:227-36
Increased Deaths
Chiu SY et al. Cancer Epidemiol Biomarkers Prev 2010;19:1219-28
n 25 yr f/u Sweden 15,658 women 45-59 n 12.7% had dense breasts
n Increased breast cancer mortality in women with dense breasts n RR 1.91 (95%CI 1.26-2.91) n Attributed to higher incidence n Shorter sojourn time
Dense Breasts, 25 Yr F/U
RR 95% CI Incidence 1.57 1.23-2.01 Tumors > 2 cm 1.79 1.22-2.63 Node + 2.46 1.66-2.62 Grade 2-3 tumor 1.80 1.39-2.34 Death 1.91 1.26-1.91
Chiu SY et al. Cancer Epidemiol Biomarkers Prev 2010;19:1219-28
Density Decreases with Age
Age 52 Age 54
Courtesy Wendie Berg, MD, PhD
7
Breast Density as Function of Age
Kerlikowske et al. JNCI 2007; 99:386-395
Dense Breasts n Heterogeneously or extremely dense n > 1/2 of women < age 50 n > 1/3 of women age ≥ 50 n Dense tissue itself a risk factor: 3-6 X
compared to fatty breasts n Mammographic sensitivity reduced: Masking
n 30 to 48% in densest breasts n Digital mammography slightly better than film
Harvey and Bovbjerg Radiology 2004;230:29-41 Boyd NF et al NEJM 2007;356:227-236
Hormones Increase Density
n Combination estrogen (E) and progesterone (P) therapy increases breast density
n Increases risk for breast cancer
Additive Risk of HT and Density
Kerlikowske K et al J Clin Oncol 2010; 28:3830-3837
Fatty Minimal Hetero Ext Dense
Premenopausal 0.46 1 1.62 2.04
Post, no HT 0.57 1 1.35 1.51
Post, E use 0.61 1 1.60 1.99
Post, E+P 0.45 1 1.58 2.09
1.32 RR stage III or IV disease in post-menopausal nonusers 1.75 RR stage III or IV disease in post-menopausal HT users
What is the referent standard?
n “Average” woman has scattered fibroglandular density
n Relative to “average”, extreme breast density only 1.5-2X risk
Biennial vs. Annual Mammography, Extremely Dense
Kerlikowske K et al JAMA Int Med 2013:173:807-816
40-49 yrs 50-74 no HT
50-74 E+P
Stage IIB, III, IV
1.89 (1.06-3.39)
1.21 (0.92-1.61)
1.56 (0.88-1.46)
Tumor Size > 2 cm
2.39 (1.37-4.18)
1.10 (0.86-1.42)
1.59 (0.97-2.61)
Node positive
1.34 (0.77-2.31)
1.14 (0.88-1.46)
1.05 (0.64-1.72)
8
Outcomes from Dense Breasts
n Cancer more often found as a lump n Clinically detected in interval between screens
n Increased risk of recurrence (if no XRT) n More often stage IIb, III n More often multifocal, multicentric,
mastectomy more often needed n May increase risk of death from breast
cancer (requires very long term follow-up)
48F screening
Courtesy Dr. Wei Yang, MD Anderson
RT CC MAG RT ML MAG
Courtesy Dr. Wei Yang, MD Anderson
n Stereotactic biopsy: High nuclear grade DCIS solid type with comedo necrosis, with microinvasion, ER, PR-, HER2 +
n Skin-sparing mastectomy, 0/4 SLN
BREAST DENSITY INFORM LAWS
24 states require notification: 67% of USA population
9
PA Act 86
n Effective 1/30/14, each mammography report shall include written notification of breast density based on BI-RADS
PA 86
This notice contains the results of your recent mammogram, including information about breast density. If your mammogram shows that your breast tissue is dense, you should know that dense breast tissue is a common finding and is not abnormal. Statistics show many women could have dense or highly dense breasts. Dense breast tissue can make it harder to find cancer on a mammogram and may be associated with an increased risk of cancer. This information about the result of your mammogram is given to you to raise your awareness and to inform your conversations with your physician. Together, you can decide which screening options are right for you, based on your mammogram results, individual risk factors or physical examination. A report of your results was sent to your physician.
SUPPLEMENTAL SCREENING
Possible tests to add to mammography
Modality vs. Mammography alone
Absolute ↑ Cancer Detection per 1000 screens
Clinical breast exam 0.3 Double Read 1 CAD 1 Tomosynthesis 1-2 Ultrasound 2-4 Molecular Breast Imaging, CE-Mammo
8
MRI 10
Summary Screening Results by Modality/Combination
Berg WA, AJR 2009;192:390 n 36% cancers seen on mammography n 40% cancers seen on US n 64% cancers seen if both mammo+US n 81% cancers seen on MRI n 93% cancers seen if both mammo+MRI
How Do We Measure Impact of Supplemental Screening?
n Reduction in interval cancer rate n Ideally fewer than 10% of all cancers
n Reduction in # node-positive cancers n Reduction in stage II-IV disease
10
TOMOSYNTHESIS
Detector
Tube
Compression paddle
Standard Mammography
Courtesy Rita Zuley, MD
Detector
Compression paddle
Courtesy Rita Zuley, MD Rafferty EA et al. Radiology 2013, 266:104-113
Digital close up Tomosynthesis close up
Invasive Ductal CA
Tomo
n 120 µm resolution vs. 70 µm 2D n 4 to 7 sec acquisition vs. 1-3 sec: greater
potential for motion n Radiation dose to pt similar to single 2D digital
mammogram: 2X dose if have both n FDA requires standard 2D mammogram in
addition to tomo (“combo” mode): can be created synthetically from projection images if facility has the software
40F with lump noted after fall on bicycle
11
Single slices from tomosynthesis
Multifocal grade 3 IDC (ER, PR, HER2 positive)
Sagittal post-contrast MRI
Oslo Screening Trial: Interim Analysis Addition of 3D (Tomo)
2D alone 2D+3D Diff. P-value Cancer Detection Rate
6.1/1000 8.0/1000 +1.9/1000 .001
False positive rate
6.1% 5.3% -0.8% <.001
Time to interpret
45 sec 91 sec +46 sec <.001
Skaane P et al Radiology, e-pub 1/7/2013
Added Cancers Detected Tomo
n 1.9 per 1000 n Nearly all invasive n 83% (19/23) with node staging N0 n 60% grade 1 n 68% spiculated masses or distortions n Same detection benefit for each category of
breast density n Requires soft tissue contrast: Likely less effective
if extremely dense Skaane P et al Radiology, e-pub 1/7/2013
12
Tomosynthesis Performance
Study Design ICDR per 1000
Absolute Change in
Recall Rate
Skaane 2013 Prospective 1.9 -0.8%
Ciatto 2013 Prospective 2.7 -2.0%
Rose 2013 Historical control 1.3 -3.2%
Friedewald 2014 Historical control 1.2 -1.6%
Greenberg 2014 Historical control 1.4 -2.6%
Overall 1.3 -1.8%
Close up of 2D Synthetic 2D from 3D acquisition: C view
Unanswered Questions Tomo
n Yield from annual (incidence) screening n Interval cancer rate, esp. in dense breasts n Yield from US after tomo (do patients
benefit from both) n Preliminary data suggest CDR of HHUS
after tomo of ~2/1000 n Hooley RJ et al 12/5/13 RSNA SS001-06 Arie Crown
MRI
Screening High-Risk Women: MRI Women
w/cancer Mammo
(%) US (%) MRI (%)
Hartman 2004 1 0 NP 1 (100)
Warner 2004 22 8 (36) 7 (32) 17 (77)
Kuhl 2005 43 14 (33) 17(40) 39 (91)
Leach 2005 35 14 (40) NP 27 (77)
Lehman 2005 4 1 (25) NP 4 (100)
Kriege 2006 45 14 (31) NP 34 (76)
Sardanelli 2007 15 9 (60) 9 (60) 13 (87)
Lehman 2007 6 2 (33) 1 (17) 4 (67)
Hagen 2007 21 8 (38) NP 16 (76)
TOTAL 192 70 (36) 34/86 (40) 155 (81)
From Berg WA, AJR 2009;192:390
13
n Of 192 women with cancer, 158 (82%) were invasive, 24 of those (15%) node positive
n Across series: 2 cancers only on US in 1037 women vs. 31 only on MRI n No need for screening US if patient is having
MRI
From Berg WA, AJR 2009;192:390
MRI Recommended for High-Risk Women
Annual MRI in addition to mammography n BRCA mutation carrier n First degree relative of BRCA carrier but
untested n Lifetime risk of 20-25% or greater as estimated
by risk model (e.g. Claus, BRCAPRO, Tyrer-Cuzick, BOADICEA)
n Prior chest radiation age 10-30
Saslow et al. Ca Cancer J Clin 2007;57:75
When to Start Screening Women at Increased Risk
n When risk is equivalent to a woman at age 40
Age Relatives with Breast Cancer BRCA 1 carrier BRCA 2
carrier None One 1º Two 1º 20 0.04 0.1 0.2 1.8 1.0 30 0.4 1.0 2.0 10 6.6 40 1.4 2.5 5.2 20 15 50 1.9 3.2 5.3 22 18 60 2.3 3.5 5.6 19 17 70 2.5 4.2 5.7 Unknown Unknown
Berg WA; AJR 2009;192:390-399
10-yr Probability (%) of Breast Cancer
When to Start Screening
n BRCA-1 carriers: begin at age 25 n BRCA-2 carriers: start by age 30 n Radiation risk of mammography highest at
young age, prevalence of dz lowest n Avoid mammography before age 30 n Annual MRI only for BRCA carriers under 30
NCCN Genetic/Familial High Risk Assessment: Breast and Ovarian Updated 2/28/2014
Efficacy MRI
Ellen Warner et al. JCO 2011;29:1664-9 n Women with pathogenic BRCA mutations n Not all women can have MRI n 445 in MRI group n 830 controls matched for age and mutation n Mean 3.2 yr follow-up
14
Stage Distribution of Cancers
MRI Cohort N=41
Controls N=77
Mean Age 48 48 DCIS 24% 12% Invasive, mean 0.9 cm 1.8 cm
≤ 1 cm 74% 35% > 2 cm 3% 29% Node + 13% 40%
Warner, E. et al. JCO 2011;29:1664-9
Cumulative Incidence
MRI Group (%) Control Group (%)
P-value
DCIS or Stage I
13.8 (9.1 to 18.5) 7.2 (4.5 to 9.9) .01
Stage II to IV 1.9 (0.2 to 3.7) 6.6 (3.8 to 9.3) .02
Hazard ratio for development of stage II-IV breast cancer associated with MRI screening was 0.30 (0.12 to 0.72, p=.008) Approximately 2% more women dx with cancer in the MRI group
Warner E et al JCO 2011;29:1664-9
Interval Cancers: MR Screening
BRCA1 BRCA2
Women 801 474
Women-Yrs 2222 1210
Cancers 73 51
Interval Cancers
8 2
Interval Ca Rate
3.6/1000 1.7/1000
% Interval Ca 10.9% 3.9% Heijnsdijk EAM et al Cancer Epidemiol Biomarkers Prev2012;21:1458-68 UK, Dutch, Canadian trials combined
Benchmarks Screening MRI
n Cancer detection rate 10/1000 n Percent node-negative >80% n Minimal cancer (≤1 cm or DCIS) >50% n Recall rate 10-15% n PPV3 (of biopsy) 20-50% n Sensitivity >80% n Specificity 85-90%
Morris EA et al BI-RADS: MRI (ACR, Reston), 2013
Insufficient Evidence for or Against MRI
n Lifetime risk of 15-20% by risk model n LCIS/ALH (LIN) or ADH n Personal history of breast cancer n Dense breasts
Saslow et al. Ca Cancer J Clin 2007;57:75
Worse Outcomes with PHBC?
Houssami NH et al JAMA 2011;305:790-799
PHBC No PHBC P-value
Interval Ca Rate per 1000
3.6 (3.2-4.1) 1.4 (1.1-1.7) <.001
Node Positive interval ca
24.5% 29.0%
Interval Ca Stage ≥IIB*
21.4% 17.9%
*% advanced stage after excluding cases with missing stage
15
PHBC Mammography Outcomes
n More interval cancers and lower sensitivity of mammography in women with PHBC
n But, no difference in rates of node positive or advanced stage disease
Berg W et al JAMA 2012;307:1394 -1404
n ACRIN 6666: 612 women had MRI after 3 rounds of screening mammo+US
n Overall yield 15/1000 of MR n 7.3 per 1000 in women with PHBC n 26.7 per 1000 in women without PHBC
n Supplemental MRI less likely to prompt unnecessary recall or biopsy for PHBC
n Sensitivity and specificity > for PHBC vs. those with other risk factors
607 women with PHBC, negative mammogram, screening MR
n 18.1 cancers per 1000 n Sensitivity of MR 91.7% n Specificity of MR 82.2% n Modeling suggests all women treated with
BCT and dx ≤ age 50 meet the 20% LTR threshold for screening MR (assuming at least 10-yr life expectancy)
Gweon et al. Radiology 2014;272:366-373
MRI Screening Average Risk Women
Schrading S et al SABCS Dec 11 2013 n 1705 MRI exams (mix of prevalent and incident
screens), no personal or family hx of breast or ovarian cancer or dx of atypia, normal mammograms; 89% had US (-)
n 54/1705 (3.2%) suspicious findings biopsied n 18/54 (33%) malignant
n ICDR 10.6 per 1000 n 11/18 (61%) invasive, median size 10 mm, N0
Courtesy Dr. Simone Schrading
MRI Screen-Detected
51F with no known risk factors
Courtesy Dr. Simone Schrading
16
Courtesy Dr. Simone Schrading
n Why isn’t screening MRI offered to everyone? n Cost n Availability of equipment/personnel n Injection of contrast n Renal function n Pacemaker, some other metal implants
FAST MR
FAST MR Full Diagnostic Protocol MIP MIP Single post-contrast sequence
One pre- and three post-contrast sequences
STIR/T2W 3 min table time 17 min table time 30 sec reading time 90 sec reading time
Kuhl CK et al JCO 2014;32:2304-2310
FAST MR Performance
FAST MR FULL PROTOCOL Sensitivity 11/11 (100) 11/11 (100) Specificity 561/595 (94.3) 559/595 (93.9) Recall rate 45/606 (7.4) 47/606 (7.8) PPV of recall 11/45 (24.4) 11/47 (23.4) BI-RADS 3 rate 53/606 (8.7) 33/606 (5.4)
Kuhl CK et al JCO 2014;32:2304-2310
n 7/11 (64%) cancers invasive; all invasive cancers T1N0 n 10/11 not seen prospectively on US n 1/11 not seen on targeted US after MR
n None were grade 1 n No interval cancers
Kuhl CK et al JCO 2014;32:2304-2310
n Abbreviated MR protocol requires further validation
n Prospective trial in development (ACRIN/ECOG)
17
Unable to Tolerate MRI
n 18.5% (1 in 5.4) (95% CI 16.4 to 20.8%) of high-risk women who had completed 3 years of annual screening with US and mammography were unable to undergo an MRI
Berg WA et al. Radiology 2010;254:79-87
Supplemental US
n Physician Performed n Technologist Performed n Automated
Handheld US
n High-frequency transducer, 12-18 MHz linear array
n Survey scanning transverse and sagittal n Document 1 image per quadrant, 1 behind
nipple for negative exam n Lesions (all studies to date): Orthogonal views ±
calipers; optional color or power Doppler image n Positive test: BI-RADS 3 or higher assessment,
or recommendation for further imaging (BI-RADS 0)
Author N screens
ICDR per
1000
Recall Rate (%)
Bx Rate (%
women)
PPV3 Bx Performed
Corsetti 9157 4.0 NS 449 (4.9) 50/623 (8.0)
Berg yr1 2659 5.3 401 (15.1) 207 (7.8) 14/264 (5.3)
Berg yr2-3
4841 3.7 356 (7.4) 242 (5.0) 21/276 (7.6)
TOTAL 16,657 4.4 10% 898 (5.4) 85/1163 (7.3)
Physician Performed US: Multicenter Results
4.9% of women had biopsies for benign findings
Tech-Performed US (USA): Prevalent Screens
Author N ICDR per
1000
Recall Rate (%)
Bx Rate (%)
PPV3 Bx Performed
Kaplan, 2001 1,862 2.7 176 (9.5) 97 (5.2) 6/96 (6.3)
Hooley, 2012 648* 4.6 154 (23.8) 46 (7.1) 3/58 (5.2)
Weigert, 2012 8,647 2.8 1,196 (13.8) 429 (5.0) 25/418 (6.7)
Parris, 2012 5,519 1.8 680 (12.3) 185 (3.3) 10/181 (5.5)
Overall 16,676 2.5 2,206 (13.2) 757 (4.5) 47/753 (6.2)
*analysis presented for women with negative screening mammograms
Berg WA and Mendelson EB. Radiology 2014;272:12-27
Is the ICDR Lower for Technologist-Performed US?
n Direct prospective comparison of technologist- and physician-performed HHUS has not been performed
n 2.5 vs. 4.3 per 1000 on prevalent screens (p<.0067) n Likely due to differences in disease prevalence with
broader populations screened
18
Disease Prevalence Affects Yield
Moderate Risk* No Known Risks P-value
Kolb 2002
14/2914 (4.8 per 1000) 14/7901 (1.8 per 1000) .011
Crystal 2003
4/318 (12.5 per 1000) 3/1199 (2.5 per 1000) <.04
Overall 18/3232 (5.6 per 1000) 17/9100 (1.9 per 1000)
*Personal hx of breast cancer or first-degree relative with breast cancer vs. no risks
Node-Negative Invasive Cancers
n Across 10 series, 475 cancers seen only on US, 415 (87.4%) invasive
n 273/303 (90.1%) with staging were node negative
n 22/91 (24%) ILC
Types of Cancers Found with Screening US
Bae MS et al Cancer Sci 2011;102:1862-1867 (Korea) US Mammo P-value
N 254 793
Age (mean, yrs) 48 52 <.0001
BCT 84.4% 68.4% <.0001
Invasive 81.2% 73.5% <.0001
Mean invasive size 1.3 cm 1.7 cm <.0001
N0 91.8 84.1 <.0001
More likely US detected: < 1 cm (RR 2.2); luminal A vs. Her-2+; 3.7x more likely to have dense breasts; 89% of US-detected cancers were in dense breasts (vs. 65% of mammo-detected)
By Participant, Yield/1000, ACRIN 6666
Year M+US M Supp. Yield, 95% CI
P-value
1 12.8 7.5 5.3 (2.1, 8.4) .0001
2 10.0 6.4 3.6 (0.9, 6.4) .004
3 13.8 9.9 3.9 (0.9, 6.8) .004
Supplemental yield of US is significant each year and similar for incidence and prevalence screens
Berg WA et al JAMA 2012;307:1394-404
Courtesy WP Evans, III, MD
60F, 5-yr risk 2.5%, 24-mo US: 12 mm grade 1 IDC-DCIS, N0
Radial Antiradial 70F personal hx rt mastectomy, BRCA-1 mutation carrier 24 mo screen US+ 19 mm grade 3 IDC-DCIS, N0
Courtesy Dr. Mary Mahoney, U Cincinnati
19
ACRIN 6666: Breast Density
Density n Yield per 1000
P-value
≤ 25% 124 0 26-40% 785 6.4 .026 41-60% 2314 3.0 .008 61-80% 2807 4.3 .0006 >80% 1443 5.5 .005
Berg WA, et al., RSNA 2009
Berg W et al JAMA 2012;307:1394 -1404
Mammo Combined Mammo+ US
Difference
CDR per 1000 PHBC 8.2 12.5 4.2
No PHBC 7.5 11.8 4.3
Sensitivity PHBC 55.9% 84.7% 28.8%
No PHBC 50% 78.8% 28.8%
Specificity PHBC 91.4% 83.1% -8.3%
No PHBC 89.4% 77.8% -11.6%
Recall rate PHBC 9.3% 17.9% 8.6%
No PHBC 11.1% 23.0% 11.9%
Bx Rate PHBC 2.2 6.9 4.7
No PHBC 2.2 9.7 7.5
PPV3 PHBC 36.8 17.8 -19.0
No PHBC 32.0 11.0 -21.0
Berg W et al JAMA 2012;307:1394 -1404
n Supplemental yield and sensitivity of US same in women with PHBC as without
n Supplemental US less likely to cause unnecessary recall or biopsy in women with PHBC than those without
n Study supports the use of annual supplemental screening with ultrasound in addition to mammography
Interval Cancer Rate: ACRIN 6666
Yr N Interval N Cancers (%) 1 2 36 5.6 2 4 29 14 3 3 46 6.5
All 9 111 8.1
Interval Ca Rate: 9/7473 screens = 1.2 per 1000 8% of all cancers
Berg WA et al JAMA 2012;307:1394-404
Interval Cancer Rate Italy
Corsetti V et al Cancer 2011;47:1021-6 n Interval cancer rate in fatty breasts
n 1.0 per 1000
n Interval cancer rate in dense breasts after adding screening US n 1.1 per 1000
Benchmarks HH Screening US
n Cancer detection rate 3-4/1000 n Percent node negative 85% n Minimal cancer (≤1 cm or DCIS) 50% n Recall rate 8-15% n PPV3 10% n Sensitivity ? n Specificity 85-90%
20
A – Tower B – Y-axis Gantry & Transducer Carrier C – X-axis Gantry D – Ultrasound Machine Monitor E – Touch Screen /
Monitor F – Transducer Holster G – Patient Bed
Semi-Automated US Automated Arm Results
Kelly KM et al Eur Radiol 2010; 20:734-742 n 4419 women, 6425 exams, 8 facilities
n 40% women at ≥ intermediate risk n 23 cancers mammography n 46 cancers M+US n Supplemental yield 3.6 per 1000 (95% CI 2.3 to 5.4) n 10% recall rate n 23/75 (31%) biopsies prompted only by ABUS showed
cancer
Automated Breast US
n 12 MHz n 15 cm footprint n 3 acquisitions in ~15
minutes n 3D dataset
n Transverse n Created coronal and
sagittal displays
ABUS Results
Brem RF et al RSNA 2012; Tabar L et al Radiology 2015
n 15,000 women BI-RADS 1 or 2 mammo, dense breasts, automated whole breast US
n 30 (2/1000) cancers only by ABUS n 25 detailed: 23 (92%) invasive, mean size 13
mm, 18 (78%) of those N0 n 20/23 (87%) ER+ n 3/22 (14%) stage IIB or higher n 13% absolute increase in recall rate
Three-Step Implementation
n 1) Does the woman have at least 10-yr life expectancy? n No, then CBE only, with mammography only if
warranted by symptoms
21
n 2) Is the patient at “high risk” for breast cancer and under age 60-70? n Yes, then MRI annually beginning:
n When ascertained to be high risk n Age 25 if BRCA1/2 or other pathogenic
mutation n 8yr prior to chest XRT
n If unable to tolerate MRI, then US
n 3) Dense? n Yes: Option to supplement annual
mammography with US beginning at age 40 n No: Tomosynthesis beginning at age 40
www.DenseBreast-info.org “Get Smart About Being Dense”
Iceland-Bargmundsson