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Deteccin de cncer de
mamaEnsayo Clnico
2000
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200,000
150,000
100,000
50,000
0
*Estimate for new invasive cases among women. Carcinoma in situ of the breast accounts for an additional 36,900 new cases annually.American Cancer Society, 1998
Breast*
Lung
Colorectal
OvarianEndometrial
Cervical
CancerLeading Causes of Cancer in Women 1998
Annual Diagnosis of Cancer in Women
200,000
150,000
100,000
50,000
0
Review ofSTATISTICS
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CancerBreast Cancer
Review ofSTATISTICS
46% of women believe that they will die of
breast cancer
Actual incidence of death due to breastcancer is 3-4%, annually
1 in 8 women will develop breast cancer
AHA Statistics; 1994
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0
20
40
60
80
100
Five-Year Relative Survival Rates by Stage
at Diagnoses*
All Stages
*Adjusted for normal life expectancy. This chart is based on cases diagnosed from 1986 to 1993, followed
through 1994.
American Cancer Society, Surveillance Research, 1997
CancerReview of
STATISTICS
Local Regional Distant
84%
97%
76%
21%
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Breast Cancer Stage Distribution 1995Cancer
Review ofSTATISTICS
National Cancer Institute: SEER Cancer Statistics Review 1973-1995
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Female Breast Cancer by Stage:
Incidence Rates, 1983-1995
CancerReview of
STATISTICS
0
10
20
30
50
40
60
Rate per 100,000
1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995
Year of Diagnosis
National Cancer Institute: SEER Cancer Statistics Review 1983-1995
Stage I
Stage IIA
In situ
Stage IIBUnknownStage IIIStage IV
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Breast Cancer MortalityCancer
Review ofSTATISTICS
0
10,000
20,000
30,000
40,000
50,000
87 88 89 90 91 92 93 94 95 96 97* 98*
*Estimated figuresAmerican Cancer Society, 1998
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Breast Self
ExaminationClinical Breast
ExaminationMammography
SCREENING
for Breast CancerProcedures
Breast Self Examination
Clinical Breast Examination
Mammography
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Breast Self
ExaminationClinical Breast
Examination
SCREENING
for Breast CancerProceduresMammography
Well-established technique
Widespread clinical acceptance Facilitates early detection of breast cancer
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Mammography
RCC
(Right Cranial
Caudal)
LCC
(Left Cranial
Caudal)
RMLO
(Right Medial
Lateral Oblique)
LMLO
(Left Medial
Lateral Oblique)
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SCREENING
Procedures
Breast Imaging Reporting And Data System
Goals
Establish Quality Assurance Tool
Standardize Reporting
Reduce Confusion
Facilitate Outcome Monitoring
BI-RADS
BI-RADS, second edition; American College of Radiology, 1995
for Breast Cancer
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Radiographic Density of the Breast:
1. The breast is almost entirely fat
2. There are scattered fibroglandular densities thatcould obscure a lesion on mammography
3. The breast is heterogeneously dense. This may
lower the sensitivity of mammography
4. The breast is extremely dense which lowers the
sensitivity of mammography
Miraluma uptake is unaffected by breast density.
SCREENING
ProceduresBI-RADS
BI-RADS, second edition; American College of Radiology, 1995
for Breast Cancer
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SCREENING
Proceduresfor Breast Cancer
BI-RADS Categories
Mammographic Findings
Category 0 - Need additional imaging evaluation
Category 1 - Negative
Category 2 - Benign finding
Category 3 - Probably benign findingshort interval
follow-up suggested
Category 4 - Suspicious abnormalitybiopsy should
be considered
Category 5 - Highly suggestive of malignancy
appropriate action should be taken
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Clinical
There are certain breast tissue types
which can compromise clear
mammographic interpretation.
Mammography:CHALLENGES
Difficult-to-Evaluate Breast Tissue:
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ClinicalMammography:
CHALLENGES
1. Breast lesions have similar mammographic attenuation
characteristics to those of dense, glandular and fibrous
tissue making the lesions less likely to be detected.
2. The density of the breast scatters the radiation and results in
less image contrast.
3. The dense breast has inhomogeneities, which make it
difficult to image the breast.
4. Higher film exposure times are needed when imaging the
dense breast to achieve adequate images.
Radiology 1993; 188:297-301
25% of women have dense breasts which are difficult to
image radiographically
Factors Contributing to Difficult to EvaluateBreast Imaging
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ClinicalMammography:
CHALLENGES
Example of Scattered Fibroglandular
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ClinicalMammography:
CHALLENGES
Example of Heterogeneously Dense
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ClinicalMammography:
CHALLENGES
Example of Extremely Dense
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Surgically scarred
Post radiation therapy fibrosis
Diffuse distribution of indistinct calcifications
Augmented by implants
ClinicalMammography:
CHALLENGES
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Miraluma is indicatedfor planar imaging as a second line
diagnostic drug after mammography to assist in the evaluation of
breast lesions in patients with an abnormal mammogram or apalpable breast mass.
Miraluma is not indicatedfor breast cancer screening, to confirm
the presence or absence of malignancy, and it is not an alternative to
biopsy.
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Diagnostic sensitivity in lesions less than 1 cm decreases
while specificity increases.
Miraluma has been rarely associated with acute severe
allergic events of angioedema and urticaria. The most
frequently reported adverse events include: headache,
breast pain (mostly associated with biopsy/surgery),
nausea and abnormal taste and smell.
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Initial Reports of Technetium Tc99m Sestamibi
Tumor Detection
Initial reports of tumor detection
preceded multicenter trial(1,2)
In vitro, 9x higher concentration in
malignant cells (3,4)
MechanismOF UPTAKE
1. Aktolun et al Clinical Nuclear Medicine, 1992 17:171-176
2. Waxman Current Opinion in Radiology; 1991 3:871-876
3. Maublant, Journal of Nuclear Medicine; 1993: 34, 1949-1952
4. Delmon-Moingeon et al, Cancer Research 1990; 50: 2198-2202
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TrialClinical
0%
100%
80%
60%
40%
20%
PPV NPV
READER 1 READER 2 READER 3 READER 1 READER 2 READER 3
Miraluma Breast Imaging Trial:
Dense vs Fatty Breast Tissue Non-Palpable Abnormality
Fatty
Dense
RESULTSfor Miraluma Breast Imaging
Data on file Bristol-Myers Squibb Medical Imaging, Inc.
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TrialClinical
Miraluma Breast Imaging Trial:
Dense vs Fatty Breast Tissue Non-Palpable Abnormality
0%
100%
80%
60%
40%
20%
Fatty
Dense
ACCURACY
READER 1 READER 2 READER 3
RESULTSfor Miraluma Breast Imaging
Data on file Bristol-Myers Squibb Medical Imaging, Inc.
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TrialClinical
RESULTSfor Miraluma Breast Imaging
0%
100%
80%
60%
40%
20%
SENSITIVITY SPECIFICITY
Miraluma Breast Imaging Trial:
Dense vs Fatty Breast Tissue Palpable Abnormality
READER 1 READER 2 READER 3 READER 1 READER 2 READER 3
Fatty
Dense
Data on file Bristol-Myers Squibb Medical Imaging, Inc.
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0%
100%
80%
60%
40%
20%
PPV NPV
READER 1 READER 2 READER 3 READER 1 READER 2 READER 3
Fatty
Dense
TrialClinical
RESULTSfor Miraluma Breast Imaging
Miraluma Breast Imaging Trial:
Dense vs Fatty Breast Tissue Palpable Abnormality
Data on file Bristol-Myers Squibb Medical Imaging, Inc.
C
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0%
100%
80%
60%
40%
20%
Fatty
Dense
ACCURACY
READER 1 READER 2 READER 3
TrialClinical
RESULTSfor Miraluma Breast Imaging
Miraluma Breast Imaging Trial:
Dense vs Fatty Breast Tissue Palpable Abnormality
Data on file Bristol-Myers Squibb Medical Imaging, Inc.
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ProtocolMiraluma Breast Imaging
Inject 20 - 30 mCi Miraluma (Tc-99m Sestamibi)
in the arm contralateral to the breast with the
suspected lesion (dorsalis pedis injection for
suspected bilateral lesions)
Begin imaging 5 minutes
post-injection in prone
position with breast freely
dependent
Anterior image in the supine
or upright position
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ProtocolMiraluma Breast Imaging
Lateral view of breast with lesion
Lateral view of contralateral breast
Anterior view in supine or upright position
Shield chest/abdominal organs or remove from
field of view
Acquisition Protocol
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RMLO LMLORCC LCC
CASE 1
Patient History: 47-year-old female.
Palpable mass in right breast.
Mammographic Findings: Bilateral implants with heterogeneously dense overlying tissue.
No suspicious masses detected in normal, magnification, and
pushback views.
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RMLO LMLORCC LCC
Pushback views Pushback views
CASE 1
Patient History: 47-year-old female.
Palpable mass in right breast.
Mammographic Findings: Bilateral implants with heterogeneously dense overlying tissue.
No suspicious masses detected in normal, magnification, and
pushback views.
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LEFT LATERALANTERIOR
CASE 1
Patient History: 47-year-old female.
Palpable mass in right breast.
Mammographic Findings: Bilateral implants with heterogeneously dense overlying tissue.
No suspicious masses detected in normal, magnification, and
pushback views.
MiralumaTM Findings: Focal uptake in left breast.
Histopathology Results: Invasive ductal carcinoma.
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RMLORCC
CASE 2
Patient History: 58-year-old female.
Palpable mass above right nipple.
Mammographic Findings: Extremely dense breasts. No suspicious masses.
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CASE 2
Patient History: 58-year-old female.
Palpable mass above right nipple.
Mammographic Findings: Extremely dense breasts. No suspicious masses.
Ultrasound Results: Revealed two suspicious masses.
Retrospective review of mammograms did not reveal findings.
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CASE 2
Patient History: 58-year-old female.
Palpable mass above right nipple.
Mammographic Findings: Extremely dense breasts. No suspicious masses.
Ultrasound Results: Revealed two suspicious masses.
Retrospective review of mammograms did not reveal findings.
MiralumaTM Findings: Multi-focal uptake (3 sites) as well as axillary node involvement.
Histopathology Results: Carcinoma with axillary metastases.
RIGHT LATERALRIGHT LATERAL WITH MARKER
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RMLO - 12/95 RMLO - 1/97 RMLO - 2/98
CASE 3
Patient History: 61-year-old female.
Fullness in the inferior aspect of the right breast.
Mammographic Findings: Scattered fibroglandular densities with no significant
abnormalities. Mammograms have remained stable over the last
3 years.
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RIGHT LATERAL
CASE 3
Patient History: 61-year-old female.
Fullness in the inferior aspect of the right breast.
Mammographic Findings: Scattered fibroglandular densities with no significant
abnormalities. Mammograms have remained stable over the last
3 years.
MiralumaTM Findings: Focal uptake in the right breast in area of palpable abnormality.
Histopathology Results: Invasive lobular carcinoma.
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LCC LMLORMLORCC
CASE 4
Patient History: 65-year-old female.
Routine screening mammogram.
Mammographic Findings: Scattered fibroglandular densities. Several enlarged lymph nodes
in the left axilla. Additional views of the left breast are
recommended.
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LCC LMLO LMLO
CASE 4
Patient History: 65-year-old female.
Routine screening mammogram.
Mammographic Findings: Scattered fibroglandular densities. Several enlarged lymph nodes
in the left axilla.
No specific mass was demonstrated on additional views of the
left breast.
FOLLOW UP MAMMOGRAMS
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LEFT LATERAL RIGHT LATERALANTERIOR
CASE 4
Patient History: 65-year-old female.
Routine screening mammogram.
Mammographic Findings: Scattered fibroglandular densities. Several enlarged lymph nodes
in the left axilla. Additional views of the left breast are
recommended. No specific mass was demonstrated on additional
views of the left breast.
Miraluma Findings: Small focal uptake in the lateral view of the left breast.
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CASE 4
Patient History: 65-year-old female.
Routine screening mammogram.
Mammographic Findings: Scattered fibroglandular densities. Several enlarged lymph nodes
in the left axilla. Additional views of the left breast are
recommended. No specific mass was demonstrated on additional
views of the left breast.
Miraluma Findings: Small focal uptake in the lateral view of the left breast.
Ultrasound Results: There is an 11mm echogenic area in the left breast which may
correspond to the Miraluma image.
Histopathology Results: Ductal carcinoma in situ.
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RCC (magnified) LMLOLCCRCC
CASE 5
Patient History: 40-year-old female.
Palpable mass right breast.
Mammographic Findings: Heterogeneously dense breasts.
Highly suspicious density at the palpable mass.
Dense breast tissue makes evaluation of the breast difficult.
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LEFT LATERAL RIGHT LATERALANTERIOR
CASE 5
Patient History: 40-year-old female.
Palpable mass right breast.
Mammographic Findings: Heterogeneously dense breasts.
Highly suspicious density at the palpable mass.
Dense breast tissue makes evaluation of the breast difficult.
MiralumaTM Findings: Three areas of focal uptake seen on the right breast.
Histopathology Results: Invasive ductal carcinoma.
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RMLORCC
CASE 6
Patient History: 29-year-old female.
Right breast mass.
Clinical exam revealed ill-defined thickening in the right breast.
Mammographic Findings: Scattered fibroglandular densities.
Comparison made to right mammogram and ultrasound from 6
months ago. No significant interval change.
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CASE 6
Patient History: 29-year-old female.
Right breast mass.
Clinical exam revealed ill-defined thickening in the right breast.
Mammographic Findings: Scattered fibroglandular densities.
Comparison made to right mammogram and ultrasound from 6
months ago. No significant interval change.
Ultrasound Results: Small simple cysts and possibly a prominent duct in the outer
right breast.
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LEFT LATERAL RIGHT LATERAL
CASE 6
Patient History: 29-year-old female.
Right breast mass.
Clinical exam revealed ill-defined thickening in the right breast.
Mammographic Findings: Scattered fibroglandular densities.
Comparison made to right mammogram and ultrasound from 6
months ago. No significant interval change.
Ultrasound Results: Small simple cysts and possibly a prominent duct in the outer
right breast.
MiralumaTM
Findings: Focal area of increased activity in the deep portion of the rightbreast.
Histopathology Results: Atypical ductal hyperplasia and ductal hyperplasia
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LCC LMLORMLORCC
APRIL
CASE 7
Patient History 64-year-old female.
Palpable abnormality in left breast.
6 month follow-up.Hormone replacement therapy.
Mammographic Findings: Scattered fibroglandular densities. Asymmetric increase density
in UOQ of left breast. Stable from prior exam.
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CASE 7
Patient History 64-year-old female.
Palpable abnormality in left breast.
6 month follow-up.Hormone replacement therapy.
Mammographic Findings: Scattered fibroglandular densities. Asymmetric increase density
in UOQ of left breast. Stable from prior exam.
LCC LMLORMLORCC
NOVEMBER
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CASE 7
Patient History 64-year-old female.
Palpable abnormality in left breast.
6 month follow-up.Hormone replacement therapy.
Mammographic Findings: Scattered fibroglandular densities. Asymmetric increase density
in UOQ of left breast. Stable from prior exam.
Ultrasound Results: Asymmetric density in outer quadrant of left breast with no
evidence of a mass.
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CASE 7
Patient History 64-year-old female.
Palpable abnormality in left breast.
6 month follow-up.Hormone replacement therapy.
Mammographic Findings: Scattered fibroglandular densities. Asymmetric increase density
in UOQ of left breast. Stable from prior exam.
Ultrasound Results: Asymmetric density in outer quadrant of left breast with no
evidence of a mass.
Miraluma
TM
Findings: Focal area of increased uptake in the left breast in the area of theincreased density. Focal area of uptake in the left axilla.
Histopathology Results: Infiltrating ductal carcinoma with lobular features.
LEFT LATERAL RIGHT LATERALANTERIOR
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CASE 8
Patient History: 46-year-old female.
Palpable fullness in right breast.
Patient had left breast cancer, lumpectomy, radiation andchemotherapy.
Mammographic Findings: Heterogeneously dense breasts. Inconclusive findings.
Ultrasound shows inconclusive findings.
LCC
MAGNIFIED VIEW
LMLO
MAGNIFIED VIEW
RMLO
MAGNIFIED VIEW
RCC
MAGNIFIED VIEW
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CASE 8
Patient History: 46-year-old female.
Palpable fullness in right breast.
Patient had left breast cancer, lumpectomy, radiation andchemotherapy.
Mammographic Findings: Heterogeneously dense breasts. Inconclusive findings.
Ultrasound shows inconclusive findings.
MiralumaTM Findings: Asymmetric bilateral areas of focal uptake.
LEFT LATERAL RIGHT LATERALANTERIOR
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CASE 8
Patient History: 46-year-old female.
Palpable fullness in right breast.
Patient had left breast cancer, lumpectomy, radiation andchemotherapy.
Mammographic Findings: Heterogeneously dense breasts. Inconclusive findings.
Ultrasound shows inconclusive findings.
MiralumaTM Findings: Asymmetric bilateral areas of focal uptake.
Ultrasound Results: Both breasts reevaluated and masses located.
Histopathology Results: Bilateral infiltrating and invasive ductal carcinoma.
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CASE 9
Patient History: 40-year-old female.
Mass in right breast UOQ for 3 months.
Mammographic Findings: Extremely dense breasts.
No suspicious masses or calcifications.
RCC LCC RMLO LMLO
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CASE 9
Patient History: 40-year-old female.
Mass in right breast/UOQ for 3 months.
Mammographic Findings: Extremely dense breasts.
No suspicious masses or calcifications.
Miraluma Findings: Focal uptake in the right breast in area of palpable mass.
Histopathology Results: Infiltrating ductal carcinoma.
RIGHT LATERAL
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LCC LMLORMLORCC
CASE 10
Patient History: 43-year-old female.
Area of suspicion in right breast upon physical exam.
Strong family history.
Mammographic Findings: Extremely dense breasts.
No suspicious masses or calcifications.
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RIGHT LATERALLEFT LATERALANTERIOR
CASE 10
Patient History: 43-year-old female.
Area of suspicion in right breast upon physical exam.
Strong family history.
Mammographic Findings: Extremely dense tissue.
No suspicious masses or calcifications.
Miraluma Findings: No areas of increased focal uptake.
Histopathology Results: None. Patient did not undergo biopsy and will be followed by her
physician.
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CASE 11
Patient History: 52-year-old female.
Mammographic Findings: Heterogeneously dense breasts.
S/P bilateral implants.
RMLO LMLO
C S
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CASE 11
Patient History: 52-year-old female.
Mammographic Findings: Heterogeneously dense breasts.
S/P bilateral implants.
Miraluma Findings: No areas of increased focal uptake.
Histopathology Results: None. Patient did not undergo biopsy and will
be followed clinically.
LEFT LATERALANTERIOR RIGHT LATERAL
C 12
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LEFT LATERAL RIGHT LATERAL
Patient History: Strong family history of breast cancer.
Previous lumpectomies for ductal carcinoma.
New suspicious mass identified in mammography.
Lumpectomy revealed ductal carcinoma with signs of lobular carcinoma.
Miraluma Findings: S/P lumpectomy revealed fibrocystic disease. Normal variant.
Surgical Follow-up: Bilateral mastectomy due to strong family history and two positive
lumpectomies.
Histopathology Results: Confirmed fibrocystic disease with no further evidence for cancer.
Case 12
C 13
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RIGHT LATERAL WITH MARKER
Patient History: Palpable mass above right nipple.
Extremely dense breasts. No suspicious masses.
Ultrasound revealed two suspicious masses.
Retrospective review of mammograms did not reveal findings.
Miraluma Findings: Multi-focal uptake (3 sites) as well as axillary node involvement.
Histopathology Results: Carcinoma with axillary metastases.
Case 13
RIGHT LATERAL
C 14
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Patient History: Patient on hormone replacement therapy.
The patient has a positive family history and has had bilateral benign breast
biopsies in the past.
Heterogeneously dense breasts. Questionable new left nodular density seen inLMLO only.
Probably normal, but equivocal (with spot compression views).
Ultrasound is probably negative.
Miraluma Findings: Mild, patchy bilateral uptake, consistent with hormone replacement therapy.
Histopathology Results: None. Patient did not undergo biopsy and will be followed by her physician.
Case 14