Deteccin de cncer de mama

Ensayo Clnico 2000

Review of

Cancer
200,000 Breast*

STATISTICS

Leading Causes of Cancer in Women 1998

150,000

100,000

Lung
Colorectal

50,000

Endometrial

Ovarian Cervical

0
Annual Diagnosis of Cancer in Women
*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

Review of
Breast Cancer

Cancer

STATISTICS

46% of women believe that they will die of breast cancer Actual incidence of death due to breast cancer is 3-4%, annually 1 in 8 women will develop breast cancer

AHA Statistics; 1994

Review of

Cancer
100 84%

STATISTICS

Five-Year Relative Survival Rates by Stage at Diagnoses*

97%
76%

80
60 40

21%
20

0
All Stages Local Regional Distant

*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

Review of

Cancer

STATISTICS

Breast Cancer Stage Distribution 1995

National Cancer Institute: SEER Cancer Statistics Review 1973-1995

Review of

Cancer
Rate per 100,000
60 50 40 30

STATISTICS

Female Breast Cancer by Stage: Incidence Rates, 1983-1995

Stage I

Stage IIA
20

In situ
Stage IIB Unknown Stage III Stage IV
1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995

10 0 1983

Year of Diagnosis
National Cancer Institute: SEER Cancer Statistics Review 1983-1995

Review of

Cancer
50,000
40,000 30,000

STATISTICS

Breast Cancer Mortality

20,000

10,000 0

87

88

89

90

91

92

93

94

95

96 97* 98*
*Estimated figures

American Cancer Society, 1998

SCREENING

Procedures
Breast Self

for Breast Cancer

Breast Self Examination

Clinical Breast Examination Mammography Examination
Clinical Breast Examination Mammography

SCREENING

Procedures
Mammography

for Breast Cancer

Well-established technique Widespread clinical acceptance Breast Self Clinical Breast Facilitates early detection of breast cancer Examination Examination

Mammography

RCC (Right Cranial Caudal)

LCC (Left Cranial Caudal)

RMLO (Right Medial Lateral Oblique)

LMLO (Left Medial Lateral Oblique)

SCREENING

Procedures
BI-RADS
Goals
Establish Quality Assurance Tool Standardize Reporting Reduce Confusion Facilitate Outcome Monitoring

for Breast Cancer

Breast Imaging Reporting And Data System

BI-RADS, second edition; American College of Radiology, 1995

SCREENING

Procedures
BI-RADS

for Breast Cancer

Radiographic Density of the Breast:

1. The breast is almost entirely fat

2. There are scattered fibroglandular densities that could 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.
BI-RADS, second edition; American College of Radiology, 1995

SCREENING

Procedures
BI-RADS Categories

for Breast Cancer

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

Mammography:

Clinical

CHALLENGES

Difficult-to-Evaluate Breast Tissue: There are certain breast tissue types which can compromise clear mammographic interpretation.

Mammography:

Clinical
1. 2. 3. 4.

CHALLENGES

Factors Contributing to Difficult to Evaluate Breast Imaging

Breast lesions have similar mammographic attenuation characteristics to those of dense, glandular and fibrous tissue making the lesions less likely to be detected. The density of the breast scatters the radiation and results in less image contrast. The dense breast has inhomogeneities, which make it difficult to image the breast. Higher film exposure times are needed when imaging the dense breast to achieve adequate images. 25% of women have dense breasts which are difficult to image radiographically
Radiology 1993; 188:297-301

Mammography:

Clinical

CHALLENGES

Example of Scattered Fibroglandular

Mammography:

Clinical

CHALLENGES

Example of Heterogeneously Dense

Mammography:

Clinical

CHALLENGES

Example of Extremely Dense

Mammography:

Clinical
Surgically scarred

CHALLENGES

Post radiation therapy fibrosis Diffuse distribution of indistinct calcifications Augmented by implants

Miraluma is indicated for 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 a palpable breast mass.

Miraluma is not indicated for breast cancer screening, to confirm the presence or absence of malignancy, and it is not an alternative to biopsy.

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.

Mechanism

OF UPTAKE

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)
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

Clinical

Miraluma Breast Imaging Trial: Dense vs Fatty Breast Tissue Non-Palpable Abnormality
100%

Trial

RESULTS

for Miraluma Breast Imaging

80%

Fatty Dense

60%

40%

20% 0%
READER 1 READER 2 READER 3 READER 1 READER 2 NPV READER 3

PPV

Data on file Bristol-Myers Squibb Medical Imaging, Inc.

Clinical

Miraluma Breast Imaging Trial: Dense vs Fatty Breast Tissue Non-Palpable Abnormality
100%

Trial

RESULTS

for Miraluma Breast Imaging

80%

Fatty Dense

60%

40%

20% 0%
READER 1 READER 2 ACCURACY READER 3

Data on file Bristol-Myers Squibb Medical Imaging, Inc.

Clinical

Miraluma Breast Imaging Trial: Dense vs Fatty Breast Tissue Palpable Abnormality
100%

Trial

RESULTS

for Miraluma Breast Imaging

80%

Fatty Dense

60%

40%

20% 0%
READER 1 READER 2 READER 3 READER 1 READER 2 SPECIFICITY READER 3

SENSITIVITY

Data on file Bristol-Myers Squibb Medical Imaging, Inc.

Clinical

Miraluma Breast Imaging Trial: Dense vs Fatty Breast Tissue Palpable Abnormality
100%

Trial

RESULTS

for Miraluma Breast Imaging

80%

Fatty Dense

60%

40%

20% 0%
READER 1 READER 2 READER 3 READER 1 READER 2 NPV READER 3

PPV

Data on file Bristol-Myers Squibb Medical Imaging, Inc.

Clinical

Miraluma Breast Imaging Trial: Dense vs Fatty Breast Tissue Palpable Abnormality
100%

Trial

RESULTS

for Miraluma Breast Imaging

80%

Fatty Dense

60%

40%

20% 0%
READER 1 READER 2 ACCURACY READER 3

Data on file Bristol-Myers Squibb Medical Imaging, Inc.

Miraluma Breast Imaging

Protocol
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

Miraluma Breast Imaging

Protocol
Acquisition Protocol

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

CASE 1
Patient History: 47-year-old female. Palpable mass in right breast. Bilateral implants with heterogeneously dense overlying tissue. No suspicious masses detected in normal, magnification, and pushback views.

Mammographic Findings:

RCC

LCC

RMLO

LMLO

CASE 1
Patient History: 47-year-old female. Palpable mass in right breast. Bilateral implants with heterogeneously dense overlying tissue. No suspicious masses detected in normal, magnification, and pushback views.

Mammographic Findings:

RCC

LCC

RMLO

LMLO

Pushback views

Pushback views

CASE 1
Patient History: 47-year-old female. Palpable mass in right breast. Bilateral implants with heterogeneously dense overlying tissue. No suspicious masses detected in normal, magnification, and pushback views. Focal uptake in left breast. Invasive ductal carcinoma.

Mammographic Findings:

MiralumaTM Findings: Histopathology Results:

ANTERIOR

LEFT LATERAL

CASE 2
Patient History: 58-year-old female. Palpable mass above right nipple. Extremely dense breasts. No suspicious masses.

Mammographic Findings:

RCC

RMLO

CASE 2
Patient History: 58-year-old female. Palpable mass above right nipple. Extremely dense breasts. No suspicious masses. Revealed two suspicious masses. Retrospective review of mammograms did not reveal findings.

Mammographic Findings: Ultrasound Results:

CASE 2
Patient History: 58-year-old female. Palpable mass above right nipple. Extremely dense breasts. No suspicious masses. Revealed two suspicious masses. Retrospective review of mammograms did not reveal findings. Multi-focal uptake (3 sites) as well as axillary node involvement. Carcinoma with axillary metastases.

Mammographic Findings: Ultrasound Results:

MiralumaTM Findings: Histopathology Results:

RIGHT LATERAL WITH MARKER

RIGHT LATERAL

CASE 3
Patient History: 61-year-old female. Fullness in the inferior aspect of the right breast. Scattered fibroglandular densities with no significant abnormalities. Mammograms have remained stable over the last 3 years.

Mammographic Findings:

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. Scattered fibroglandular densities with no significant abnormalities. Mammograms have remained stable over the last 3 years. Focal uptake in the right breast in area of palpable abnormality. Invasive lobular carcinoma.

Mammographic Findings:

MiralumaTM Findings: Histopathology Results:

RIGHT LATERAL

CASE 4
Patient History: 65-year-old female. Routine screening mammogram. Scattered fibroglandular densities. Several enlarged lymph nodes in the left axilla. Additional views of the left breast are recommended.

Mammographic Findings:

RCC

LCC

RMLO

LMLO

CASE 4
Patient History: 65-year-old female. Routine screening mammogram. Scattered fibroglandular densities. Several enlarged lymph nodes in the left axilla. No specific mass was demonstrated on additional views of the left breast.

Mammographic Findings:

FOLLOW UP MAMMOGRAMS

LCC

LMLO

LMLO

CASE 4
Patient History: 65-year-old female. Routine screening mammogram. 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. Small focal uptake in the lateral view of the left breast.

Mammographic Findings:

Miraluma Findings:

ANTERIOR

LEFT LATERAL

RIGHT LATERAL

CASE 4
Patient History: 65-year-old female. Routine screening mammogram. 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. Small focal uptake in the lateral view of the left breast.

Mammographic Findings:

Miraluma Findings:

Ultrasound Results:

There is an 11mm echogenic area in the left breast which may correspond to the Miraluma image.
Ductal carcinoma in situ.

Histopathology Results:

CASE 5
Patient History: 40-year-old female. Palpable mass right breast. Heterogeneously dense breasts. Highly suspicious density at the palpable mass. Dense breast tissue makes evaluation of the breast difficult.

Mammographic Findings:

RCC

RCC (magnified)

LCC

LMLO

CASE 5
Patient History: 40-year-old female. Palpable mass right breast. Heterogeneously dense breasts. Highly suspicious density at the palpable mass. Dense breast tissue makes evaluation of the breast difficult. Three areas of focal uptake seen on the right breast. Invasive ductal carcinoma.

Mammographic Findings:

MiralumaTM Findings: Histopathology Results:

ANTERIOR

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. Scattered fibroglandular densities. Comparison made to right mammogram and ultrasound from 6 months ago. No significant interval change.

Mammographic Findings:

RCC

RMLO

CASE 6
Patient History: 29-year-old female. Right breast mass. Clinical exam revealed ill-defined thickening in the right breast. Scattered fibroglandular densities. Comparison made to right mammogram and ultrasound from 6 months ago. No significant interval change. Small simple cysts and possibly a prominent duct in the outer right breast.

Mammographic Findings:

Ultrasound Results:

CASE 6
Patient History: 29-year-old female. Right breast mass. Clinical exam revealed ill-defined thickening in the right breast. Scattered fibroglandular densities. Comparison made to right mammogram and ultrasound from 6 months ago. No significant interval change. Small simple cysts and possibly a prominent duct in the outer right breast. Focal area of increased activity in the deep portion of the right breast. Atypical ductal hyperplasia and ductal hyperplasia

Mammographic Findings:

Ultrasound Results:

MiralumaTM Findings:

Histopathology Results:

LEFT LATERAL

RIGHT LATERAL

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.

APRIL

RCC

LCC

RMLO

LMLO

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.

NOVEMBER

RCC

LCC

RMLO

LMLO

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.
Asymmetric density in outer quadrant of left breast with no evidence of a mass.

Ultrasound Results:

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.
Asymmetric density in outer quadrant of left breast with no evidence of a mass. Focal area of increased uptake in the left breast in the area of the increased density. Focal area of uptake in the left axilla. Infiltrating ductal carcinoma with lobular features.

Ultrasound Results: MiralumaTM Findings:

Histopathology Results:

ANTERIOR

LEFT LATERAL

RIGHT LATERAL

CASE 8
Patient History: 46-year-old female. Palpable fullness in right breast. Patient had left breast cancer, lumpectomy, radiation and chemotherapy.

Mammographic Findings:

Heterogeneously dense breasts. Inconclusive findings. Ultrasound shows inconclusive findings.

RCC MAGNIFIED VIEW

LCC MAGNIFIED VIEW

RMLO MAGNIFIED VIEW

LMLO MAGNIFIED VIEW

CASE 8
Patient History: 46-year-old female. Palpable fullness in right breast. Patient had left breast cancer, lumpectomy, radiation and chemotherapy.

Mammographic Findings:
MiralumaTM Findings:

Heterogeneously dense breasts. Inconclusive findings. Ultrasound shows inconclusive findings.

Asymmetric bilateral areas of focal uptake.

ANTERIOR

LEFT LATERAL

RIGHT LATERAL

CASE 8
Patient History: 46-year-old female. Palpable fullness in right breast. Patient had left breast cancer, lumpectomy, radiation and chemotherapy.

Mammographic Findings:
MiralumaTM Findings:

Heterogeneously dense breasts. Inconclusive findings. Ultrasound shows inconclusive findings.

Asymmetric bilateral areas of focal uptake.

Ultrasound Results:
Histopathology Results:

Both breasts reevaluated and masses located.

Bilateral infiltrating and invasive ductal carcinoma.

CASE 9
Patient History: 40-year-old female. Mass in right breast UOQ for 3 months. Extremely dense breasts. No suspicious masses or calcifications.

Mammographic Findings:

RCC

LCC

RMLO

LMLO

CASE 9
Patient History: 40-year-old female. Mass in right breast/UOQ for 3 months. Extremely dense breasts. No suspicious masses or calcifications. Focal uptake in the right breast in area of palpable mass. Infiltrating ductal carcinoma.

Mammographic Findings: Miraluma Findings: Histopathology Results:

RIGHT LATERAL

CASE 10
Patient History: 43-year-old female. Area of suspicion in right breast upon physical exam. Strong family history. Extremely dense breasts. No suspicious masses or calcifications.

Mammographic Findings:

RCC

LCC

RMLO

LMLO

CASE 10
Patient History: 43-year-old female. Area of suspicion in right breast upon physical exam. Strong family history. Extremely dense tissue. No suspicious masses or calcifications. No areas of increased focal uptake. None. Patient did not undergo biopsy and will be followed by her physician.

Mammographic Findings: Miraluma Findings: Histopathology Results:

ANTERIOR

LEFT LATERAL

RIGHT LATERAL

CASE 11
Patient History: 52-year-old female.

Mammographic Findings:

Heterogeneously dense breasts. S/P bilateral implants.

RMLO

LMLO

CASE 11
Patient History: 52-year-old female.

Mammographic Findings:
Miraluma Findings: Histopathology Results:

Heterogeneously dense breasts. S/P bilateral implants.

No areas of increased focal uptake. None. Patient did not undergo biopsy and will be followed clinically.

ANTERIOR

LEFT LATERAL

RIGHT LATERAL

Case 12
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. S/P lumpectomy revealed fibrocystic disease. Normal variant.

Miraluma Findings:

Surgical Follow-up:
Histopathology Results:

Bilateral mastectomy due to strong family history and two positive lumpectomies.
Confirmed fibrocystic disease with no further evidence for cancer.

LEFT LATERAL

RIGHT LATERAL

Case 13
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. Multi-focal uptake (3 sites) as well as axillary node involvement.

Miraluma Findings:

Histopathology Results:

Carcinoma with axillary metastases.

RIGHT LATERAL WITH MARKER

RIGHT LATERAL

Case 14
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 in LMLO only. Probably normal, but equivocal (with spot compression views). Ultrasound is probably negative. Mild, patchy bilateral uptake, consistent with hormone replacement therapy. None. Patient did not undergo biopsy and will be followed by her physician.

Miraluma Findings: Histopathology Results:

ANTERIOR

LEFT LATERAL

RIGHT LATERAL