Ca mama-Ensayo clínico

8/13/2019 Ca mama-Ensayo clnico

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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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CHALLENGES

Example of Scattered Fibroglandular


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CHALLENGES

Example of Heterogeneously Dense


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CHALLENGES

Example of Extremely Dense


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Surgically scarred

Post radiation therapy fibrosis

Diffuse distribution of indistinct calcifications

Augmented by implants


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


Dense vs Fatty Breast Tissue Non-Palpable Abnormality

0%

100%

80%

60%

40%

20%

Fatty

Dense

ACCURACY

READER 1 READER 2 READER 3




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TrialClinical


0%

100%

80%

60%

40%

20%

SENSITIVITY SPECIFICITY


Dense vs Fatty Breast Tissue Palpable Abnormality


Fatty

Dense



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0%

100%

80%

60%

40%

20%

PPV NPV


Fatty

Dense

TrialClinical





C


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0%

100%

80%

60%

40%

20%

Fatty

Dense

ACCURACY

READER 1 READER 2 READER 3

TrialClinical






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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





pushback views.


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LEFT LATERALANTERIOR

CASE 1





pushback views.

MiralumaTM Findings: Focal uptake in left breast.

Histopathology Results: Invasive ductal carcinoma.


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RMLORCC

CASE 2


Palpable mass above right nipple.

Mammographic Findings: Extremely dense breasts. No suspicious masses.


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CASE 2




Ultrasound Results: Revealed two suspicious masses.

Retrospective review of mammograms did not reveal findings.


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CASE 2




Ultrasound Results: Revealed two suspicious masses.


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


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


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


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




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





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





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


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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CASE 5


Palpable mass right breast.


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


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


Right breast mass.





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


Right breast mass.





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






LCC LMLORMLORCC

NOVEMBER


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CASE 7






Ultrasound Results: Asymmetric density in outer quadrant of left breast with no

evidence of a mass.


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CASE 7






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.



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CASE 8


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






MiralumaTM Findings: Asymmetric bilateral areas of focal uptake.



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CASE 8






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


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


Mass in right breast/UOQ for 3 months.



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


Area of suspicion in right breast upon physical exam.

Strong family history.




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RIGHT LATERALLEFT LATERALANTERIOR

CASE 10


Area of suspicion in right breast upon physical exam.

Strong family history.

Mammographic Findings: Extremely dense tissue.


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



S/P bilateral implants.

RMLO LMLO

C S


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CASE 11



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.


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

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