NUCLEAR MEDICINE IN BREAST CANCER

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NUCLEAR MEDICINE IN BREAST CANCER
Workshop on Positron Emission Mammography Lisbon,
1 2 July 2002

• Ana Isabel Santos
• Serviço de Medicina Nuclear Hospital Garcia de
  Orta
• Almada - Portugal

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IMAGING IN BREAST CANCER Aims

• Initial diagnosis of breast cancer

• Initial staging of axillary lymph nodes

• Evaluation of treatment response

• Staging and re-staging

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IMAGING IN BREAST CANCER Aims

• Initial diagnosis of breast cancer

• Initial staging of axillary lymph nodes

Use of PET approved by Medicare in February 2002
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IMAGING IN BREAST CANCER Aims

• Initial diagnosis of breast cancer

• Initial staging of axillary lymph nodes

• Evaluation of treatment response

• Staging and re-staging

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INITIAL DIAGNOSIS OF BREAST CANCER
widely available method
5 years survival rate
Feig SA. Semin Nucl Med. 1999 XXIX (1) 3-15
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INITIAL DIAGNOSIS OF BREAST CANCER
? age
? screening
? mortality
Feig SA. Semin Nucl Med. 1999 XXIX (1) 3-15
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INITIAL DIAGNOSIS OF BREAST CANCER
Accurate enough for detection of early disease?
gt 1 cm
lt 1 cm
Cancer in situ
Detection Mode
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8
6
Clinical Examination
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53
59
Mammography
Mammography Clinical Examination
55
36
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Baker LH Breast Cancer Detection Demonstration
Project Five-Year summary report. Ca-A Cancer J
Clin. 1982 32 194-225
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INITIAL DIAGNOSIS OF BREAST CANCER
Accurate enough for detection of early disease?
Full-Field Digital Mammography (FFDM) versus
Film-Screen Mammography (FSM)
gt 7000 women / 40 years old ? 4 945 screening
exams
Recall Rate
(p lt 0.001)
11.5
13.9
Hendrick E. Multicentric Trial by the US Army
Breast Cancer Research and Material Command. 2000
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INITIAL DIAGNOSIS OF BREAST CANCER
Accurate enough for the detection of early
disease?

• available for population screening with
  favorable cost-benefit ratio

• effective in reducing mortality for breast cancer

• better performances of full-field digital
  mammography (favorable cost-benefit ratio with
  CAD)

But,

• Low Negative Predictive Rate (Sensitivity 79)

• Low Positive Predictive Rate (17 26 in women
  aged 40 49 years)

There is a need for new and effective
supplementary imaging techniques
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INITIAL DIAGNOSIS OF BREAST CANCER
Supplementary Imaging Methods
Morphological
Morphofunctional
Functional


MRI

MR Spectroscopy

Angiogenesis with MR

US

Doppler US

Elastography

Scintimammography

PET
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INITIAL DIAGNOSIS OF BREAST CANCER
Imaging Methods
Mammography versus MRI versus Scintimammography
versus PET
EXPERIENCE BASED MEDICINE
NOT
EVIDENCE BASED MEDICINE
TRENDS....
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SCINTIMAMMOGRAPHY
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SCINTIMAMMOGRAPHY
Image of the breast and of the axilla, obtained
after the intravenous administration of molecules
with biochemical affinity for tumour cells,
labelled with photon emission radionuclides
201Tl Cox et al, 1976 99mTc-sestamibi (MIBI)
Muller et al, 1987 99mTc-tetrafosmin Rambaldi
et al, 1996 111In-DTPA-octreotide,
131I-E-17-?-iodovinyl estradiol e
131I-16-?-estradiol 32P, 197Hg-cloromedrine,
67Ga, 99mTc-MDP, 99mTc-DTPA, ...
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SCINTIMAMMOGRAPHY
99mTc-Sestamibi (MIBI) Mechanism of Uptake in
Tumour Cells
From Buscombe et al. Scintimammography. A
Guide to Good Practice. 1998. Gibbs Associates
Limited
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SCINTIMAMMOGRAPHY
1994 1998 gt 2000 pts, with lesions detected by
mammography and/or clinical evaluation, with
histological comprovation of malignancy
Sensitivity 80 to 90 (average
85) Specificity 89
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(No Transcript)
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SCINTIMAMMOGRAPHY
Lumachi et al. Eur J Nucl Med. 2001 28 1776 -
1780
Accuracy of technetium-99m sestamibi
scintimammography and X-Ray mammography in
premenopausal women with suspected breast cancer

• 87 women, aged 32 52 (mean 47 years)
• breast lesions Ø 4 20 mm (mean 12 mm)

Mammography
Scintimammography
MRI
Sensitivity
80.6
80.6
gt90
Specificity
60
93.3
p lt 0.005
60 - 90
PPV
90.6
98.3
NPV
39.1
50
Accuracy
77
82.8
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SCINTIMAMMOGRAPHY

• 192 pts (190 W 2 M), aged 32 83 (mean 58
  years)

sensitivity for 175 histologicaly proven
carcinomas
MRI
SPET
Planar Im
gt90
Total
95.8
75.9
p lt 0.0005
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SCINTIMAMMOGRAPHY

• 192 pts (190 W 2 M), aged 32 83 (mean 58
  years)

specificity for 17 histologicaly proven benign
lesions
NS
For the detection of the primary lesion,
scintimammography seems to perform no worse
than MRI...
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SCINTIMAMMOGRAPHY

• 192 pts (190 W 2 M), aged 32 83 (mean 58
  years)

diagnosis of lymph node involvement in 173 ALND
MRI
SPET
Planar Im
?
Sensitivity
93
52.3
p lt 0.0005
Non palpable nodes
90.5
41.3
p lt 0.0005
Specificity
91
100
p lt 0.05
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SCINTIMAMMOGRAPHY
Multi-Drug Resistance Gene-I
Involved in the resistance to chemotherapeutic
drugs
? the Rate of Efflux from cancer cells may be
useful to predict the response of a tumour to
chemotherapy
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SCINTIMAMMOGRAPHY
TREND...

• Initial diagnosis of breast cancer

- Has potential to compete with other modalities,
including MRI...

• Initial staging of axillary lymph nodes

- Probably better than other modalities,
including MRI...

• Prediction of treatment response

- Probably better than other modalities,
including MRI...
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POSITRON EMISSION TOMOGRAPHY
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POSITRON EMISSION TOMOGRAPHY
Positron Emission Radionuclides
11C - Carbon
15O - Oxigen
13N - Nitrogen
18F - Fluor
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POSITRON EMISSION TOMOGRAPHY
Possibility to biologically characterize breast
cancer

• Energetic metabolism
• Transport of aminoacids and protein synthesis
• DNA synthesis
• Estrogen receptor expression
• Blood flow
• Antigen expression
• Receptor density
• Chemosensitivity
• Hypoxia in neoplastic tissue

Molecular Imaging...
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POSITRON EMISSION TOMOGRAPHY
Glucose
2-18F-fluoro-2-desoxi-D-glucose (FDG)
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POSITRON EMISSION TOMOGRAPHY
Glucose Metabolism in Cancer Cell
overexpression of some glucose transporters
GLUT-1 and GLUT-3
overexpression and modifications of glycolitic
enzymes
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FDG-PET IN THE DIAGNOSIS OF PRIMARY BREAST CANCER
(Whole-Body PET Scanners)
Bombardieri et al. Q J Nucl Med. 2001 45 (3)
245-256
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FDG-PET IN THE DIAGNOSIS OF PRIMARY BREAST CANCER
(Whole-Body PET Scanners)
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FDG-PET IN THE DIAGNOSIS OF AXILLARY LYMPH NODE
INVOLVEMENT
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FDG-PET IN THE DIAGNOSIS OF PRIMARY BREAST
CANCER AND REGIONAL LYMPH NODE INVOLVEMENT

• better expertise needs to be developped

• development of breast dedicated scanners
• (theoretical state-of-the-art PET scanners
  resolution 5mm)

POSITRON EMISSION MAMMOGRAPHY (PEM)

• Less expensive
• Potentially more sensitive
• Could lead the way to radionuclide-guided
  biopsies

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INITIAL DIAGNOSIS OF BREAST CANCER
Imaging Methods
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INITIAL DIAGNOSIS OF BREAST CANCER
Radioguided Excision of Occult Lesions Versus Wire
Localization
RF injected on the lesion
reduced excision volume and better lesion centring
Luini A. British J Surgery. 1999 86 522 - 525
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Nuclear Medicine in Breast Cancer
DIAGNOSIS OF AXILLA LYMPH NODE INVOLVEMENT

• The non invasive investigation of the axilla has
  a low NPV for the diagnosis of axillary
  involvement FN 21 a 38

• Scintimammography and PET, although more
  accurate than other non invasive methods, still
  do not detect micrometastasis

• Prophylatic lymphadenectomy seems to benefit
  mortality rates only in tumours with Ø gt 3cm

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RADIOGUIDED SENTINEL LYMPH NODE BIOPSY
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Nuclear Medicine in Breast Cancer
DIAGNOSIS OF AXILLA LYMPH NODE INVOLVEMENT
lymphatic trapping of molecules of small
diameter, labelled with radionuclides
Detection with ?-probe
Pre-operative imaging
Per-operative detection
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Nuclear Medicine in Breast Cancer
DIAGNOSIS OF AXILLA LYMPH NODE INVOLVEMENT
Breast Cancers with Ølt3 cm and no clinical and/or
mammographic evidence of axilla lymph node
involvement
Scintimammography versus PET/PEM
Positive
Negative
Lymphadenectomy
Radioguided Sentinel Lymph Node Biopsy
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NUCLEAR MEDICINE IN BREAST CANCER TRENDS...

• Initial diagnosis of breast cancer

- Scintimammograpy and PET/PEM has potential to
compete with other modalities, as complement to
mammography screening???

• Initial staging of axillary lymph nodes

- Scintimammograpy, PET/PEM, Sentinel Lymph Node
Biopsy has no competition from other modalities

• Evaluation of treatment response

- Molecular Imaging probably will have no
competition from other modalities

• Staging and re-staging

- PET has no competition from other modalities
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IMAGING IN BREAST CANCER NEEDS...
Initial Diagnosis of Breast Lesions
Surely there is a need for supplementary imaging
to mammography (even to diagnostic full-field
digital mammography)
US versus MRI versus NUCLEAR MEDICINE versus
MOLECULAR IMAGING

• NM and MI need dedicated devices with biopsy
  guided possibility

• All need evidence based on clinical trials