PET/CT in Breast Cancer

Rodolfo Núñez Miller, M.D.

Nuclear Medicine and Diagnostic Imaging Section

Division of Human Health

International Atomic Energy Agency

Vienna, Austria

Overview

Introduction

Locorregional staging

Distant (Sistemic) staging

FDG PET in skeletal metastasis

Monitoring response to neoadjuvant therapy

Monitoring response to metastatic disease

Positron Emission Mammography (PEM) and BSGI

Metabolic Flare

Future directions: molecular imaging

Breast Cancer

Is the second leading cause of cancer mortality in

women.

Although the incidence continues to rise, mortality has

declined over the past several years.

This decline has been attributed to both, early diagnosis

and more effective treatment.

Advances in molecular cancer biology, are bringing a

better understanding of breast cancer pathogenesis and

progression, which translates into new and effective

treatments.

Personalized target therapy.

http://www.iarc.fr/

Locoregional Staging with FDG

PET/CT

There is currently no clinical role for routine FDG PET/CT

axillary staging in women with newly diagnosed breast

cancer.

Locoregional Staging with FDG

PET/CT in patients at high risk for

nodal disease FDG PET is highly specific for axillary nodal metastases.

There may be a certain role for preoperative FDG PET/CT in certain

patient populations, such as LABC, IBC, plexopathy and

symptomatic metastasis.

In these cases, if confirmed by PET, US guided tissue sampling of

abnormal findings can confirm the diagnosis.

FDG PET of the Internal Mammary

Nodes

Is seen in approximately 25% of patients with LABC.

Is predictive of both, likelihood and pattern of treatment failure,

consistent with IM nodal disease involvement and progression.

PET/CT in Inflammatory Breast

Cancer (IBC) Study by Carkaci et al., demonstrated that in newly diagnosed

unilateral IBC (n=41), FDG PET/CT was positive for ipsilateral

axillary nodal involvement in 90%, ipsilateral subpectoral nodes in

44%, and distant metastasis in 49% (17% unknown before PET/CT).

FDG PET/CT should be considered in the initial staging of IBC.

Carkaci et al. JNM 2009; 50: 231-238

Retrospective Analysis of 18F-FDG PET/CT for Staging

Asymptomatic Breast Cancer Patients Younger Than 40

Years. Riedl CC et al. JNM October 2014

PET/CT revealed distant metastases in 17% of asymptomatic stage IIB breast cancer

patients younger than 40 y.

Although guidelines of the National Comprehensive Cancer Network recommend

against systemic staging in patients with stage II disease, our data suggest that PET/CT

might be valuable in younger patients with stage IIB and III disease.

PET/CT revealed distant metastases in 17% of asymptomatic stage IIB breast cancer

patients younger than 40 y.

Although guidelines of the National Comprehensive Cancer Network recommend

against systemic staging in patients with stage II disease, our data suggest that PET/CT

might be valuable in younger patients with stage IIB and III disease.

Distant (Systemic) Staging with

FDG PET

Current NCCN practice guidelines, recommend FDG

PET as an option for patients with stage 4 disease. In

this setting it has been shown to be both, sensitive and

specific.

FDG PET can be particularly helpful in identifying occult

sites of disease; thus affecting therapeutic options.

FDG PET or PET/CT can reveal in this setting unknown

metastasis in locoregional and mediastinal nodal basins,

which are not obtimally evaluated by conventional

imaging.

39 year old woman with left breast cancer, treated with surgery (Febr,

2010) followed by chemo. There is known liver involvement. Referred

for re-staging after initial therapy.

Systemic Staging with FDG PET

FDG PET and PET/CT can improve staging and alter therapeutic options in patients suspected to have recurrent breast cancer and distant metastatic disease.

FDG PET can change or affect treatment in up to 44% of patients suspected to have locorregional recurrence.

43 year old woman with left breast cancer, treated initially with surgery,

followed by chemo and RT during 2008. PET/CT requested to re-stage

after initial therapies.

October 2009

43 year old woman with left breast cancer, treated initially with surgery,

followed by chemo and RT during 2008. PET/CT requested to re-stage

after initial therapies.

October 2009

She gets treated with additional chemo. PET/CT is requested 6 months

later to assess response to therapy.

April 2010

October 2009

She gets treated with additional chemo. PET/CT is requested 6 months

later to assess response to therapy.

October 2009

April 2010

Staging with FDG PET and

PET/CT: When does it help? Is not recommended for routine staging of breast cancer.

FDG PET can provide additional information in staging or re-staging

cases when results of conventional imaging are equivocal or

conflicting.

Evaluating asymptomatic patients with rising serum tumor markers

without clinical symptoms. FDG PET in this scenario is more

accurate than conventional imaging. In a recent study* FDG PET/CT

was 90% sensitive for diagnosing recurrent tumor, affecting clinical

management in 51% of patients.

* Randan L et al. Cancer 2006; 107(11):2545-2551

54 year old woman with breast cancer. Referred for re-staging

purposes.

FDG PET and PET/CT of Skeletal

Metastases

FDG PET is complementary to bone scintigraphy, which remains

the standard imaging modality for surveying the skeleton for

metastatic disease.

FDG PET better for osteolitic. BS better for osteoblastic.

In the “future” F18 Fluoride PET may offer improve bone metastasis

detection compared to FDG and BS.

FDG FDG Na18F Na18F

Monitoring Response to Therapy

with FDG PET and PET/CT

Neoadjuvant

Metastatic Disease

Monitoring response to

Neoadjuvant Therapy

Limitations of conventional anatomic imaging.

Neoadjuvant Therapy can improve surgical options and

provide prognostic information.

One of the main objectives is to assess response of the

primary tumor to the treatment regime.

Most studies measure the change in FDG uptake to mid-

therapy compared to baseline.

50% or more decline in FDG uptake.

Monitoring response to

Neoadjuvant Therapy FDG PET may serve as an earlier predictor of response.

Absence of FDG uptake is not a reliable indicator of pCR.

Dedicated Molecular Breast

Imaging Devices

PEM

BSGI

BSGI

The concept – Greater access, close to chest

wall, able to image breast only

with no background activity

and scatter from surrounding

organs.

– Greater maneuverability

– Less intimidating

Enabling Technology – CZT detectors, low dead

space.

– Registered colimation

– Optimized pixel size

Positron Emission Mammography

(PEM)

The latest design allows for 12 tomographic slices and PEM directed

biopsies.

Advantages in the detection with

PEM

• The advantages are:

- Greater spatial resolution.

- Improved geometric sensitivity.

- Shorter time of image acquisition.

- Less attenuation in comparison with PET

• Fairly small size, with possibility of doing biopsies directed by PEM.

62 y-o IDC 2.4cm mass, PEM ratio 3.4,

0.6 cm satellite

RMLO LMLO Images of PEM cortesy of Dr. Javier Villanueva-Meyer

57 y-o IDC unexpected 10 foci in L breast, index

lesion 2 cm, PEM ratio 3.7

RCC LCC

RMLO LMLO

43 y old IDC + DCIS index lesion 1,7 cm. PEM

ratio 7.7 . Multifocal + cysts

46 y-o IDC triple negative, R lumpectomy,

8 year FU in remission

RCC LCC

Limitations of PEM

• False Negatives – Posterior Lesions

– Tale of the breast

– Precision IDC > ILC > DCIS

• False Positives – Recent Biopsy

– Fat necrosis

– Fibroadenoma

– Other benign lesions

PEM as alternative to MR

Patients with doubtful / equivocal lesions,

which cannot be evaluated by MR

(claustrophobia, pacemakers, which

happens in approx. 15% of cases).

Assessment of response to Neoadjuvant

therapy.

Monitoring Response to Metastatic

Disease

FDG PET can be particularly useful in this setting to evaluate the

response to systemic therapy , since conventional imaging is often

challenging in these cases (e.g. skeleton).

Changes in FDG can be prognostic.

Combination of FDG and Na-18F can be helpful to assess the

skeleton. However, Na-18F can also have a “flare response”.

Metabolic flare

ER+ Tamoxifen

Transient increase in metabolic activity of breast cancer within 1 to 2 wks after starting tamoxifen

The increase is about +25% in responders while non responders have no change

Seen with FDG and FES

Dehdashty & Mortimer

Metabolic Flare

Dehdashti et al. Eur J Nucl Med 1999. 26:51-56.

Future Directions: Molecular

Imaging

Tumor Perfusion and Angiogenesis Imaging.

- 15Oxigen water, imbalance of metabolism and perfusion (high mb, and

poor perfusion) is associated with poor response and early relapse.

- Assess tumor neovasculature, PET probes (RGD peptides) bind to

integrins (α5β3) in neovessels

Tumor Receptor Imaging.

- 18Fluoro 17-β-estradiol (FES)

- 68Ga-labelled F(ab’)2 fragment of trastuzumab, measuring regional

HER2 expression in animal models.

Early Response Imaging.

- FLT. Lilkely to become important in the future.

- 124 I Annexin V for apoptosis.

CONCLUSIONS

FDG PET and PET/CT have been shown to be most helpful in

staging recurrent or metastatic breast cancer, and in evaluating the

response of LABC and metastatic disease to treatment.

Emerging data support the use of FDG PET/CT in advance axillary

disease and evaluation of regional nodal spread in LABC.

Currently FDG and occasionally Fluoride PET are used in clinical

practice.

It is likely that future studies will benefit from tracers other than FDG,

for example FES and FLT.

As breast cancer diagnosis and therapy become increasingly

molecular and individualized, PET/CT imaging will play a

progressively more important role in breast cancer patient care.

Thank You