[18F]Fluoroestradiol-PET/CT Imaging of Invasive Lobular Carcinoma
[18F]Fluoroestradiol-PET/CT Imaging of Invasive Lobular Carcinoma
FES PET/CT imaging for invasive lobular cancer
According to the National Comprehensive Cancer Network (NCCN) 2018 guidelines FDG-PET/CT may
 be performed as an alternative to a contrast-enhanced CT of the chest, abdomen and pelvis and
 Tc-99m MDP bone scan for evaluation of distant metastatic disease in newly diagnosed stage
 III breast cancer patients. FDG-PET/CT is usually not obtained for stage I or stage II breast
 cancer patients. Prior studies have demonstrated FDG-PET/CT can identify sites of unsuspected
 metastatic disease in newly diagnosed breast cancer patients thereby altering treatment
 decisions given that palliative management is typical for stage IV disease, whereas
 neoadjuvant therapy followed by surgery and postoperative radiation may be considered for
 stage II and operable stage III disease. These guidelines consider invasive breast cancer as
 a single entity and do not consider whether tailoring imaging techniques for subtypes of
 breast cancer may be beneficial. However, prior research suggests that FDG-PET/CT may be more
 appropriate as an alternative to CT and bone scan for patients with invasive ductal carcinoma
 (IDC) rather than invasive lobular carcinoma (ILC) as FDG demonstrates comparatively reduced
 sensitivity for ILC metastases. Compared to IDC, ILC is more often occult on mammography,
 ultrasound, and FDG-PET/CT; which is of importance for clinical management as ILC is more
 often multifocal and bilateral compared to IDC. Clinical breast examination also has lower
 sensitivity for detection of ILC compared to IDC, even for large tumors, as ILC may be
 indistinguishable from normal breast tissue on palpation.

 A prior study evaluating systemic staging of newly diagnosed patients with stage I-III
 invasive breast cancer found that FDG-PET/CT is 1.98 times less likely to reveal unsuspected
 distant metastatic disease for women with ILC compared to IDC. In this study, all IDC
 metastases demonstrated FDG avidity whereas 25% of ILC metastases (3 of 12) were not FDG
 avid. Detection of local axillary metastatic disease on FDG-PET/CT was also lower for ILC (0
 of 146 patients) compared to IDC (7 of 89 patients) despite data from the Surveillance,
 Epidemiology and End Results (SEER) database demonstrating similar rates for lymph node
 metastases between IDC and ILC. Another study evaluating FDG-PET/CT for the diagnosis of
 primary breast cancer found that the false negative rate for detection of ILC by FDG was 65%
 (15 of 23 cases) compared to 23% for IDC (23 of 97 cases) when matching for tumors of the
 same size. A final study reported a false negative rate of FDG for ILC detection of 13% (2 of
 15 patients). Mechanistically, ILC may not take up FDG as avidly as IDC due to lower tumor
 microvascularity, cellular density, proliferation rate, and number of GLUT transporters. ILC
 osseous metastatic disease is also more frequently occult on FDG-PET/CT compared to IDC as
 ILC osseous metastases are more frequently sclerotic, whereas FDG-PET/CT is more sensitive
 for lytic osseous metastases. Sclerotic ILC osseous metastases also may be indistinguishable
 from benign bone islands on CT at initial staging, thereby necessitating biopsy or imaging
 follow-up for confirmation of osseous metastatic disease. Improved imaging strategies for
 primary and metastatic ILC are therefore warranted.

 Multiple studies have proven the efficacy of FES-PET/CT for imaging evaluation of ER+
 invasive breast malignancy (evaluating both IDC and ILC together, with the large majority of
 cases comprising IDC) but, to our knowledge, no prior study has focused FES-PET/CT evaluation
 only to cases of ILC, nor have prior studies compared FES-PET/CT directly with FDG-PET/CT for
 evaluation of newly diagnosed ILC. Given that all prior studies on FES-PET/CT have grouped a
 small number of ILC cases with a larger number of IDC cases, the imaging performance of
 FES-PET/CT specifically for ILC is unknown. ILC demonstrates higher rates of ER positivity
 than IDC with prior studies showing greater than 90% positivity for cases of ILC. Data from
 the SEER database also shows ILC demonstrates higher overall expression of ER than IDC (ILC
 95% positive for ER, n=17,503 vs IDC 74% positive for ER, n=172,379). FES-PET/CT may
 therefore be suitable for imaging evaluation of a high proportion of patients with ILC.
Inclusion Criteria:

 -  Adults aged 18 years or greater

 -  All patients or legal guardians are willing and able to sign a written informed
 consent and HIPAA authorization in accordance with local and institutional guidelines.

 -  Histologically confirmed invasive lobular carcinoma within the past 12 weeks confirmed
 from biopsy of primary tumor or metastasis.

 -  Patient is willing to have their clinical records reviewed for at least 24 months
 after enrollment.

 Exclusion Criteria:

 -  Patients with known allergic or hypersensitivity reactions to previously administered
 radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune
 diseases may be enrolled at the Investigator's discretion.

 -  Patients who require monitored anesthesia for PET/CT scanning.

 -  Patients who are too claustrophobic to undergo PET/CT scanning.

 -  Pregnancy or current breast feeding.

 -  Any patient that is medically unstable defined as patient requiring inpatient
 hospitalization or needing evaluation at an acute care or urgent care facility at time
 of imaging.

 -  Patients undergoing treatment with estrogen receptor agonists (such as fulvestrant and
 tamoxifen) within 5 weeks of the FES-PET/CT scan. (Note that aromatase inhibitors and
 luteinizing hormone-releasing hormone agonists do not affect ER expression, or binding
 of FES to ER, and do not need to be discontinued or considered for inclusion or
 exclusion of patients).

 -  Patient who have had the site(s) of biopsy proven invasive lobular carcinoma
 surgically resected.