Imaging Analysis

Does FDG PET/CT negativity after neoadjuvant therapy in breast cancer imply absence of residual malignancy?

A 37-year-old woman was diagnosed with bilateral synchronous invasive lobular breast cancer, ER/PR-positive and HER-2/neu negative. Her initial mammogram showed a 2.5-cm mass in the left breast and 1.5-cm axillary lymph node. On PET/CT there was 2.3-cm left subareolar enhancing mass with an standardized uptake value of 7.7, 1.5-cm left axillary lymph node with an standardized uptake value of 5.3 with no evidence of distant metastasis. MRI breast showed 3.5 × 3.5 cm, 1 × 0.8 cm and 1.3 cm masses in the upper outer quadrant of left breast and 3.5 × 2 cm mass in the upper inner quadrant of right breast. The patient received neoadjuvant chemotherapy with four cycles of dose-dense doxorubicin and cyclophosphamide followed by four cycles of dose-dense paclitaxel with good clinical response.

On repeat MRI of the breast there was interval decrease in size to 1.5 × 0.8 cm, with resolution of two other masses in upper outer quadrant of left breast and minimal enhancement in the right breast. PET/CT showed no discrete mass or uptake in the breast with no evidence of distant metastasis. The patient underwent bilateral mastectomy and axillary lymph node dissection. The right mastectomy specimen showed no residual disease and right axillary lymph nodes were negative. However, in the left mastectomy specimen there was a 2.5-cm poorly differentiated residual invasive carcinoma with ductal and lobular features and two of the left axillary lymph nodes were positive for involvement with malignancy.

Munir Ghesani, MD, is an Associate Clinical Professor of Radiology at Columbia University College of Physicians and Surgeons and Attending Radiologist at St. Luke’s-Roosevelt Hospital Center.

Vamsee Torri, MD, is a fellow in Hematology/Oncology at St. Luke’s-Roosevelt Hospital Center.

Figure 1: Axial CT, PET, coregistered PET and CT images at the level of breast
Figure 1: Axial CT, PET, coregistered PET and CT images at the level of breast parenchyma as well as maximal intensity projection images demonstrate symmetric low-grade metabolic activity in breast parenchyma bilaterally, which may be merely physiologic in this premenopausal patient. There is no obvious asymmetric soft tissue mass or abnormal focal hypermetabolic activity.

Figure 2: Axial CT, PET, coregistered PET and CT images at the level of axilla
Figure 2: Axial CT, PET, coregistered PET and CT images at the level of axilla do not demonstrate any asymmetric axillary lymphadenopathy or focal abnormal hypermetabolic activity. There are bilateral axillary lymph nodes which do not meet radiographic criteria for significance. In addition, these lymph nodes demonstrate preserved fatty hilum; low-grade metabolic activity associated with these lymph nodes is often benign, such as in the setting of reactive hyperplasia.

Figure 3: Axial, coronary and sagittal PET images as well as MIP PET images
Figure 3: Axial, coronary and sagittal PET images as well as MIP PET images demonstrate prominent metabolic activity in the bone marrow, which, given the clinical context, is most consistent with chemotherapy effect.

Source: M Ghesani

DISCUSSION

PET/CT is shown to detect metastatic lesions and identify equivocal lesions on conventional imaging. In breast cancer, FDG PET has been used for defining the extent of recurrent or metastatic disease. FDG PET modality of imaging has 88% sensitivity and 80% specificity for primary breast lesion, 61% sensitivity and 80% specificity for axillary metastases, and 93% sensitivity and 79% specificity for metastatic disease. Serial FDG PET has been widely studied during the neoadjuvant treatment of locally advanced breast cancer with a significant standardized uptake value uptake difference; standardized uptake value did not vary much in nonresponders (based on pathology findings) but was markedly decreased to background levels in 94% of responders. The sensitivity to detect malignant lesions decreases with low grade tumors and lesions <1 cm. PET/CT and breast MRI should complement each other for treatment planning in this subgroup.

The above case and discussion illustrate the possibility of false negativity of PET/CT after neoadjuvant therapy, as microscopic and sometimes gross residual disease may still be present. These false negative findings are more likely to occur in lobular carcinoma, given relatively lower accuracy of FDG PET imaging in this subtype of breast carcinoma when compared to ductal carcinoma. It is likely that improvement in PET/CT technology, introduction of specific biomarkers for imaging (including specific markers for cellular proliferation) and advances in MRI techniques may further improve accuracy of imaging modalities for detection of residual breast carcinoma after neoadjuvant therapy.

For more information:

  • Rosen EL, Eubank WB, Mankoff DA. FDG PET, PET/CT, and breast cancer imaging. Radiographics. 2007;27 Suppl1:S215-S229.
  • Rousseau C, Devillers A, Sagan C, et al. Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F] fluorodeoxyglucose positron emission tomography. J Clin Oncol. 2006;24:5366-5372.
  • Kumar R, Chauhan A, Zhuang H, et al. Clinicopathologic factors associated with false negative FDG-PET in primary breast cancer. Breast Cancer Res Treat. 2006;98:267-274.
  • Iagaru A, Masamed R, Silberman H, et al The role of F-18 FDG PET/CT and breast MRI in the management of breast cancer. J Clin Oncol. 2006;24:10778.

A 37-year-old woman was diagnosed with bilateral synchronous invasive lobular breast cancer, ER/PR-positive and HER-2/neu negative. Her initial mammogram showed a 2.5-cm mass in the left breast and 1.5-cm axillary lymph node. On PET/CT there was 2.3-cm left subareolar enhancing mass with an standardized uptake value of 7.7, 1.5-cm left axillary lymph node with an standardized uptake value of 5.3 with no evidence of distant metastasis. MRI breast showed 3.5 × 3.5 cm, 1 × 0.8 cm and 1.3 cm masses in the upper outer quadrant of left breast and 3.5 × 2 cm mass in the upper inner quadrant of right breast. The patient received neoadjuvant chemotherapy with four cycles of dose-dense doxorubicin and cyclophosphamide followed by four cycles of dose-dense paclitaxel with good clinical response.

On repeat MRI of the breast there was interval decrease in size to 1.5 × 0.8 cm, with resolution of two other masses in upper outer quadrant of left breast and minimal enhancement in the right breast. PET/CT showed no discrete mass or uptake in the breast with no evidence of distant metastasis. The patient underwent bilateral mastectomy and axillary lymph node dissection. The right mastectomy specimen showed no residual disease and right axillary lymph nodes were negative. However, in the left mastectomy specimen there was a 2.5-cm poorly differentiated residual invasive carcinoma with ductal and lobular features and two of the left axillary lymph nodes were positive for involvement with malignancy.

Munir Ghesani, MD, is an Associate Clinical Professor of Radiology at Columbia University College of Physicians and Surgeons and Attending Radiologist at St. Luke’s-Roosevelt Hospital Center.

Vamsee Torri, MD, is a fellow in Hematology/Oncology at St. Luke’s-Roosevelt Hospital Center.

Figure 1: Axial CT, PET, coregistered PET and CT images at the level of breast
Figure 1: Axial CT, PET, coregistered PET and CT images at the level of breast parenchyma as well as maximal intensity projection images demonstrate symmetric low-grade metabolic activity in breast parenchyma bilaterally, which may be merely physiologic in this premenopausal patient. There is no obvious asymmetric soft tissue mass or abnormal focal hypermetabolic activity.

Figure 2: Axial CT, PET, coregistered PET and CT images at the level of axilla
Figure 2: Axial CT, PET, coregistered PET and CT images at the level of axilla do not demonstrate any asymmetric axillary lymphadenopathy or focal abnormal hypermetabolic activity. There are bilateral axillary lymph nodes which do not meet radiographic criteria for significance. In addition, these lymph nodes demonstrate preserved fatty hilum; low-grade metabolic activity associated with these lymph nodes is often benign, such as in the setting of reactive hyperplasia.

Figure 3: Axial, coronary and sagittal PET images as well as MIP PET images
Figure 3: Axial, coronary and sagittal PET images as well as MIP PET images demonstrate prominent metabolic activity in the bone marrow, which, given the clinical context, is most consistent with chemotherapy effect.

Source: M Ghesani

DISCUSSION

PET/CT is shown to detect metastatic lesions and identify equivocal lesions on conventional imaging. In breast cancer, FDG PET has been used for defining the extent of recurrent or metastatic disease. FDG PET modality of imaging has 88% sensitivity and 80% specificity for primary breast lesion, 61% sensitivity and 80% specificity for axillary metastases, and 93% sensitivity and 79% specificity for metastatic disease. Serial FDG PET has been widely studied during the neoadjuvant treatment of locally advanced breast cancer with a significant standardized uptake value uptake difference; standardized uptake value did not vary much in nonresponders (based on pathology findings) but was markedly decreased to background levels in 94% of responders. The sensitivity to detect malignant lesions decreases with low grade tumors and lesions <1 cm. PET/CT and breast MRI should complement each other for treatment planning in this subgroup.

The above case and discussion illustrate the possibility of false negativity of PET/CT after neoadjuvant therapy, as microscopic and sometimes gross residual disease may still be present. These false negative findings are more likely to occur in lobular carcinoma, given relatively lower accuracy of FDG PET imaging in this subtype of breast carcinoma when compared to ductal carcinoma. It is likely that improvement in PET/CT technology, introduction of specific biomarkers for imaging (including specific markers for cellular proliferation) and advances in MRI techniques may further improve accuracy of imaging modalities for detection of residual breast carcinoma after neoadjuvant therapy.

For more information:

  • Rosen EL, Eubank WB, Mankoff DA. FDG PET, PET/CT, and breast cancer imaging. Radiographics. 2007;27 Suppl1:S215-S229.
  • Rousseau C, Devillers A, Sagan C, et al. Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F] fluorodeoxyglucose positron emission tomography. J Clin Oncol. 2006;24:5366-5372.
  • Kumar R, Chauhan A, Zhuang H, et al. Clinicopathologic factors associated with false negative FDG-PET in primary breast cancer. Breast Cancer Res Treat. 2006;98:267-274.
  • Iagaru A, Masamed R, Silberman H, et al The role of F-18 FDG PET/CT and breast MRI in the management of breast cancer. J Clin Oncol. 2006;24:10778.