Imaging Analysis

Skeletal metastases in breast carcinoma: classic patterns of treatment response

This case focuses on a 51-year-old woman with a history of right breast cancer initially palpated during a routine physical examination in 2010.

Surgical pathology revealed invasive ductal carcinoma with positive lymph nodes. She subsequently received systemic chemotherapy and radiation. She completed chemotherapy in 2013.

She presented in 2016 with low back pain. A CT scan showed an L4 lesion suspicious for osseous metastasis, which was confirmed by bone biopsy.

Munir Ghesani, MD, FACNM
Munir Ghesani

The patient currently is receiving treatment with palbociclib (Ibrance, Pfizer) and letrozole (Femara, Novartis).

Imaging findings

A CT scan of the abdomen and pelvis in December 2016 showed an irregular lytic lesion involving the L4 vertebral body with interruption of the cortex, suspicious for neoplastic disease.

Subsequent contrast-enhanced MRI of the lumbar spine confirmed a focal marrow-replacing lesion that involved the L4 vertebral body corresponding to the lytic lesion identified on CT examination, likely representing metastatic disease from the patient’s known breast carcinoma.

The patient underwent an [18F]-FDG PET/CT examination, which demonstrated bilateral breast prostheses, without metabolically active foci in the breasts to suggest local or marginal recurrence of primary malignancy. However, imaging detected multiple metabolically active osseous lesions, including a lytic T6 lesion that involved the vertebral body and right transverse process, a lytic right anterior 9th rib lesion, a lytic L4 vertebral body lesion, a sclerotic right sacral body lesion and a lytic left acetabular lesion.

Under CT guidance and sterile technique, a Laurane bone biopsy system was used to obtain several core samples from the L4 vertebral body lesion via a left transpedicular approach. Pathology results appeared consistent with metastatic breast carcinoma — specifically ER-positive, PR-positive, HER-2-negative disease.

Palliative treatment commenced.

A 6-month follow up [18F]-FDG PET/CT demonstrated overall positive treatment response, with decreased activity and increased sclerosis of multiple metabolically active skeletal metastases as follows:

  • Increased sclerosis of destructive, FDG-avid T6 lesion within the vertebral body and right transverse process, maximum standard uptake value (SUV)max 4.2 (previously, SUVmax 9);
  • T9 right transverse process lesion, SUVmax 3.8 (previously, SUVmax 6.6);
  • Increased sclerosis of the destructive, FDG-avid L4 vertebral body lesion, SUVmax 4.5 (previously, SUVmax 13.2); and
  • Decreased activity and increased sclerosis of additional lesions within the sacrum and acetabulum.

In contrast, some of the lesions had progressed in the interval, as determined by:

  • Increased FDG avidity of the destructive, FDG-avid right anterior 9th rib lesion, SUVmax 8.7 (previously, SUVmax 6.3); and
  • Slight enlargement and increased FDG avidity of the lytic L4 spinous process lesion, SUVmax 6 (previously, SUVmax 5.3).

Imaging showed no evidence of any new focus of skeletal metastatic disease.

Discussion

Skeletal metastases are the most common type of bone tumor among adults, and they are primarily caused by hematogenous spread of tumor to red marrow-rich axial skeleton: vertebrae (typically the posterior vertebral body and pedicle), ribs, pelvis and skull.

Depending on the primary tumor, most osseous metastases represent a combination of bone resorption and formation, and are classically divided into predominantly sclerotic, lytic, or mixed sclerotic and lytic lesions. Breast cancer frequently metastasizes to the skeleton, and osseous metastases are found in 70% of patients with stage IV disease. Therefore, it is important to be familiar with the common, validated diagnostic imaging studies utilized in the assessment of treatment response in patients with skeletal metastatic disease.

There is a role for multiple imaging modalities in the initial detection and subsequent follow-up of osseous lesions in patients with metastatic disease. Classically, CT and bone scintigraphy are considered more sensitive for cortical-based lesions, whereas FDG PET and MRI are highly sensitive for the assessment of marrow-based lesions. Therefore, a multimodality diagnostic approach often is used in a complementary fashion.

Figure 1. Follow-up restaging PET/CT demonstrates mixed treatment response in the L4 vertebra
Images from the most recent examination appear in the first row. Images from the prior examination appear in the second row. Each row has three images. They show (from left) the fusion of PET and CT, CT alone and PET alone. All images are in axial projections.
Figure 1. Follow-up restaging PET/CT demonstrates mixed treatment response in the L4 vertebra, as evidenced by increased sclerosis of the destructive, FDG-avid L4 vertebral body lesion (SUVmax 4.5; previously, SUVmax 13.2) but slight enlargement and increased FDG avidity of the lytic L4 spinous process lesion (SUVmax 6; previously, SUVmax 5.3).
 Figure 2. Follow-up restaging PET/CT demonstrates favorable treatment response in the right hemi-sacrum, with decreased FDG avidity and increased sclerosis in the metastatic focus.
Figure 2. Follow-up restaging PET/CT demonstrates favorable treatment response in the right hemi-sacrum, with decreased FDG avidity and increased sclerosis in the metastatic focus.
Figure 3. Follow-up restaging PET/CT demonstrates favorable treatment response in T6 as evidenced by increased sclerosis of the destructive
Figure 3. Follow-up restaging PET/CT demonstrates favorable treatment response in T6 as evidenced by increased sclerosis of the destructive, FDG-avid lesion involving the vertebral body and right transverse process (SUVmax 4.2; previously, SUVmax 9).

Images courtesy of M. Ghesani, MD, reprinted with permission.

Tc-99m methylene diphosphonate bone scintigraphy routinely is utilized as the initial screening modality of choice for the detection of both lytic and sclerotic osseous metastases. Osseous lesions typically demonstrate increased radiotracer uptake — ie, a hot spot — on a bone scan, though on occasion a purely lytic metastasis may be undetectable on bone scan or may appear as a photopenic defect — ie, a cold spot — of decreased or absent activity corresponding to the lesion.

In patients with widespread skeletal metastatic disease, a “superscan” pattern with diffusely increased osseous uptake and diminished renal and soft tissue activity may be seen. Although CT per se typically is not as useful in the initial detection of skeletal involvement, it is very helpful in clearly defining the extent of bony involvement and assessing the associated risk for pathologic fractures, which is primarily dependent on anatomic location and is considered proportional to the degree of cortical involvement and extent of disease.

[18F]-FDG PET typically can detect abnormal metabolic activity in metastatic lesions, even prior to morphologic changes on structural — or anatomic — imaging studies.

In patients with skeletal involvement, FDG PET is considered complementary to bone scintigraphy, as it is superior for the detection of lytic and intramedullary metastases, although less reliable in discerning sclerotic, osteoblastic lesions. FDG PET/CT is very effective for the successful assessment of treatment response in patients on palliative therapy, which is far more challenging when utilizing conventional imaging studies alone.

Although stage IV breast carcinoma remains an incurable disease, patients with osseous metastases often respond well to systemic therapy and have a preserved quality of life. Therefore, it is crucial to carefully monitor and routinely evaluate treatment success in these patients.

Multiple studies have shown a decrease in FDG uptake (SUV/SUVmax values) of 50% or greater to hold favorable prognostic implications, and that metabolic treatment response can be detected as early as after a single cycle of systemic chemotherapy.

Of note, bone scintigraphy findings may appear paradoxically progressed — a so called “flare-up” response — despite positive response to treatment, whereas early detection of osseous treatment response often is difficult with CT and MRI.

Newly validated bone-specific radiotracers such as [18F] sodium-fluoride have increased the accuracy of PET functional studies for the detection and monitoring of osteoblastic — or sclerotic — metastases. With the advent of molecular imaging, there also is increasing interest in the validation of additional radiopharmaceuticals — such as [18F] fluoroestradiol PET — to image ER expression. They have shown promising results for predicting response to ER-based endocrine therapy.

Similarly, radiolabeled HER-2 antibodies and antibody fragments, such as 89Zr-trastuzumab PET/CT, are under investigation in patients with HER-2-positive metastatic breast cancer who undergo targeted treatment.

Advanced hybrid imaging techniques, such as the use of combined FDG PET and whole-body diffusion-weighted MRI, may prove useful in multiparametric qualitative and quantitative assessment of treatment response in this patient population. Specifically, use of FDG PET/MRI augmented with diffusion-weighted imaging for both staging and response assessment allows us to take advantage of the synergies offered by combined metabolic, physiologic and structural imaging.

In this case, the patient underwent restaging [18F]-FDG PET/CT to assess for treatment response of biopsy-proven osseous metastatic disease. Her 6-month follow-up PET/CT showed increasing sclerosis and decreasing FDG activity in the majority of skeletal lesions, consistent with an overall favorable response to palliative therapy. A small percentage of lesions that progressed showed concordant findings on both PET and CT.

References:

Azad GK, Cook GJ. Clin Radiol. 2016;doi:10.1016/j.crad.2016.01.026.

Chen YC, et al. Breast Cancer Res. 2010;doi:10.1186/bcr2781.

Cook GJ, et al. J Nucl Med. 2016;doi: 10.2967/jnumed.115.157867.

Iagaru A, et al. Mol Imaging Biol. 2012;doi:10.1007/s11307-011-0486-2.

Kannivelu A, et al. Semin Musculoskelet Radiol. 2014;doi:10.1055/s-0034-1371017.

Macedo F, et al. Oncol Rev. 2017;doi: 10.4081/oncol.2017.321.

Plecha DM and Faulhaber P. Eur J Radiol. 2017;doi:10.1016/j.ejrad.2017.05.006.

Rosen EL, et al. Radiographics. 2007;doi:10.1148/rg.27si075517.

Ulaner GA, et al. J Nucl Med. 2016;doi:10.2967/jnumed.115.157909.

Woolf DK, et al. Ann Oncol. 2015;doi:10.1093/annonc/mdu558.

For more information:

Munir Ghesani, MD, FACNM, is assistant professor of radiology and director of PET/CT fellowship at NYU Langone Medical Center in New York. He also is a HemOnc Today Editorial Board Member. He can be reached at munir.ghesani@nyumc.org.

Ana M. Franceschi, MD, is a neuroradiology fellow at NYU Langone Medical Center.

Disclosures: Ghesani and Franceschi report no relevant financial disclosures.

This case focuses on a 51-year-old woman with a history of right breast cancer initially palpated during a routine physical examination in 2010.

Surgical pathology revealed invasive ductal carcinoma with positive lymph nodes. She subsequently received systemic chemotherapy and radiation. She completed chemotherapy in 2013.

She presented in 2016 with low back pain. A CT scan showed an L4 lesion suspicious for osseous metastasis, which was confirmed by bone biopsy.

Munir Ghesani, MD, FACNM
Munir Ghesani

The patient currently is receiving treatment with palbociclib (Ibrance, Pfizer) and letrozole (Femara, Novartis).

Imaging findings

A CT scan of the abdomen and pelvis in December 2016 showed an irregular lytic lesion involving the L4 vertebral body with interruption of the cortex, suspicious for neoplastic disease.

Subsequent contrast-enhanced MRI of the lumbar spine confirmed a focal marrow-replacing lesion that involved the L4 vertebral body corresponding to the lytic lesion identified on CT examination, likely representing metastatic disease from the patient’s known breast carcinoma.

The patient underwent an [18F]-FDG PET/CT examination, which demonstrated bilateral breast prostheses, without metabolically active foci in the breasts to suggest local or marginal recurrence of primary malignancy. However, imaging detected multiple metabolically active osseous lesions, including a lytic T6 lesion that involved the vertebral body and right transverse process, a lytic right anterior 9th rib lesion, a lytic L4 vertebral body lesion, a sclerotic right sacral body lesion and a lytic left acetabular lesion.

Under CT guidance and sterile technique, a Laurane bone biopsy system was used to obtain several core samples from the L4 vertebral body lesion via a left transpedicular approach. Pathology results appeared consistent with metastatic breast carcinoma — specifically ER-positive, PR-positive, HER-2-negative disease.

Palliative treatment commenced.

A 6-month follow up [18F]-FDG PET/CT demonstrated overall positive treatment response, with decreased activity and increased sclerosis of multiple metabolically active skeletal metastases as follows:

  • Increased sclerosis of destructive, FDG-avid T6 lesion within the vertebral body and right transverse process, maximum standard uptake value (SUV)max 4.2 (previously, SUVmax 9);
  • T9 right transverse process lesion, SUVmax 3.8 (previously, SUVmax 6.6);
  • Increased sclerosis of the destructive, FDG-avid L4 vertebral body lesion, SUVmax 4.5 (previously, SUVmax 13.2); and
  • Decreased activity and increased sclerosis of additional lesions within the sacrum and acetabulum.

In contrast, some of the lesions had progressed in the interval, as determined by:

  • Increased FDG avidity of the destructive, FDG-avid right anterior 9th rib lesion, SUVmax 8.7 (previously, SUVmax 6.3); and
  • Slight enlargement and increased FDG avidity of the lytic L4 spinous process lesion, SUVmax 6 (previously, SUVmax 5.3).
PAGE BREAK

Imaging showed no evidence of any new focus of skeletal metastatic disease.

Discussion

Skeletal metastases are the most common type of bone tumor among adults, and they are primarily caused by hematogenous spread of tumor to red marrow-rich axial skeleton: vertebrae (typically the posterior vertebral body and pedicle), ribs, pelvis and skull.

Depending on the primary tumor, most osseous metastases represent a combination of bone resorption and formation, and are classically divided into predominantly sclerotic, lytic, or mixed sclerotic and lytic lesions. Breast cancer frequently metastasizes to the skeleton, and osseous metastases are found in 70% of patients with stage IV disease. Therefore, it is important to be familiar with the common, validated diagnostic imaging studies utilized in the assessment of treatment response in patients with skeletal metastatic disease.

There is a role for multiple imaging modalities in the initial detection and subsequent follow-up of osseous lesions in patients with metastatic disease. Classically, CT and bone scintigraphy are considered more sensitive for cortical-based lesions, whereas FDG PET and MRI are highly sensitive for the assessment of marrow-based lesions. Therefore, a multimodality diagnostic approach often is used in a complementary fashion.

Figure 1. Follow-up restaging PET/CT demonstrates mixed treatment response in the L4 vertebra
Images from the most recent examination appear in the first row. Images from the prior examination appear in the second row. Each row has three images. They show (from left) the fusion of PET and CT, CT alone and PET alone. All images are in axial projections.
Figure 1. Follow-up restaging PET/CT demonstrates mixed treatment response in the L4 vertebra, as evidenced by increased sclerosis of the destructive, FDG-avid L4 vertebral body lesion (SUVmax 4.5; previously, SUVmax 13.2) but slight enlargement and increased FDG avidity of the lytic L4 spinous process lesion (SUVmax 6; previously, SUVmax 5.3).
 Figure 2. Follow-up restaging PET/CT demonstrates favorable treatment response in the right hemi-sacrum, with decreased FDG avidity and increased sclerosis in the metastatic focus.
Figure 2. Follow-up restaging PET/CT demonstrates favorable treatment response in the right hemi-sacrum, with decreased FDG avidity and increased sclerosis in the metastatic focus.
Figure 3. Follow-up restaging PET/CT demonstrates favorable treatment response in T6 as evidenced by increased sclerosis of the destructive
Figure 3. Follow-up restaging PET/CT demonstrates favorable treatment response in T6 as evidenced by increased sclerosis of the destructive, FDG-avid lesion involving the vertebral body and right transverse process (SUVmax 4.2; previously, SUVmax 9).

Images courtesy of M. Ghesani, MD, reprinted with permission.

Tc-99m methylene diphosphonate bone scintigraphy routinely is utilized as the initial screening modality of choice for the detection of both lytic and sclerotic osseous metastases. Osseous lesions typically demonstrate increased radiotracer uptake — ie, a hot spot — on a bone scan, though on occasion a purely lytic metastasis may be undetectable on bone scan or may appear as a photopenic defect — ie, a cold spot — of decreased or absent activity corresponding to the lesion.

PAGE BREAK

In patients with widespread skeletal metastatic disease, a “superscan” pattern with diffusely increased osseous uptake and diminished renal and soft tissue activity may be seen. Although CT per se typically is not as useful in the initial detection of skeletal involvement, it is very helpful in clearly defining the extent of bony involvement and assessing the associated risk for pathologic fractures, which is primarily dependent on anatomic location and is considered proportional to the degree of cortical involvement and extent of disease.

[18F]-FDG PET typically can detect abnormal metabolic activity in metastatic lesions, even prior to morphologic changes on structural — or anatomic — imaging studies.

In patients with skeletal involvement, FDG PET is considered complementary to bone scintigraphy, as it is superior for the detection of lytic and intramedullary metastases, although less reliable in discerning sclerotic, osteoblastic lesions. FDG PET/CT is very effective for the successful assessment of treatment response in patients on palliative therapy, which is far more challenging when utilizing conventional imaging studies alone.

Although stage IV breast carcinoma remains an incurable disease, patients with osseous metastases often respond well to systemic therapy and have a preserved quality of life. Therefore, it is crucial to carefully monitor and routinely evaluate treatment success in these patients.

Multiple studies have shown a decrease in FDG uptake (SUV/SUVmax values) of 50% or greater to hold favorable prognostic implications, and that metabolic treatment response can be detected as early as after a single cycle of systemic chemotherapy.

Of note, bone scintigraphy findings may appear paradoxically progressed — a so called “flare-up” response — despite positive response to treatment, whereas early detection of osseous treatment response often is difficult with CT and MRI.

Newly validated bone-specific radiotracers such as [18F] sodium-fluoride have increased the accuracy of PET functional studies for the detection and monitoring of osteoblastic — or sclerotic — metastases. With the advent of molecular imaging, there also is increasing interest in the validation of additional radiopharmaceuticals — such as [18F] fluoroestradiol PET — to image ER expression. They have shown promising results for predicting response to ER-based endocrine therapy.

Similarly, radiolabeled HER-2 antibodies and antibody fragments, such as 89Zr-trastuzumab PET/CT, are under investigation in patients with HER-2-positive metastatic breast cancer who undergo targeted treatment.

Advanced hybrid imaging techniques, such as the use of combined FDG PET and whole-body diffusion-weighted MRI, may prove useful in multiparametric qualitative and quantitative assessment of treatment response in this patient population. Specifically, use of FDG PET/MRI augmented with diffusion-weighted imaging for both staging and response assessment allows us to take advantage of the synergies offered by combined metabolic, physiologic and structural imaging.

PAGE BREAK

In this case, the patient underwent restaging [18F]-FDG PET/CT to assess for treatment response of biopsy-proven osseous metastatic disease. Her 6-month follow-up PET/CT showed increasing sclerosis and decreasing FDG activity in the majority of skeletal lesions, consistent with an overall favorable response to palliative therapy. A small percentage of lesions that progressed showed concordant findings on both PET and CT.

References:

Azad GK, Cook GJ. Clin Radiol. 2016;doi:10.1016/j.crad.2016.01.026.

Chen YC, et al. Breast Cancer Res. 2010;doi:10.1186/bcr2781.

Cook GJ, et al. J Nucl Med. 2016;doi: 10.2967/jnumed.115.157867.

Iagaru A, et al. Mol Imaging Biol. 2012;doi:10.1007/s11307-011-0486-2.

Kannivelu A, et al. Semin Musculoskelet Radiol. 2014;doi:10.1055/s-0034-1371017.

Macedo F, et al. Oncol Rev. 2017;doi: 10.4081/oncol.2017.321.

Plecha DM and Faulhaber P. Eur J Radiol. 2017;doi:10.1016/j.ejrad.2017.05.006.

Rosen EL, et al. Radiographics. 2007;doi:10.1148/rg.27si075517.

Ulaner GA, et al. J Nucl Med. 2016;doi:10.2967/jnumed.115.157909.

Woolf DK, et al. Ann Oncol. 2015;doi:10.1093/annonc/mdu558.

For more information:

Munir Ghesani, MD, FACNM, is assistant professor of radiology and director of PET/CT fellowship at NYU Langone Medical Center in New York. He also is a HemOnc Today Editorial Board Member. He can be reached at munir.ghesani@nyumc.org.

Ana M. Franceschi, MD, is a neuroradiology fellow at NYU Langone Medical Center.

Disclosures: Ghesani and Franceschi report no relevant financial disclosures.