Integration of Imaging in the Management of Breast Cancer
http://www.100md.com
《临床肿瘤学》
Department of Surgery and Radiology, University of California, San Francisco, San Francisco, CA
Advances in imaging have the potential to significantly impact how woman with breast cancer are treated. This issue of the Journal of Clinical Oncology Special Series has three papers on imaging in which three modalities are discussed. First, Koomen et al1 discuss opportunities to improve the accuracy and effectiveness of mammography. Next, Dr Hylton2 presents the current and future roles that magnetic resonance imaging (MRI) can potentially play in the management of breast cancer. Finally, Drs Quon and Gambir3 discuss the increasing and evolving role of positron emission tomography (PET) in the diagnosis and management of breast cancer. They conclude by discussing new radiopharmaceuticals and the potential to target and/or monitor specific metabolic pathways.
Mammography is still a critical component of breast cancer screening and diagnosis. It is still the only screening imaging modality that has been shown to decrease mortality from breast cancer. However, the performance of mammography needs to be optimized. Digital mammography will increase the ability to store and reliably retrieve images and separate the acquisition of the images from the interpretation. Koomen et al1 present the current results of trials that compare standard mammography with digital mammography for screening. At present, it does not appear that digital mammography is more effective than film screen mammography, but it is too early to make a determination, so the results of large ongoing prospective trials are eagerly awaited. However, the routine acquisition of digitized images has enabled the development of other technologies that may improve accuracy, such as mammogram tomography and computer-aided detection. The authors also introduce the concept that breast cancer screening strategies can be better tailored to an individual woman's risk so that resources are concentrated on those who will have the most to benefit. It is critical to remember that there is a great deal of benefit for those who can safely avoid screening and the attendant false-positive biopsies. That shifts the focus of research to use emerging technology to develop breast cancer risk stratification. One such technology already accepted and used to stratify risk is genetic testing, or the sequencing of BRCA1 and BRCA2 to look for a cancer-causing mutation. We normally do not screen women under the age of 40 years for breast cancer. However, young women with a known mutation are told to get routine mammography starting at age 30, or 10 years prior to the earliest onset of cancer in an affected relative. Recent studies suggest that both MRI and mammography play an important role in screening.4,5 Other emerging technologies that may play a role in risk stratification include single nucleotide polymorphisms and proteomics. Time will tell if such information will be sufficient to direct screening using breast imaging.
MRI is rapidly becoming a part of breast imaging. While MRI is probably the most sensitive tool to evaluate a known cancer, assess extent of disease, and screen young women with BRCA mutations, the attendant lack of specificity can cause problems. Many clinicians are struggling with MRI images of uncertain significance and the lack of generally available targeted biopsy tools. Thus it is imperative that we thoughtfully deploy the technology to optimize the information it can provide. MRI of the breast allows us to evaluate the extent and pattern of tumor in the breast and thus it is being evaluated for measuring response to therapy in a very quantitative manner, before surgery.6-8 If successful, MRI could catalyze a change in the approach to evaluating the impact of current systemic therapies and targeted biologic agents. MRI may also provide a tool for the evaluation of high-risk women including those with ductal carcinoma-in-situ of the breast, and to help us find quicker and more efficient ways to test prevention strategies.6,9,10 The challenge, of course, is to develop methods to minimize false positives, to more easily evaluate and/or localize lesions that enhance, and to bring down the cost associated with all of these procedures.
PET is likely to have greatest contribution where it can be integrated with emerging molecular tools. Currently, PET does not add to the detection and diagnosis of breast cancer. In terms of staging the axilla, it has limited sensitivity. It can add to standard imaging in the detection of distant tumor spread. PET has the potential to improve radiation treatment planning and to monitor response to treatment, particularly for locally advanced breast cancer. However, as PET evolves, and as new radiotracers are being evaluated, it could have the capacity to interrogate specific molecular pathways and identify response. There are hundreds of new biologic agents in development and we can no longer afford the time or expense of evaluating these agents one at a time. Sophisticated molecular tools are being developed to measure changes in targeted pathways, but we will need a noninvasive method to measure these changes, particularly in the metastastic setting. PET could be a very important modality and should be developed in concert with targeted agents. It very well may become a tool to rapidly screen agents directed against a specific receptor or pathway. Each pathway may require its cognate imaging agent; this may be a barrier due to the time required to develop and test each agent. Alternately, functional targets may best be directed at common final pathways such Akt. Regardless of approach, the goal is to develop imaging tools that that can serve as an assay of the impact on the intended pathway. This may shorten the evaluation of promising agents by years, and make it less expensive to successfully evaluate agents and successfully move them to, phase III trials.11 Functional imaging with PET may be one of those tools.
Breast imaging currently plays a critical role in the management of breast cancer patients and is likely to become more important. Digital mammography, MRI, and PET all have tremendous potential but require continued careful evaluation in large prospective studies. Organizationally, we will need to make changes in our clinical infrastructure to support the integration of new technology, evaluate how we integrate and improve new technology, and to accommodate the anticipated changes in practice that inevitably arise when new technology replaces existing interventions.12
Author's Disclosures of Potential Conflicts of Interest
The author indicated no potential conflicts of interest.
REFERENCES
Koomen M, Pisano ED, Kuzmiak C, et al: Future directions in breast imaging. J Clin Oncol 23:1674-1677, 2005
Hylton N: Magnetic resonance imaging of the breast: Opportunities to improve breast cancer management. J Clin Oncol 23:1678-1684, 2005
Quon A, Gambhir SS: FDG-PET and beyond: Molecular breast cancer imaging. J Clin Oncol 23:1664-1673, 2005
Warner EPD, Plewes DS, Shumak RS, et al: Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol 19:3524-3531, 2001
Kriege M, Brekelmans CT, Boetes C, et al: Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351:427-437, 2004
Esserman L: Neoadjuvant chemotherapy for primary breast cancer: Lessons learned and opportunities to optimize therapy. Ann Surg Oncol 11:3S-8S, 2004
Esserman L, Kaplan E, Partridge S, et al: MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer. Ann Surg Oncol 8:549-559, 2001
Partridge SC, Gibbs J, Lu Y, et al: Accuracy of MR imaging for revealing residual breast cancer in patients who have undergone neoadjuvant chemotherapy. AJR Am J Roentgenol 179:1193-1199, 2002
Esserman L: A surgeon's strategy for optimizing breast cancer therapy. Ann Surg Oncol 10:2003
Hwang ES, Esserman L: Neoadjuvant hormonal therapy for ductal carcinoma in situ: Trial design and preliminary results. Ann Surg Oncol 11:37S-43S, 2004
Zia MI, Siu LL, Pond GR, et al: Comparison of outcomes of phase II trials (P2Ts) and subsequent randomized control trials (RCTs) using identical therapeutic regimens. Proc Am Soc Clin Oncol 23:S17, 2004 (abstr 6000)
Joy JE, Pehoet E, Petitti DB: Saving Women's Lives: Strategies for Improving Breast Cancer Detection and Diagnosis. Washington, DC, The National Academies Press, 2004(Laura Esserman)
Advances in imaging have the potential to significantly impact how woman with breast cancer are treated. This issue of the Journal of Clinical Oncology Special Series has three papers on imaging in which three modalities are discussed. First, Koomen et al1 discuss opportunities to improve the accuracy and effectiveness of mammography. Next, Dr Hylton2 presents the current and future roles that magnetic resonance imaging (MRI) can potentially play in the management of breast cancer. Finally, Drs Quon and Gambir3 discuss the increasing and evolving role of positron emission tomography (PET) in the diagnosis and management of breast cancer. They conclude by discussing new radiopharmaceuticals and the potential to target and/or monitor specific metabolic pathways.
Mammography is still a critical component of breast cancer screening and diagnosis. It is still the only screening imaging modality that has been shown to decrease mortality from breast cancer. However, the performance of mammography needs to be optimized. Digital mammography will increase the ability to store and reliably retrieve images and separate the acquisition of the images from the interpretation. Koomen et al1 present the current results of trials that compare standard mammography with digital mammography for screening. At present, it does not appear that digital mammography is more effective than film screen mammography, but it is too early to make a determination, so the results of large ongoing prospective trials are eagerly awaited. However, the routine acquisition of digitized images has enabled the development of other technologies that may improve accuracy, such as mammogram tomography and computer-aided detection. The authors also introduce the concept that breast cancer screening strategies can be better tailored to an individual woman's risk so that resources are concentrated on those who will have the most to benefit. It is critical to remember that there is a great deal of benefit for those who can safely avoid screening and the attendant false-positive biopsies. That shifts the focus of research to use emerging technology to develop breast cancer risk stratification. One such technology already accepted and used to stratify risk is genetic testing, or the sequencing of BRCA1 and BRCA2 to look for a cancer-causing mutation. We normally do not screen women under the age of 40 years for breast cancer. However, young women with a known mutation are told to get routine mammography starting at age 30, or 10 years prior to the earliest onset of cancer in an affected relative. Recent studies suggest that both MRI and mammography play an important role in screening.4,5 Other emerging technologies that may play a role in risk stratification include single nucleotide polymorphisms and proteomics. Time will tell if such information will be sufficient to direct screening using breast imaging.
MRI is rapidly becoming a part of breast imaging. While MRI is probably the most sensitive tool to evaluate a known cancer, assess extent of disease, and screen young women with BRCA mutations, the attendant lack of specificity can cause problems. Many clinicians are struggling with MRI images of uncertain significance and the lack of generally available targeted biopsy tools. Thus it is imperative that we thoughtfully deploy the technology to optimize the information it can provide. MRI of the breast allows us to evaluate the extent and pattern of tumor in the breast and thus it is being evaluated for measuring response to therapy in a very quantitative manner, before surgery.6-8 If successful, MRI could catalyze a change in the approach to evaluating the impact of current systemic therapies and targeted biologic agents. MRI may also provide a tool for the evaluation of high-risk women including those with ductal carcinoma-in-situ of the breast, and to help us find quicker and more efficient ways to test prevention strategies.6,9,10 The challenge, of course, is to develop methods to minimize false positives, to more easily evaluate and/or localize lesions that enhance, and to bring down the cost associated with all of these procedures.
PET is likely to have greatest contribution where it can be integrated with emerging molecular tools. Currently, PET does not add to the detection and diagnosis of breast cancer. In terms of staging the axilla, it has limited sensitivity. It can add to standard imaging in the detection of distant tumor spread. PET has the potential to improve radiation treatment planning and to monitor response to treatment, particularly for locally advanced breast cancer. However, as PET evolves, and as new radiotracers are being evaluated, it could have the capacity to interrogate specific molecular pathways and identify response. There are hundreds of new biologic agents in development and we can no longer afford the time or expense of evaluating these agents one at a time. Sophisticated molecular tools are being developed to measure changes in targeted pathways, but we will need a noninvasive method to measure these changes, particularly in the metastastic setting. PET could be a very important modality and should be developed in concert with targeted agents. It very well may become a tool to rapidly screen agents directed against a specific receptor or pathway. Each pathway may require its cognate imaging agent; this may be a barrier due to the time required to develop and test each agent. Alternately, functional targets may best be directed at common final pathways such Akt. Regardless of approach, the goal is to develop imaging tools that that can serve as an assay of the impact on the intended pathway. This may shorten the evaluation of promising agents by years, and make it less expensive to successfully evaluate agents and successfully move them to, phase III trials.11 Functional imaging with PET may be one of those tools.
Breast imaging currently plays a critical role in the management of breast cancer patients and is likely to become more important. Digital mammography, MRI, and PET all have tremendous potential but require continued careful evaluation in large prospective studies. Organizationally, we will need to make changes in our clinical infrastructure to support the integration of new technology, evaluate how we integrate and improve new technology, and to accommodate the anticipated changes in practice that inevitably arise when new technology replaces existing interventions.12
Author's Disclosures of Potential Conflicts of Interest
The author indicated no potential conflicts of interest.
REFERENCES
Koomen M, Pisano ED, Kuzmiak C, et al: Future directions in breast imaging. J Clin Oncol 23:1674-1677, 2005
Hylton N: Magnetic resonance imaging of the breast: Opportunities to improve breast cancer management. J Clin Oncol 23:1678-1684, 2005
Quon A, Gambhir SS: FDG-PET and beyond: Molecular breast cancer imaging. J Clin Oncol 23:1664-1673, 2005
Warner EPD, Plewes DS, Shumak RS, et al: Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol 19:3524-3531, 2001
Kriege M, Brekelmans CT, Boetes C, et al: Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351:427-437, 2004
Esserman L: Neoadjuvant chemotherapy for primary breast cancer: Lessons learned and opportunities to optimize therapy. Ann Surg Oncol 11:3S-8S, 2004
Esserman L, Kaplan E, Partridge S, et al: MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer. Ann Surg Oncol 8:549-559, 2001
Partridge SC, Gibbs J, Lu Y, et al: Accuracy of MR imaging for revealing residual breast cancer in patients who have undergone neoadjuvant chemotherapy. AJR Am J Roentgenol 179:1193-1199, 2002
Esserman L: A surgeon's strategy for optimizing breast cancer therapy. Ann Surg Oncol 10:2003
Hwang ES, Esserman L: Neoadjuvant hormonal therapy for ductal carcinoma in situ: Trial design and preliminary results. Ann Surg Oncol 11:37S-43S, 2004
Zia MI, Siu LL, Pond GR, et al: Comparison of outcomes of phase II trials (P2Ts) and subsequent randomized control trials (RCTs) using identical therapeutic regimens. Proc Am Soc Clin Oncol 23:S17, 2004 (abstr 6000)
Joy JE, Pehoet E, Petitti DB: Saving Women's Lives: Strategies for Improving Breast Cancer Detection and Diagnosis. Washington, DC, The National Academies Press, 2004(Laura Esserman)