Diagnostic Oncologic Imaging - Essay Example

Despite rise in the incidence of breast cancer all over the world, early detection and advances in treatment strategies have lead to improved prognosis of the disease. Recent advances in diagnostic imaging have contributed significantly to the establishment of early diagnosis of the malignancy either when screened routinely or when presented with suspected clinical symptomatology. There has been an effort to ascertain the pathological, functional and anatomical features of breast cancer through non-invasive diagnostic technology. However, as of now, invasive sampling and histopathological study remains the best method of confirming diagnosis of breast cancer. Researchers are on the search for novel non-invasive technology to establish the diagnosis of breast cancer and stage it. SPECT and PET scintigraphy offer some hope in this regard, but more research is warranted to completely rely on these diagnostic modalities for diagnosis and staging of breast cancer. Introduction It is a well known fact that oncologic imaging and oncologic therapy are clinical and scientific companions. Most often than not, cancers are detected through some imaging modality either through routine screening of high risk groups or through evaluation of clinical symptomatology and signs (1). Many advances have occured in the technology of imaging diagnosis since the advent of X-ray imaging. Current imaging modalities like computed tomography, positron emission tomography, single photon emission computed tomography, magnetic resonance imaging and nuclear imaging have taken diagnostic imaging of oncologic conditions to a different level by providing a clear picture of the the tumor. The newer optical approach methods of Ultrasound imaging complements the other diagnostic imaging methods (1). In this article, the application of imaging in the diagnosis and managment of breast cancer will be discussed to gain a holistic view of the application of diagnostic imaging in breast oncology. Epidemiology Breast cancer is the leading cause of death due to cancers in women all over the world. The last 2 decades have seen a rise in the research pertaining to diagnosis and management of breast cancer resulting in early identification of the disease, early institution of treatment, more efficient treatments with less toxicity and improved prognosis (2). According to surveys in 2002, the breast cancer incidence rates varied internationally. While Mozambique demonstrated an incidence rate of 3.9 cases per 100,000, United States reported 101.1 cases per 100,000 (2). The American Cancer Society has estimated 1.4 million new cases of invasive breast cancer all over the world in 2008. Research has shown that the incidence of breast cancer is rising globally, but, at the same time mortality associated with breast cancer is decreasing due to advanced diagnosis and treatments. It accounts for 15 percent of deaths due to cancer in women. The current incidence in the united States is estimated to be 120 cases per 100,000 women (3). The current life time risk of acquiring breast cancer is different for different parts of the world. In the United States, the estimated risk is 12.7 percent for all women. The risk also varies between different ethnic groups. The risk for African-American has been estimated to be 9.98 percent and that for non-Hispanic Whites has been estimated to be 12.7 percent (2). The 5-year survival rate is 98 percent for Stage -1 cancer and that for stage-5 is about 16 percent (3). Etiology The major risk factors for the development of breast cancer are female gender, family history of breast cancer, advanced age, age of first child birth, previous history of breast cancer, hormone replacement therapy, genetic predisposition, history of atypical hyerplastic lesions in the breast and history of noninvasive lesions in the breast (4). The incidence of breast cancer is hundred times more in women than in men, As age advances, the risk of breast cancer also increases from 1:5900 to 1: 290 from the third decade through the eigth decade (4). If the birth of the first child occurs beyond 30 years of age, the risk is double than in women who deliver their first child at an age less than 20 years. 5- 10 percent of breast cancer is attributable to inherited factors (4). Pathophysiology Histologically, malignant tumors of the breast are mainly epithelial in nature. Other histological types include adenocarcinoma, angiosarcoma and primary lymphoma(4). The cancer lesions may be invasive or non-invasive. Invasiveness is the most important determinant of the prognosis of breast cancer. Non-invasive lesions are of two types: ductal carcinoma in situ or DCIS and lobular carcinoma in situ or LCIS. Of these, DCIS is more common (4). In DCIS, the ductal epithelial cells undergo malignanat transformation and proliferate inside their lumen. The invasiveness is limited by the basement memebrane. As the cancer cells grow, the cells outstrip their blood supply making the tumor become necrotic centrally (4). The necrotic tissue can calcify and when present, this can be detected through mammography (4). The pathologic subtypes of DCIS are papillary, micropappilary, comedo, cribriform and solid (4). Most of the times, lesions of DCIS are a combination of more than one pathologic subtype. Comedo DCIS is a risk factor for ipsilateral breast cancer. The development of LCIS is similar to DCIS and it emerges from the epithelial cells. The growth however follows a lobular pattern and thus does not develop central necrosis or calcification. Hence it is difficult to diagnose LCIS through mammography. Both DCIS and LCIS have invasive properties. However, the most common invasive breast cancers are epithelial ductal carcinoma. The course of treatment in any breast cancer is decided by many attributes of breast cancer like the size and surgical margin, presence of hormone receptors, nuclear and histologic grade, S-phase fraction, DNA content, tumor necrosis, vascular invasion and the amount of tumor which is intraductal (4). Breast Cancer Imaging 1. Mammography This is the most frequently used method of screening for breast cancer. The cranicaudal and oblique two-view mammography is the most prefered technique employed for this purpose (3). Other techniques which may be useful in evaluating indeterminate radiodensities are magnified images, additional angled views, compression images and alterations in exposure and alsterations in contrast. Generally, mammography is a sensitive investigation, but the sensitivity reduces in younger women and in those whose breasts are dense, or have implants or have scars due to previous surgery. The positive predictive value of this test is 10 percent and thus other imaging modalities like ultrasound or Magnetic Resonance Imaging (MRI) need to be used to distinguished between cystic and solid radiodensities (3). Also, mammography cannot define the edges of the lesions properly. Mammography is most useful when there is calcification. It can not only detect calcification but also determine whether the calcification is benign or malignant. Beningn calcification is scattered diffusely and there will be crescentic "tea-cupping." Malignant calcification is characterized by presence of isolated clusters of calcification, varying sizes punctate and branching of linear pattern. Recent advances in mammography like computer-aided detection mammography, contrast-enhanced mammography and digital mammography help in delineating the lesion to a better extent (3). Digital mammography is equipped with digital receptor system than film cassettes, thus allowing scope for alteration in the magnification, contrast, brightness and orientation of the mammogram. One advantage with this recent advance is that it can detect lesions even in younger women and in those with dense breasts. Other benefits include shorter exposure and examination time, faster image acquisition, decreased need for repeat mmmography, good contrast between dense and nondense breasts and allows easy storage of images for futher review and discussion (3). Contrast-enahnced mammography employs injection of iodinated contrast agents and identification of site of their concentration. This method is used mainly to evaluate aggressive cancers and allows construction of 3-D images (3). Computer aided detection mammography allows analysis of scanned and digitalised mammographic films. It highlights areas of suspicious cancer and thus is useful in evaluating dense breasts (3). 2. Ultrasonography Ultrasonography can be used in conjunction with mammography and is most useful in distinguishing between cystic and solid lesions (3). It is also useful in delineating the size of the lesion. It allows accurate biopsy of the suspicious area. The sensitivity of ultrasound in palpable lesion in 68- 70 percent and the specificity is 74- 94 percent (3). The positive predictive value is 92 percent (3). Ultrasonographic features of malignant breast lesion includes poorly defined borders of the lesion, disruption of tissue layers, heterogeneous internal echoes, perception of depth greater than height, superficial echo enhancement and higher vascular density and flow rates on doppler images (3). Current sophisticated ultrasonography allows higher resolution of masses. Conjunct use of doppler characterises the pattern of blood flow and thus helps in differentiating between malignant and benign lesions. It also aids in differentiating between normal, reactive and metastatic lymphnodes. 3. Magnetic resonance imaging or MRI The role of MRI in breast cancer is to detail various architectural abnormalities in the breast and to detect lesions as small as 2- 3mm (3). It ascertains the exact size of the malignant lesion and evaluates the presence of multifocal disease, thus throwing light on the surgical requirements of the cancer. The sensitivity of MRI is 86-100 percent, specificity is 21- 97 percent and the positive predictive value is 52 percent (3). MRI is versatile because of different sequences, rapid-imaging, fat suppression, high resolution, subtraction and dynamic sequences. Of these, the most useful sequence for breast cancer imaging is the dynamic imaging because it can distinguish between benign and malignant lesions and it can also delineate lesions of repeat breast cancer in those who have scarred tissue due to previous conservative therapy. When used with gadolinium-diethylenetriamine penta-acetic acid enhancement, the time-signal curves show a strong enahncement due to high vascularity of malignant lesions (3). High spatial resolution of MRI allows mapping of vascular function and thus provides a non-invasive overview of neoangiogenesis of breast cancer tissue (5).Thus MRI is useful to stage breast cancer thus providing useful clues for treatment, allows better detection of recurrence of cancer and facilitates improved screening of high-risk population. 4. Scintimammography This method of imaging employs radioisotope for imaging of breast tissue. The isotope used is Technetioum TC 99m Sestamibi (3). This isotope concentrates in the mitochondria and through mamaography it is possible to pick up signals of his isotope. The higher the metabolic rate of the malignancy, the higher the intensity of signal. The efflux of this isotope compound is related to the expression of multidrug resistance protein and thus signals from this isotope help in predicting resistance to chemotherapy. The technique is less sensitive than MRI for delineating lesions less than 1 cm and it use is most pronounced in palpable breast masses and detection of anxillary involvement. The sensitivity of scintigraphy is 76- 95 percent in palpable lesions and 52- 91 percent in impalpable lesions (3). The specificity is 62- 94 percent in palpable lesions and 94 percent in impalpable lesions (3). The positive predictive value is 70- 83 percent (3). Scintimammorgraphy has a major role in the assessment of tumor response to chemotherapy treatment of breast cancer. Another use of scintimammography is the ability to detect locally recurrent brast cancer. This is an important feature because, detection of recurrent breast cancer is challenging in view of architectural changes subsequent to radiotherapy and surgery and scintimammography has a sensitivity of 78 percent in detecting recurrent disease as against 42 percent for mammography (3). 5. Single-photon emission computed tomography or SPECT Images produced through SPECT are 3 -dimensional reconstructions of planar images acquired through rotation around the patient over a 180 degree or 360 degree arc (3). The radiopharmaceuticals used in SPECT for breast cancer imaging are 99m Tc-diphosphonates for detection of bone metastasis, 201- Thallium choride, 99m Tc-tetrofosmin and 99m Tc- methoxyisobutylisonitrile (6). 6. Positron emission tomography or PET PET is the best imaging modality for detection and evaluation of breast cancer. It is very sensitive and very specific. But the cost of technique and the decreased availability of the equipment limits its frequent use. PET allows study of various attributes of cancer physiology like oxygen consumption, vascularization, changes in metabolic activity and tumor receptor status. The most commonly employed labeled metabolite to study breast cancer tissue is fluorinated glucose ot 18- F Fluorodeoxyglucose or 18FDG (3). The sensitivty of PET imaging for breast cancer is 96 percent and the specificity is 100 percent. It is useful for axilla assessment, scarred breast and multifocal lesions (3). PET allows detections of annhilation photons that are produced by the disintegration of radioisotopes which emit positrons. Other than 18FDG, 3′-deoxy-3′-18F-fluorothymidine or 18F-FLT and 16α-18F-fluoro-17β-estradiol or 18F-FES are being used in PET (6). Newer systems offer integrated computed tomography in which simultaneous PET and CT imaging is done. This integration allows the radiologists to explore the sensitivity of PET with excellent anatomical localisation properties of computed tomography (6). 7. Imaging recurrent and metastatic breast cancer The most commonly used restaging imaging procedures for recurrent and metastatic breast cancer are computed tomography of chest and abdomen, MRI of brain, spine and in selected cases bone imaging and radionucleotide bone scintigraphy (6). Imaging studies play a major role in confirming recurrence and to assess the extent of local and systemic involment of the disease. Such an evaluation is necessary to ascertain the extent to which treatment can be provided. For examle, presence of visceral metastases is associated with poor prognosis and thus the choice of therapy is mainly palliative. 18FDG-PET is currently thought to be the best imaging modality to detect, evaluate and assess recurrent breast cancer. The sensitivity of PET in detecting metastases has been reported to be 98 percent (6). 8. Imaging for assessing response to treatment The most useful tool to assess response to chemotherapy is PET imaging. In those who respond to treatment, there will be a decrease in the uptake of the isotope compound 18FDG. PET is also useful to evaluate response of bone metastases to therapy (6). 9. Imaging estrogen receptor expression Few radioligands for scintigraphy and fluorinated ligands for PET imaging have been developed to ascertain the presence of hormone receptors to assess the type of therapy to be instituted. Some research has shown the usefulness of 123- I- iodovinyl-11β-methoxyestradiol or MIVE scintigraphy in assessing the presence of receptors in the breast tissue, nodes and metastases (6). 10. Role of radiolabeled nucleosides and aminoacids Upltake of 18- F Fluorothymidine correlates with the percentage of cells in the S-phase due to reflection of activity of thymidine kinase-1. Some researchers have proposed using this as a PET tracer for establishing the diagnosis of breast cancer. Research has shown that the tumor contrast with this agent is comparable with that of 18-F-FDG. Several radiolabeled aminoacids have been developed for detection of breast cancer though PET. However, there are not much reports of the benefits of these coumponds over other diagnostic methods. The radiolabeled aminoacids which have been studied to ascertain the diagnosis of breast cancer are 11-C- Tyrosine, L-18-F- alpha- methyltyrosine, 11-C-Methionine and 18-F- Fluoroalanine (6). These compounds are also useful to evaluate the response to treatment. The uptake of 11-C-methionine from metastaic tissue decreases when the disease is in a stable condition or is responsive to treatment and the uptake is increased in progressive disease (6). 11. Role of monoclonal antibodies scintigraphy Sigma receptors are a family of binding sites which are expressed in high amounts in breast cancer cell lines. Of interest are the sigma-1 and sigma-3 receptors considered as subtypes of opiate receptors. These receptors are present in breast cancer tissue and absent in normal breast tissue. Thus detection of these receptors using monoclonal antibodies helps in the detection of breast cancer and its metastases (6). Antibodies that are produced from a single type of immune cell are called monoclonal antibodies. They are all identical because they are clones of a single parent cell. Recombinant DNA technology by genetic engineering is the main method of antibody production for medical use. 12. Imaging of other molecular targets Other ligands whiich have been studied and found useful in the detection of breast cancer are radiolabelled metalloproteinase inhibitors through which measurement of invasion capacity is possible and labeled peptides which detect the receptors that are overexpressed on the cell surface of the breast issue (6). 13. Molecular imaging Molecular imaging may be defined as "the in vivo characterization and measurement of biological processes at the cellular and molecular level, is an attempt to image the molecular make-up of the macrofeatures currently visualized using classical diagnostic imaging modalities" (7). Molecular imaging of breast tissue is based on the discovery that cell-surface internalizing receptors like transferin receptor are overexpressed in malignancy states and thus may be useful in grading breast cancer and ascertaining the prognosis. Conjugation of ligands for transferrin receptor to an magnetic resonance contrast agent like superparamagnetic monocrystalline ironoxide nanoparticles can selectively increase the uptake of these contrast agents into cells which overexpress these receptors resulting in altered magnetic resonance signal basilon (7). This method of imaging is yet in a research stage. 14. Optical imaging Optical imaging allows assessment of functional and molecular characreristics of the breast cancer tissue. The main light absorbers in the breast will allow exploration of the characteristics of the tissue are oxyhemoglobing and deoxyhemoglobin. Through this technology it is possible to quantify vasculatization and oxygen saturation of breast tumors. As such, angiogenesis and hypoxia are important correlates of breast malignancy and evidence of these features through optical imaging confirms the diagnosis. Other propeties of optical imaging which make it useful despite low resolution are sensitivity for photon detection and use of nonionising radiation (8). Conclusion Scintigraphic mammography is useful to assess palpable breast masses and also for evaluating recurred breast cancer. SPECT and PET are useful adjunct imaging methods for the detection and staging or primary breast cancer, but due to their insufficient sensitivity to detect tumor deposits of less than one cm, they cannot replace invasive diagnostic technology. FDGPET imaging is useful to restage recurrent breast cancer and metastases and also provide an overview of response to new treatment regimen. Further research is warranted in the application of other tracers which are better and more specific that FDG but with little information about their side effects. References 1. Shields, A.F., and Price, P. (2007). Role of Imaging in Cancer Treatment. In:In Vivo Imaging of Cancer Therapy. Humana Press 2. Swart, R., Downey, L., Lang, J., et al (2009). Breast Cancer. Emedicine from WebMD. Retrieved on 6th November, 2009 from http://emedicine.medscape.com/article/283561-overview 3.. Singhal, H., Gohel, M.S., Kaur, K., Thomson, S. (2008). Breast Cancer Evaluation. Emedicine from WebMD. 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