Diagnostic Radiography - Essay Example

1 – Introduction This assignment outlines the proposed diagnosis and management of a hypothetical case: a forty-eight year old female who presents with a breast lump and pain in her lower back. Particular emphasis will be laid on the various forms of diagnostic radiography that may be applicable in providing an initial diagnosis (or diagnoses, if the two symptoms have unrelated causes) and in following the patient’s progress. 1.1 – Relevant diseases The most obvious disease suspected in this case is breast cancer, the first overt symptom of which is typically a breast lump. Since breast cancer frequently metastasises to the bones, and since some invasive breast cancers can shed cells even before the initial tumour has reached a sufficient size to be detected on breast self-examination (BSE), there is a possibility that the lower-back pain in this case may be the result of Stage IV invasive breast cancer; however, it is equally possible that the breast lump is a non-cancerous cyst, a non-invasive carcinoma in situ, or an invasive tumour that has not yet spread beyond its immediate environment. In any of the latter cases, the lower-back pain must be diagnosed and treated as a completely separate problem from the breast lump. 1.2 – The breast and breast cancer The breast contains glands called lobules that secrete milk, and a network of ducts to carry the milk from the lobules to the nipples. In the course of a woman’s menstrual cycles, each month the lobular and ductal tissues of the breast undergo a period of growth (in preparation for eventually feeding a baby should pregnancy occur), followed by apoptosis and shrinkage if pregnancy does not occur. These repeated rapid growth cycles create an opportunity for errors to accumulate in the DNA of ductal and lobular cells; and so lead to the likelihood of eventual malignancy in these tissues. Thus, the vast majority of cancers in the breast originate in the lobules and the milk ducts. Around 80% of malignant breast cancers are ductal carcinomas, and most of the remainder are lobular carcinomas. (Cancer Research UK, September 2006) The ducts and lobules are supported and surrounded by fatty tissue and ligaments, and are supplied by blood vessels and lymph ducts. These lymph ducts drain the breast primarily to the nearest lymph nodes in the armpits (the axillary lymph nodes); and these axillary lymph nodes are generally the first place outside the affected breast itself where metastatic cells from a breast tumour can be detected. The presence or absence of secondary axillary carcinoma is thus a major factor in staging breast cancer. Neoplasms in the breast, whether ductal or lobular, can be either invasive or non-invasive (types that remain in situ). Of the non-invasive breast neoplasms, lobular carcinoma in situ (LCIS) does not normally present as a breast lump, and – while it represents a risk factor for future neoplasms in either breast – is nowadays generally treated conservatively by increased vigilance rather than by surgery or other aggressive treatment. Ductal carcinoma in situ (DCIS) does typically form one or more lumps in the breast, and, as it is highly likely eventually to develop invasive characteristics, is normally treated by some form of surgical excision, sometimes followed by mild adjunctive therapy such as radiation if clean surgical margins have not been achieved. Invasive breast tumours are treated by surgery, often followed by more aggressive adjunctive therapy. 1.3 – Risk factors for breast cancer A number of risk factors for breast cancer have been identified, including the following: (American Cancer Society, September 2006, plus specific additional references as noted.) High-risk hereditary mutations BRCA1 and BRCA2 may cause a lifetime risk of contracting breast cancer as high as 84% (Frank, 1998). Inherited mutations in other genes are less dangerous, but have been shown to cause a substantial increase in breast-cancer risk: ATM (Walsh and King, 2007), CHEK2 (CHEK2 Consortium, 2004), and the tumour-suppressor p53 gene. (Walsh and King, 2007) Family history of breast cancer, particularly if the relative’s breast cancer occurred before the age of 50. Previous personal history of breast cancer. Even if the first cancer was completely eliminated, there is a three- to fourfold increased risk of contracting a second cancer of the same sort, in either breast. Benign abnormal proliferative growth of breast tissue, particularly if atypical cells are present. Previous chest radiation (for example, as a treatment for lymphoma); the risk is especially high if the patient was still an adolescent at the time of radiation exposure. Early menarche (before age 12) or late menopause (after age 55) are associated with a somewhat elevated risk of breast cancer – possibly because such women have undergone more cycles of rapid growth of breast tissue, and thus have had more opportunities to accumulate harmful mutations in these tissues. Not having children by the age of 30 also slightly raises breast-cancer risk – perhaps for the same reason. Breast-feeding one’s children, particularly over a period greater than a year, appears to reduce breast-cancer risk. Hormone replacement therapy (HRT) and, possibly, use of birth-control pills. The increased breast-cancer risk of HRT is especially severe in the case of combined oestrogen-progesterone therapy; oestrogen alone does not appear to raise breast-cancer risk significantly. Lifestyle factors: Heavy drinking, obesity (especially adult-onset obesity in the abdominal area), and lack of exercise have all been associated with increased risk of contracting breast cancer. It should be noted, however, that all known risk factors for breast cancer (other than being female and growing older) account for only a minority of cases of the disease. Most breast cancer – at least based on current knowledge – “just happens” and is not associated with any risk factor other than having breasts. 1.4 – Back pain Lower-back pain is extremely common, and may derive from a variety of causes: (DICE, 2001. ) Muscle strain or spasm, or sprained ligament Various disc problems, including herniated discs Arthritis Osteoporosis “Referred pain” caused by problems somewhere else – such as ovarian or kidney problems Degeneration of bone due to cancer If the patient in question is suffering from an invasive breast cancer that has already spread beyond the region of the initial tumour, it is quite possible that her lower-back pain is the result of bone metastases. Bone is one of the most common sites for breast-cancer metastasis, and the spine, in turn, is the most frequent site of bone metastases (followed by the pelvis, femurs, and the skull). Vertebral metastasis can lead to vertebral collapse with spinal cord compression, with severe consequences for the patient. Obviously, if this is indeed the cause of the patient’s lower-back pain, urgent intervention will be required to prevent further deterioration. (Souhami & Tobias 2003) At the same time, it must be remembered that lower-back pain due to metastasized cancer is very much a worst-case scenario, and is not to be considered as a high probability until and unless cancer is diagnosed and spread of the disease appears likely. Considering that Stage IV breast cancer is considered incurable (albeit treatable to a degree), it would be cruel and irresponsible to cause a patient to worry about metastatic cancer as a cause of her lower-back pain before cancer has even been diagnosed. 2 – Diagnosis and Treatment In the current case, two broad possibilities must be considered. First, the breast lump may be benign or pre-cancerous (i.e. DCIS); in this case the patient’s back pain is almost certainly caused by muscular strain or another “conventional” problem. Alternatively, the breast lump may be malignant, in which case there is some likelihood that the back pain is being caused by metastatic spread of the cancer to the spine. The probability that the patient has bone metastases is obviously fairly low if the tumour appears to have been found and excised before it has begun to spread (i.e. clean surgical margins, no axillary lymph node involvement); but even in this case, prudence requires that investigation of the lower back take into account the possibility that some malignant cells have escaped the original tumour and have caused bone metastases. If the patient does not have cancer, diagnosis and treatment of her lower-back pain should proceed without reference to her breast lump. The extent to which various imaging techniques are used will depend on her medical history (including any recent activity that may have caused muscle strain or disc problems), the results of physical examination, the duration and severity of her pain, and the extent to which she suffers from any related problems such as loss of mobility, loss of bladder control, and so on. If cancer has been diagnosed but there is no indication that disease has spread outside the affected breast, there is still an overwhelming probability that the patient’s lower-back pain is unrelated to the cancer. According to Baker (1977), only 1.5% of women (1 out of 64) diagnosed with Stage I or II breast cancer were found by bone scan to have a metastatic bone lesion; this compared to 24% of women with Stage III breast cancer. (Yeh 1995; this study found 2% of women with Stage I or II cancer to have bone metastases.) Accordingly, it would seem prudent to use imaging techniques somewhat more proactively with even an early-stage breast cancer diagnosis, while avoiding frightening the patient needlessly. A diagnosis of breast cancer that has spread outside the breast changes the probabilities significantly. In this case, bone metastasis becomes a very likely cause of the patient’s lower-back pain; and given the degenerative nature of bone metastases, the course of diagnosis must be altered to focus on this possibility and, if necessary, begin urgent treatment to prevent spinal collapse. 2.1 – Diagnosis of breast cancer The first stage in diagnosing a patient’s breast lump is a thorough physical examination of her breasts, axillae, and the base of her neck. This should be followed by bilateral mammography, ultrasound examination of any suspicious areas (including, of course, the palpable breast lump), and possibly by biopsy. MRI has been investigated as an alternative imaging method for breast-cancer screening; other imaging modalities are not applicable to this aspect of the patient’s case. While this patient will most likely undergo biopsy, discussion of the various biopsy techniques is outside the scope of this assignment. 2.1.1 – Mammography Mammography creates images of the breast tissues using low-dosage (and generally long-wavelength, typically Mo-K) X-rays. Compression of the breast at the time of imaging has the benefit of providing clearer images, as a result of decreased scatter and reduction of patient motion. Mammography is the most widely used screening technique for breast cancer; however, it is notoriously less reliable in detecting cancers in women under the age of 50, as their breast tissue is generally denser. Non-calcified tumours in young women are particularly likely to escape detection by mammogram. (Fosbinder & Kelsey, 2002; Hersh, 2004). A recent large-scale U.K. study of mammography in women aged 50 to 64 showed an overall sensitivity of 86.6% and overall specificity of 96.8%. Within this cohort there was no significant difference in specificity or sensitivity for women of different ages, although it should be remembered that the cohort did not include women under 50 (Banks 2004). Digital mammography (where the image is captured electronically and can be manipulated to enhance contrast) holds out promise for increasing diagnostic accuracy in breast cancer, particularly for younger women with denser breasts. According to Pisano et al, 2005, digital and film mammography are similar with respect to the overall diagnostic accuracy. However, the authors maintain that digital mammography is more accurate in women under the age of 50 years, women with radiographically dense breast tissue, and premenopausal or perimenopausal women. (See also Taft & Taylor, 2001) Conventional mammography, then, should not be considered reliable as a means of ruling out malignancy in women with dense breast tissue. In the current case, mammography should be used not to rule out breast cancer, but simply to get a picture of what is going on in both breasts, as a supplement to physical examination. In other words, any positive findings will be relevant, while negative findings (at least for the palpable breast lump) will be viewed sceptically. 2.1.2 – Ultrasound Ultrasound examination involves the use of very high frequency sound, directed into the body from a transducer placed in contact with the skin. The reflected images are received by the same transducer and converted into electrical signals, then formed into images for evaluation. Two recent developments are expected to enhance the value of ultrasound examinations: small ultrasound probes have been developed that allow their placement very close to the area of critical interest to provide images with high clarity; the area covered, however, is small. Contrast agents have also been developed that provide highly detailed images (Armstrong & Wastie, 1998). The original role of ultrasound in diagnosis of breast cancer was based on its ability to differentiate between cystic and solid lesions, and it continues to be a favoured way of obtaining a ‘second look’ after abnormalities have been found by mammography or MRI. Ultrasound is also useful as a “first line” diagnostic tool for younger women whose breasts are too dense for reliable interpretation of mammogram results. Ultrasound scans do not use ionising radiation and are thus safe; ultrasound is also the only real-time imaging modality available. As a result, ultrasound is frequently used to provide accurate targeting for breast biopsies. A Singapore study (Sim et al. 2004) comparing ultrasound with mammography and MRI for a group of women with an average age of 42 (and ranging from 25 to 58) demonstrated sensitivity of 83.3% and specificity of 65.5% for ultrasound. This compared with sensitivity of only 53.9% for mammography and 93.3% for MRI; mammography and MRI had specificities of 85.7% and 63.6% respectively. (Note that the much lower sensitivity of mammography in this study compared with the figure of 86.6% quoted above probably reflects the inadequacy of mammography in dealing with the denser breasts of premenopausal women.) When mammography and ultrasound were used in combination, sensitivity improved to 92.9% and specificity was 62.5% – essentially the same values as achieved by MRI, which is much more expensive and less widely available than mammography and ultrasound. Ultrasound is also used as a first-line test to detect liver metastases in breast-cancer patients; however, this procedure would be applicable to the current patient only if she were diagnosed with high-risk, late-stage cancer (Kasem 2006). For this patient, ultrasound will provide further information on the likelihood that her breast lump is malignant; in addition, it will help her doctor decide what form of biopsy will be most appropriate, and possibly assist him/her in carrying out the biopsy itself. 2.1.3 – Magnetic Resonance Imaging Magnetic Resonance Imaging (MRI) is proving to be extremely useful in many areas of body imaging. One significant advantage of MRI is that it is non-invasive and non-irradiating; it also can provide multiple-plane and multiple-orientation views. Though the specific role of MRI in breast imaging is still evolving, it offers hope of improved early diagnosis of breast cancer, and with that the possibility of reducing breast cancer mortality. (Shah et al, 2005). MRI has been recognized as the most sensitive modality for the detection of invasive breast cancer, particularly in younger women at high risk for the disease (Lalond, Davis & Trop, 2005), although it is expensive and prone to false-positive readings. As noted above, Sim et al. (Sim 2004) measured sensitivity and specificity of MRI in a mixed-age group of women at 93.3% and 63.6%; a larger U.S. study (Bluemke et al. 2004) measured sensitivity of 88.1% and specificity of 67.7%, with no difference in performance for varying breast density, tumor histology, or menopausal status. While MRI’s high sensitivity does offer promise as a screening technology for premenopausal women at high risk for breast cancer, it has not proven superior to combined use of mammography and ultrasound. There is no reason to use MRI in investigating the current patient’s breast lump, as it would not add significantly to what could be found through mammography and ultrasound. However, MRI might be useful in determining the cause of her lower-back pain; this will be discussed below. 2.2 – Resolving lower-back pain As discussed above, the diagnostic strategy for this patient’s lower-back pain will depend in part on the outcome of tests on her breast lump; if she is free of cancer, her back will be diagnosed in a “conventional” fashion, while if she has advanced cancer the possibility of metastasis to the spine must be investigated urgently. A diagnosis of early-stage cancer will suggest an intermediate course in resolving her lower-back pain. Depending on the resolution of the patient’s breast lump, as well as on her medical history and physical examination results, it may be advisable to begin with a conservative strategy in which no imaging techniques at all are used to investigate her back (Staiger et al. 1999). If she does not have cancer, has no neurological symptoms, and there is no other indication of serious injury or disease, a several-week course of bed rest, pain medication, and perhaps physiotherapy would be very likely to achieve good results; and if her pain persists or worsens, imaging techniques will be part of a more aggressive diagnostic strategy (Humphreys et al. 2002). 2.2.1 – Conventional “X-ray” radiography While conventional radiography is still the most commonly used first-line imaging technique for resolving back pain, it is far too imprecise to be completely satisfactory. Radiographs can reveal vertebral alignment along with disc and vertebral body height, and can give some impression of bone density and structure; they can also reveal severe bone damage from osteolytic bone metastases, which give a “moth-eaten” appearance on X-ray films (Jarvik and Deyo 2002). However, radiographs of the spine have a low sensitivity in detecting bone metastases: around 60% with 95-96% specificity (ibid). As radiography does not resolve soft tissue, it is a poor technique for diagnosing herniations and other disc problems. At the same time, radiography is convenient, safe (as it involves only low-dose radiation), and inexpensive; so it is worth using even though further imaging techniques are often required. 2.2.2 – Computed tomography (CT) CT scanning provides highly detailed images of bone; in this regard it is superior to MRI, and is thus better at detecting arthritis. CT is also less expensive than MRI, and presents fewer problems for patients with a tendency towards claustrophobia or who have pacemakers or metallic inserts. On the other hand, it involves higher radiation dosages than conventional X-ray radiography, and while it provides better images of soft tissue than conventional radiography, it does not resolve soft tissue such as vertebral discs as well as MRI (Sukerkar 2007). CT, like MRI, tends to have low specificity for back pain – that is, both methods often detect problems even in patients with no symptoms, so there is a significant likelihood that either method will indicate a structural problem that is in fact unrelated to the patient’s pain. 2.2.3 – Magnetic Resonance Imaging (MRI) Like CT, MRI provides highly detailed pictures of anatomical features. MRI is less able to show details of hard bone tissues than CT, but is significantly better at visualizing soft tissues. MRI does not use ionizing radiation and is thus considered very safe, but it is unsuitable for patients with cardiac pacemakers or metallic body implants. MRI is also expensive, and can be difficult for patients with any tendency towards claustrophobia, as the patient must lie still for a prolonged period inside a metal enclosure that produces rather loud and disturbing noises. Like CT, MRI tends to create false-positive results, finding possible causes of back pain that are in fact asymptomatic. MRI is the most sensitive method available for diagnosing many possible sources of lower-back pain, including malignancy, disc problems, and infections; and thus it would be used for the current patient either as a follow-up to conventional radiography or immediately if severe problems (oncological or neurological) are suspected. (Sukerkar 2007) MRI is also highly useful for diagnosing various diseases of internal organs; thus abdominal MRI might become useful to the current patient in searching for sources of referred pain (such as ovarian or kidney problems) or in locating any additional abdominal metastases in Stage IV breast cancer. 2.2.4 – Bone scintigraphy Bone scintigraphy (more commonly called simply “bone scanning”) involves injection of a radioactive compound (usually technetium-based) that is taken up in place of calcium anywhere that bone is being (re-)constructed. Radioactive decay from this compound is measured, and areas with disproportionately high uptake show up as “hot spots” on the scan. Bone metastases typically show up as multiple, asymmetric “hot spots”. Bone scanning is much more sensitive in detecting bone metastases than conventional radiography (see http://tinyurl.com/2qfxdg or http://www.breastcancercare.org.uk/content.php?page_id=481 ); it also has the advantage that it covers the entire skeleton; so – unlike MRI or CT – it gives a good overall picture of the presence of bone disease. On the other hand, bone scans do not give a precise indication of the state of bone in any particular area; MRI or CT are still needed when a detailed picture is required. Also, bone scans detect the body’s response to breakdown of bone, and not tumour activity itself; this means that a bone scan may miss some forms of bone metastasis that a PET scan would detect (Fujimoto et al. 2006). 2.2.5 – Positron emission tomography (PET) PET scanning is a newer nuclear-medicine approach, which uses 18F-fluorodeoxyglucose to measure areas of unusually high metabolic activity such as tumours. Because PET measures metabolism rather than calcium uptake, is can detect unusual levels of metabolic activity in various tissues – unlike scintigraphy, which displays only bone remodelling. Studies have shown that PET scanning is somewhat less sensitive than conventional bone scintigraphy in detecting osteoblastic (bone building) metastases, but is significantly more sensitive in detecting osteolytic (bone destroying) metastases. As the latter have a poorer patient prognosis, PET scanning would appear to be a very promising alternative to conventional bone scans (Cook 1998, Fujimoto 2006). 2.3 – Treatment options Assuming the patient has some form of breast cancer or pre-cancerous condition, various forms of treatment and follow-up may be required. The possibilities are far too numerous to cover in detail, but they range from doing nothing other than standard monitoring (if the breast lump turns out to be a fluid-filled cyst with no atypical cells), to enhanced monitoring (for LCIS or other benign condition with atypical cells), to excisional biopsy/lumpectomy (for DCIS; it is doubtful that excisional biopsy alone would be considered adequate for a palpable malignant tumour), to hormonal therapy, to adjuvant radiation and/or adjuvant chemotherapy, to localized radiation to provide symptomatic relief from pain and immobility caused by bone metastases. (Bisphosphonate drugs are also commonly used in treating bone metastases.) Follow-up would typically include bone scans if metastasis is established or suspected, along with monitoring of serum alkaline phosphatase levels; follow-up mammography and perhaps ultrasound would be part of surveillance as long as disease is either absent or in remission. Lower-back pain also can be treated in various ways, depending on the severity of the pain, associated neurological problems, the cause(s) of pain as determined by imaging, and of course any connection of the lower-back pain with cancer, if diagnosed. Treatment options (assuming that cancer is not involved) can range from bed rest and anti-inflammatory medications, to physiotherapy, to surgery to correct disc problems and the like. Follow-up would likely involve further radiography and/or MRI or CT, when and if further symptoms develop. 3 – Conclusions This case represents a fairly typical medical situation: A patient complains of two symptoms, each of which may be caused by something entirely benign (a fluid-filled cyst, a strained muscle) or by something that could ultimately cause death or severe disability (breast cancer, severe spine problems including damage from bone metastases). Each symptom by itself is most likely to be of benign origin; and the two symptoms are most likely not connected to each other. However, some of the more threatening scenarios are very dangerous indeed. The task of the treating physician in such a case is to find the causes of the patient’s symptoms quickly and accurately, taking into account the possibility of the more threatening possible scenarios while also minimizing unnecessary upset to the patient and using health-system resources efficiently. Good medical care requires awareness of when time is an ally (for example, in letting a strained muscle heal naturally with bed rest) and when it is an enemy (i.e. when cancer may be progressing or an infection is unchecked). Intelligent use of appropriate imaging technologies for diagnosis and follow-up is crucial to a successful medical strategy, along with good examination and questioning technique. Word count – 4109. References Wherever possible, current U.K.-based references have been selected. In some cases, e.g. Cook 1998, U.K.-based research has been published in non-U.K. journals. Aiello, J. E. et al. 2004. “Rate of Breast Cancer Diagnoses Among Postmenopausal Women With Self-Reported Breast Symptoms”. Journal of the American Board of Family Practice, vol. 17, no. 6, pp. 408-415. American Cancer Society, Inc. (revised 18 September 2006), “What Are the Risk Factors for Breast Cancer?”, accessed at http://tinyurl.com/5y4lr . Armstrong, P. & Wastie, L.M. 1998. Diagnostic Imaging. Fourth Edition. Blackwell Science. Oxford. R R Baker, E R Holmes, 3rd, P O Alderson, N F Khouri, and H N Wagner, Jr, “An evaluation of bone scans as screening procedures for occult metastases in primary breast cancer”, Annals of Surgery, v.186(3), September 1977. (This study has been cited as recently as 2001.) Accessed at http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1396331&blobtype=pdf . Banks, Emily, et al., “Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study”, British Medical Journal (BMJ) vol. 329, August 2004. Bartella, L. 2006. “MR Spectroscopy Aids Breast Cancer Diagnosis”. Radiology, vol. 239, pp. 686.692. David A. Bluemke et al., “Magnetic Resonance Imaging of the Breast Prior to Biopsy”, Journal of the American Medical Association (JAMA), Vol. 292 No. 22, December 2004, pp. 2735-2742. Bombardieri, E. & Gianni, L. 2004. ‘The choice of the correct imaging modality in breast cancer management’. European journal of nuclear medicine and molecular imaging, vol.31, suppl. 1, pp. S179-S186. Buscombe et al. 2004. “Position of nuclear medicine modalities in the diagnostic work-up of breast cancer”. The quarterly journal of nuclear medicine and molecular imaging, vol.48, no.2, pp. 109-118. Cancer Research UK (revised 29 September 2006), “Invasive ductal breast cancer”, accessed at http://www.cancerhelp.org.uk/help/default.asp?page=5071 . See also the linked pages on lobular breast cancer and rare types. The CHEK2 Breast Cancer Case-Control Consortium (lead author: Dr. Douglas Easton, Cancer Research U.K. Genetic Epidemiology Unit), “CHEK2*1100delC and Susceptibility to Breast Cancer: A Collaborative Analysis Involving 10,860 Breast Cancer Cases and 9,065 Controls from 10 Studies”, The American Journal of Human Genetics, June 2004, 74(6): 1175–1182 Caruso, M.L., et al, 1998, The Oncologist, Vol. 3, No. 1, 45-49. G.J. Cook, S. Houston, R. Rubens, M.N. Maisey, and I. Fogelman, “Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions”, Journal of Clinical Oncology, 1998; 16: pp. 3375-3379. Destounis, S. 2006. “The Role of MRI and ‘Second-Look’ Ultrasound for Evaluation of Breast Cancer”. Applied Radiology, vol. 35, no. 10, pp. 10-20. Directorate of Information and Clinical Effectiveness (DICE), Highland NHS Board, “Topic of the Month: Acute and Chronic Low Back Pain”, Issue #3, December 2001, accessed at http://tinyurl.com/ytncta . Philip Finch, “Technology Insight: imaging of low back pain”, Nature Clinical Practice Rheumatology (2006) 2, pp. 554-561. Fosbinder, A.R. & Kelsey, A. C. 2002. Essentials of Radiologic Science, McGraw-Hill, London. Frank, Thomas S., “Hereditary Risk of Breast and Ovarian Carcinoma: Role of the Oncologist”, The Oncologist, vol. 3, no. 6, 403-412, December 1998. Ryota Fujimoto et al., “Diagnostic accuracy of bone metastases detection in cancer patients: Comparison between bone scintigraphy and whole-body FDG-PET”, Annals of Nuclear Medicine, vol. 20, no. 6, pp. 399-408, 2006. Galinsky, D. et al. 2005. ‘Effect of breast magnetic resonance imaging on the clinical management of breast cancer’. The Israel Medical Association Journal, vol. 7, no.11, pp. 700-703. Haber, S. 1997. Breast Cancer. Free Association Books Ltd. London. Harnett, A. 2002. Case Studies in BREAST CANCER, Greenwich Medical Media Ltd. London. Hersh, R.M. “Imaging the Dense Breast”. Applied Radiology, vol. 33, no. 1, pp. 22-26. S. Craig Humphreys, Jason C. Eck, and Scott D. Hodges, “Neuroimaging in Low Back Pain”, American Family Physician, 1 June 2002, pp 2299-2306. Jeffrey G. Jarvik and Richard A. Deyo, “Diagnostic Evaluation of Low Back Pain with Emphasis on Imaging”, Annals of Internal Medicine, vol. 137 issue 71, October 2002, pp. 586-597 Jones, P. A. et al. 2003. ‘RECENT TECHNICAL ADVANCES’ in Textbook of RADIOLOGY AND IMAGING Volume 2, ed. David Sutton, Churchill Livingstone, Edinburgh, pp. 1819-1845. Josefson, D. 2000. “Mammography no better than physical breast examination”, British Medical Journal (BMJ), vol. 321, no. 7264, pp. 788-789. Abdul R. Kasem, Anil Desai, Simon Daniell, Prakash Sinha, “Bone Scan and Liver Ultrasound Scan in the Preoperative Staging for Primary Breast Cancer”, The Breast Journal 12 (6), pp. 544–548, 2006. Lalond, L., Davis, J. & Trop, I. (2005). “Magnetic resonance imaging of the breast: current indications”. Canadian Association of Radiologists Journal, vol.56, no.5, pp. 301-308. Madlensky, L, et al. 2005. “Is family history related to preventive health behaviors and medical management in breast cancer patients?” Breast cancer research and treatment. vol. 90, no.1, pp. 47-54. Metastatic Tumours to the Brain and Spine, American Brain Tumour Association, 1993, ISBN: 0-944093-26-4. Michell, J. M. 2003. ‘THE BREAST’ in Textbook of RADIOLOGY AND IMAGING Volume 2, ed. David Sutton, Churchill Livingstone, Edinburgh, pp. 1451-1488. National Cancer Institute, U.S. National Institutes of Health (reviewed 6 February 2002), “Fact Sheet: Genetic Testing for BRCA1 and BRCA2: It's Your Choice”, accessed at http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA . Osuch, R.J., Bonham, L.V. & Morris, L.L. (2002). “Primary Care Guide to Managing a Breast Mass: Step-by-Step Workup”, Medscape General Medicine, [Online] Available at: http://www.medscape.com/viewarticle/443381 Padwal, Monali, Elements of Breast Imaging Basics, GE Healthcare, 2007. Extracted on 13th February, 2007, from: http://gehealthcare.com/usen/ultrasound/education/products/cme_breast.html#1 Pisano, E.D. et al. 2005. “Diagnostic performance of digital versus film mammography for breast-cancer screening”. New England Journal of Medicine, vol. 353, pp. 1773-1783. Shah, K.S. et al. 2005. “Imaging a Primer for the Primary Care Physician”. Journal of the American Board of Family Practice, vol. 18, no.6, pp. 478-290. Sim, Hendriks, and Fook-Chong, “Breast Ultrasound in Women With Familial Risk of Breast Cancer”, Annals Academy of Medicine Singapore 2004; 33:600-6. Smith, Robert A., et al, American Cancer Society Guide for Breast Cancer Screening, 2003 Update, CA Cancer J Clin 2003; 53; 141-169. Souhami, R. & Tobias, J. 2003, Cancer and its management, Fourth Edition, Blackwell Science Ltd. Oxford. Thomas O. Staiger, Douglas S. Paauw, Richard A. Deyo, Jeffrey G. Jarvik, “Imaging studies for acute low back pain”, Postgraduate Medicine, vol. 105, no. 4, April 1999. Preeti A. Sukerkar, “Imaging modalities for back pain”, American Medical Association Virtual Mentor. 2007; 9:119-122, accessed at http://www.ama-assn.org/ama/pub/category/17223.html . Taft, R., & Taylor, A. 2001. “Potential Improvement in Breast Cancer Detection With a Novel Computer-Aided Detection System”. Applied Radiology, vol. 30, no.12, pp. 25-28. Veronesi, Andrea, et al, “Familial Breast Cancer: characteristics and outcome of BRCA 1-2 positive and negative cases”, BMC Cancer 2005; 5: 70. Walsh, T. and King, M. C., “Ten genes for inherited breast cancer”, Cancer Cell, 2007 Feb;11(2):103-5. Wright, T., & McGechan, A. 2003. “Breast cancer: new technologies for risk assessment and diagnosis”. Molecular diagnosis, vol.7, no.1, pp. 49-55. Karen A. Yeh, Lucio Fortunato, John A. Ridge, John P. Hoffman, Burton L. Eisenberg and Elin R. Sigurdson, “Routine bone scanning in patients with T1 and T2 breast cancer: A waste of money”, Annals of Surgical Oncology, Volume 2, Number 4 / July, 1995 Read More