PET imaging in breast cancer.

The basis of tumour imaging with PET is a specific uptake mechanism of positron emitting radiopharmaceuticals. Among the potential tracers for breast cancer (fluorodeoxyglucose, methionine, tyrosine, fluoro-estradiol, nor-progesterone), 2-deoxy-2-fluoro-D-glucose labelled with fluorine (FDG) is the most widely used radiopharmaceutical because breast cancer is particularly avid of FDG and 18F has the advantages of a relatively long physical half-life. Mammography is the first choice examination in studying breast masses, due to its very good performances, an excellent compliance and the best value regarding the cost/effectiveness aspects. However FDG-PET revealed to be effective in the study of patients with ambiguous mammographies. The FDG uptake in tissue correlates with the histological grade and potential aggressiveness of breast cancer and this may have prognostic consequences. Besides the evaluation of breast lesions, FDG-PET shows a great efficacy in staging lymph node involvement prior surgery and this could have a great value in loco-regional staging. Whole body PET provides also information with regard to metastasis localizations both in soft tissue and bone, and plays an important clinical role mainly in detecting recurrent metastatic disease. In fact for its metabolic characteristics PET visualizes regions of enhanced metabolic activity and can complements other imaging modalities based on structural anatomic changes. Even though CT and MRI show superior resolution characteristics, it has been demonstrated that PET provides more accurate information in discriminating between viable tumour, fibrotic scar or necrosis. Several clinical evidences demonstrated that FDG-PET is also able to predict wether cancer will respond to the therapy, or, when applied at the end of the treatment, it can assess the response to the therapy. These statements are coming from the examination of more than 2000 breast cancer patients included in 88 articles or abstracts on studies in which FDG-PET was used for breast cancer detection.     

Radioimmunodetection and therapy of breast cancer

Breast cancer is the second most-common cause of cancer death in women in the United States. Although more than 60% of patients can now be cured by initial treatment, the rest, although perhaps receiving palliation with currently available therapy, will die of their disease. Early detection of micrometastasis and improved treatment strategies are needed. Monoclonal antibody (mAb)-based imaging and tumor targeted therapy holds the potential to impact these problems. The most significant results of systemically administered antibody-based radiopharmaceuticals for detection and targeted therapy (radioimmunotherapy [RIT]) of breast cancer give strong evidence that this potential can be realized. Interest in immunoimaging recently has focused on small mAb modules used with 18F, 64Cu, or 124I to detect minimal disease in breast cancer by positron emission tomography or single-photon emission computed tomography. Reported therapy trials in advanced breast cancer have yielded objective responses and minimal toxicity. These studies have spanned several radionuclides as well as several mAb, fragments and approaches, including dose intensification with bone marrow support; combined therapy with other modalities (ie, CM-RIT); biodegradable peptide linkers; and pretargeting. RIT evaluated in clinical breast cancer trials has delivered as much as 4000 cGy to metastatic breast cancer per therapy dose with marrow stem cell support. Preclinical studies have demonstrated further promising strategies for breast cancer. RIT studies must address the key issue: enhancing the therapeutic index (tumor effect verses most sensitive normal tissue (bone marrow) effect). Approaches now include newly engineered mAb, scFv modular constructs, blood clearance on demand, enhanced pretargeting, applications of both alpha and beta emitting radionuclides, and combination therapy using molecular triggers for therapeutic synergy. These strategies for detection and treatment of metastatic breast cancer should lead to notable clinical impact on management and cure of breast cancer.     

Circulating tumor markers and nuclear medicine imaging modalities: breast, prostate and ovarian cancer.

Clinical oncologists have always shown great interest in circulating tumor markers. There are several markers that in the clinical routine are a signal of particular tumor types; some of them are strictly tissue-specific such as prostatic specific antigen (PSA) for prostatic cancer, AFP and HCG for germ cell tumors of the testis and ovary, others such as CA 15.3, CA125, CEA or cytokeratins are less specific since their elevations can be found in different varieties of cancers even if they are preferentially associated to a certain tumor type, thus are considered markers for breast, ovarian cancer and colon adenocarcinoma. The most useful clinical applications of these parameters is their determination during the follow-up of the treated patients, in order to detect the tumor recurrence early, and also to evaluate the evolution of the disease by monitoring the treatment responses. During follow-up, increasing levels of tumor markers can be observed even several months before the clinical demonstration of cancer recurrence. The association of tumor marker tests with imaging modalities can lead to several advantages: the first is to confirm the diagnosis of relapses, possibly before the appearence of the related clinical symptoms due to tumor growth; the second is to localize the sites of lesions, while tumor markers provide only a general indication of the existence of metastases; the third is to make possible a correct whole body restaging. In the assessment of cancer response tumor markers are often very reliable and their changes are faster than the morphological ones. Among all the imaging modalities, nuclear medicine plays an important role in detecting recurrences and metastatic localizations as it is able to investigate functional rather than morphological aspects of tumors, and provide different information in comparison to morphologic imaging. In addition, the scintigraphic techniques offer the possibility to evaluate treatment responses, confirming or not the information from biochemical changes. This review aims to show some examples (breast, prostate and ovarian cancer) in which the combination of nuclear medicine imaging modalities and tumor marker tests is proposed for clinical practice. The advantages and some critical aspects are discussed on the basis of the clinical findings and the most important clinical indications are described.     

Fluorodeoxyglucose-PET in the management of breast cancer

FDG-PET can be helpful in the diagnosis of primary breast cancer, especially in patients with dense breast tissue, significant fibrocystic changes, fibrosis after radiotherapy, and inconclusive results from MR imaging and other imaging modalities. PET has a limited role in patients with very small tumors and with well-differentiated and lobular types of breast cancer. In preoperative staging, FDG-PET has a low sensitivity for detection of regional lymph node involvement. Also, current PET imaging techniques can easily miss micrometastases. FDG-PET, however, has high positive predictive value for the axillary lymph node involvement, especially patient with advanced tumors. Compared with conventional imaging modalities, FDG-PET provides high diagnostic accuracy in detecting recurrent or metastatic breast carcinoma. FDG-PET seems to be highly useful for monitoring response to therapeutic interventions. This technique can identify response to therapy earlier than any other imaging method currently available. Obviously, identification of nonresponding patients could greatly improve patient management by allowing termination of ineffective and toxic therapies.     

MRI in breast cancer diagnosis and treatment

Breast cancer diagnosis and treatment are important health care issues in the Industrialized World. About 180,000 new breast cancers are discovered annually in the United States. Because this cancer often occurs in premenopausal women, breast cancer is a leading cause of potential life years lost. Breast magnetic resonance imaging (MRI) is capable of producing detailed information concerning the extent and character of breast lesions. The technique and alternatives for generating high-resolution breast MR images are reviewed. Characteristic features of a pulse sequence for breast imaging includes heavy T₁ weighting and magnetization transfer weighting for more effective gadolinium contrast, fat suppression, and rapid acquisition time. MRI is best employed for breast cancer diagnosis as a supplement to conventional breast imaging. Diagnostic groups particularly well suited to breast MRI include women with radiographically dense breasts, silicone augmentation, and postoperative scar. The capacity of breast MRI to show disease extent is employed to plan and localize for breast-conservation therapy. Tumor size and multiple tumors can be characterized for more-effective surgical management. Ductal carcinoma in situ can be imaged and staged for tailored therapy. MRI-directed biopsy and localization can be used to optimize lumpectomy surgery and reduce the potential for histologically positive margins. MRI can define the effectiveness of radiation therapy and chemotherapy to provide improved information on nonsurgical treatment of breast cancer. The clinical implementation of breast MRI in the future depends on the careful coordination of quality MRI images and interpretations with skillful therapeutic management.     

Positron emission tomography in evaluating the response to treatment of brain tumors, lymphomas and breast cancer

Positron emission tomography (PET) with the glucose analogue (18)F-FDG is increasingly used to monitor tumour response in patients undergoing chemotherapy, radiotherapy or new therapeutic schemes including antiangiogenesis and molecular targeted cancer treatment. PET as a functional imaging technology provides timely, quantitative, cross-sectional, non invasive assessment of several biologic processes targeted by the above-mentioned therapies. Tests by the camera PET can be useful in distinguishing between radiation necrosis or scarring and tumour recurrence, thus evaluating response to therapy. The information provided by this technique is more sensitive and specific than that provided by conventional anatomic imaging modalities such as computerised tomography, magnetic resonance imaging or ultrasound and superior in evaluating the effectiveness of various treatment regimens early during therapy or after the completion of therapy. With this information in hand, physicians can modify ineffective therapy and consequently improve patient's outcome and reduce the cost of treatment. In the present review article we discuss the contribution of tests performed by the PET camera, mainly using (18)F-FDG as a radiotracer, in the evaluation of treatment response in patients with brain tumours, lymphomas and breast cancer.     

Ultrasound for breast cancer screening and staging

The question then arises whether and for whom BWBS should be recommended. As yet there are no scientific criteria on which to base an answer, and the examination should not be considered the standard of care until its benefits can be established prospectively. We know that mass screening mammography will detect occult cancers in two to seven of every 1000 women screened, depending on patient age and whether the screens are prevalence or incidence examinations. Should we expect a similar yield for survey US? Kopans commented that Kolb's cancer detection rate was lower than would be expected from a mammographic prevalence screen. This was not a reasonable comparison. These women all had negative findings on screening mammography and would normally be told to have repeat screening mammography 1 year later. Kolb's cancer detection rate using US was comparable to a mammographic incidence screen, so the cancer diagnoses of these fortunate women were advanced by 1 year. To maximize the yield, it is obvious that US has little to offer over mammography in women with fatty breasts because mammography is less likely to be falsely negative. The group of patients in whom incidental cancers would be expected to be found more commonly are those with dense breasts who also are at higher-than-average risk either because of a previous personal history of breast cancer (Fig. 2) or a significant family history. Because it would be impractical to consider BWBS for all women with radiographically dense breasts, it would be useful to know what its potential yield would be in the relatively smaller group of high-risk patients. Annual mammography remains the standard of care for breast cancer screening. However, in our practice in Vancouver, I suggest that high-risk women undergo mammography and US annually, recognizing that this goes beyond the standard of care. Instead of having both examinations simultaneously, I recommend that they alternate the two modalities at 6-month intervals. Theoretically, this could increase lead-time in the detection of occult cancers. The usefulness of this approach remains to be determined. BWBS for staging in women known to have breast cancer has tremendous promise and should be considered for any breast cancer patient with dense breast tissue in whom the finding of additional unsuspected foci would change the planned management. The cost of implementation would be substantial but considerably less than staging MRI. A large-scale study comparing these two modalities is needed, including assessment of the impact of identifying additional mammographically occult lesions on breast cancer mortality.     

X线摄影和螺旋CT诊断乳腺良恶性肿瘤的评价

目的：参照X线摄影在乳腺疾病诊断方面的特点．评价用螺旋CT扫描乳腺技术的诊断价值。方法：将外科手术证实的156例乳腺疾病患者分为乳腺癌组和非乳腺癌组．观察X线摄影和螺旋CT扫描对乳腺良恶性疾病诊断的准确性，并比较各自的优缺点。结果：156例有乳腺肿块的患者中．经手术和病理证实乳腺癌65例．乳腺良性疾病91例。65例乳腺癌中有10例乳腺X线摄影检查为阴性．其中4例因腺体致密而不能确诊。这4例中螺旋CT检出2例阳性病变。乳腺X线摄影诊断的敏感性和特异性分别为84．6％和83．5％．螺旋CT扫描为83．1％和76．9％。乳腺X线摄影和螺旋CT扫描的阳性预测值分别为78．6％和72．0％，其阴性预测值为88．4％和86．4％。结论：对于乳腺良恶性肿瘤的检查．首选乳腺X线。必要时CT可作为补充。     

The role of magnetic resonance imaging in early detection of recurrent breast cancer

Purpose

The purpose of this work was the evaluation of new advances of magnetic resonance imaging (MRI) in diagnosis of recurrent breast cancer after conservative surgery, chemotherapy and radiotherapy.

核医学乳腺专用显像仪在乳腺癌诊疗中的应用

核医学乳腺专用显像仪包括乳腺专用伽玛射线显像（BSGI）和正电子发射乳腺显像（PEM）仪,两者分辨率高,不受乳腺组织密度、假体植入、瘢痕形成等因素的影响,可以诊断直径仅为3mm的病灶。笔者综述了BSGI和PEM在乳腺癌早期诊断、治疗方案选择以及疗效评价等方面的应用。     

FDG-PET for axillary lymph node staging in primary breast cancer

Management of the axilla in patients with operable breast cancer is still one of the most controversial areas in clinical oncology. The best procedure to examine the lymph nodes is still standard axillary lymph node dissection; nevertheless, the morbidity associated with this procedure is well known. Based on these considerations, it is important for progress in the treatment of operable breast cancer that strategies are found that permit a less invasive method of axillary sampling which does not impair the patient's quality of life. The technique of sentinel lymph node (SLN) biopsy has recently been proposed for this purpose, with very important results. SLN has now become routine practice in the surgical management of breast cancer, and in many institutions patients with a negative SLN biopsy are spared axillary dissection, while those with a positive SLN biopsy are submitted to axillary node dissection. The good accuracy of SLN biopsy represents a significant advance in the management of primary breast cancer; however, false negative axillary results can occur in a variable percentage of patients, and the contribution of the SLN procedure to the detection of metastases in the internal mammary and supraclavicular lymph nodes is not clear. Among the recently developed imaging modalities, positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) has in particular been applied to the study of lymph node metastases in cancer patients. Several clinical studies have been carried out to evaluate the accuracy of PET in the axillary staging of operable primary breast cancer. These studies have sometimes provided conflicting results, either supporting the possibility of using FDG-PET to select patients who need axillary dissection or questioning whether FDG-PET can accurately assess the axillary status in primary breast cancer. All the limitations and the advantages of FDG-PET are discussed in this paper, by examining the performance of scanner technology and the possible causes of the false negative results. In the experience of the authors, comparing FDG-PET with SLN biopsy in the same series of patients, the results seem to indicate that the lower sensitivity of PET is restricted to micrometastases. Of course, this limitation of PET has to be analysed in relation to the importance of such small axillary metastases for the outcome of patients with breast cancer. The added value offered by PET in breast cancer staging in comparison with intraoperative detection of the sentinel node lies in the fact that FDG-PET is a non-invasive procedure that allows, within a single examination, the biological characterisation of breast cancer and viewing of the entire body.     

The role of sentinel node biopsy in breast cancer management: an overview

Regional lymph nodes surgical management is an integral part of breast cancer therapy. One of the most important therapeutic problems is the risk of surgical treatment which is too wide or inadequate due to the lack of correct presurgical information on the conditions of regional lymph nodes. For melanoma the problem was solved combining surgical accuracy with the slightest surgical resection, using sentinel node biopsy. In breast cancer the removal of axillary nodes proved to be unnecessary in more than 50% of cases. The first international studies on the use of sentinel node biopsy in breast carcinoma for the identification of patients who do not need axillary clearance suggest the high accuracy of the technique. Some practical problems still exist, however, and the optimisation of the method is not yet complete. The use of sentinel node biopsy in breast cancer treatment might be able to provide distinctive clinical information, which can improve our knowledge about the disease?'s biological behaviour and about its treatment.     

Computer-aided detection/diagnosis of breast cancer in mammography and ultrasound: a review

Breast cancer is the most common form of cancer among women worldwide. Early detection of breast cancer can increase treatment options and patients' survivability. Mammography is the gold standard for breast imaging and cancer detection. However, due to some limitations of this modality such as low sensitivity especially in dense breasts, other modalities like ultrasound and magnetic resonance imaging are often suggested to achieve additional information.Recently, computer-aided detection or diagnosis (CAD) systems have been developed to help radiologists in order to increase diagnosis accuracy. Generally, a CAD system consists of four stages: (a) preprocessing, (b) segmentation of regions of interest, (c) feature extraction and selection, and finally (d) classification. This paper presents the approaches which are applied to develop CAD systems on mammography and ultrasound images. The performance evaluation metrics of CAD systems are also reviewed.     

T1 stage breast cancer: adjuvant hypofractionated conformal radiation therapy to tumor bed in selected postmenopausal breast cancer patients--pilot feasibility study.

PURPOSE: To explore the feasibility of a short course of hypofractionated conformal radiation therapy to the tumor bed as part of a breast preservation protocol in postmenopausal patients with nonpalpable pT1N0 stage breast cancer. MATERIALS AND METHODS: The tumor bed was imaged at computed tomography (CT) in the prone position on a dedicated table. The same table and position were used for treatment with a 4-MV linear accelerator. The planning target volume was the tumor bed plus a 1-2-cm margin defined at postmastectomy CT. A regimen of five fractions was tested in this pilot dose study. Cosmesis was assessed by patients and physicians before treatment and 36 months after treatment. RESULTS: Ten consecutive patients who were eligible for the study were assigned to one of three dose-per-fraction regimens; nine were treatable with the proposed technique on the basis of CT findings. Patients received five fractions over 10 days (total dose range, 25-30 Gy): Three received 5.0 Gy per fraction; four, 5.5 Gy; and two, 6.0 Gy. At minimum follow-up of 36 months (range, 36-53 months), all patients were alive and disease free with good to excellent cosmesis. CONCLUSION: Hypofractionated conformal breast radiation therapy is feasible. Further studies are warranted.     

Inflammatory breast cancer: challenges and developments

Inflammatory breast cancer (IBC) is a rare and exceedingly aggressive type of cancer that is often mistaken for other conditions. Because it spreads throughout the breast tissue, imaging modalities are not sensitive enough to allow for a conclusive diagnosis. Treatment typically is patterned after treatment for aggressive non-IBC breast cancer. This article is a Directed Reading. Your access to Directed Reading quizzes for continuing education credit is determined by your area of interest. For access to other quizzes, go to www.asrt.org/store. This article also meets Medical Dosimetrist Certification Board (MDCB) CE requirements.     

应用影像学方法评价乳腺癌新辅助化疗疗效

新辅助化疗治疗乳腺癌已经成为一种趋势,针对新辅助化疗的一系列研究正在开展。早期评价乳腺癌治疗疗效能避免对新辅助化疗无效者的过度治疗,支持有效者继续治疗。多种影像学评价方法相继应用于新辅助化疗的疗效评价。     

Therapeutic potential of melatonin for breast cancer radiation therapy patients

Melatonin is an endogenous hormone primarily known for its action on the circadian rhythms. But pre-clinical studies are reporting both its radioprotective and radiosensitizing properties, possibly mediated through an interaction between melatonin and the regulation of estrogens. Melatonin pre-treatment prior to ionizing radiation was associated with a decrease in cell proliferation and an increase in p53 mRNA expression, leading to an increase in the radiosensitivity of breast cancer cells. At the same time, a decrease in radiation-induced side effects was described in breast cancer patients and in rodent models. This review examines the potential for melatonin to improve the therapeutic outcomes of breast radiation therapy, specifically estrogen receptor positive patients. Evidence suggests that melatonin may offer a novel, non-toxic and cheap adjuvant therapy to improve the existing treatment modalities. But further research is required in the clinical setting before a clear understanding of its therapeutic benefits is determined.     

Computer-aided tumour classification and treatment selection in breast cancer.

In order to provide a common basis for treatment decisions and the future evaluation of breast cancer therapy, the breast cancer protocol used in our clinic was formulated for the computer. A system for the simulation of clinical reasoning was used which allows the physician to express the medical logic as a series of inferences to be confirmed or rejected on the basis of Boolean combinations of medical criteria. The system enables the physician to rearrange these criteria into a questionnaire for complete and accurate recording of patient data. These data are then fed into the computer to produce a patient status report and treatment recommendations. The data from 26 patients in various stages of breast cancer have been processed by the computer and the computer's conclusions compared to the assessment made by a junior physician in our department. In three cases the staging was not identical, in 15 cases the treatment decisions were not identical and in all cases investigations were left out by the physician. The system has been of considerable value in standardising patient examination and treatment and in training inexperienced physicians.     

Efficacy of three-dimensional image fusion of lymphoscintigraphy and MDCT data sets in breast cancer

The aim of this study was to evaluate the clinical usefulness of image fusion of lymphoscintigraphy with (99m)Tc phytate and volume-rendering images generated by multidetector-row CT (MDCT) in patients with breast cancer. The subjects were 25 patients with clinically negative nodes. Data from the two imaging modalities were fused on a personal computer. Thirty-five axillary sentinel nodes were identified by lymphoscintigraphy. The anatomical locations of sentinel nodes in 27 patients were clearly demonstrated by 3D-fusion imaging (84%). Image fusion of lymphoscintigraphy with (99m)Tc phytate and volume-rendering images is helpful for sentinel node biopsy in breast cancer.     

Patient information preferences among breast and prostate cancer patients

Preferences for information about their disease and treatment were collected from 392 patients who had been treated for either breast or prostate cancer an average of 2 years previously. Type of information that they had received, their ratings of its value to them and their preferred format for further information were examined. The most common and most preferred form of information was through doctor interview, followed by educational booklets. Prostate cancer patients preferred videotapes; breast cancer patients tended to prefer individualized approaches including a tour of the department. Effects of age, educational levels, occupational backgrounds and self-reports for anxiety and depression at the time of the survey and at time of diagnosis were analysed. Prostate cancer patients who were most severely depressed showed a preference for not receiving any information at all, perhaps reflecting a tendency towards withdrawal.