Detection Of Breast Cancer Recurrence Research Articles

Early Detection of Recurrent Breast Cancer Using Metabolite Profiling

We report on the development of a monitoring test for recurrent breast cancer, using metabolite-profiling methods. Using a combination of nuclear magnetic resonance (NMR) and two-dimensional gas chromatography-mass spectrometry (GC×GC-MS) methods, we analyzed the metabolite profiles of 257 retrospective serial serum samples from 56 previously diagnosed and surgically treated breast cancer patients. One hundred sixteen of the serial samples were from 20 patients with recurrent breast cancer, and 141 samples were from 36 patients with no clinical evidence of the disease during ∼6 years of sample collection. NMR and GC×GC-MS data were analyzed by multivariate statistical methods to compare identified metabolite signals between the recurrence samples and those with no evidence of disease. Eleven metabolite markers (seven from NMR and four from GC×GC-MS) were shortlisted from an analysis of all patient samples by using logistic regression and 5-fold cross-validation. A partial least squares discriminant analysis model built using these markers with leave-one-out cross-validation provided a sensitivity of 86% and a specificity of 84% (area under the receiver operating characteristic curve = 0.88). Strikingly, 55% of the patients could be correctly predicted to have recurrence 13 months (on average) before the recurrence was clinically diagnosed, representing a large improvement over the current breast cancer-monitoring assay CA 27.29. To the best of our knowledge, this is the first study to develop and prevalidate a prediction model for early detection of recurrent breast cancer based on metabolic profiles. In particular, the combination of two advanced analytical methods, NMR and MS, provides a powerful approach for the early detection of recurrent breast cancer.

Primary Breast Lymphoma After Mastectomy With Reconstruction

Primary breast lymphoma accounts for only 0.05%–1.1% of all breast malignancies, and less than 1% of all cases of non-Hodgkin lymphoma. Although primary breast lymphoma may present clinical similarities to breast carcinoma, the majority of cases lack the typical features of breast malignancy or lymphoma. We describe a case of primary breast lymphoma in a reconstructed breast, 8 years after a mastectomy for breast cancer. To the best of our knowledge, this is the first reported case in the worldwide literature of primary breast lymphoma in a reconstructed breast. We will discuss the diagnostic and treatment strategies involved in the management of primary breast lymphoma, and the effect of breast reconstruction on the detection of recurrent breast cancer.

Early detection of recurrent breast cancer using metabolite profiling.

1037 Background: The growing field of metabolite profiling (or metabolomics) focuses on the quantitative detection of multiple small molecules that provide tremendous information on biological status. In particular, detectable perturbations in the metabolite profile often result from pathophysiological stimuli, such as from cancer. We report on the development of metabolite profile for use as an early test for recurrent breast cancer. As is the case for early detection of primary breast cancer, it is anticipated that earlier recurrence diagnoses will not only improve survival but also help clinicians determine the best therapeutic strategies for patients by avoiding under or over treatment. Methods: We apply a combination of nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) to analyze the metabolite profiles of 257 serial serum samples from breast cancer patients consisting 116 samples from breast cancer recurrence and 141 samples from breast cancer patients with no evidence of disease (NED). NMR and GC-MS data were analyzed by combining advanced univariate and multivariate statistical methods and comparison of individual spectral features between patients with and without recurrent breast cancer. Results: From multivariate analysis of 42 targeted metabolites, ten metabolite markers (7 from NMR and 3 from GC-MS) were used to build a regression model with high accuracy (AUROC >0.89 using 10 fold cross validation) with a sensitivity of 82% and specificity of 84% using a training set of samples. When the model was tested on an independent set of patient samples, it yielded a sensitivity of 76% and a specificity of 83% (AUROC >0.85). Strikingly, over 60% of the patients could be correctly predicted to have recurrence on average 10 months before clinical diagnosis, which represents a large improvement over the current diagnostic assays CA 27.29 and CA 15-3. To the best of our knowledge, this is the first study to develop and validate a prediction model for early detection of recurrent breast cancer based on metabolic profiles. Conclusions: The combination of NMR and MS provide a powerful approach for the development of metabolic profile-based diagnostic tests for detecting breast cancer recurrence. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Matrix-Bio Matrix-Bio Matrix-Bio Matrix-Bio

Serial determination of CEA and CA 15.3 in breast cancer follow-up: An assessment of their diagnostic accuracy for the detection of tumour recurrences

We studied the diagnostic accuracy of carcinoembryonic antigen (CEA) and cancer antigen 15.3 (CA 15.3) in detecting breast cancer recurrence. Biomarker follow-up determinations, made over 900 patients, were related to local–regional or distant recurrence using statistical models for longitudinal data. The diagnostic accuracy was quantified in terms of sensitivity, specificity and Youden index. The biomarkers were poorly predictive of local–regional recurrence. As for distant recurrence, the best diagnostic accuracy was obtained considering the two biomarkers jointly and combining two positivity criteria: a value above the normal limit or a difference between two consecutive measurements greater than the critical difference for at least one biomarker. A third criterion, based on within-patient comparison between follow-up determinations and a baseline, failed to improve the above result. CEA and CA 15.3 might play a role in patient monitoring during follow-up for the search of distant recurrence.

Breast Reconstruction after Surgery for Breast Cancer

A 45-year-old woman with breast cancer elects to undergo mastectomy and is referred to a plastic surgeon for evaluation for postmastectomy breast reconstruction. For some patients, breast reconstruction restores body image and sexuality and improves the quality of life. Reconstructive surgery does not interfere with detection of breast-cancer recurrence. Special considerations apply to patients who require radiation therapy.

Impact on survival of early detection of isolated breast recurrences after the primary treatment for breast cancer: a meta-analysis

The purpose was to establish the impact on survival of early detection of a local recurrence of breast cancer as compared to late detection. A meta-analysis was carried out using Cochrane review manager software (RevMan version 4.2). Studies were included if women were treated for primary breast cancer without evidence of distant metastasis at primary diagnosis and if these concerned routine follow-up strategies focusing on the early detection of curable recurrences. Data regarding the risk for death were derived from each study. Multi level models were used to study heterogeneity by using MLWin. Thirteen studies concerning 2,263 patients were included. Early detection of breast cancer recurrences during follow-up gave a significantly better survival as compared to late detected recurrences (HR: 1.68 (95% CI: 1.48-1.91)). Survival was better when the recurrence was found by mammography instead of physical examination or in patients without symptoms as compared to those with symptoms (HR: 2.44 (95% CI: 1.78-3.35); HR: 1.56 (95% CI: 1.36-1.79), respectively). If all breast cancer recurrences would be detected earlier, that 5-8 deaths (i.e. an absolute reduction in mortality of 17-28%) would be avoided by performing routine follow-up during a 10 year-period for 1,000 breast cancer patients. These data support the hypothesis that detection of isolated loco-regional or contra-lateral breast cancer recurrences in patients without symptoms has beneficial impact on survival of breast cancer patients when compared to late symptomatic detection.

99mtc-Sestamibi Scintimammography in Detection of Recurrent Breast Cancer

The aim of this study was to asses the accuracy of 99mTc-sestamibi scintimammography in patients with suspected recurrent breast cancer in the breast or loco regional tissues. After routine analyses in twenty-eight women (clinical examination, ultrasound, X-ray mammography, and fine needle aspiration biopsy) they were examined by scintimammography. All patients with suspected recurrent cancer in the breast or loco regional tissues (19) undergone surgery and the final diagnosis was determined by histopathological examination. Another 9 patients were followed 6-24 months. The scintigraphic studies were correlated with radiological findings and/or with histopathology. There were 19 patients with recurrent tumours (15 with loco-regional recurrent and 4 in another breast). X-ray mammography identified 13 of these cancers. 99mTc-sestamibi scintimammography identified seventeen of recurrent breast cancers. In the seven out of nine patients without cancer, scintimammography were reported as having no changes consistent with cancer. X-ray mammography showed suspected cancer lesions in four out of nine patients without cancer. There were two false-positive scintimammograms and one false negative. Axillary lymph node recurrence occurred in four patients. All of them were positive on scintimammography. 99mTc-sestamibi scintimammography showed higher sensitivity, specificity and accuracy per patient than did X-ray mammography (90,9% vs. 63,6%, 71,4% vs. 57,1% and 83,3% vs. 61,1%, respectively). To identifying recurrent breast cancer disease is better to use scintimammography than X-ray mammography.

Influence of CA 15-3 blood level and doubling time on diagnostic performances of 18F-FDG PET in breast cancer patients with occult recurrence

To evaluate the influence of CA 15-3 blood level and doubling time on diagnostic performances of 18F-FDG PET in breast cancer patients with occult recurrence. Thirty-five 18F-FDG PET examinations in 32 patients with CA 15-3 blood level above the normal range, and negative conventional imaging within 3 months before PET examination were included in this retrospective study. PET examinations were reviewed blindly by two experienced nuclear medicine physicians who were unaware of any clinical, biological or radiological information. CA 15-3 assays performed prior to the PET examinations and all using the same technique were collected and used for doubling time calculation if (1) no therapeutic modification occurred in the meantime, and (2) the delay between assays was less than 6 months. Median CA 15-3 blood levels were higher in the positive PET group (100 U x ml(-1)) than in the negative group (65 U x ml(-1)) (P=0.04). The likelihood of depicting recurrence was higher in patients with a short doubling time (<180 days) (P=0.05), a CA 15-3 blood level >60 U x ml(-1) (P=0.05), and when a short doubling time was associated with a CA 15-3 blood level >60 U x ml(-1) (P=0.03). The likelihood of depicting recurrence was influenced by CA 15-3 blood level and doubling time. Further studies are required to confirm that selections of patients based on those criteria could improve the sensitivity of positron emission tomography in the detection of breast cancer recurrence, particularly in the case of low CA 15-3 blood level.

American Society of Clinical Oncology 2006 Update of the Breast Cancer Follow-Up and Management Guidelines in the Adjuvant Setting

To update the 1999 American Society of Clinical Oncology (ASCO) guideline on breast cancer follow-up and management in the adjuvant setting. An ASCO Expert Panel reviewed pertinent information from the literature through March 2006. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. The evidence supports regular history, physical examination, and mammography as the cornerstone of appropriate breast cancer follow-up. All patients should have a careful history and physical examination performed by a physician experienced in the surveillance of cancer patients and in breast examination. Examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For those who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. Patients at high risk for familial breast cancer syndromes should be referred for genetic counseling. The use of CBCs, chemistry panels, bone scans, chest radiographs, liver ultrasounds, computed tomography scans, [18F]fluorodeoxyglucose-positron emission tomography scanning, magnetic resonance imaging, or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine breast cancer follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination. Careful history taking, physical examination, and regular mammography are recommended for appropriate detection of breast cancer recurrence.

Magnetic resonance mammography in the evaluation of recurrence at the prior lumpectomy site after conservative surgery and radiotherapy

IntroductionThe aim was to assess the value of magnetic resonance mammography (MRM) in the detection of recurrent breast cancer on the prior lumpectomy site in patients with previous conservative surgery and radiotherapy.MethodsBetween April 1999 and July 2003, 93 consecutive patients with breast cancer treated with conservative surgery and radiotherapy underwent MRM, when a malignant lesion on the site of lumpectomy was suspected by ultrasound and/or mammography. MRM scans were evaluated by morphological and dynamic characteristics. MRM diagnosis was compared with histology or with a 36-month imaging follow-up. Enhancing areas independent of the prior lumpectomy site, incidentally detected during the MRM, were also evaluated.ResultsMRM findings were compared with histology in 29 patients and with a 36-month follow-up in 64 patients. MRM showed 90% sensitivity, 91.6% specificity, 56.3% positive predictive value and 98.7% negative predictive value for detection of recurrence on the surgical scar. MRM detected 13 lesions remote from the scar. The overall sensitivity, specificity, positive predictive value and negative predictive value of MRM for detection of breast malignancy were 93.8%, 90%, 62.5% and 98.8%, respectively.ConclusionMRM is a sensitive method to differentiate recurrence from post-treatment changes at the prior lumpectomy site after conservative surgery and radiation therapy. The high negative predictive value of this technique can avoid unnecessary biopsies or surgical treatments.

Comparison of ultrasound controlled aspiration puncture to clinical examination in detection of breast cancer recurrence

Background: Breast carcinoma recurrence appears in 5%-30% of cases, after the completion of breast cancer treatment. Recurrence appears on thoracic wall (chest wall), on the skin, on the breast tissue remaining after the surgery, equal sided axillary lymph nodes, supraclavicular lymph nodes or on the internal mammary lymph nodes. Recurrence often stays undetected by clinical examination, while it can be detected by ultrasound and punctured under ultrasound control. Cytological confirmation of malignant cells represents a signal to commence a specific recurrence treatment. Methods: Aspiration puncture under ultrasound control has been performed within 128 patients. Only 38 patients, out of 128, did not have distant metastasis at the moment of recurrence detection, so the recurrence was surgically removed and was subjected to the histopathological analysis. The results of definite histopathological analysis were compared to the clinical results and cytological results, which had been obtained preoperatively. Results: 31 patients, out of above mentioned 38 patients, have had breast carcinoma recurrence, while 7 patients have had benign tumor lesion. Clinical diagnoses were correct in 47.4% of cases, and incorrect for 52.6%. False positive finding result happened in 7.89% cases and false negative finding result happened in 39.47% cases. Ultrasound diagnoses were correct for 86.84% of patients and incorrect for 13.16% of patients. Cytological analysis of material obtained by aspiration puncture under ultrasound control produced correct diagnoses for 86.84% of patients. 13.16% of patients had inconsistent cytological and histopathological findings result. Cytological analysis has detected malignant cells for 5.26%, but the recurrence was not histopathologically confirmed, which points that the results were falsely positive. Falsely negative results were confirmed for 7.89%. Conclusion: Clinical examination was reliable for 52.6% of patients examined. Cytological analysis of material obtained by ultrasound-controlled puncture was reliable for 86.84% of patients examined. Aspiration puncture followed by cytological analysis gave falsely negative result for 7.89% of patients examined, while clinical examination gave falsely negative result for 39.47% of patients examined. Aspiration puncture gave falsely positive result for 5.26%, and clinical examination gave falsely positive result for 7.89%. Aspiration puncture is simple, easy to perform, without damaging effect for the patient or the medical personnel, it is not expensive and it is significantly more reliable than clinical examination itself for detection of breast carcinoma recurrence. .

Ultrasonography of the axilla in the follow-up of breast cancer patients who have a negative sentinel node biopsy and who avoid axillary clearance

The clinical value of ultrasonography of the axilla in detection of breast cancer recurrence is not known among patients who have a negative sentinel node biopsy and avoid axillary clearance. We studied a cohort of 205 such patients using ultrasonography one and three years after breast surgery. A recurrent tumour was found in the axilla in only two (0.5%) of the total of 383 ultrasound examinations performed during the study, and only one (0.3%) of the 369 examinations performed at the scheduled study visits revealed cancer. None of the ultrasound examinations was false positive, and no study participant was subjected to unnecessary surgery due to ultrasound monitoring. We conclude that the rate of breast cancer recurrence in the ipsilateral axilla is low following sparing of the axillary contents, and that monitoring of such patients with repeated ultrasound examinations is unlikely to be cost-effective.

A meta-analysis of FDG-PET for the evaluation of breast cancer recurrence and metastases

To evaluate the diagnostic performance of 18F-2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) in the evaluation of breast cancer recurrence and metastases. Articles published in medical journals during January 1995-June 2004 were identified by a systematic Medline search, supplemented by a manual search of the references listed in original and review articles. Studies that evaluated FDG-PET with a dedicated camera for the diagnosis of breast cancer recurrence or metastases, and reporting sufficient data to permit calculation of sensitivity and specificity, were included in the analysis. Two reviewers independently reviewed the eligibility and abstracted data regarding the sample population, technical imaging characteristics of FDG-PET, and the number of true positives, true negatives, false positives and false negatives. Differences between readers were resolved by consensus. We used meta-analytic methods to estimate the pooled sensitivity, false positive rate, and the maximum joint sensitivity and specificity. Eighteen studies met the inclusion criteria. Sixteen studies included patient-based data, comprising a sample size of 808 subjects, and eight studies included lesion-based data, totaling 1013 lesions. Among the studies with patient-based data, the median sensitivity was 92.7%, and the median specificity was 81.6%. The pooled sensitivity was 90% [95% confidence interval (86.8-93.2)], and the pooled false positive rate was 11% [95% confidence interval (7.8-14.6)], after the exclusion of outliers. The maximum joint sensitivity and specificity, was 88% [95% confidence interval (86.0-90.6)]. These results indicate that FDG-PET is a valuable tool for detecting breast cancer recurrence and metastases.

The use of scintimammography for detecting the recurrence of loco-regional breast cancer: histopathologically proven results.

99mTc tetrofosmin scintimammography has been shown to be an accurate diagnostic test in patients with a symptomatic breast lesion and for whom a non-diagnostic mammogram has been obtained. Since a physical examination and conventional imaging modalities have their limitations in the detection of recurrent breast cancer, and survival is related to the extent of recurrent disease, complementary imaging modalities are warranted. To evaluate the role of 99mTc tetrofosmin scintimammography in detecting the recurrence of loco-regional breast cancer. Fifty-four patients underwent 55 scintimammography studies because either there were clinical indications of breast metastases, or there was a recurrence of metastases in the chest wall, and/or an evaluation of axillary, parasternal, supraclavicular and/or infraclavicular lymph node metastases was required. Planar breast imaging was performed 10 min after intravenous injection of 700 MBq 99mTc tetrofosmin. 99mTc tetrofosmin scintimammography was diagnostic in 50 of the 55 studies. An unknown lung metastasis was detected in one patient, and an unknown bone metastasis of the sternum was detected in another. Tumour involvement remained undetected in one neck node metastasis. Three patients had false positive scintimammography results, with 99mTc tetrofosmin uptake in an axillary, infraclavicular and parasternal lymph node, respectively. A fourth patient showed 99mTc tetrofosmin uptake in the scar, which appeared to be an inflammatory lesion, proven by a histopathological biopsy and 1 year clinical follow-up. 99mTc tetrofosmin scintimammography accurately detected 100% of the local recurrences independently of the extent of the preceding surgical intervention. The sensitivity and specificity of the technique for the detection of regional recurrent disease were 93% and 90%, respectively. These results are substantially higher than those of other imaging modalities.

Detection of recurrent breast cancer after TRAM flap reconstruction.

Breast cancer remains a significant cause of morbidity and mortality among women today. The transverse rectus abdominis myocutaneous (TRAM) flap has played a substantial role in the reconstruction of defects secondary to mastectomy. Although such reconstruction has not been shown to adversely affect survival or local recurrence, specific screening modalities for recurrence in this population of patients have not been delineated. Three patients were examined retrospectively at the authors' institution. They presented with local recurrences of breast cancer after mastectomy and TRAM flap reconstruction. All patients' recurrences were detected on physical examination, and all had the diagnosis of recurrent carcinoma made on biopsy of the mass. A review of the literature demonstrates that mammography, ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), scintimammography, and biopsy have all been used as adjuncts to clinical examination in detecting recurrence. Subsequent treatment of recurrent breast cancer is determined by the results of a metastatic workup and the receptor status of the tumor. The most reliable form of diagnosis of recurrent breast cancer after TRAM flap reconstruction remains fine-needle, core, or open biopsy if indicated.

The prognostic value of the tumor marker CA 15-3 at initial diagnosis of patients with breast cancer.

CA 15-3 has been most widely used as a serum tumor marker in follow-up and detection of breast cancer recurrence. In this study we have specifically focused upon the prognostic implications and utility of preoperative CA 15-3 levels. We have identified on our database 414 patients with breast cancer in whom serial levels of the serum tumor marker CA 15-3 had been determined at diagnosis and follow-up. We have analyzed the follow-up and clinical outcomes in these patients and from this data we have assessed the potential of CA 15-3 as a predictor of five-year overall and disease-free survival. Our results show that an initially elevated CA 15-3 level is associated with a very poor prognosis in both early and late stage disease. Elevated pre-biopsy CA 15-3 levels are associated with 14% five-year disease-free survival rates and 17% overall survival rates at five years. In contrast, normal CA 15-3 levels are associated with 47% five-year disease-free survival rates and 54% overall survival rates at five years (p<0.01). Comparison of five-year survival rates between patients with elevated and normal CA 15-3 levels in early breast cancer (stage I and II) also showed significant differences, with survival being 41% and 75%, respectively (p<0.01).

Contrast-enhanced colour Doppler ultrasonography in suspected breast cancer recurrence.

Postoperative scarring and radiotherapy changes in the conservatively treated breast often mimic breast cancer recurrence, resulting in many unnecessary biopsies. Local breast cancer recurrence may be detected more accurately with contrast-enhanced colour Doppler imaging. Fifty-eight women with suspected local breast cancer recurrence were evaluated prospectively by means of conventional and contrast-enhanced colour Doppler imaging before surgical biopsy. Sensitivity for the detection of breast cancer recurrence using contrast enhancement was 94 per cent (specificity 67 per cent). Contrast enhancement significantly increased overall diagnostic accuracy, from 80 to 90 per cent (P < 0. 04). Contrast-enhanced colour Doppler imaging is a highly accurate method for detecting local breast cancer recurrence. Its adoption may substantially reduce biopsy rates.

Evaluation of an intensive strategy for follow-up and surveillance of primary breast cancer.

Controversies over the frequency and intensity of the follow-up care of breast cancer patients exist. Some physicians have adopted an intensive approach to follow-up care that consists of frequent laboratory tests and routine imaging studies, including chest radiographs, bone scans, and CT scans, whereas others have established a minimalist approach consisting of only history, physical examinations, and mammograms. Our objective was to evaluate the role of intensive follow-up on detection of breast cancer recurrence and to examine the impact of follow-up on overall survival. During a 10-year period (1986-1996), 129 patients with recurrent disease were identified from a prospective database of 1898 breast cancer patients. The patients with recurrent disease were divided into minimalist or intensive groups according to method of detection. Twenty-seven of 126 (21%) patients were assigned to the intensive method of detection group (LFT, CEA, CA 15-3, chest radiograph, CT scan, and bone scan); 99 of 126 (79%) patients were assigned to the minimal detection group (history, physical examination, and mammography). Distant disease to the bone was the most common initial tumor recurrence, at 27%. History, physical examination, and mammography detected recurrent cancer in approximately the same amount of time as LFTs, tumor markers, CT scans, and chest radiographs (P = .960). When the recurrent patients were divided into intensive and minimalist groups and analyzed by time to detection of recurrence, there was no significant difference between the time to detection in those recurrences detected by intensive methods and those recurrences detected by minimalist methods (P = .95). The independent variables age, tumor size, type of surgery, number of positive nodes, time to recurrence, method of detection, and site of recurrence (regional or distant) were subject to univariate and multivariate analysis by the Cox proportional hazards model. Only two variables had an impact on survival by multivariate analysis: early timing of the recurrence (P = .0011) and the site of the recurrence (P = .02). Timing was defined as early (< or =365 days from the time of diagnosis to recurrence) or late (> or =365 days from the time of diagnosis to recurrence). Early recurrence was the first variable found to be significant on stepwise forward regression analysis. The primary site of recurrence was significant at step two. The method of detection--intensive or minimal--did not significantly affect survival (P = .18). There is no survival benefit to routine intensive follow-up regimens in detecting recurrent breast cancer. Expensive diagnostic tests such as bone scans, CT scans, and serial tumor markers are best used for detection of metastasis in symptomatic patients.

Use of blood tumour markers in the detection of recurrent breast cancer

Breast cancer remains the most common malignancy in women in Western countries. The search for specific tumour markers which might aid the diagnosis and monitoring of treatment has increased over the last decade owing to the continuing high mortality rate from this disease. Today a large number of markers have been proposed for breast cancer, including mucins, CEA, oncoproteins, milk proteins, cytokeratins, etc. Of these CEA and CA153 are the most commonly used in clinical practice. Other MUC1-gen family tests (e.g. MCA, CA549, B27.29, BRMA) have been reported to have a similar sensitivity and specificity as CA15-3. The use of several mucins simultaneously does not improve the efficacy obtained compared with using only one of them. For this reason CEA and one mucin have been recommended where serial assay of blood markers is indicated. Certain tumour markers look promising but are still under evaluation (e.g. cytokeratins, TPS, TPA, CYFRA 21.1) and soluble oncoproteins (c-erbB2). The main clinical applications of tumour markers are in disease monitoring, prognosis and early detection of recurrence. Tumour marker sensitivity in patients with locoregional breast cancer is low (15-35%) and they are not useful for diagnostic purposes. However, patients with local recurrence with elevation of CA15-3 have a shorter time to symptomatic metastases compared to patients with local recurrence and a normal CA 15-3 level. Tumour marker sensitivity and specificity increase significantly in patients with metastatic recurrence. CEA and CA15-3 (or other MUC-1 related antigen) levels are abnormal in more than 80% of patients with advanced disease. These results suggest that serial determinations of tumour markers may be useful in the early diagnosis of recurrence. To use tumour markers in early diagnosis we have to know their sensitivity and specificity and to compare their

Diagnostic features of 225 consecutive cases of cancer recurrence in the conserved breast

The diagnostic features of 225 consecutive cases of cancer recurrence (186 true recurrences, 39 new primary cancers) in the conserved breast were reviewed. The sensitivity of palpation, mammography, ultrasonography or fine needle aspiration cytology was 69.8, 66.1, 73.3 and 77.8%, respectively. The sensitivity was not significantly influenced by previous radiotherapy, type of recurrence (new primary or true recurrence), or patient age. Although the sensitivity of mammography was lower (60.6 vs 69.3%) in the presence of dense compared with fatty breasts, this did not explain most of the mammographic false negatives, some of which were likely to be due to the masking effect of surgical scar and distortion. In the study period suspicion of breast recurrence following diagnostic evaluation resulted in 34 unnecessary benign biopsies, giving a positive predictive value for biopsy of 86.8%. Of 171 recurrences undergoing a triple diagnostic approach (palpation, mammography/ultrasonography, cytology), recurrence was suspected by at least one, two or three tests in 99.3, 81.8 or 40.3% of cases, respectively. A multimodal diagnostic approach is necessary to maximize the sensitivity of detecting breast cancer recurrence after conservation therapy, and should be employed routinely.