Diagnosis Of Recurrent Breast Cancer Research Articles

The diagnostic accuracy of mammography and ultrasonography for recurrent breast cancer after breast conserving treatment

ObjectiveTo evaluate the performance of mammography and breast ultrasonography to diagnose tumor recurrence in patients after breast conserving therapy. Material and MethodsImaging findings of 130 breast cancer patients treated by breast conserving therapy (BCT) who have followed up with mammography and ultrasonography at our center between 1 st January 2010 and 1st January 2016 were interpreted by two radiologists. The information of recurrent tumor and baseline data were blinded. Imaging interpretation followed the ACR Breast imaging-reporting and data system (BI-RADS) 5th edition guideline. Findings of mammography, breast ultrasonography, demographic data and histological data were recorded and analyzed. ResultsThe presence of mass in mammography (P-value=0.025) and internal vascularity in mass in ultrasonography (P-value<0.001) were associated with recurrent tumor at the surgical bed. All the recurrent tumors were interpreted as BI-RADS 4 (71 patients) with sensitivity= 100%, specificity= 89.5%. BIRADS4 is significant in the diagnosis of recurrent breast cancer in BCT patients (AUC of the ROC curve = 0.742 and 95% CI=(0.7–0.79)). ConclusionThe presence of mass in mammography and internal vascularity in the mass in ultrasonography are the imaging findings which were significantly related to recurrent tumor at surgical bed in patient with breast conserving treatment.

Evaluation of Serum Fructosamine as Diagnostic Marker of Postoperative Recurrence in the Patients with Breast Cancer.

A series of laboratory parameters were screened to identify the proper serum markers that could be used to predict breast cancer recurrence at an early stage. A case-control retrospective study on 224 patients without postoperative recurrence and 43 patients with postoperative recurrence of breast cancer was performed. The edgeR software package was used to identify the test indicators expressed differently between the two groups. Univariate analysis was used to screen for diagnostic marker that could predict postoperative recurrence of breast cancer. In addition, the differential test indicators at different time points from surgery to recurrence were collected in patients with postoperative recurrence of breast cancer as a verification database. We screened out three test indicators (TBA, GSP, and URBC) for differential expression, which were all expressed downregulated in the postoperative recurrence group of breast cancer. Univariate analysis suggested that only the difference in GSP levels between the two groups was statistically significant (P = 0.001). ROC curve analysis showed that the area under the curve of GSP was 0.662, while the area under the curve of GSP+AFP+CEA+CA125+CA153+age was increased to 0.828. In addition, serum GSP levels were significantly reduced after recurrence compared with before recurrence in breast cancer patients (P < 0.01). In summary, GSP could be used for early diagnosis of breast cancer recurrence after surgery, and the predicted value of combining GSP, tumor markers, and age was better than that of individual indicators.

Abstract P3-01-12: The impact of COVID-19 on diagnosis of recurrent breast cancer

Abstract Background - Physical distancing for COVID-19 led to decreased in-person patient follow up assessments and delayed imaging appointments. Herein we describe for the first time the impact of delays in diagnostic investigations of patients with an history of early-stage breast cancer (BC) in the largest public cancer center of Lombardy, the Italian region most affected by the pandemic. Methods - This single-institution retrospective study included three observational periods. The first pandemic peak period (March-April 2020) corresponding to the interruption of follow up imaging; the post-peak period (May-December 2020); the pre-pandemic period represented by the five previous years (January 2015- December 2019) as control. The flow of diagnostic activities was compared among the different years. Moreover, the number and characteristics of recurrent BC cases (rBC) diagnosed in the post-peak period were compared to the figures observed in pre-pandemic years, when imaging was regularly carried out, using descriptive statistics. A further comparison was performed between the characteristics of scheduled and delayed rBC diagnosed after the first peak. Results - During the first pandemic peak, diagnostic investigations declined by 81.2% (from 1032 in January-February to 194 in March-April), a drop which was not identified in the same period of the pre-pandemic years, before rebounding to 1065 in May-June, 832 July-August (reflecting the summer physiological drop), 1334 September-October, and 879 November-December. The average number of rBC cases of 16 (range 12-25) in March-April of the pre-pandemic period declined to a value as low as 4 during the first pandemic peak. Thereafter, the number of rBC cases began a steady increase, until reaching a total of 27 in September-October 2020, almost doubling the mean of 14.8 (range 11-21) achieved in the corresponding months of 2015-2019. As a result, the absolute number of rBC cases was 76 in 2020 and on average 78.4 (range 70 - 95) in pre-pandemic years, and the rBC proportion of 1.42% (76/5336; 95% exact confidence interval, CI: 1.12-1.78%) in 2020 was slightly higher than the average proportion of 1.26% of the five previous years, though the latter being well included in the CI of the 2020 proportion. No difference in primary tumor presentation and age at initial diagnosis was found among recurrent patients before and after the pandemic. Of the rBC cases reported during 2020, 10 were from 513 patients with postponed follow up who were finally diagnosed between September-December. As compared to patients on schedule, delayed rBC cases did not present with ductal carcinoma in situ, and reported a median tumor size of 18 mm (range 4.3-90 mm), which was 20% higher than the median of 15 mm (3.1-34) observed for scheduled patients. Distribution of luminal-like, triple negative and HER2-overexpressing BC subtypes among evaluable rBC cases was 75%, 12.5%, 12.5% in scheduled and 66%, 11% and 22% in delayed cases, respectively. Conclusions - Our data showed a slight decrease in the absolute number of rBC during 2020 despite a rebound of examinations, and an increased size of invasive recurrence following the 2-month stop of the first pandemic peak. The full impact of the COVID-19 pandemic on recurrent cancer diagnosis will be known when national population-based data become available in the coming years. Citation Format: Serena Di Cosimo, Catherine Depretto, Rosalba Miceli, Paolo Baili, Silva Ljevar, Milena Sant, Claudio Ferranti, Secondo Folli, Massimiliano Gennaro, Filippo G de Braud, Claudio Vernieri, Maria Carmen De Santis, Laura Lozza, Andrea Vingiani, Giancarlo Pruneri, Giovanni Apolone, Alfonso Marchianò, Gianfranco P Scaperrotta. The impact of COVID-19 on diagnosis of recurrent breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-01-12.

Role of Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) in Differentiating Post Therapeutic Changes from Recurrent Malignant Breast Lesions

AbstractBackground: Patients follow-up subsequent to conservative breast therapy (BCT) is essential due to tumor recurrence with rates ranging between 1% and 2% annually. It occurs commonly during a period of 3-7 years after being subjected to BCT. Timely and early detection of breast cancer recurrence is believed to remarkably improve and assist long-term sur-vival.Aim of Study: To assess new advances of Magnetic Res-onance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) in diagnosis of recurrent breast cancer after conservative surgery, chemotherapy and radiotherapy and differentiate it from post therapeutic changes.Patients and Methods: The current study was conducted on 20 patients proved to be breast carcinoma by histopatho-logical grading. Six patients were presented with breast lump, three patients were presented by nipple discharge, four patients were presented by diffuse breast enlargement and seven patients were presented for post-operative follow-up at El-Demerdash Hospital during the period from October 2018 to April 2019.Results: A strong positive correlation is detected between choline peak findings and the level of Ki67, the higher the choline the higher the Ki67 the more aggressiveness is the tumor.Conclusion: Both dynamic contrast enhanced MRI and MRS are valuable tools in the evaluation of post-operative breast having high sensitivity and specificity to differentiate between benign post-operative changes and recurrent malignant tumor. On the other hand, MRI on the breast can assist to avoid unnecessary interventions and optimizes diagnosis of recurrence in its early stages.

Detection of Breast Cancer Recurrence by Using Positron Emission Tomography with 18 Fluorodeoxyglucose (FDG-PET)-Computed Tomography (CT) and Tumor Markers

Abstract Background: Breast cancer is responsible for nearly 15% of death in female cancer related death in western countries and is cosidered the second leading cause to death due to cancer in females. In Egypt, it is the most common cancer in female, representing about 38.8% of total cancer cases in women. Early diagnosis of recurrent breast cancer is crucial to selection of the most appropriate therapy. FDG-PET/CT has been used for diagnosis, staging, monitoring response to therapy, and restaging patients with breast cancer. Although FDG-PET/CT may have limited diagnostic value in detecting small primary breast tumors, in staging of the axillary region, and in detecting osteoblastic metastases, it is superior to conventional imaging modalities in detecting distant metastases and in monitoring response to therapy. Aim of Study: To evaluate the role of PET/CT and tumor markers in detection of breast cancer recurrence in Clinical Radio-Diagnosis Department. Patients and Methods: Twenty five female patients their age was from 22-67 years (mean 43 years) all with breast cancer history and elevated serum tumor markers after their initial diagnosis were retrospectively evaluated. PET/CT results were confirmed by further imaging, and follow-up. Changes in further management based on PET/CT were recorded. Results: The patients' age was from 22-67 years. Most of them were (60%) were premenopausal. In this study, 92% had Infiltrating Ductal Carcinoma (IDC) while only 2 patients (8%) had Infiltrating Lobular Carcinoma (ILC), fourteen patients (56%) had recurrence of tumor, and 11 (44%) patients showed no further evidence of disease. Fourteen patients had abnormal PET/CT studies, and 11 patients had normal studies with an overall sensitivity, specificity, and accuracy of 85.7%, 81.8%, and 84%, respectively. PET/CT was compared with contrast-enhanced CT and had a higher sensitivity (85.7% vs. 71.4%), specificity (81.8% vs. 45.4%), and accuracy (84% vs. 60%). PET/CT was also compared with tumor markers and had a higher sensitivity (85.7% vs. 78.5%), specificity (81.8% vs. 18.1%), and accuracy (84% vs. 52%).Conclusion: FDG-PET/CT was superior to conventional imaging modalities in diagnosis of breast cancer recurrence.

Utility of CA 15-3 in diagnosis of Breast Cancer Recurrence. An Observational Study.

Background : CA 15-3 is the commonest tumor marker for breast cancer. Elevated serum levels of this marker was shown to be a predictor of disease recurrence in patients with localized breast cancer. This study aimed to determine the sensitivity of serum CA 15-3 level in the detection of breast cancer recurrence in relation to the molecular subtype of breast cancer, type of recurrence and the number and sites of distant metastasis.&#x0D; Methods : Retrospective observational study of patients with localized breast cancer followed until relapse. Serum level of CA 15-3 at first documentation of relapse was compared between patients in respect to the molecular subtype of breast cancer, type of recurrence and the number and sites of metastasis. &#x0D; Results : Elevation of CA 15-3 were found in 56% of patients at relapse. Only 6% of patients with locoregional relapse shows elevation of this marker compared with 62% of patients with distant metastasis. Elevation of CA 15-3 were more sensitive for detection of relapse in patients with luminal subtype (62%) than in patients with HER2 enriched (45%) and triple negative (35%) breast cancers. The test was more sensitive in patients with bone (69%), lung (65%) and liver (62%) metastasis than in patients with brain metastasis (25%). &#x0D; Conclusions : CA 15-3 is a relatively sensitive marker for detection of breast cancer recurrence. However, this sensitivity may be hampered in patients with isolated locoregional relapses and in patients with HER2 enriched and triple negative breast cancers.

Seeing results: Outcomes from offering breast cancer survivorship care for more than 10 years.

32 Background: The University of Tennessee Medical Center (UTMCK), Knoxville Tennessee is the region’s sole academic medical center. Annually, 3000 new patients are seen within the Cancer Institute (CI) of UTMCK, and over 13% are breast cancer patients. Under the leadership of our director, Surgical Oncologist Dr. John L. Bell, survivorship care has been offered to these patients for almost twenty years. This combination has created a unique opportunity for us to look at long term results of offering disease-specific survivorship care, and what effect it has made upon detection of recurrence. Methods: Tumor registry data was utilized to examine the influence of survivorship care upon detection of recurrence. All patients treated from 1999 – 2015 with a diagnosis of recurrent breast cancer were selected out of the tumor registry. These patients were then stratified by time to recurrence, and mean, median, and range were calculated in time to recurrence (TR) by month. Results: A total of 223 patients with recurrent breast cancer were identified in our tumor registry out of 4422 total breast cancer patients treated by UTMCK from 1999 – 2015, recurrence rate of 5.04%. The mean TR for this cohort was 43.9 months. The median TR was 33 months, and the range of TR varied from 4 months to 166 months. All patients were followed for a minimum of five years following their diagnosis, and by 60 months, 73.99% of all recurrences were identified. Conclusions: Offering disease specific survivorship care to breast cancer patients is beneficial to both patients and our institution. When recurrence is diagnosed, survivorship care is valuable by helping to identify these cases as early as possible, to get patients back into active treatment sooner in the disease process. We have demonstrated that this is not a recent phenomenon reflective of current practice changes and accreditation requirements, and have validated this with our institution’s long history of providing survivorship care services for breast cancer patients dating back to the last century.

CEA, CA15.3 and 18-FDG PET in the follow-up of early breast cancer (BC) patients (pts): A prospective, multicentric, randomized trial—KRONOS patient-oriented new surveillance study Italy.

TPS11627 Background: Current recommendations for breast cancer (BC) surveillance in asymptomatic patients (pts) include only mammography and physical examination and arise from two trials conducted in the 80’s. Since then new findings about BC biology, treatment and the introduction of cutting-edge diagnostic technologies such as 18-FDG PET have deeply modified our clinical scenarios. The aim of this prospective randomized trial is to verify if the serial measurement of CEA and CA15-3 followed by 18-FDG PET can anticipate the diagnosis of BC recurrence compared to control arm by estimation of the difference of restricted mean survival time (RMST) between the two arms. If the end-point will be met a subsequent extension trial will investigate the impact of the earlier diagnosis of distant metastases on survival. Methods: Pts diagnosed with stage I-III BC, who underwent adequate surgery are eligible. Special histologies and low-risk cases according to St. Gallen criteria are excluded. The study includes pts at the beginning of the follow-up after the conclusion of primary treatment (cohort 1), and pts that have concluded without relapse the first 5 years of follow-up (cohort 2). Eligible pts will be randomized in a 1:1 ratio to follow-up according to local practice (control arm) or to three-monthly serial dosing of CEA and CA15-3 and subsequent 18 FDG-PET only in case of an increase of CEA and/or CA 15.3 greater than a critical difference compared to baseline (experimental arm). The following stratification factors will be used: node negative vs positive, HER2 negative vs positive, ER positive vs negative. Eight-hundred pts will be enrolled over 3 years. For such a calculation, we made the assumption of a 20% baseline 5-year incidence of relapse. The target reduction of three months in RMST implies a median time of diagnostic anticipation, conditional on having BC recurrence, of 10 months. The follow-up will continue until 10 years from surgery. Since 23rd October 2014 573 pts have been enrolled. The present trial was approved by the Ethical Committee of each participating centre and is registered on Clinical trial information: NCT02261389.

Quality of life in patients with recurrent breast cancer after second breast-conserving therapy in comparison with mastectomy: the German experience.

Although some studies suggest that breast-conserving therapy (BCT) shows better psychosocial outcomes than mastectomy in patients with primary breast cancer, little is known about the outcomes of these surgical options in recurrent breast cancer. We investigated differences in overall survival and re-recurrence rates as well as psychosocial outcomes among patients who underwent BCT or mastectomy after the diagnosis of recurrent breast cancer in a single-center setting. 124 of 186 eligible patients who underwent surgical treatment for breast cancer recurrence completed the questionnaires on quality of life (EORTC QLQ-C30 and -BR23), fear of progression (PA-F-KF), anxiety and depression (HADS), and body image (BIS). Women after breast-conserving surgery (n=46) showed significantly better outcomes than women after mastectomy (n=61) with respect to body image (P<0.001 in BIS and p<0.001 in BR23), social functioning (p=0.016), emotional functioning (p=0.028), and role functioning (p=0.043). There were no significant group differences regarding anxiety, depression, and fear of progression as well as re-recurrence and survival rates. Predictors of good quality of life were partnership (OR 2.46), higher monthly family income (OR 3.54), and higher professional qualification (OR 4.3) in our group of patients. Our results indicate that patients treated with breast-conserving therapy after recurrent breast cancer perceive lower impairments in body image and several aspects of quality of life than patients treated with mastectomy.

Abstract OT3-05-01: Three-monthly dynamic evaluation of CEA and CA15-3 (followed by 18-FDG PET) vs usual practice in the follow-up of early breast cancer (BC) patients (pts): A prospective randomized trial (KRONOS-patient-oriented new surveillance study, Italy)

Abstract Background: Current guidelines for BC surveillance in asymptomatic pts recommend annual mammography and periodical physical examination. These recommendations arise from two trials conducted in the 1980's: since then no other randomized controlled trials (RCTs) have been conducted on BC follow-up. However our knowledge on BC biology, diagnosis of metastases and treatment has improved. The aim of this prospective RCT is to verify if the serial measurement of CEA and CA15.3 (followed by 18-FDG PET) can anticipate the diagnosis of breast cancer recurrence compared to control arm. If this intermediate end-point will be met a subsequent extension trial will investigate the impact of the earlier diagnosis of distant metastases on survival. Methods: Pts diagnosed with stage I-III BC, who underwent adequate surgery are eligible. Special histologies and low-risk cases according to St. Gallen criteria are excluded. We will include pts at the beginning of the follow-up after the conclusion of primary treatment (cohort 1), and pts that have concluded without relapse the first 5 years of follow-up (cohort 2). Eligible pts will be randomized in a 1:1 ratio to follow-up according to local practice (control arm) or to three-monthly serial dosing of CEA and CA15.3 and subsequent imaging studies (18-FDG PET) only in case of an increase of CEA and/or CA 15.3 greater than a critical difference (CEA +100% and/or CA15.3 +75%) compared to baseline (experimental arm). The following stratification factors will be used: node negative vs positive, HER2 negative vs positive, ER positive vs negative. Eight-hundred pts will be enrolled over 3 years. For such a calculation, we made the assumption of a 20% 5-year incidence of relapse. The target reduction of 3 months in restricted mean survival time (RMST) between the two arms implies a median time of diagnostic anticipation, conditional on having breast cancer recurrence, of 10 months. The follow-up will continue until 10 years from surgery. The first patient was enrolled on 23rd October 2014, up to now 434 pts have been enrolled. The present trial was approved by the Ethical Commitee of S. Orsola-Malpighi Hospital and is registered on clinicaltrials.gov (NCT02261389). Citation Format: Zamagni C, Gion M, Mariani L, Stieber P, Quercia S, Rubino D, Bernardi A, Cacciari N, Fini A, Lenzi M, Minichillo S, Pizzirani C, Pagliaro M, Tomasini S, Barbieri E. Three-monthly dynamic evaluation of CEA and CA15-3 (followed by 18-FDG PET) vs usual practice in the follow-up of early breast cancer (BC) patients (pts): A prospective randomized trial (KRONOS-patient-oriented new surveillance study, Italy) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-05-01.

Diagnostic efficacy of 18F-FDG-PET or PET/CT in breast cancer with suspected recurrence

The early detection of suspiciously recurrent breast cancer is of significant importance. The aim of the present meta-analysis was to evaluate the overall diagnostic accuracy of fluorine-18 fluorodeoxyglucose (F-FDG)-PET or PET/computed tomography (CT) for the detection of relapse in suspected recurrent breast cancer. Medline, Embase, Web of Science, and Cochrane databases were searched for articles on suspiciously recurrent breast cancer and F-FDG-PET or PET/CT up to 10 January 2016. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC) were calculated. A meta-regression analysis was carried out to explore potential sources of heterogeneity. A total of 26 studies with 1752 patients with suspiciously recurrent breast cancer were included for the analysis; among these, 56.8% because of elevation of tumor markers, in 33.9%, there was suspicion on conventional imaging modalities, and in 9.4%, suggestive clinical symptoms or physical examinations were found. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of F-FDG-PET or PET/CT were 0.90 [95% confidence interval (CI), 0.88-0.90], 0.81 (95% CI, 0.78-0.84), 4.64 (95% CI, 3.50-6.14), 0.12 (95% CI, 0.08-0.16), and 46.52 (95% CI, 29.44-73.51), respectively. In addition, the overall AUC of F-FDG-PET or PET/CT was 0.9358. Meta-regression analysis showed that type of imaging modality (PET over PET/CT) might be a potential source of heterogeneity (P=0.0799). Furthermore, a subgroup analysis indicated that PET/CT appeared to harbor more specificity in the diagnosis of recurrent breast cancer (0.823 vs. 0.796, P=0.035). The increased AUC suggested increased accuracy of PET/CT over PET (0.9477 vs. 0.9111). F-FDG-PET, and in particular F-FDG-PET/CT, seemed to be a more valuable supplement to current surveillance techniques to detect relapse in suspected recurrent breast cancer patients.

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

PurposeThe 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. IntroductionBreast conservation surgery followed by breast radiotherapy and chemotherapy produces changes on both physical examination and on post-treatment breast imaging. Distinguishing these normal treatment-related findings from breast cancer recurrence in the original lumpectomy site or elsewhere in the breast (new primary tumors) is challenging.Our prospective study is done on fifty female patients who had undergone breast-conserving therapy at least 6months since the end of radiation therapy. All cases were suspected for either recurrence or post-operative complications by clinical examination in conjunction with mammography and/or US. Confirmation of different lesions was achieved by fine needle aspiration biopsy, core or excisional biopsy. All patients were examined by dynamic contrast enhanced MRI (DCE-MRI). If one of imaging modalities suspected recurrence, all of the imaging modalities were performed.From our study we concluded that MRI is useful examination that can provide very valuable information in patient with suspected recurrence. It is a technique that offers not only information on lesion cross sectional morphology but also on functional lesion features such as tissue perfusion and enhancement kinetics.

There is more to the picture than meets the eye: Population-based study on biopsy verification of suspected breast cancer recurrences.

542 Background: Core biopsy/Fine needle aspiration (Bx) is recommended to confirm the diagnosis of Recurrent Breast Cancer (RBC). Up to 10% of all Bx are not RBC but benign or other malignancy. Hor...

Breast cancer recurrence in esophagus, stomach, and liver, 15 years following primary surgery: report of a case

Metastasis of breast cancer to the gastrointestinal tract is relatively rare. We hereby report a case of breast cancer recurrence in the esophagus, stomach, and liver, 15 years following primary surgery. A 67-year-old woman presented with a 2-month history of dysphagia. Fifteen years previously, she had undergone right mastectomy for breast carcinoma. Upper gastrointestinal endoscopy revealed circumferential stenosis without mucosal abnormality in the lower esophagus and enlarged gastric folds and defective extension in the upper stomach. Biopsy specimens from the esophagus and gastric folds were consistent with invasive lobular carcinoma. Abdominal computed tomography and magnetic resonance imaging showed two hepatic tumors, and liver biopsy revealed breast cancer recurrence. Immunohistochemistry supported the diagnosis of breast cancer recurrence in the esophagus, stomach, and liver. Gastrointestinal metastases should be considered for patients with breast cancer who present with gastrointestinal symptoms, even if the primary tumor was treated many years previously.

Label-free DNA detection using two-dimensional periodic relief grating as a visualized platform for diagnosis of breast cancer recurrence after surgery

In this study we fabricated a nanopillar array of silicon oxide, involving very-large-scale integration (VLSI) and reactive ion etching (RIE), as two-dimensional periodic relief gratings (2DPRGs) on Si surfaces. Thiolated oligonucleotide was successively immobilized on the thiol functionalized surfaces of 2DPRGs by disulfide bond as an optical probe to detect a human genomic DNA (hgDNA584), related to breast cancer recurrence after surgery, from a biological specimen. The oligonucleotide-bound 2DPRG alone produces insignificant structure change, but upon hybridization with hgDNA584 leads to a dramatic change of the pillar scale due to hgDNA584 filling inside the 2DPRG layers. The performance of the sensor was evaluated by capturing hgDNA584 on the oligonucleotide-bound 2DPRGs and measuring the effective refractive index (neff), resulting of color change from pure blue to red, observed by naked eyes along an incident angle of 20–30°. The surface-bound 2DPRG based assay with the chemoresponsive diffraction grating signal transduction scheme results in an experimentally simple DNA detection protocol, displaying attributes of both detection methodologies: the high sensitivity and selectivity afforded by 2DPRG probes and the experimental simplicity, and miniaturization potential provided by the diffraction-based sensing technology.

The quest for reliable biomarkers to identify new and recurrent cancer

rightly point out that currently approved biomarkers have focused on the assessment of single proteins, even though no single biomarker has demonstrated sufficient sensitivity and reproducibility for clinical use in the diagnosis of breast cancer among individuals presumed to be healthy and disease free. Approved biomarkers for the diagnosis of recurrent breast cancer perform rather poorly and are not in routine use in most large centers. The authors cite investigations with autoantibodies and DNA methylation as holding particular promise in biomarker development for the diagnosis of new and recurrent breast cancer. For many years, prostate-specific antigen (PSA) was considered one of the best diagnostic cancer markers, and was part of clinical practice. However, the lack of specificity of PSA as a marker for prostate cancer, combined with the relatively benign nature of prostate cancer progression in many men who develop the disease has led clinicians to question its continued use. Because national bodies such as the US Preventive Services Task Force now recommend against PSA screening for prostate cancer, the research community has searched for other noninvasive markers such as proteins, circulating tumor cells and nucleic acids in the blood or urine of patients with prostate cancer. As Sardana and Diamandis point out, these markers, in combination with PSA, are being evaluated to develop a multiple-biomarker approach to the diagnosis of new and recurrent prostate cancer [2]. Adenocarcinoma of the pancreas (pancreatic cancer) is generally lethal. The reasons for this are many, but certainly one of the most important is late diagnosis. Survival is rare in the absence of early diagnosis, yet >50% of individuals with very small lesions confined to the pancreas are alive 5 years after diagnosis. Indeed, as Batra et al. point out, pancreatic cancers on average have a relatively long time There has been measurable progress in personalizing the treatment of adult malignancies. Once the diagnosis of cancer is made and the tumor is available, it can be genotyped and phenotyped to optimize the intervention that will be administered. Moreover, large-scale assessment of tumors has allowed the development of targeted therapies based on the mutations that drive tumor progression. Far less progress has been made in the development of biomarkers for the diagnosis of new or recurrent cancer. Perhaps this is not surprising, given the multitude of mutational and epigenetic events that can occur during cancer development and progression. In this issue of Biomarkers in Medicine, we review the state of the science in biomarker development for breast, ovarian, prostate and pancreatic cancer. Tang and Gui review the current state of breast cancer biomarker research, and future directions [1]. They present four principal areas of promise from biomarker development� combining new with established markers to optimize cancer diagnosis; using biomarkers for the early determination of treatment response and disease recurrence/survival; guiding therapy; and facilitating the identification of the most promising drug candidates for therapeutics worthy of further development. The articles in this themed issue focus on the first and second areas� the diagnosis of new and recurrent cancer. The authors review several serum and tissue markers that have been identified as clinically useful in the management of patients with breast cancer. One major advantage of biomarker research for individuals with cancer is the presence of tumor tissue for analysis, which is not present in individuals without such a diagnosis. Tissue sampling in the absence of a suspicion of cancer is difficult to justify. For this reason, body fluid analysis holds greater promise in biomarker development for individuals without the presence of a lesion that requires biopsy. The authors Foreword

A Case of Multidisciplinary Treatment for a Massive Locoregional Recurrence of Breast Cancer

A 36-year-old woman presented to our hospital with a huge tumor, measuring 11 cm in diameter, in her left breast. She had a past history of preoperative systemic chemotherapy and breast-conserving surgery for her left breast cancer 6 months before in another hospital. The tumor fixed stiffly on the chest wall, and invasion to the pectoral muscle was suspected. Because computed tomography showed a small metastatic nodule in the left lung, she initially received systemic chemotherapy. After six cycles of anthracycline treatment, the lung nodule disappeared, while the locoregional tumor remained unchanged (Fig. 1A and B, red arrows). Surgery to reduce the tumor burden and improve her quality of life was proposed, and the patient underwent tumorectomy with autologous latissimus dorsi musculocutaneous flap reconstruction. Macroscopic examination of the resected specimen revealed a large, expanding solid mass (Fig. 2, green arrows) with cystic change indicating tumor necrosis (Fig. 2, blue arrow). Pathologically, the tumor consisted of high-grade invasive ductal carcinoma with massive lymphatic invasion. Because these findings were consistent with those of the primary tumor resected in the previous hospital, the diagnosis of recurrent breast cancer was confirmed. Pathological examination also showed that the tumor was very close to, but not invading, the major pectoral muscle (Fig. 3, black arrows), and most of the tumor cells were viable (chemotherapeutic effect; Grade 0). Two months after the second surgery, locoregional recurrence as well as lung metastasis were detected, and the patient underwent oral fluoropyrimidine S-1 monotherapy.

Use of Magnetic Resonance Imaging in Detection of Breast Cancer Recurrence: A Systematic Review

Diagnosis of breast cancer recurrence can be difficult as a result of the presence of scar tissue in the breast. Magnetic resonance imaging (MRI) may be superior to traditional imaging in diagnosis of recurrence because of its ability to differentiate malignancy from scarring. Current guidelines on investigation of suspected breast cancer recurrence recommend MRI when other investigations have equivocal findings. We performed the first systematic review on this topic. Literature search revealed 35 potentially relevant studies; 10 were included in final analysis. Included were clinical studies comparing MRI with another diagnostic modality for diagnosis of breast cancer recurrence, with at least 10 patients, in the English language. Data extraction focused on sensitivity and specificity of standard diagnostic modalities and MRI for diagnosis of local disease recurrence. In total 494 patients were assessed across 10 studies; all were case series. Sensitivity of MRI for detection of recurrence ranged 75-100 %, while specificity ranged 66.6-100 %. Both sensitivity and specificity increased when MRI was performed after a longer time interval from the original surgery, although the longest follow-up reported was only 36 months. A negative MRI can avoid the need for further biopsy. Available data are based on clinically heterogeneous case series and superiority over standard triple assessment for breast cancer recurrence has not been proven. At present, MRI cannot be recommended in the routine diagnostic assessment for breast cancer recurrence but has a potentially useful role as a second-line investigation. A negative MRI is more useful than a positive MRI as positive MRIs require further investigation.

FDG-PET/CT in the diagnosis of recurrent breast cancer

An advantage of PET/CT has been demonstrated for diagnosis of several tumor entities. In patients with breast cancer, early diagnosis and accurate restaging of recurrence after surgery is important for selection of the most appropriate therapeutic strategy. Purpose To evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG), for follow-up of patients with suspected recurrent breast cancer. Forty-seven patients with suspected recurrent breast cancer underwent PET/CT. The PET and PET/CT images were interpreted without knowledge of the results of other diagnostic modalities, and compared with each other with reference to the final diagnosis. Twenty-five (53%) patients suffered tumor recurrence. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 96%, 91%, 92%, 95%, and 94%, respectively. In comparison with PET, PET/CT had a higher sensitivity and accuracy (96% vs. 80% and 94% vs. 81%, respectively). The difference in diagnostic accuracy between PET/CT and PET was significant (P < 0.05). The present findings indicate that PET/CT is an accurate, sensitive and reliable modality for screening and detection of breast cancer recurrence. PET/CT appears to be an effective surveillance tool, as it is able to cover the whole body in a single procedure and shows good performance.

Recurrent invasive lobular carcinoma presenting as a ruptured breast implant

BackgroundFor years, the treatment for invasive lobular carcinoma (ILC) has been mastectomy secondary to the lack of studies investigating the efficacy of breast conservation therapy on patients afflicted with ILC and due to the lack of long-term follow up investigating locoregional recurrence in this patient population. In this article we report the clinical course of a patient diagnosed with ILC.Case reportWe describe the case of a 50-year-old woman with stage IIB (T2N1M0) ER/PR positive right breast ILC who underwent a right modified radical mastectomy, postoperative chemotherapy, a prophylactic left simple mastectomy with bilateral breast reconstruction and tamoxifen. Approximately 12 years later, she presented with a deflated breast implant and recurrent breast cancer with metastatic spread. She received palliative radiotherapy then palliative chemotherapy. Unfortunately, she succumbed to the cancer less than a year after being diagnosed with metastatic disease.ConclusionsThis may be the first case report of a ruptured breast implant presenting at the same time as the diagnosis of recurrent breast cancer.