Martín Velasco

Preoperative Staging of Large Primary Breast Cancer With [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Compared With Conventional Imaging Procedures

PURPOSE To evaluate the utility of positron emission tomography (PET) and [(18)F]fluorodeoxyglucose in the initial staging of large primary breast tumors. PATIENTS AND METHODS This prospective study was approved by the ethics committee, and all patients gave their informed consent before enrollment. Sixty consecutive patients with large (> 3 cm) primary breast cancer diagnosed by clinical examination and breast magnetic resonance imaging (MRI) were entered onto the study. The mean age was 57 +/- 13 years. Chest computed tomography (CT), liver ultrasonography, bone scan, and PET/CT were performed in all patients. All findings were histologically confirmed, and/or at least 1 year of follow-up was required. Correlation between parameters was calculated using Pearsons correlation coefficient. P < .05 was considered statistically significant. RESULTS Primary tumor was identified by both PET/CT and MRI in all patients. Multifocal and/or multicentric tumors were found in 19 patients by MRI. Axillary lymph node metastases were found in 20 of 52 patients. Extra-axillary metastatic lymph nodes were also found in three patients. One patient showed an infiltrated lymph node in the contralateral axilla. The sensitivity and specificity for PET/CT to detect axillary lymph nodes metastases were 70% and 100%, respectively. PET/CT diagnosed all extra-axillary lymph nodes. The overall sensitivity and specificity of PET/CT in detecting distant metastases were 100% and 98%, respectively; whereas the sensitivity and specificity of conventional imaging were 60% and 83%, respectively. PET led to a change in the initial staging in 42% of patients. CONCLUSION PET/CT underestimates locoregional lymph node staging in large primary breast cancer patients. PET/CT is a valuable tool to discard unsuspected extra-axillary lymph nodes and distant metastases.

Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients

SummaryTo evaluate the utility of CEA and CA 15.3 for early diagnosis of recurrence, serial serum determinations of both antigens were performed in 1023 patients (follow-up: 1–10 years, mean 6.2 years) with primary breast cancer (CA 15.3 in 533 cases) and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). 246 patients developed metastases during follow-up.Results: CEA and CA 15.3 were elevated (> 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis in 40% (98/246) and 41% (37/91) of the patients with recurrence, with a lead time of 4.9 ± 2.2 and 4.2 ± 2.3 months, respectively. When patients with locoregional recurrences were excluded, sensitivity improved to 46% (CEA) and 54% (CA 15.3), and to 64% with both tumor markers (CEA and/or CA 15.3). Higher levels of both CEA and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse, and a higher lead time were found in ER+ (CEA) or PgR+ patients (CA 15.3) than in those that were negative for these receptors in the primary tumor (p < 0.001). Specificity of the tumor markers was 99% for both CEA (777 NED patients) and for CA 15.3 (444 NED patients), respectively. In conclusion, CEA and CA 15.3 are useful tools for early diagnosis of metastases, mainly in those patients with ER+ or PR+ tumors.

Clinical relevance of sentinel lymph nodes in the internal mammary chain in breast cancer patients

PurposeDespite the widespread use of sentinel lymph node (SLN) biopsy in breast cancer patients, some controversy exists about the correct management of extra-axillary nodes, especially those located in the internal mammary chain. The aim of this study was to evaluate the incidence of SLNs in this region, calculate the lymphoscintigraphic and surgical detection rates and evaluate the clinical impact on staging and therapeutic decisions.MethodsThe study involved 383 consecutive women diagnosed with early breast cancer with T1 or T2 tumours. Eight patients had a bilateral tumour, which brought the total to 391 lesions. Lymphoscintigraphy was performed on the day before surgery by injection of 99mTc-labelled nanocolloid. The injection site was subdermal (68 patients), peritumoural (107 patients) or intratumoural (216 patients). During surgery a gamma probe was used to guide the surgeon and the SLNs were removed. SLNs were analysed by a conventional pathological study and processed for H&E examination and immunohistochemistry.ResultsLymphoscintigraphy detected at least one SLN in 369 out of the 391 procedures (94.4%). SLNs were found in the axillary chain in 367 cases and in the internal mammary chain in 55. In two of these 55 cases (3.6%), the SLN was the only one detected. There was no drainage to the internal mammary chain in any case of subdermal injection but such drainage was found in 15.9% of cases with peritumoural injection and 17.6% of those with intratumoural injection. Compared with tumours located in the outer quadrants, a higher percentage of tumours located in the inner quadrants showed drainage to the internal mammary chain (p<0.001). A total of 42 SLNs in the internal mammary chain could be removed in 32 patients without appreciable morbidity. In 20 cases both axillary and internal mammary SLNs were negative, in four both were positive, and in five axillary SLNs were positive and internal mammary SLNs were negative. More interestingly, in the remaining patient with both axillary and internal mammary SLNs, the axillary SLN was negative while malignant cells were found in the internal mammary region. In the evaluation of the clinical impact of internal mammary SLN biopsy, we found that staging was modified from pN1a to pN1c in four patients and, more importantly, from pN0 to pN0(i+) in one patient. The change in stage led to a modification of the postoperative treatment plan with respect to radiotherapy and systemic therapy.ConclusionEvaluation of the SLNs in the internal mammary chain provides more accurate staging of breast cancer patients. If internal mammary sampling is not performed, patients can be understaged. This technique can offer a better indication of those patients who will benefit from selective treatment options like radiotherapy to this region or systemic therapy.

Radiologic and Pathologic Findings in Breast Tumors with High Signal Intensity on T2-weighted MR Images

Various histopathologic components in benign and malignant breast lesions may generate hyperintense signal at T2-weighted magnetic resonance (MR) imaging. A comparison of the specific histologic features found in breast lesions with a high-signal-intensity appearance on unenhanced T2-weighted turbo spin-echo MR images obtained without spectral fat suppression shows that this MR imaging characteristic is often suggestive of the differential diagnosis. Histopathologic features that may produce high signal intensity in breast lesions include extensive necrosis, a cystic or microcystic component, an adipose or sebaceous component, mucinous stroma, loose myxoid stroma, stromal edema, and hemorrhagic changes. A more nuanced understanding of the correlation between the MR imaging appearance and specific pathologic findings may help radiologists achieve earlier and more accurate differentiation among this group of breast lesions.

Prospective Evaluation of Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 15.3 (CA 15.3) in Patients with Primary Locoregional Breast Cancer

BACKGROUND The utility of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) as prognostic factors in primary breast cancer is unclear. METHODS We prospectively studied CEA and CA 15.3 in the sera of 2062 patients with untreated primary breast cancer diagnosed between 1984 and 2008. RESULTS Increased CEA (>5 microg/L) and CA 15.3 (>30 kU/L) concentrations were found in 12.7% and 19.6% of the patients, respectively, and 1 or both tumor markers were increased in 28% (570 of 2062). Increases in each tumor marker correlated with larger tumor sizes and nodal involvement. Tumor size, estrogen receptor (ER), and CEA were independent prognostic factors by multivariate analysis in the total group [disease free survival (DFS) and overall survival (OS)] as well as in node-positive (NP) and node-negative (NN) patients. Nodal involvement and histological grade were independent prognostic factors in the total group as well as in NP patients. By contrast, adjuvant treatment and CA 15.3 were independent prognostic factors only in NN patients (DFS and OS). All patients with CEA >7.5 microg/L had recurrence during follow-up. Use of both tumor markers allowed discrimination of the groups of risk in T1 NN patients: 56.3% of recurrences were seen when 1 or both tumor markers were increased, whereas only 9.4% of recurrences were seen in T1 NN patients without increases of either marker. CONCLUSIONS CEA and CA 15.3 are useful prognostic factors in NP and NN breast cancer patients. CEA >7.5 microg/L is associated with a high probability of subclinical metastases.

A practical approach to intraoperative evaluation of sentinel lymph node biopsy in breast carcinoma and review of the current methods

BackgroundSentinel lymph node (SLN) biopsy is increasingly becoming an alternative method for assessing axillary status in breast carcinoma patients. Intraoperative SLN evaluation can potentially select patients for immediate axillary clearance and spare most of them a second surgical procedure. Nevertheless, no standard protocol for intraoperative SLN evaluation has been developed. The aims of this study were to establish the reliability of SLN intraoperative evaluation in breast carcinoma staging, to review the published methods currently used, and to propose a standard protocol.MethodsOne hundred fifty-two SLNs were collected from 86 patients. Lymphoscintigraphy, blue dye, and gamma camera intraoperative controls were used for localization. Each SLN was sliced 2 mm thick and was intraoperatively evaluated by using the combination of frozen section and imprint cytology. The final examination included standard hematoxylin and eosin staining, and, in case of persistent negativity, further sectioning, including hematoxylin and eosin combined with immunohistochemistry (CAM5.2 cytokeratin), was performed.ResultsThe combination of frozen section and imprint cytology for intraoperative SLN evaluation yielded an intraoperative sensitivity of 78% and a specificity of 100%. All macrometastases (>2 mm) were detected during surgery, as were 2 micrometastases. Final examination detected seven more micrometastases, six of which consisted of isolated tumor cells.ConclusionsWe propose a fast, cost-effective, and accurate procedure for SLN evaluation that is useful for making intraoperative decisions, feasible for most institutions, and reliable because of its high sensitivity (100% for macrometastases) and specificity.

Predicting Non-Sentinel Lymph Node Status in Breast Cancer Patients with Sentinel Lymph Node Involvement: Evaluation of Two Scoring Systems

Abstract:  The aim of this study was to validate a nomogram and a scoring system to predict non‐sentinel lymph node status in breast cancer patients with sentinel lymph node (SLN) involvement. A total of 516 breast cancer patients underwent sentinel lymph node biopsy at our institution from January 2001 to August 2006. A prospective database was used to identify breast cancer patients with a positive SLN biopsy examination who underwent a completion axillary lymph node dissection. A total of 114 patients were identified. The Memorial Sloan‐Kettering Cancer Center (MSKCC) nomogram and an axilla scoring system from Paris (Hôpital Tenon) were used to predict the probability of having non‐SLN involvement. One hundred fourteen patients were included in the study. The areas under the receiver operating characteristics (ROC) curves were 0.671 (95% CI: 0.552–0.790) for the MSKCC nomogram and 0.703 (95% CI: 0.596–0.811) for the Tenon score. The univariate analysis shows that size of SLN metastases, the number of positive and negative SLN and the proportion of positive SLN were statistically significant. On multivariate logistic regression analysis, the size of SLN metastases and the proportion of positive SLN were statistically significant. The two scoring systems are similar according to their area under ROC curves, but should be improved to be valid and determinant to the general population. Meanwhile, the use of scoring systems could be applied in an individual manner in some patients.

Single reading with computer-aided detection performed by selected radiologists in a breast cancer screening program.

OBJECTIVES To assess the impact of shifting from a standard double reading plus arbitration protocol to a single reading by experienced radiologists assisted by computer-aided detection (CAD) in a breast cancer screening program. METHODS This was a prospective study approved by the ethics committee. Data from 21,321 consecutive screening mammograms in incident rounds (2010-2012) were read following a single reading plus CAD protocol and compared with data from 47,462 consecutive screening mammograms in incident rounds (2004-2010) that were interpreted following a double reading plus arbitration protocol. For the single reading, radiologists were selected on the basis of the appraisement of their previous performance. RESULTS Period 2010-2012 vs. period 2004-2010: Cancer detection rate (CDR): 6.1‰ (95% confidence interval: 5.1-7.2) vs. 5.25‰; Recall rate (RR): 7.02% (95% confidence interval: 6.7-7.4) vs. 7.24% (selected readers before arbitration) and vs. 3.94 (all readers after arbitration); Predictive positive value of recall: 8.69% vs. 13.32%. Average size of invasive cancers: 14.6±9.5mm vs. 14.3±9.5mm. Stage: 0 (22.3/26.1%); I (59.2/50.8%); II (19.2/17.1%); III (3.1/3.3%); IV (0/1.9%). Specialized breast radiologists performed better than general radiologists. CONCLUSIONS The cancer detection rate of the screening program improved using a single reading protocol by experienced radiologists assisted by CAD, at the cost of a moderate increase of the recall rate mainly related to the lack of arbitration.

Neoadjuvant Systemic Therapy in Breast Cancer: Association of Contrast-enhanced MR Imaging Findings, Diffusion-weighted Imaging Findings, and Tumor Subtype with Tumor Response

Purpose To investigate the performance of tumor subtype and various magnetic resonance (MR) imaging parameters in the assessment of tumor response to neoadjuvant systemic therapy (NST) in patients with breast cancer and to outline a model of pathologic response, considering pathologic complete response (pCR) as the complete absence of any residual invasive cancer or ductal carcinoma in situ (DCIS). Materials and Methods This was an institutional review board-approved retrospective study, with waiver of the need to obtain informed consent. From November 2009 to December 2014, 111 patients with histopathologically confirmed invasive breast cancer who were undergoing NST were included (mean age, 54 years; range, 27-84 years). Breast MR imaging was performed before and after treatment. Presence of late enhancement was assessed. Apparent diffusion coefficients (ADCs) were obtained by using two different methods. ADC ratio (mean posttreatment ADC/mean pretreatment ADC) was calculated. pCR was defined as absence of any residual invasive cancer or DCIS. Multivariate regression analysis and receiver operating characteristic analysis were performed. Results According to their immunohistochemical (IHC) profile, tumors were classified as human epidermal growth factor receptor 2 (HER2) positive (n = 51), estrogen receptor (ER) positive/HER2 negative (n = 40), and triple negative (n = 20). pCR was achieved in 19% (21 of 111) of cases; 86% of them were triple-negative or HER2-positive subtypes. Absence of late enhancement at posttreatment MR imaging was significantly associated with pCR (area under the curve [AUC], 0.85). Mean ADC ratio significantly increased when pCR was achieved (P < .001). A κ value of 0.479 was found for late enhancement (P < .001), and the intraclass correlation coefficient for ADCs was 0.788 (P < .001). Good correlation of ADCs obtained with the single-value method and those obtained with the mean-value methods was observed. The model combining the IHC subtype, ADC ratio, and late enhancement had the highest association with pathologic response, achieving an AUC of 0.92 (95% confidence interval: 0.86, 0.97). Conclusion Triple-negative or HER2-positive tumors showing absence of late enhancement and high ADC ratio after NST are associated with pCR.

Dynamic Contrast-Enhanced MRI Reveals the Extent and the Microvascular Pattern of Breast Ductal Carcinoma In Situ

To report the role of magnetic resonance imaging (MRI) in assessing the extent of breast ductal carcinoma in situ (DCIS). To assess whether the microvascularity pattern in DCIS correlates with magnetic resonance enhancement. Eighty‐five histologically proven DCIS (77 pure DCIS, eight microinvasive DCIS) were prospectively studied with MRI. The morphology of magnetic resonance enhancement and the kinetic curve was recorded. Histopathologically, intraductal lesions were classified according to Van Nuys score. Tumor microvascularity was immunohistochemically assessed in a subset of 24 DCIS evaluating the number of microvessels, microvascularity area, and microvascularity pattern (diffuse or periductal). On the mammogram, 74% of DCIS appeared as microcalcifications. On MRI, 70% of DCIS showed enhancement. Non‐mass‐like uptake was observed in 78% of cases. The mean size of nonenhancing carcinomas was significantly lower than that of enhancing carcinomas (p = 0.033). The diffuse pattern was more frequent than the periductal pattern. A significant relationship between the morphology of MR enhancement and the microvascularity pattern was observed (p = 0.036); thus, 90% of DCIS showing segmental enhancement on MRI displayed a diffuse pattern while all DCIS with ductal enhancement showed a periductal pattern. There was a significant relationship between the maximum area of microvascularity and the vascular pattern (p = 0.015); periductal patterns showed larger areas than diffuse patterns. The lesion size was significantly larger as the Van Nuys score increased (p < 0.001) and was also related to the number of microvessels (p = 0.012). The mean area of microvascularity of DCIS was significantly larger as the Van Nuys score increased (p = 0.02). Breast MRI helps depict the extent of DCIS and reveals its microvascular pattern.