Presence Of Axillary Lymph Node Metastasis Research Articles

Deep learning radiomics for prediction of axillary lymph node metastasis in patients with clinical stage T1-2 breast cancer.

This study investigates whether deep learning radiomics of conventional ultrasound images can predict preoperative axillary lymph node (ALN) status in patients with clinical stages T1-2 breast cancer (BC). This study retrospectively analyzed the preoperative ultrasound data of 892 patients with BC, who were classified into training (n=535), validation (n=178), and test (n=179) cohorts. Linear combinations of the selected features were weighted by their coefficients to obtain the predicted score. Then, deep learning radiomic features were extracted from the ultrasound images to evaluate the ALN status. Receiver-operating characteristic curves were drawn, followed by the calculation of the area under the curve (AUC) to assess the accuracy of the prediction model in predicting axillary lymph node metastasis (ALNM) in the three cohorts. Deep learning radiomics combined with radiomics and clinical parameters was the optimal diagnostic predictor of the ALN status in the absence and presence of ALNM, with the AUC of 0.920 (95% confidence interval: 0.872 and 0.968, respectively). Additionally, this combination could also differentiate low-load ALNM [N + (1-2)] from heavy-load ALNM with ≥3 positive nodes [N + (≥3)] in the test cohort, with the AUC of 0.819 (95% confidence interval: 0.568 and 1.00, respectively). Conclusively, deep learning radiomics of ultrasound images is a non-invasive approach to predicting preoperative ALNM in BC.

Correlation Among Tumor Size, Histopathological Grade and the Expression of RAC1 Protein with Breast Cancer Metastasis to Ipsilateral Axillary Lymph Nodes

Breast cancer (BC) is the most common cancer affecting women worldwide. Mastectomy is the standard treatment for breast cancer. The purpose of axillary lymph nodes (ALN) dissection in mastectomy is to examine the status and the presence of metastasis in ALN. This study is an analytic observational cross-sectional study coupled with a categorical comparative study in 60 BC patient’s with- and without-ALN metastasis. The data that used in this study were histopathological data from patients medical record and immunohistochemistry (IHC) of RAC1 expression data. The immunohistochemistry was performed with a cutoff point based on the result of a receiver operating characteristics (ROC). This study combined BC tumor size, histopathological grade, and expression of RAC1 protein in correlation with known risk factors on metastasis to ALN. From 60 subjects, there were 63.3 % (38) ALN (+) and 36.7 % (22), ALN (−). BC of T2 tumor size, grade 2 and RAC1(−), the ALN metastasis chance was 0.6 %. T2 tumor size, grade 2 and RAC1(+), the ALN metastasis chance was 4.5 %. T2 tumor size, grade 3 and RAC1(−), the ALN metastasis chance was 3.0 %. T2 tumor, grade 3 and RAC1(+), the ALN metastasis chance was 18.8 %; T3 tumor size, grade 3 and RAC1(−), the ALN metastasis chance was 12.7 %. T3 tumor size, grade 3 and RAC1(+), the ALN metastasis chance was 52.2 %; T4b tumor size, grade 3, RAC1(−) and RAC1(+), the ALN metastasis chance was 40.8 and 83.8 %, respectively. We conclude that smaller tumor size and lower histopathological grading with RAC1(−) has lesser possibility to ALN metastasize. HIGHLIGHTS Breast cancer (BC) is a malignant neoplasm originating from epithelial cells of the ducts and breast glands in the area of the lobules and terminal ducts known as the terminal duct lobular unit (TDLU) and the surgery performed is breast-conserving treatment or mastectomy that examine the status and the presence of metastasis in ALN RAC1 is a member of the RHO-GTPase family that plays an important role in the migration process, loss of adhesions between cells, and tumor metastasis also found in BC so it was used as parameter in this study Tumor size, histopathological grading, and the expression of RAC1 protein has correlation with with BC metastasis to the axillary lymph nodes that the smaller the tumor size, the lower the histopathological grading with RAC1(-) GRAPHICAL ABSTRACT

A Clinical-Radiomics Model for Predicting Axillary Pathologic Complete Response in Breast Cancer With Axillary Lymph Node Metastases.

PurposeTo develop a clinical–radiomics model based on radiomics features extracted from MRI and clinicopathologic factors for predicting the axillary pathologic complete response (apCR) in breast cancer (BC) patients with axillary lymph node (ALN) metastases.Materials and MethodsThe MR images and clinicopathologic data of 248 eligible invasive BC patients at the Peking University First Hospital from January 2013 to December 2020 were included in this study. All patients received neoadjuvant chemotherapy (NAC), and the presence of ALN metastases was confirmed through cytology pre-NAC. The data from January 2013 to December 2018 were randomly divided into the training and validation sets in a ratio of 7:3, and the data from January 2019 to December 2020 served as the independent testing set. The following three types of prediction models were investigated in this study. 1) A clinical model: the model was built by independently predicting clinicopathologic factors through logistic regression. 2) Radiomics models: we used an automatic segmentation model based on deep learning to segment the axillary areas, visible ALNs, and breast tumors on post-NAC dynamic contrast-enhanced MRI. Radiomics features were then extracted from the region of interest (ROI). Radiomics models were built based on different ROIs or their combination. 3) A clinical–radiomics model: it was built by integrating radiomics signature and independent predictive clinical factors by logistic regression. All models were assessed using a receiver operating characteristic curve analysis and by calculating the area under the curve (AUC).ResultsThe clinical model yielded AUC values of 0.759, 0.787, and 0.771 in the training, validation, and testing sets, respectively. The radiomics model based on the combination of MRI features of breast tumors and visible ALNs yielded the best AUC values of 0.894, 0.811, and 0.806 in the training, validation, and testing sets, respectively. The clinical–radiomics model yielded AUC values of 0.924, 0.851, and 0.878 in the training, validation, and testing sets, respectively, for predicting apCR.ConclusionWe developed a clinical–radiomics model by integrating radiomics signature and clinical factors to predict apCR in BC patients with ALN metastases post-NAC. It may help the clinicians to screen out apCR patients to avoid lymph node dissection.

Prognostic Prediction of BRCA Mutations by 18F-FDG PET/CT SUVmax in Breast Cancer

Objectives:This study aimed to investigate the prognostic prediction of germline BRCA1 and BRCA2 mutations by comparing the maximum standardized uptake value (SUVmax) obtained from 18fluoride-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), which is considered a prognostic factor in breast cancer (BC).Methods:Retrospective interdisciplinary laboratory results of 92 patients with BC who had germline BRCA1 or BRCA2 mutation profiles and underwent 18F-FDG PET/CT were compared. Genotyping was made by next-generation sequencing, and PET/CT scans were re-evaluated. The histopathological data, genetic results, and clinical demographics of all patients were recorded. Patients were divided into two groups in accordance with the presence of germline BRCA1 and/or BRCA2 mutations. Between-group statistical comparison was performed.Results:In PET/CT performed for primary staging, patients with BRCA-positive BC had significantly higher SUVmax (p=0.039), larger tumor size (p=0.025), and presence of axillary nodal metastases (p=0.023) than patients with BRCA-negative BC. Although the Ki-67 index was higher in the BRCA-positive group than BRCA-negative group, this difference was not significant (p=0.157). Moreover, in the BRCA-positive and negative groups, SUVmax, Ki-67 index, and tumor size, grade, and stage were significantly correlated with each other.Conclusion:The results of this study showed a strong association between BRCA mutations and SUVmax, which indicates the poor prognosis of BC.

Metabolic and volume-based parameters of (18F)FDG PET/CT for primary mass and axillary lymph node metastasis in patients with invasive ductal carcinoma: a retrospective analysis in relation to molecular subtype, axillary lymph node metastasis and immunohistochemistry and inflammatory markers.

To evaluate metabolic and volume-based parameters of 18-Fluorodeoxyglucose positron emission tomography/computed tomography ((F)FDG PET/CT) for primary mass and axillary lymph node (ALN) metastasis in relation to molecular subtype, and immunohistochemistry and inflammatory markers in patients with invasive ductal carcinoma. A total of 129 patients (mean±SD age: 49.2±13.0 years) with invasive ductal breast cancer who had (F)FDG PET/CT imaging prior to chemotherapy or surgery were included in this single-center retrospective study. Data on patient age, molecular subtype, ALN metastasis status, inflammatory markers, immunohistochemistry markers and (F)FDG PET/CT imaging parameters for primary mass and ALN were recorded. ALN metastasis was evident in 52.7% of patients and associated with significantly higher median diameter (P=0.027), MTV (P<0.001) and TLG (P<0.001). NLR was positively correlated with all primary mass (p ranged from 0.041 to 0.001) and ALN (P ranged from 0.026 to <0.001) PET parameters. PET parameters did not change with respect to molecular subtype or immunohistochemistry markers. Primary mass and ALN metastasis PET parameters showed significant positive correlations for TLG (r=0.274, P=0.001) and SUVmax (r=0.358, P<0.001). In conclusion, our findings in a retrospective cohort of invasive ductal breast cancer patients revealed primary mass PET parameters to significantly differ with respect to ALN metastasis status and NLR levels, but not according to molecular subtype or immunohistochemistry markers. Accordingly, our findings highlight the value of acquisition of preoperative PET/CT imaging and role of both metabolic and volume-based parameters in predicting aggressiveness of the tumor as correlated with presence of ALN metastasis and high NLR.

A predictive factor for axillary lymph node metastasis in invasive ductal breast cancer: the value of tumor and breast volume ratio

Background: The objective of this study was to witness the effect of tumor volume/breast volume ratio on the presence of axillary lymph node metastasis and to examine the strategy in surgical treatment approach for patients.Methods: This study was carried out prospectively by examining the patients undergoing modified radical mastectomy surgery due to breast cancer (n=99). Breast volumes were measured through liquid overflow method in graduated bowl tumor volume was measured according to ellipsoid volume formula with diameters determined by pathological specimen, ultrasonography or MRI.Results: Axillary lymph node metastasis (ALNM) was positive in 64.6% of them (n=64). Average breast volume was found to be 693.89cm³ in the measurement of mastectomy materials. Average tumor volume was found to be 9.58cm³. In line with these results, average tumor volume/breast volume (vTm/vMm) ratio was: 0.0176. Author found axillary lymph node metastasis possibility significantly higher in patients with vTm/vMm ratio&gt;0.016 (Odds ratio 9.437, p-value 0.007).Conclusions: The presence of ALNM is the most important factor in indicating the prognosis of patients with invasive breast cancer and planning the treatment. Thus, knowing whether there exists an ALNM or not during preoperative period draws the attention of both the doctors performing treatment and patients. In this study efficiencies of largest tumor diameter, tumor volume and tumor volume (vTm)/Breast volume (vMm) ratio in indicating ALNM presence in cases with T2 invasive ductal breast cancer were evaluated. It was found that vTm/vMm ratio was a recent and effective prognostic criterion in determining ALNM.

Tumor characteristics of lung cancer in predicting axillary lymph node metastases

AimIn lung cancer, axillary lymph node metastases (ALM) are rare, and according to the 8th grading system, it is classified as M1b disease. The aim of this study is to evaluate (i) the presence of ALM, and (ii) the effect of the primary tumors characteristics on the development of ALM. MethodsWe performed a descriptive cross-sectional study, with retrospective revision, to identify ALM. ResultsThere were 157 patients included in this analysis: ALM (63 patients) and control group (94 patients). The presence of extrathoracic lymph node, contralateral pulmonary parenchymal and distant metastasis and all SUVmax values were significantly higher in the study group versus the control group (p<0.05). The SUVmax value of the primary tumor was not a predictor of ALM. According to the primary histopathologic diagnosis, small cell lung cancer was found to cause ALM development 3.4 times as much as squamous cancer (SQC) (OR: 3.40 (95% CI 1.3–10.20), p=0.029) and adenocarcinoma group was found to cause ALM development 4 times as much as SQC (OR: 4.02 (95% CI 1.73–9.34), p=0.001). The likelihood of developing ALM was significantly higher in tumor located in the central and upper lobe versus the lower lobe. ConclusionThe finding of ALM on PET/CT images, the necessity of histopathologic confirmation is determined according to the results of primary tumor localization, primary tumor histopathology, M stage on PET/CT imaging, localization of ALM according to primary tumor, and N stage on PET/CT imaging.

Early-stage invasive ductal carcinoma: Association of tumor apparent diffusion coefficient values with axillary lymph node metastasis

PurposeTo evaluate any association between tumor apparent diffusion coefficient (ADC) values and axillary lymph node metastasis (ALNM) in early-stage invasive ductal carcinoma. Materials and methodsRecords of 270 invasive ductal carcinoma patients with stages T1 and T2 disease who underwent breast magnetic resonance imaging, including diffusion-weighted imaging with b values of 0 and 1000s/mm2 were reviewed retrospectively. The tumor ADC values were analyzed for their utility in predicting ALNM using multivariate regression analysis and receiver operating characteristic (ROC) curve analysis. ResultsOf the 270 patients, 58 (21.5%) experienced ALNM. The mean tumor ADC values were significantly lower in patients with ALNM than in those without metastasis (0.880×10−3 vs. 0.999×10−3mm2/s, P<0.001). A ROC curve demonstrated a tumor ADC value of 0.991×10−3mm2/s to be the optimal cut-off for predicting ALNM. In a multivariate analysis, lower tumor ADC (≤0.991×10−3mm2/s; adjusted odds ratio (OR)=5.861, P<0.001), large tumor size (>2cm; adjusted OR=3.156, P=0.002) and the presence of lymphovascular invasion (adjusted OR=4.125, P<0.001) were independent variables associated with ALNM. When tumor ADC value was added to known risk factors (i.e., tumor size and lymphovascular invasion), a significant improvement in the accuracy of risk prediction for axillary node metastasis was shown (c-statistic=0.758 vs. 0.816, P=0.026). ConclusionIn early-stage invasive ductal carcinoma, lower tumor ADC values are associated with the presence of ALNM.

Targeting and limiting surgery for patients with node-positive breast cancer.

The presence of axillary nodal metastases has a significant impact on locoregional and systemic treatment decisions. Historically, all node-positive patients underwent complete axillary lymph node dissection; however, this paradigm has changed over the last 10 years. The use of sentinel lymph node dissection has expanded from its initial role as a surgical staging procedure in clinically node-negative patients. Clinically node-negative patients with small volume disease found on sentinel lymph node dissection now commonly avoid more extensive axillary surgery. There is interest in expanding this role to node-positive patients who receive neoadjuvant chemotherapy as a way to restage the axilla in hopes of sparing women who convert to node-negative status from the morbidity of complete nodal clearance. While sentinel lymph node dissection alone may not accomplish this goal, there are novel techniques, such as targeted axillary dissection, that may now allow for reliable nodal staging after chemotherapy.

Detection of micro-metastases by serial sectioning and immuno-histochemical validation of sentinel nodes in patients with breast carcinoma

Background Examination of sentinel lymph node (SLN) biopsy can give accurate nodal staging for breast cancer and assist in the management of patients. Serial sectioning and immuno-histochemical (IHC) staining of SLN can improve detection of micro-metastases. Methods Twenty-five patients with clinically node-negative breast cancer were recruited. A combination of radiotracer and blue-dye were used for identification of SLN. The nodes were thinly sliced and embedded. Serial sectioning and immuno-histochemical staining against AE1/3 were done if initial H&E sections were negative. Results Three cases (12%) had no tumour at initial H&E sections but tumour was found at serial levels and with IHC validation. These were micro-metastases of less than 2 mm diameter. Four other cases with macro-metastases were found at initial H&E sections of the SLN. Three false negative cases had axillary nodal (ALN) metastases with no tumour in the SLN despite levelling and IHC staining. Discussion and conclusion Thin slicing of tissue and serial sectioning improved the detection of micro-metastases. However, immuno-histochemical validation did not additionally increase the sensitivity of detection. The presence of ALN metastases without SLN involvement could be due to discontinuous or skip metastases to non-sentinel nodes or poor technique resulting in missed detection of the SLN.

Feasibility of sentinel lymph node biopsy in breast cancer patients clinically suspected of axillary lymph node metastasis on preoperative imaging

BackgroundGenerally, sentinel lymph node biopsy (SLNB) is performed in patients with clinically negative axillary lymph node (LN). This study was to assess imaging techniques in axillary LN staging and to evaluate the feasibility of SLNB in patients clinically suspected of axillary LN metastasis on preoperative imaging techniques (SI).MethodsA prospectively maintained database of 767 breast cancer patients enrolled between January 2006 and December 2009 was reviewed. All patients were offered preoperative breast ultrasound, magnetic resonance imaging, and positron emission tomography scanning. SI patients were regarded as those for whom preoperative imaging was “suspicious for axillary LN metastasis” and NSI as “non-suspicious for axillary LN metastasis” on preoperative imaging techniques. Patients were subgrouped by presence of SI and types of axillary operation, and analyzed.ResultsFor 323 patients who received SLNB, there was no statistically significant difference in axillary recurrence (P=0.119) between SI and NSI groups. There also was no significant difference in axillary recurrence between SLNB and axillary lymph node dissection (ALND) groups in 356 SI patients (P=0.420). The presence of axillary LN metastasis on preoperative imaging carried 82.1% sensitivity and 45.9% specificity for determining axillary LN metastasis on the final pathology.ConclusionsSLNB in SI patents is safe and feasible. Complications might be avoided by not performing ALND. Therefore, we recommend SLNB, instead of a direct ALND, even in SI patients, for interpreting the exact nodal status and avoiding unnecessary morbidity by performing ALND.

P4-09-16: Factors Affecting the Development of Axillary Lymph Node Metastases in T1a-T1b Breast Cancers.

Abstract Background: The presence of axillary nodal metastases is a poor prognostic indicator in patients with breast cancer. In the majority of patients, axillary nodal involvement correlates with tumor size and most commonly in tumors greater that 1 cm. Many series report an incidence of axillary nodal metastases in 3–37% of patients with tumors less than or equal to 2 cm. The presence of axillary nodal metastases will often change the stage of the cancer and role of adjuvant systemic treatment; therefore, it is important to understand what features are associated with these small lymph node positive tumors. The purpose of this study is to identify characteristics of T1a and T1b breast cancers that present with axillary nodal metastasis. Methods: A retrospective review of a prospective database identified 878 patients with T1a and T1b breast cancer. Pathologic features including tumor grade, hormone receptor status, lymphatic and vascular invasion, Her-2 neu status, and tumor histology were examined in patients with and without axillary nodal metastases. Pearson's χ2 test along with stepwise linear regression analysis were used to determine which factors were associated with the development of axillary nodal metastases. Results: There were 289 T1a lesions and 589 T1b lesions studied. Four independent variables were found to be associated with axillary nodal metastases in T1a-T1b breast cancer. As illustrated in Table 1, a significant difference was seen in nodal positivity among patients with ER negative tumors compared to those with ER positive tumors (p=.0000). An increased incidence of nodal positivity was also observed among patients with LVI compared with those without LVI (p= .0000). A significant difference was observed in nodal positivity among patients with perineural invasion compared to those without (p=.0006). An increased incidence of nodal positivity was also observed among T1a and T1b tumors with a higher histologic grade (p= 0409, p= .0001). Of note, when comparing T1a to T1b breast cancers, there was no significant difference found among the identified exposure variables of interest. Conclusion: In this series, the overall prevalence of nodal positivity in T1a and T1b breast cancer is 12%. An absence of a relationship between T1a and T1b cancers with nodal positivity was observed. However, the presence of nodal positivity showed a significant correlation with ER negativity, LVI, perineural invasion, and higher histologic grades. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-16.

Fluorouracil, Epirubicin, and Cyclophosphamide With Either Docetaxel or Vinorelbine, With or Without Trastuzumab, As Adjuvant Treatments of Breast Cancer: Final Results of the FinHer Trial

Docetaxel has not been compared with vinorelbine as adjuvant treatment of early breast cancer. Efficacy and long-term safety of a short course of adjuvant trastuzumab administered concomitantly with chemotherapy for human epidermal growth factor receptor 2 (HER2) -positive cancer are unknown. One thousand ten women with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive three cycles of docetaxel or vinorelbine, followed in both groups by three cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC). Women with HER2-positive cancer (n = 232) were further assigned to either receive or not receive trastuzumab for 9 weeks with docetaxel or vinorelbine. The median follow-up time was 62 months after random assignment. Women assigned to docetaxel had better distant disease-free survival (DDFS) than those assigned to vinorelbine (hazard ratio [HR] = 0.66; 95% CI, 0.49 to 0.91; P = .010). In the subgroup of HER2-positive disease, patients treated with trastuzumab tended to have better DDFS than those treated with chemotherapy only (HR = 0.65; 95% CI, 0.38 to 1.12; P = .12; with adjustment for presence of axillary nodal metastases, HR = 0.57; P = .047). In exploratory analyses, docetaxel, trastuzumab, and FEC improved DDFS compared with docetaxel plus FEC (HR = 0.32; P = .029) and vinorelbine, trastuzumab, and FEC (HR = 0.31; P = .020). The median left ventricular ejection fraction of trastuzumab-treated patients remained unaltered during the 5-year follow-up; only one woman treated with trastuzumab was diagnosed with a heart failure. Adjuvant treatment with docetaxel improves DDFS compared with vinorelbine. A brief course of trastuzumab administered concomitantly with docetaxel is safe and effective and warrants further evaluation.

Impact of axillary nodal metastases on lymphatic mapping and sentinel lymph node identification rate in patients with early stage breast cancer

The aim of this study was to define the impact of the presence of axillary nodal metastases on lymphatic mapping and sentinel lymph node (SLN) identification rate in patients with early breast cancer. Two hundred and forty-six lymphatic mapping procedures were performed with both labelled nanocolloid and blue dye, followed by SLN biopsy and/or complete axillary dissection. The following parameters were recorded: patient's age, tumour laterality and location, tumour size, tumour histology, tumour stage, tumour grade, lymphovascular invasion, radiotracer injection site (subdermal-peritumoural/peri-areolar), SLN visualisation at lymphoscintigraphy, SLN metastases (presence/absence, size) and other axillary metastases (presence/absence, number). Discriminant analysis was used to analyse the data. SLNs were identified by labelled nanocolloid alone in 94.7% of tumours, by blue dye alone in 93.5% and by the combined technique in 99.2%. Discriminant analysis showed the gamma probe SLN identification rate to be significantly limited by the presence of axillary nodal metastases. In particular, the size of SLN metastases and the number of other axillary metastases were the most important variables in reducing the gamma probe SLN identification rate (p = 0.004 and p = 0.002, respectively). On the other hand, high tumour grade was the only parameter limiting the blue dye SLN identification rate. The accuracy of lymphatic mapping with labelled nanocolloid is limited by the presence of axillary nodal metastases, and particularly by the degree of SLN tumoural invasion and the presence and number of other axillary nodal metastases. Neither of these elements seems to interfere with the blue dye identification rate. The combination of the two tracers maximises the SLN identification rate.

Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma.

The outcome and prognostic factors of 217 women with invasive lobular carcinoma (ILC) and those of 1121 women with invasive ductal carcinoma (IDC) of the breast were compared. The patients were followed up for 10-43 years. Women with ILC had axillary nodal metastases less frequently than those with IDC (43% vs 53%, P = 0.02), although there was no difference in the primary tumour size between the groups. ILCs were more frequently of low grade, had lower mitotic counts and had less tumour necrosis. Furthermore, ILCs had lower S-phase fractions and were more often DNA diploid in flow cytometric analysis than IDCs (P < 0.0001 for all comparisons). The 5- and 30-year corrected survival rates of women with ILC were 78% and 50%, respectively, compared with 63% and 37% for women with IDC (P = 0.001). Small pT1NOMO ILCs (n = 41) had 100% 10-year and 83% 20-year corrected survival rates. In a multivariate analysis, a large primary tumour size, the presence of axillary nodal metastases, a high mitotic count and the presence of tumour necrosis all had an independent prognostic value in ILC. We conclude that ILC is associated with better survival than IDC.

DNA index and S-phase fraction and their combination as prognostic factors in operable ductal breast carcinoma

The prognostic significance of DNA ploidy, DNA index (DI), and S-phase fraction (SPF) and their various combinations were studied together with 16 other clinicopathologic factors in 222 patients with operable invasive ductal breast carcinoma. The patients have been followed for a minimum of 22 years after the diagnosis or until death. Nuclear DNA content was determined by flow cytometry from paraffin-embedded tissue. Patients with DNA diploid cancer (n = 57, 26%) had better survival rate corrected for intercurrent deaths than patients with nondiploid cancer (P = 0.002), and also, a small SPF (less than or equal to 14%, calculated in 134 cases) was associated with a favorable outcome in a univariate analysis (P = 0.01). The prognostic value of the DI and SPF was increased if they were combined. The most effective combination was obtained if diploid cancers were grouped together with DNA aneuploid cancers with a DI less than 2.1 and an SPF less than 14%. This combination had considerable prognostic value in a univariate analysis (P = 0.0002) and had independent prognostic value (P = 0.04) in Cox's multivariate analysis together with the primary tumor size (P less than 0.001) in axillary node negative patients but not in axillary node positive patients. In the whole series the presence of axillary nodal metastases (P less than 0.001), high mitotic count (P less than 0.001), a large primary tumor size (P = 0.001), poorly circumscribed tumor margin (P = 0.005), and slight or absent tubule formation (P = 0.05) were the only independent prognostic factors in a multivariate analysis.

Comparison of immunocytochemical and biochemical assays for estrogen receptor in fine needle aspirates and histologic sections from breast carcinomas

An immunocytochemical assay using a monoclonal antibody specific for estrogen receptor (ER-ICA) was performed on needle aspirates and on histologic sections (mastectomy and biopsy specimens) from 55 patients with breast cancer. A total of 82 ER-ICAs were performed, with matched cytologic and histologic specimens in 27 patients, cytology alone in 15, and histology alone in 13. ER-ICA results were described by a histochemical score (H score) based on intensity-weighted percentages of staining cells. The H scores were compared with results of sucrose density gradient (SDG) analysis of histologic specimens (mastectomy, resection, or biopsy). An H score greater than or equal to 10 and an SDG value greater than or equal to 10 fmol/mg protein were considered positive. The sensitivity of cytologic ER-ICA was 94%, the specificity 100%. The sensitivity of histologic ER-ICA was 67%, the specificity 90%. Correlating cytologic H score with Black's nuclear grade showed that grade 1 (the most anaplastic) carcinomas demonstrated the lowest H scores (mean, 7.3 +/- 29.8), whereas the highest H scores were noted in grade 3 tumors (mean, 150.0 +/- 88.1). Both SDG and ER-ICA showed ER values to be lower in premenopausal than postmenopausal women. There was no correlation between H score and presence of axillary nodal metastases or tumor size. An overall good correlation was demonstrated between immunohistochemical methods and biochemical analysis.

Vimentin—a new prognostic parameter in breast carcinoma?

This report describes a positive relationship between vimentin expression in infiltrating ductal breast carcinoma, and high tumour growth fraction. Vimentin expression is potentially a predictor of aggressive behaviour, and such carcinomas may benefit from early adjuvant therapy. Eighty-four malignant breast neoplasms were stained with monoclonal anti-vimentin and anti-cytokeratin antibodies. The tumour growth fractions were determined by immunostaining cryostat sections with the Ki-67 antibody. Seven (9.2 per cent) of 76 infiltrating ductal carcinomas co-expressed cytokeratin and vimentin intermediate filaments in more than 50 per cent of neoplastic cells. In each case, the corresponding Ki-67 count was much greater than 40 per cent, significantly higher than the mean growth fraction for all tumours examined (P less than 0.0001). Vimentin immunoreactivity was also positively related to the histological grade of the ductal carcinomas (P less than 0.002) and inversely related to tumour ER count (P less than 0.0002) and patient age (P less than 0.01). No relationship was observed between vimentin positivity and either the presence of axillary nodal metastases or primary tumour size.