Positive Axillary Lymph Node Status Research Articles

Ki67 and P53 expression in breast cancer and their correlation with clinicopathological parameters

Breast carcinoma is the most common malignancy in females and is a leading cause of death. Treatment depends upon various pathological and prognostic markers like lymph node status, size, type and grade of the tumour which influences the outcome of breast cancer. Markers like Ki-67 and p53 have been studied extensively and their roles in breast cancer are yet to be established.We evaluated the expression of Ki67 and P53 in breast cancer and their association with other clinico-pathological factors was studied. Ki67 and P53 expression was assessed in 60 breast cancer cases admitted to our hospital over a period of one year. Association with other prognostic parameters was evaluated. Statistical analysis was done by Chi square test and a p value of <0.05 was taken as significant. 43.33% cases had low proliferative Ki-67 score whereas 56.67% of the cases were highly proliferative. p53 expression was seen in 41.66% cases. Ki-67 and p53 expression were not significantly related to age, menopausal status, and tumour size whereas a significant correlation was seen with positive axillary lymph node status, high histological grade, negative hormone receptor status (ER, PR) and positive HER2/neu expression. Significant association was seen between Ki-67 and p53 expression.Ki67 and P53 may be considered as a valuable biomarker in breast cancer patients which can help in planning treatment strategies.

Mammographic density changes during neoadjuvant breast cancer treatment: NeoDense, a prospective study in Sweden

ObjectivesTo assess if mammographic density (MD) changes during neoadjuvant breast cancer treatment and is predictive of a pathological complete response (pCR). MethodsWe prospectively included 200 breast cancer patients assigned to neoadjuvant chemotherapy (NACT) in the NeoDense study (2014–2019). Raw data mammograms were used to assess MD with a fully automated volumetric method and radiologists categorized MD using the Breast Imaging-Reporting and Data System (BI-RADS), 5th Edition. Logistic regression was used to calculate odds ratios (OR) for pCR comparing BI-RADS categories c vs. a, b, and d as well as with a 0.5% change in percent dense volume adjusting for baseline characteristics. ResultsThe overall median age was 53.1 years, and 48% of study participants were premenopausal pre-NACT. A total of 23% (N = 45) of the patients accomplished pCR following NACT. Patients with very dense breasts (BI-RADS d) were more likely to have a positive axillary lymph node status at diagnosis: 89% of the patients with very dense breasts compared to 72% in the entire cohort. A total of 74% of patients decreased their absolute dense volume during NACT. The likelihood of accomplishing pCR following NACT was independent of volumetric MD at diagnosis and change in volumetric MD during treatment. No trend was observed between decreasing density according to BI-RADS and the likelihood of accomplishing pCR following NACT. ConclusionsThe majority of patients decreased their MD during NACT. We found no evidence of MD as a predictive marker of pCR in the neoadjuvant setting.

Correlation between apparent diffusion coefficient values in breast magnetic resonance imaging and prognostic factors of breast invasive ductal carcinoma.

Background:We wanted to examine whether the apparent diffusion coefficient values obtained by diffusion-weighted imaging techniques could indicate an early prognostic assessment for patients with Invasive Ductal Carcinoma and, therefore, influence the treatment decision making.Objective:The main objective was to evaluate the correlation between the apparent diffusion coefficient values obtained by diffusion-weighted imaging and the key prognostic factors in breast invasive ductal carcinoma. Secondary objectives were to analyze the eventual correlations between magnetic resonance imaging findings and prognostic factors in breast cancer; and to perform a comparison between results in 1.5 and 3.0 T scanners.Methods:Breast magnetic resonance imaging with diffusion-weighted imaging sequence was performed on 100 patients, who were proven histopathologically to have breast invasive ductal carcinoma. We compared the apparent diffusion coefficient values, obtained previous to biopsy, with the main prognostic factors in breast cancer: tumor size, histologic grade, hormonal receptors, Ki67 index, human epidermal growth factor receptor type 2, and axillary lymph node status. The Mann-Whitney U test and the Kruskal-Wallis analysis were used to establish these correlations.Results:The mean apparent diffusion coefficient value was inferior in the estrogen receptor-positive group than in the estrogen receptor-negative group (1.04 vs 1.17 × 10–3 mm2/s, P = .004). Higher histologic grade related to larger tumor size (P = .002). We found association between spiculated margins and positive axillary lymph node status [odds ratio = 4.35 (1.49–12.71)]. There were no differences in apparent diffusion coefficient measurements between 1.5 and 3.0 T magnetic resonance imaging scanners (P = .513).Conclusions:Low apparent diffusion coefficient values are related with positive expression of estrogen receptor. Larger tumors and spiculated margins are associated to worse prognosis. Rim enhancement is more frequently observed in estrogen receptor-negative tumors. There are no differences in apparent diffusion coefficient measurements between different magnetic resonance imaging scanners.

Vitamin D deficiency is associated with poor breast cancer prognostic features in postmenopausal women

This study aimed to evaluate the association between pretreatment vitamin D (VD) deficiency with breast cancer prognostic features in Brazilian postmenopausal women. An analytical cross sectional study was conducted with 192 women, aged 45–75 years, attended at University Hospital. Women with recent diagnosis of breast cancer, in amenorrhea >12months and age ≥45 years, without medication use or clinical conditions that interfere with VD values were included. Clinical and anthropometric data were collected. Serum level of 25 hydroxyvitamin D [25(OH)D] was measured in all patients until 20days after breast cancer diagnosis, and was classified as normal (≥30ng/mL), insufficiency (20–29ng/mL) and deficiency (<20ng/mL). Data on breast cancer (histopathological type, grade, tumor stage, lymph node status), hormone status (estrogen receptor, ER, progesterone receptor, PR), human epidermal growth factor receptor type 2 (HER2) and epithelial proliferative activity (Ki-67) were collected. For statistical analysis, the t-student test, the Gamma Distribution (asymmetric variables), the chi-square test and the logistic regression (OR-odds ratio) were used. The median 25(OH)D level was 25.8ng/mL (range 12.0–59.2ng/mL). Sufficient vitamin D levels were detected in 65 patients (33.9%), whereas insufficient levels in 92 patients (47.9%), and deficient levels in 35 patients (18.2%). Participants with insufficient and deficient 25(OH)D levels had a higher proportion of tumors with a high grade and locally advanced and metastatic disease, more positive lymph node, a lower proportion of ER, PR positives tumors and higher Ki-67(p<0.05). Patients with normal vitamin D had a higher frequency of luminal A (47.7%) and luminal B (32.2%) tumors when compared to patients with vitamin D insufficiency or deficiency. Furthermore, all cases of triple negative were detected in women with low VD levels. Multivariate analysis, after adjusting for age, time since menopause and BMI, showed that insufficient and deficient level of vitamin D were significantly associated with negative estrogen receptor (OR 3.77 CI 95% 1.76–8.09 and OR 3.99 CI 95% 1.83–8.68), high Ki-67 (OR 2.50, CI 95% 1.35–4.63, and OR 2.62, CI 95% 1.40–4.98), and positive axillary lymph node status (OR 1.59, CI 95% 1.03–2.33, and OR 1.58, CI 95% 1.02–2.92) respectively. In Brazilian postmenopausal women with breast cancer, there was an association between vitamin D insufficiency or deficiency and tumors with worse prognostic features. Low vitamin D levels were shown to be a risk factor for ER negative tumors, with positive axilla and a higher rate of cell proliferation.

Clinical study of co-relation between positive axillary lymph node status and size of the tumor in breast malignancies

Background: Breast lump in women is a common clinical condition encountered in day-to-day surgical practice and needs thorough evaluation. This study is focused on co-relation between axillary lymph nodal status and the size of the breast tumor through clinical, radioimaging, and pathological studies. The axillary lymph node study also helps to differentiate benign from malignant breast lumps. Patients and Methods: This study was carried out in the Department of Surgery, Great Eastern Medical School (GEMS) Hospital, Ragolu, Srikakulam, Andhra Pradesh, India. A total of 45 patients were selected for the study from among admitted cases to the Department of Surgery through clinical assessment, laboratory investigations, and ultrasound findings. After confirming the diagnosis of breast malignancy by fine needle aspiration cytology and Trucut biopsy in few cases, the patient had undergone operative intervention. Later, the specimens were sent for histopathological study. Results: Breast malignancy was found more commonly among female patients of 45–64 years of age with an incidence of 66% in present studies. Lump in the breast was the common presenting feature in all patients. Ultrasound findings and Trucut biopsy have shown high sensitivity and specificity up to 97–99%. Conclusion: The present study concludes that for the tumor size <10 mm, axillary lymph node dissection may not be needed. Larger the size of the tumor, the more probability of lymph nodal metastasis.

Clinical and epidemiological profile of women with breast cancer managed in a public referral hospital in northeastern Brazil.

To evaluate the clinical and epidemiological profile of women with breast cancer, managed in the Breast Service at Hospital Get6lio Vargas (HGV). A descriptive, observational cross-sectional study, involving 174 breast cancer patients, managed at the Breast Service at HGV in Teresina, in the northeast of Brazil, from May 2011 to June 2014. Epidemiological variables included age group, age at menarche, age at first childbirth, and menopause. The tumor characteristics studied were histological type, TNM classification, and staging. The results were organized in distribution tables. Breast carcinoma was more common in patients aged 60 and over, in multiparous women, and in women who were menopausal before age 55. The most common histological type was ductal invasive carcinoma T2N1MO (Stage IIB) in 83 (48%) women. The current study shows that the majority of carcinomas were Stage II or advanced tumors, with clinically positive axillary lymph node status and weak correlation with reproductive risk factors.

Internal mammary node adenopathy on breast MRI and PET/CT for initial staging in patients with operable breast cancer: prevalence and associated factors.

To evaluate the prevalence of and factors associated with internal mammary node (IMN) adenopathy on MRI and PET/CT used for initial staging in patients with operable breast cancer. A total of 1320 patients diagnosed with invasive breast carcinoma between January 2011 and December 2015 underwent MRI and PET/CT for initial staging. The patients were considered to have IMN adenopathy when MRI revealed IMNs with the longest diameter of 5mm or greater and a standardized uptake value greater than that of the mediastinal blood pool/contralateral parasternal area on PET/CT. The prevalence was determined as overall percentage of patients with IMN adenopathy, as well as percentages among patients who received neoadjuvant chemotherapy and those who did not. The association of IMN adenopathy with factors was evaluated using multivariate logistic regression analysis. Of the 1320 patients, 35 patients [2.7%; 95% confidence interval (CI) 1.8-3.6%] had IMN adenopathy, with a total of 49 IMNs. Among patients without and with neoadjuvant chemotherapy (n=1092 and n=228, respectively), IMN adenopathy was identified in 13 (1.2%; 95% CI 0.6-2.0%) and 22 patients (9.6%; 95% CI 6.0-14.6%), respectively. Inner tumor location [odds ratio (OR) 5.9; P=.002] and positive axillary lymph node status (OR 4.4; P<.0001) were associated with IMN adenopathy. IMN adenopathy was identified at initial staging with PET/CT and MRI with a prevalence of 2.7%. Inner tumor location and positive axillary lymph node status were associated with IMN adenopathy.

Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Potential clinical significance of ERβ ON promoter methylation in sporadic breast cancer

The aim of the study was to assess how hypermethylation of the ON promoter of the estrogen receptor beta (ERβ) gene affects its expression (at the mRNA and protein level) and to correlate these with some clinical and histopathological parameters. A total of 131 samples of frozen breast cancer tissue was analyzed. A custom-designed, two-step PCR method was used to measure the methylation index of the ERβ gene ON promoter region. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to quantify mRNA of the ERβ1 isoform, while ERβ1 protein was determined using the Western blot method. There was a significant difference in the methylation index of the ERβ gene ON promoter between the groups of patients with negative and positive axillary lymph node status (P = 0.03). In addition, the methylation index of the ON promoter was positively correlated with estrogen receptor alfa (ERα) protein levels (ρ = 0.31, P = 0.02). There was a significant difference in the methylation index of the ON promoter between the progesterone receptor (PR)-negative and PR-positive groups of patients (P = 0.01). ERβ1 protein levels were negatively correlated with ERα protein (ρ = -0.27, P < 0.01). The methylation index of the ON promoter could be a more reliable additional parameter for prediction and/or prognosis in breast cancer than ERβ1-mRNA and/or protein levels.

9. Studies of sentinel lymph node biopsy after preoperative chemotherapy in breast cancer patients

S 735 of the study will promote a more structured breast cancer surgical care and better patient information service. To our best knowledge, this is the largest related preoperative investigation in the English language literature and the first one in the Central and Eastern European region. 9. Studies of sentinel lymph node biopsy after preoperative chemotherapy in breast cancer patients T. Kinoshita, T. Hojo, J. Suzuki, K. Jimbo, K. Taruno, S. Asaga, M. Yoshida, H. Tsuda 1 National Cancer Centre Hospital, Surgical Oncology Division, Tokyo, Japan National Cancer Centre Hospital, Pathology Division, Tokyo, Japan Background: Despite the increasing use of both sentinel lymph node biopsy (SLNB) and preoperative chemotherapy (PST) in patients with operable breast cancer, there is still limited information on the feasibility and accuracy of SLNB following PST. In this study, the feasibility and accuracy of SLNB for breast cancer patients with clinically negative lymph nodes after PSTwere investigated. In addition, we evaluated a new automated assay system for cytokeratin 19 mRNA, the one-step nucleic acid amplification (OSNA) assay (Sysmex), to detect lymph node metastasis of breast cancer after PST. Materials and methods: Between 2003 and 2008, 200 patients with Stage II and III breast cancer previously treated with PST were enrolled in this study. The eligible criteria for PST were (a) primary tumor > 3cm or (b) positive axillary lymph node status on initial examination. FNA biopsy was performed for clinically or ultrasonographically suspicious axillary lymph nodes. The patients then underwent SLNB, which involved a combination of intradermal injection over the tumor of radiocolloid and subareolar injection of blue dye. This was followed by Level I/ II axillary lymph node dissection (ALND). Surgically obtained 84 lymph nodes from 21 breast cancer patients received PST were examined with both OSNA assay and HE five hundred & seventy patients of stage I to III breast carcinoma have autologous breast reconstruction with modified extended LDF with added vascularised chest wall fat; 47% had SSM and the remaining had NSM. Age ranges from 23 to 53 years (median 1⁄4 40.5). Results: Subjective patient satisfaction was excellent in 71%, good in 20%, fair in 7% & poor in 2% of cases. Bilateral size & shape symmetry are excellent in 56%, good in 26%, fair in 12% & poor in 6% patient. The overall RT-related complications are 9 %, the most common complications are skin burns (5%) & fat necrosis (4%). Patients are followed for mean follow up of 75.5 months (2-96). Conclusion: Modified extended latissimus dorsi myocutaneous flap with added vascularised chest wall fat is a single stage totally autologous breast reconstruction allows reconstruction without the additional cost of an implant, many complications of synthetic implants, micro vascular procedure second stage surgery or surgical manipulation in the other breast. In addition the overall survival & local recurrence rates were similar to MRM.

Study of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer.

104 Background: Despite the increasing use of both sentinel lymph node biopsy (SLNB) and preoperative chemotherapy (PST) in patients with operable breast cancer, there is still limited information on the feasibility and accuracy of SLNB following PST. In this study, the feasibility and accuracy of SLNB for breast cancer patients with clinically negative lymph nodes after PST were investigated. In addition, conditions that may affect SLN biopsy detection and false-negative rates with respect to clinical tumor response and clinical tumor/nodal status before PST were analyzed. Methods: Between 2003 and 2008, 200 patients with stage II and III breast cancer previously treated with PST were enrolled in this study. The eligible criteria for PST were (a) primary tumor &gt; 3cm or (b) positive axillary lymph node status on initial examination. FNA biopsy was performed for clinically or ultrasonographically suspicious axillary lymph nodes. The patients then underwent SLNB, which involved a combination of intradermal injection over the tumor of radiocolloid and subareolar injection of blue dye. This was followed by Level I/II axillary lymph node dissection (ALND). Results: The median patient age was 49 years, and the median primary tumor size was 4.9 cm. The overall SLN identification rate was 94.5% (189 of 200). In 178/189 patients (94%) the SLN accurately predicted the axillary status. Eleven patients had a false-negative SLN biopsies, yielding a false-negative rate of 12.9%. There were no significant differences in the SLN identification rate according to tumor classifications before PST, the clinical nodal status before PST, the clinical tumor response after PST, or pathological response of the tumor after PST, although the SLN identification rate tended to be lower in patients with a T4 primary tumor. Conclusions: Our data and some reports suggested that SLNB was feasible method for axillary staging in breast cancer patients who received PST even in patients who initially with lymph node positive disease. However, false-negative rate of SLNB in patients with clinical and pathological complete tumor response tended to be higher than other group.

Factores asociados con estrés oxidativo en mujeres con cáncer de mama

Objective: To assess the association between physiological, physical, lifestyle and nutritional variables and oxidative stress biomarkers in women with breast cancer. Methods: This cross-sectional study was conducted on 55 women newly diagnosed with breast cancer. The extent of oxidative stress was analyzed by the measurement of plasma lipid hydroperoxides (LH), thiobarbituric acid reactive substances (TBARS), protein carbonyl, whole blood reduced glutathione (GSH) and serum antioxidant capacity (AC). Diet data were obtained from food frequency questionnaire. Linear regression was used to determine the association between the variables studied and oxidative stress biomarkers. The protein carbonyl data was not included in the linear regression analyses since the data did not show a normal distribution, even after logarithmic and other transformations. Results: After adjusting for energy intake, the intake of chicken and high-fat dairy products was associated with increased levels of LH, while vitamin E intake was associated with decreased LH levels (R2 = 23.8%). Intake of oils was associated with increased levels of TBARS (R2 = 6.82%). Positive axillary lymph node status was associated with decreased levels of GSH (R2 = 9.31%). Increasing age was directly associated with levels of AC, while animal fat, dairy product, and sweet food intakes were associated with low levels of AC (R2 = 41.42%). Conclusion: Intake of chicken, vitamin E, dairy products (particularly high-fat dairy products), oils, animal fat, and sweet foods, along with axillary lymph node status and age, may be important determinants of oxidative stress in women with breast cancer.

Factors associated with oxidative stress in women with breast cancer.

To assess the association between physiological, physical, lifestyle and nutritional variables and oxidative stress biomarkers in women with breast cancer. This cross-sectional study was conducted on 55 women newly diagnosed with breast cancer. The extent of oxidative stress was analyzed by the measurement of plasma lipid hydroperoxides (LH), thiobarbituric acid reactive substances (TBARS), protein carbonyl, whole blood reduced glutathione (GSH) and serum antioxidant capacity (AC). Diet data were obtained from food frequency questionnaire. Linear regression was used to determine the association between the variables studied and oxidative stress biomarkers. The protein carbonyl data was not included in the linear regression analyses since the data did not show a normal distribution, even after logarithmic and other transformations. After adjusting for energy intake, the intake of chicken and high-fat dairy products was associated with increased levels of LH, while vitamin E intake was associated with decreased LH levels (R² = 23.8%). Intake of oils was associated with increased levels of TBARS (R² = 6.82%). Positive axillary lymph node status was associated with decreased levels of GSH (R² = 9.31%). Increasing age was directly associated with levels of AC, while animal fat, dairy product, and sweet food intakes were associated with low levels of AC (R² = 41.42%). Intake of chicken, vitamin E, dairy products (particularly high-fat dairy products), oils, animal fat, and sweet foods, along with axillary lymph node status and age, may be important determinants of oxidative stress in women with breast cancer.

Using Complications Associated With Postmastectomy Radiation and Immediate Breast Reconstruction to Improve Surgical Decision Making

To identify factors independently associated with surgical complications in oncologic and reconstructive surgery and to examine sentinel lymph node (SLN) biopsy data, along with variables that are typically known prior to definitive resection, for their ability to impact the prediction of need for postmastectomy irradiation (PMRT). Retrospective review. University hospital. Mastectomy patients with stage I to III breast cancer treated in 2000 to 2008. Complication rates of oncologic and reconstructive surgery requiring reoperation and clinicopathologic variables that independently predict complications and/or PMRT administration by multivariate analysis. Among 100 of 302 mastectomy patients who underwent PMRT, complications occurred in 44% who underwent immediate breast reconstruction (IBR) and 7% who did not (P<.001). Postmastectomy irradiation independently predicted the occurrence of a complication (odds ratio, 3.3; P<.001). Implants were removed in 31% of patients who underwent PMRT and 6% of patients who did not (P=.005). Three percent of patients with T2 or smaller tumors and zero positive SLN required PMRT. Among those with T2 tumors, 49% with a positive axilla lymph node underwent PMRT. Independent predictors of PMRT need were T2 vs T1 tumors, positive axillary lymph node status, and the number of positive SLNs, with odds ratios of 5.8 (P<.001), 14.5 (P<.001), and 2.1 (P=.001), respectively. Postmastectomy irradiation was associated with a high rate of surgical complications and implant loss among patients who underwent IBR. Determining the number of positive SLNs prior to definitive resection and reconstructive operations may reduce complications and implant loss by guiding surgical decision making. Patients with a negative SLN are unlikely to require PMRT. Those with positive SLN(s) are high-risk IBR candidates with a quantifiable PMRT risk.

Stage migration due to introduction of the sentinel node procedure: a population-based study

Introduction of sentinel node biopsy (SNB) as an axillary staging procedure in breast cancer patients could have led to upstaging as well as downstaging of their disease. Intensified pathological processing could have led to upstaging due to presence of micrometastases, whereas the described false negative rate of 5% could be a cause of downstaging. We investigated whether or not the introduction of the sentinel node procedure has changed the incidence of axillary nodal micrometastases and induced stage migration on a population based level. Data from the population based Eindhoven Cancer Registry were used on all (n=17100) women diagnosed with invasive breast cancer in the South-East region of The Netherlands in the period 1994-2005. The percentage of patients staged with SNB increased from 0% in 1994 to 62% in 2005. The percentage of patients with micrometastases increased from 1.0% in 1994 to 4.3% in 2005 (P<0.0001), whereas no significant increase was observed of the proportion of patients with positive axillary lymph nodes. After adjustment for tumor size, age at diagnosis and histology the probability of having a positive axillary lymph node status was 10% higher in period 2003-2005, as compared to period 1994-1996. Furthermore, women diagnosed in the period 2003-2005 had a 3.5 times higher risk of having micrometastases compared to women diagnosed in the period 1994-1996 (i.e., before the introduction of SNB). The introduction of SNB in the Southeast region of The Netherlands has led to stage migration, as is reflected by the small but significant increase of the proportion of patients with positive axillary lymph nodes after adjustment for tumor size and age.

P53 Codon 72 Polymorphism Predicts the Pathologic Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer

Recent studies have highlighted that the p53 codon 72 polymorphism plays a crucial role in modulating wild-type p53 apoptotic capacity, and as such may influence the response to chemotherapy. Thus, the purpose of this study was to investigate whether the p53 codon 72 polymorphism might influence pathologic response to neoadjuvant chemotherapy in primary breast cancer. One hundred and ten operable breast cancer patients received anthracycline-based neoadjuvant chemotherapy and p53 codon 72 polymorphism status was analyzed by PCR-RFLP. The distribution of initial clinical stage, tumor size, estrogen receptor or progesterone receptor status, menopausal status, or erbB2 expression was not significantly different among the polymorphic variants. However, we found that only 13% (3 of 23) of patients with the Pro/Pro variant had a good pathologic response, defined as a complete pathologic response or minimal residual disease. In comparison, 40% (22 of 55) or 37.5% (12 of 32) of patients with the Pro/Arg or Arg/Arg variant had a good pathologic response (P = 0.019). Moreover, patients with the Pro/Pro variant were more likely to have a positive axillary lymph node status than those with the Pro/Arg or Arg/Arg variant (P = 0.007). Furthermore, in multivariate analysis, p53 codon 72 polymorphism was found to be a strong predictor of pathologic response (odds ratio 6.7, 95% confidence interval, 1.4-31.2; P = 0.016). Our study indicates that breast cancer patients with the Pro/Pro variant may be less sensitive to anthracycline-based treatment than those with the Pro/Arg or Arg/Arg variant and suggests that analysis of p53 codon 72 polymorphism may provide a simple predictive marker for selecting the right breast cancer patients to anthracycline-based neoadjuvant chemotherapy in clinical setting.

Ultrasound criteria for ductal invasive breast cancer are modified by age, tumor size, and axillary lymph node status

To evaluate the influence of distinct clinicopathological parameters on ultrasound criteria for ductal invasive breast cancer. The hardcopy prints of 337 ductal invasive breast cancers were analyzed. Ten ultrasound criteria (shape, orientation, echogenicity, echo pattern, calcifications, margin, margin contour, lesion boundary, surrounding tissue, and posterior acoustic features) were defined and correlated to age, tumor size, axillary lymph node status, and histological grading in a multivariate analysis. Tumors in women < or = 50 years displayed more often an indistinct margin (p = 0.003) and an enhanced/indifferent posterior ultrasound transmission (p = 0.008). Tumors in an advanced T-stage showed more frequently an irregular shape ( p = 0.006), an orientation parallel to the skin ( p = 0.01), hypoechogenicity ( p < 0.0001), and less often calcifications ( p = 0.002). A positive axillary lymph node status was significantly correlated to oval/round shape ( p = 0.004), hyper-/isoechogenicity ( p = 0.001), and a homogeneous echo pattern ( p = 0.002). Grading showed no correlation to the examined ultrasound criteria. Breast ultrasound criteria, which are used to differentiate benign from malignant breast lesions, are influenced by age, size and lymph node status. These clinical conditions should be considered in the ultrasound diagnosis of breast lesions.

Molecular detection of cancer cells in bone marrow and peripheral blood of patients with operable breast cancer. Comparison of CK19, MUC1 and CEA using RT-PCR

We have compared three different RT-PCR procedures to measure cytokeratin 19 ( CK19), carcinoembryonic antigen ( CEA) and mucin MUC1 gene expression in order to determine their diagnostic value in detecting tumour cells in bone marrow aspirates of patients with operable breast cancer. In an experimental model, the best sensitivity was observed for CK19 and MUC1 RT-PCR assays, although only the CEA and CK19 assays showed good specificity. The study of 42 patients showed that a ‘ CK19 positive/ CEA positive’ RT-PCR assay in bone marrow correlated positively with a positive axillary lymph node status (N 0 versus N 1–3, P<0.05). Both assays were also positive in 17% of node negative patients. RT-PCR assays were more sensitive in bone marrow than in peripheral blood. Our results suggest that CK19 and CEA RT-PCR assays are powerful methods for detecting disseminated breast cancer cells. A larger study with long-term follow-up is required in order to clarify their clinical usefullness.

Detection of malignant breast tumours in dense breast tissue: results of99mTc-tetrofosmin scintimammography related to surgery

AimsTo assess the contribution of99mTechnetium tetrofosmin (99mTc-TF) scintimammography for staging of breast lesions in patients with a suspicious or non-diagnostic mammogram to reduce unnecessary surgical procedures in future.MethodsFifty patients with suspicious physical examinations and/or mammography underwent99mTc-TF breast imaging.ResultsScintimammography with99mTc-TF was positive in 37 patients (36 true positive, one false positive) and negative in 13 patients (12 true negative, one false negative). The detection of a malignant tumour by99mTc-TF was independent of the density of the breast tissue. In 33 patients with a malignant breast tumour99mTc-TF was diagnostic with respect to axillary status, but in four out of 19 patients with a histologically positive axillary lymph node status, tumour involvement remained undetected by scintigraphy. Moreover, in four patients, scintimammography revealed an additional discrete area of increased99mTc-TF uptake, which proved to be second primary breast cancers.Conclusions99mTc-TF scintimammography appears to be an accurate diagnostic test in patients with a symptomatic breast lesion and a non-diagnostic mammogram, also in those patients with dense breast tissue. This procedure may also have potential for the detection of second primary breast cancers in an early stage.

α-Linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer

The association between the levels of various fatty acids in adipose breast tissue and the emergence of visceral metastases was prospectively studied in a cohort of 121 patients with an initially localised breast cancer. Adipose breast tissue was obtained at the time of initial surgery, and its fatty acid content analysed by capillary gas chromatography. A low level of alpha-linolenic acid (18:3n-3) in adipose breast tissue was associated with positive axillary lymph node status and with the presence of vascular invasion, but not with tumour size or mitotic index. After an average 31 months of follow-up, 21 patients developed metastases. Large tumour size, high mitotic index, presence of vascular invasion and low level of 18:3n-3 were single factors significantly associated with an increased risk of metastasis. A Cox proportional hazard regression model was used to identify prognostic factors. Low 18:3n-3 level and large tumour size were the two factors predictive of metastases. These results suggest that host alpha-linolenic acid has a specific role in the metastatic process in vivo. Further understanding of the biology of this essential fatty acid of the n-3 series is needed in breast carcinoma.