Primary Operable Invasive Breast Cancer Research Articles

Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value—an analysis of 2473 invasive breast cancer patients

BackgroundThe value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance.Material and methodsPatients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis.Results2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI–ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden.ConclusionThe diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.

Five-year survival in luminal breast cancer patients: relation with intratumoral activity of proteasomes.

The purpose of the study was to analyze the relationship between the caspase-like (CL) and chymotrypsin-like (ChTL) activities of proteasomes and the 5-year overall and metastasis-free survival rates in patients with luminal breast cancer. The study included 117 patients with primary operable invasive breast cancer (T1-2N0-1M0). Tissue samples from breast cancer patients were obtained as a result of the radical mastectomy or breast conserving surgery, which was a first line of therapy. The ChTL and CL proteasomes activities in the tumor tissue and in the surrounding adjacent breast tissues were assessed using the fluorometric method. The coefficients of ChTL (cChTL) and CL (cCL) proteasomes activities were also determined. The coefficients were calculated as the ratio of the corresponding proteasomes activity in the tumor tissue to the surrounding adjacent breast tissues. Within 5 years of follow-up, hematogenous metastases occurred in 14% of patients with luminal A breast cancer, in 31% of patients with luminal B human epidermal growth factor receptor-2 (HER-2) negative and in 23% of patients with luminal B HER-2 positive breast cancers. The study protocol was approved by the Local Ethics Committee of the Cancer Research Institute of Tomsk National Research Medical Center. Written informed consent was obtained from all patients. An increase in the ChTL and CL proteasomes activities was shown in all studied molecular subtypes of breast cancer compared to adjacent tissues. It was found that the cChTL of >35.9 U/mg protein and the cCL of >2.21 in breast cancer patients were associated with the development of distant metastases. In patients with luminal A breast cancer, the 5-year metastasis-free survival rates were associated only with the value of cCL of proteasomes (log-rank test: P=0.008). In patients with luminal B HER-2 negative breast cancer, the 5-year metastasis-free survival rates were associated with the levels of ChTL and cCL proteasomes activities (log-rank test: P=0.02 and P=0.04, respectively). The data obtained on the correlation of 5-year metastasis-free survival rates with the level of proteasomes activities indicate the possibility of their use as additional prognostic criteria for breast cancer.

A study of predictive and prognostic histopathologic factors in breast conservation therapy

Background: Breast cancer is the second most common cancer after cervical cancer in Indian. Presently breast conservation therapy (BCT) is the preferred treatment for stage I and II breast cancer. Therefore, the present study was undertaken to identify and study these histopathologic factors and correlate them with local recurrence rate. Method: The pathology records of a tertiary cancer referral hospital were systemically scrutinized for two years and 106 women in the age group of 25-70 years with primary operable invasive breast cancer treated by breast conversation therapy (BCT) were studied in depth. Follow-up ranged for 2 to 3 years. Every patient was followed up every 6 monthly by the onco-surgeon and radiotherapist. Cases in which the pathology slides and / or blocks were not available were excluded. Result: The mean age of all the patients was 43.1 years. (Range: 25-67 years.) Majority of the patients are in the age group of 35-44 years (44.3%). Most of the tumours occurred in the upper outer quadrant (62.3%). IDC forms the main group (93.4%) in the various cases studied. Out of 99 IDC only 89 are pure IDC and 10 are with other components. Majority of the cases belongs to grade-III (63.2%). Maximum tumour size is in the range of 2-5 cm (52.8%). Necrosis was one of the main histological factor observed in the present study (12.3%). Overall 7.5% of our patients developed local recurrence, most of them occurred within the first year. Conclusion: Predictive and prognostic histopathologic factors which increase the risk of recurrence are, Presence of extensive intraductal component, Positive cut margin of resection, Presence of Lymphovascular invasion.

Abstract P4-02-07: Comparison of breast cancer molecular subtyping by Immunohistochemistry and by BluePrint® next generation RNA sequencing-based test at University Hospitals Leuven and Curie Institute Paris

Abstract Background MammaPrint® (MP) and BluePrint® (BP) are microarray-based tests with MP being prognostic for distant recurrence and BP enabling stratification into breast cancer molecular subtypes (Luminal, HER2, Basal-type). Recently, a CE marked MP and BP targeted RNA Next Generation Sequencing (NGS)-based kit was developed at Agendia and validated at University Hospitals Leuven and Curie Institute Paris. Here we compare breast cancer molecular subtype stratification defined by immunohistochemistry (IHC) and by MP and BP NGS- and microarray- based tests. Patients and Methods In this study, 124 primary operable invasive breast cancer patients were included at University Hospitals Leuven and at Curie Institute (n=80 Leuven; n=44 Curie) with the following histological subtypes: ductal-NOS (n=100), lobular (n=16), mucinous (n=3), tubular (n=2), others (n=3). Patients with bilateral breast cancer or with >3 positive lymph nodes were excluded. Surrogate breast cancer subtypes based on IHC were defined as follows: luminal if ≥10% estrogen receptor (ER) expression; triple negative if <10% ER and progesterone receptor (PR) expression and HER2 stained negative by IHC and/or FISH; HER2+ if HER2 receptor stained positive (2+ or 3+) by IHC and/or FISH. Luminal subtypes were further stratified into Luminal A-like (HER2 negative, Ki-67<14%, PR≥20%) and Luminal B-like (HER2 negative or positive, Ki-67 ≥14%, PR<20%). When Ki-67% was not available, tumors with grade 1 or 2 were classified as Luminal A-like and with grade 3 as Luminal B-like. IHC subtypes were compared to the BP NGS and microarray molecular subtypes (Luminal-, HER2- and Basal-type). To further stratify BP luminal type tumors, MP test was used as follows: Luminal A (BP Luminal and MP low risk) and Luminal B (BP Luminal and MP high risk). Results Concordance between IHC and MP/BP NGS subtyping was 75.0% (93/124), while concordance between MP/BP on NGS and microarray was 89.5% (111/124). MP/BP NGS subtyping identified more low risk Luminal A tumors compared to IHC (54.0%, (67/124) vs 44.3% (55/124)). Notably, concordance was excellent for triple-negative and, to less extent for HER2 driven tumors (Luminal B-like-HER2 positive and HER2+). IHC vs. MP/BP NGS molecular subtyping (n=124) MP/BP NGSIHCLuminal ALuminal BHER2-positiveBasalTotalLuminal A-like4690055Luminal B-like, HER2-negative16210037Luminal B-like, HER2-positive565016HER2-positive00303Triple negative0101213Total6737812124Microarray vs MP/BP NGS molecular subtyping (n=124) MP/BP NGSMicroarrayLuminal ALuminal BHER2 positiveBasalTotalLuminal A6040064Luminal B7310038HER2-positive028010Basal0001212Total6737812124 Conclusion This study shows a discordance of 25.0% between IHC and BP/MP NGS subtyping. This is in line with previous findings where IHC was compared to molecular subtyping based on microarray (Viale 2017, Whitworth 2014) underlining the complementarity of genomic testing in early stage breast cancer. Moreover, we observed a high concordance between NGS and microarray molecular subtyping, which suggests a successful translation of the MP/BP microarray test to a MP/BP NGS test. Citation Format: Darrigues L, Slembrouck L, Mittempergher L, Delahaye LJ, Vanden Bempt I, Vander Borght S, Vliegen L, Sintubin P, Raynal V, Bohec M, Reyes C, Rapinat A, Helsmoortel C, Jongen L, Hoste G, Neven P, Wildiers H, Smeets A, Nevelsteen I, Punie K, Van Nieuwenhuysen E, Han S, Laurent C, Vincent-Salomon A, Laas-Faron E, Witteveen AT, Neijenhuis S, Glas AM, Floris G, Reyal F. Comparison of breast cancer molecular subtyping by Immunohistochemistry and by BluePrint® next generation RNA sequencing-based test at University Hospitals Leuven and Curie Institute Paris [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-07.

Shear Wave Speed of the Lesion in Preoperative Breast Ultrasonography: Association with Disease-free Survival of Patients with Primary Operable Invasive Breast Cancer

We aimed to investigate the relationship between shear wave speed (SWS) of the lesion on preoperative breast ultrasonography (US) and disease-free survival of patients with primary operable invasive breast cancer. This retrospective study was approved by our Institutional Review Board. The requirement for informed consent was waived. A total of 195 consecutive newly diagnosed invasive breast cancer patients (age 33-83 years; mean 54.0 years) with preoperative breast US with SWS measurement of the lesion were identified. They underwent surgery between May 2012 and May 2013. SWS was measured at the center and three marginal zones in the main tumors, and the maximum value was used for analyses. For 35 patients who underwent primary systemic therapy (PST), the maximum SWS before PST was used. Cox proportional hazards modeling was used to identify the relationship between clinical-pathologic factors and disease-free survival. Fourteen recurrences occurred at 6-47 months (mean 22.3 months) after surgery. On multivariate analysis, a positive history of PST (hazard ratio [HR] = 4.93; 95% confidence interval [CI]: 1.66, 14.70; P = .004), adjuvant chemotherapy (HR = 3.67; 95% CI: 1.11, 12.1; P = .033), and higher maximum SWS (HR = 1.55; 95% CI: 1.07, 2.23; P = .020) were associated with poorer disease-free survival. Higher maximum SWS on preoperative US, in addition to a positive history of PST and adjuvant chemotherapy, was significantly associated with poorer disease-free survival of patients with invasive breast cancer.

Abstract P1-07-06: The relationship between Klintrup-Makinen score and cancer-specific survival in primary operable breast cancer

Abstract Introduction It is increasingly being recognised that cancer prognosis is dependent on a complex interaction of tumour factors and the host response. The degree of inflammatory response at the invasive tumour edge, as measured by the Klintrup-Makinen score, has been shown to have prognostic relevance in some cancers but its role in breast cancer remains unclear. Aim To evaluate the relationship between Klintrup-Makinen score and prognosis in primary operable breast cancer. Methods Patients who underwent surgery for primary operable invasive breast cancer between 1995 and 2007 were studied. Full section haematoxylin and eosin slides from surplus tissue from each breast cancer were analysed. Each was visually scored for the level of inflammatory infiltrate at the invasive edge of the tumour, according to Klintrup-Makinen criteria. Kaplan Meier survival analysis was performed using SPSS. Results 1195 patients were included in the study, of which 298 had a Klintrup-Makinen score (KM) of 0 (no inflammatory cells at the invasive edge), 589 had a score of 1, 238 had a score of 2 and 70 had a Klintrup-Makinen score of 3 (high inflammatory cell infiltrate). 833 (69.7%) patients were ER positive and 172 (14.4%) patients were HER2 positive. Median follow up was 158 months (28-183) and there were 234 cancer deaths. Patients with the highest and lowest KM scores had the best prognosis (10 year breast cancer specific survival (BCSS) 84% for KM score 3 and 82% for KM score 0), while those with KM score 2 had the worst prognosis with 67% 10 year cancer specific survival (p=0.003). When analysed by subtype, in ER negative patients 10 year BCSS was 95% in KM 0 patients, 80% for KM 3, 72% for KM 1 and 67% for KM 2 (p=0.082). Conversely, in HER2 positive patients, the best prognosis was seen in patients with KM 3 with 86% 10 year BCSS but patients with KM 0 had the worst prognosis (BCSS 62%), but this did not reach significance (p=0.544). Conclusion The Klintrup-Makinen score appears to have a prognostic role in primary operable invasive breast cancer, however there is a suggestion that it varies between tumour subtypes. Further work is required to further define this role for each molecular subtype. Citation Format: Morrow ES, Gujam F, Mohammed ZMA, McMillan DC, Edwards J. The relationship between Klintrup-Makinen score and cancer-specific survival in primary operable breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-06.

Predictors of lymphovascular invasion identified from pathological factors in Chinese patients with breast cancer.

This study aimed to evaluate correlations between lymphovascular invasion (LVI) and the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), Ki-67, CK5/6, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, BCL11A and P53 in invasive breast cancer and to identify predictors of LVI based on these pathological factors. In all, 392 paraffin-embedded tissues from consecutive patients with primary operable invasive breast cancer were included. Immunohistochemistry (IHC) was retrospectively performed using a tissue microarray (TMA) of the paraffin-embedded tissues. LVI-positive rates were compared using the χ2 test. Correlations between pathological factors were assessed using Spearman's test. Binary logistic regression was employed in multivariate analyses of statistically significant factors. The results showed that LVI positivity was significantly higher in patients with HER-2-positive expression or high Ki-67 expression. HER-2 expression was weakly positively correlated with Ki-67 expression. HER-2-positive expression and high Ki-67 expression were found to be risk factors for LVI, and associations between LVI and other pathological factors were not significant. Therefore, HER-2-positive expression and high Ki-67 expression are predictors of LVI, whereas the expression of ER, PR, CK5/6, EGFR, VEGF, E-cadherin, BCL11A and P53 is not associated with LVI in invasive breast cancer.

Computer-aided Diagnosis-generated Kinetic Features of Breast Cancer at Preoperative MR Imaging: Association with Disease-free Survival of Patients with Primary Operable Invasive Breast Cancer.

Purpose To retrospectively investigate the relationship between the kinetic features of breast cancer assessed with computer-aided diagnosis (CAD) at preoperative magnetic resonance (MR) imaging and disease-free survival in patients with primary operable invasive breast cancer. Materials and Methods This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. The authors identified 329 consecutive women (mean age, 52.9 years; age range, 32-88 years) with newly diagnosed invasive breast cancer who had undergone preoperative MR imaging and surgery between January 2012 and February 2013. All MR images were retrospectively reviewed by using a commercially available CAD system, and the following kinetic parameters were noted for each lesion: peak enhancement (highest pixel signal intensity in the first series obtained after administration of contrast material), angio-volume (total volume of the enhancing lesion), and delayed enhancement profiles (the proportions of washout, plateau, and persistently enhancing component within a tumor). Cox proportional hazards modeling was used to identify the relationship between CAD-generated kinetics and disease-free survival after adjusting for clinical-pathologic variables. Results A total of 36 recurrences developed at a median follow-up of 50 months (range, 15-55 months). CAD-measured peak enhancement at preoperative MR imaging enabled differentiation between patients with and patients without recurrence (area under the receiver operating characteristic curve = 0.728; 95% confidence interval [CI]: 0.676, 0.775; P < .001). Multivariate Cox analysis showed that a higher peak enhancement (hazard ratio [HR] = 1.001; 95% CI: 1.000, 1.002; P = .004), a higher washout component (HR = 1.029; 95% CI: 1.005, 1.054; P = .017), and lymphovascular invasion at histopathologic examination (HR = 3.011; 95% CI: 1.302, 6.962; P = .010) were associated with poorer disease-free survival. Conclusion Higher values of CAD-measured peak enhancement and washout component at preoperative MR imaging were significantly associated with poorer disease-free survival of patients with primary operable breast cancer. © RSNA, 2017.

CT staging for breast cancer patients with poor prognostic tumours

The aim of this study was to assess the value of computed tomography (CT) staging of the chest, abdomen and pelvis in patients with poor prognostic tumours and no symptoms of metastatic disease in those who have undergone primary surgical management for the treatment of breast cancer.Patients who had primary operable invasive breast cancer treated by surgery over a 2-year period were retrospectively identified. Pathological data from the surgical resection were used to calculate the Nottingham Prognostic Index. Patients with no symptoms of distant metastases who underwent CT staging of the chest, abdomen and pelvis as a result of being placed in the poor prognostic group were identified. The presence and sites of metastatic disease or any indeterminate finding were documented. Additional investigations generated as a result of the staging CT and the outcome were also recorded.Sixty-seven patients (80%) in the poor prognostic group underwent a staging CT. Forty-seven patients (70%) had no signs of metastatic disease on the staging CT. Two patients (3%) were diagnosed with metastatic disease, on the basis of the initial CT scan. Eighteen patients (27%) had an indeterminate finding requiring further investigation, generating 21 additional imaging tests – following this only one additional patient was diagnosed with metastatic disease. Seventeen patients with an initially indeterminate finding did not have metastatic disease, giving a false-positive rate of 25%. In total, three patients (4%) had a final diagnosis of metastatic disease.The routine use of CT staging in patients with no symptoms of distant metastases with primary operable breast cancer even when in a poor prognostic group is of limited value, with a low pick-up rate of metastatic disease and considerable risk of false-positive findings.

Prognostic value of proliferation assay in the luminal, HER2-positive, and triple-negative biologic classes of breast cancer

IntroductionAlthough the prognostic significance of proliferation in early invasive breast cancer has been recognized for a long time, recent gene-expression profiling studies have reemphasized its biologic and prognostic value and the potential application of its assessment in routine practice, particularly to define prognostic subgroups of luminal/hormone receptor-positive (HR+) tumors. This study aimed to assess the prognostic value of a proliferation assay by using Ki-67 immunohistochemistry as compared with mitotic count scores.MethodProliferation was assessed by using Ki-67 labeling index (Ki-67LI) and mitotic scores in a large (n = 1,550) and well-characterized series of clinically annotated primary operable invasive breast cancer with long-term follow-up. Tumors were phenotyped based on their IHC profiles into luminal/HR+, HER2+, and triple-negative (TN) classes. We used a split-sample development and validation approach to determine the optimal Ki-67LI cut-offs.ResultsThe optimal cut-points of Ki-67LI were 10% and 50% for the luminal class. Both Ki7LI and MS were able to split luminal tumors into subgroups with significantly variable outcomes, independent of other variables. Neither mitotic count scores nor Ki-67LI was associated with outcome in the HER2+ or the TN classes.ConclusionsAssessment of proliferation by using Ki-67LI and MS can distinguish subgroups of patients within luminal/hormone receptor-positive breast cancer significantly different in clinical outcomes. Overall, both Ki-67 LI and mitotic-count scores showed comparable results. The method described could provide a cost-effective method for prognostic subclassification of luminal/hormone receptor-positive breast cancer in routine clinical practice.

P5-14-24: The Long Term Prognostic Impact of Real-Time Quantitative RT-PCR Detection of Cytokeratin 19 mRNA in Preoperative Bone Marrow Aspirates of Early Breast Cancer Patients.

Abstract Purpose: Several studies have evaluated the prognostic effect of bone marrow micrometastases at the time of surgery in early breast cancer, but few studies have long term outcome data. We report here a cohort with more than ten years follow-up. Materials and methods: 131 patients with primary operable invasive breast cancer were enrolled in the protocol from February 1998 to September 1999. Bone marrow aspirates, obtained from the iliac crest or the sternum, were analyzed with real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) for the presence of cytokeratin 19 (CK19) mRNA. All patients received standard therapy and follow-up. After a median follow-up of 133 months, data about disease recurrence (invasive disease free survival, IDFS) and survival (breast cancer specific survival (BCSS) and overall survival (OS)) were collected. A control group consisted of archived cDNA samples from 38 patients with hematological malignant antecedents in complete remission and without known gene arrangements. The upper limit of the 95% confidence interval of the level of CK19 positive cells is this group was used as cut-off (260 cytokeratin 19+ cells / 5 × 106 leucocytes) to determine bone marrow status in breast cancer patients. Results: 69 bone marrow samples from breast cancer patients (52,7 %) were considered CK19 positive. IDFS was 60.9 % and 79 % for CK19+ and CK19- patients, respectively (log-rank p-value = 0,036). When CK19 was evaluated as a continuous variable, IDFS also correlated significantly with the level of CK19 mRNA in bone marrow aspirates (p-value = 0,019). Except for lymph node status (ANOVA linear regression p-value = 0.022), there was no significant correlation between the level of CK19+ cells in the bone marrow and classical prognostic factors (pathological tumor stage, tumor size, differentiation grade, hormonal receptor status). In multivariate Cox-regression analysis correcting for tumor size, differentiation grade, lymph node status, hormone receptor status, tumor stage and treatment modalities (surgical procedure, chemotherapy, radiotherapy and antihormonal therapy), the CK19 bone marrow status still was a significant predictor of IDFS. (p-value = 0.042) Differences in BCSS (78 % of CK19 + patients and 84 % of CK19 — patients) and OS (75 % in CK 19 + patients and 74 % in CK 19 — patients) were not statistically significant. (log rank p-values 0.087 and 0.883, respectively). Conclusion: This study demonstrates the long term (&amp;gt;ten years) prognostic effect of CK19 mRNA detection with RT-PCR in the bone marrow of operable breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-24.

Pathological and Patient Factors Affecting the Accuracy of Ultrasound Combined with Fine Needle Aspiration Cytology in Pre-Operative Staging of the Axilla in Breast Cancer.

Abstract Introduction:Ultrasound combined with fine needle aspiration cytology is effective in pre-operative staging of the axilla in breast cancer. Accurate pre-operative diagnosis of lymph node metastases allows for a one stage axillary operation and may also influence decisions regarding neo-adjuvant chemotherapy and breast reconstruction. The aim of this study is to identify pathological and patient factors that influence the accuracy of ultrasound and FNAC in determining the status of the axilla pre-operatively.Methods:Three hundred patients with primary operable invasive breast cancer had an axillary ultrasound pre-operatively. If the ultrasound was normal the patient was offered a sentinel node biopsy. If it identified equivocal or pathological nodes a fine needle aspirate cytology was performed. If the cytology was malignant then an axillary node clearance was performed.Results:Ultrasound combined with FNAC correctly determined the status of the axilla pre-operatively in 78% of cases. Sensitivity for the detection of metastases was 32% with 100% specificity. Factors affecting the accuracy of ultrasound and FNAC were the pathological size of tumour (p&amp;lt;0.05) and the size of the metastases (p&amp;lt;0.05). Age of the patient, pathological grade and type of tumour did not significantly affect the accuracy of the procedure.Conclusion:Ultrasound combined with fine needle aspirate cytology can be used effectively to determine the status of the axilla pre-operatively. All patients regardless of age or their particular tumour characteristics should be offered this procedure pre-operatively. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5020.

The use of ultrasound in pre-operative assessment of the axilla in breast cancer.

Abstract Abstract #1019 Introduction&amp;#x2028; Sentinel lymph node biopsy is now standard practice in axillary staging in breast cancer. It is associated with less morbidity than an axillary node clearance. A drawback of sentinel node biopsy is the need for a second surgical procedure if the sentinel node shows metastases. Clinical examination of the axilla has been the standard pre-operative assessment but this has been shown to be unreliable. More recently ultrasound has been used to identify axillary metastases pre-operatively. The aim of our study is to assess the role of pre-operative ultrasound and fine needle aspirate cytology in refining the selection of patients for whom sentinel node biopsy is appropriate.&amp;#x2028; Methods&amp;#x2028; Three hundred patients with primary operable invasive breast cancer had axillary ultrasound preoperatively. If the ultrasound was normal the patient was offered a sentinel node procedure. If it identified equivocal nodes a fine needle cytology was performed. If the cytology was benign a sentinel node biopsy was performed. If the cytology was malignant then an axillary node clearance was performed. In cases where pathological nodes were identified on imaging, cytology was performed to confirm malignancy. An axillary node clearance was then performed.&amp;#x2028; Results.&amp;#x2028; Eighty three percent of our patients (n=249) had a normal axillary ultrasound pre-operatively. Of these 74.5% had a benign sentinel node biopsy. Sixty two percent of patients with equivocal nodes on pre-operative imaging had metastases on final histology (n=19). Of these 63% (n=12) were correctly identified pre-operatively with fine needle aspirate cytology of the equivocal node and had an axillary node clearance performed form the outset. Ultrasound identified pathological nodes in 7% of our patients (n=20). Malignancy was confirmed on cytology and an axillary node clearance was performed.&amp;#x2028; Using ultrasound and fine needle aspirate cytology to assess the axilla pre-operatively sentinel node biopsy was performed in 265 patients (88%). Of these, 74.8% had a benign final histology. Thirty two patients had a pre-operative diagnosis of nodal metastases and had an axillary node clearance. All 32 had lymph node metastases on final histology. Factors that predicted for a malignant sentinel node were lymphovascular invasion (p&amp;lt;0.001), tumour grade (p&amp;lt;0.008) and size of tumour (p&amp;lt;0.001).&amp;#x2028; Conclusion&amp;#x2028; Eighty eight percent of our patients had a sentinel lymph node biopsy to stage the axilla. Pre-operative ultrasound combined with cytology correctly determined the status of the node in 78% of cases. Our rate of second axillary operations was reduced by 32%. Importantly all patients diagnosed with node metastases pre-operatively and advised to have an axillary node clearance did have metastases on final histology. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1019.

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (P⩽0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer.

Total loss of MHC class I is an independent indicator of good prognosis in breast cancer

Tumours can be recognised by CTL and NK cells. CTL recognition depends on expression of MHC Class I loaded with peptides from tumour antigens. In contrast, loss of MHC Class I results in NK activation. In our study a large set of samples from patients with primary operable invasive breast cancer was evaluated for the expression of MHC Class I heavy and light by immunohistochemical staining of 439 breast carcinomas in a tissue microarray. Forty-seven percent (206 of 439) of breast carcinomas were considered negative for HLA Class I heavy chain (HC10), whereas lack of anti-beta2m-antibody staining was observed in 39% (167 of 424) of tumours, with only 3% of the beta2m-negative tumours expressing detectable HLA Class I heavy chain. Correlation with patient outcome showed direct relationship between patient survival and HLA-negative phenotype (log rank = 0.004). A positive relationship was found between the intensity of expression of MHC Class I light and heavy chains expression and histological grade of invasive tumour (p < 0.001) and Nottingham Prognostic Index (p < 0.001). To investigate whether HLA Class I heavy and light chains expression had independent prognostic significance, Cox multivariate regression analysis, including the parameters of tumour size, lymph node stage, grade and intensity of HC10 and anti-beta2m staining, was carried out. In our analysis, lymph node stage (p < 0.001), tumour grade (p = 0.005) and intensity of MHC Class I light and heavy chains expression were shown to be independent prognostic factors predictive of overall survival (p-values HC10 = 0.047 and beta2m = 0.018).

Safe selection criteria for breast conservation without radical excision in primary operable invasive breast cancer

In a previous series from this unit of 263 women with primary operable breast cancer treated by macroscopic lumpectomy and breast irradiation, local recurrence was high. An audit at a median follow up of 36 months showed 56 (21%) ipsilateral breast recurrences. Eighteen of these recurrences were aggressive and uncontrolled. Multivariate analysis shows patient age, lymphovascular invasion, tumour size and nodal status to be predictive of local recurrence (Locker AP, et al., Br J Surgery 1989, 76, 890-894). New selection criteria for breast conservation were defined based on these data and also on securing an adequate clear margin of excision. In a subsequent prospective series of 275 women fulfilling these criteria, 6 women (2.2%) developed ipsilateral breast recurrence at the same median follow up of 36 months. In none was this uncontrolled and aggressive. Breast conservation, without radical excision, is safe as long as the selection criteria described are followed.

19. Selection criteria for breast conservation in primary operable invasive breast cancer

19. Selection criteria for breast conservation in primary operable invasive breast cancer

Age-related differences in breast cancer treatment

More than half of the cases of breast cancer treated in the United States occur in women over age 65. This study investigates age-related differences in breast cancer therapy. A retrospective review of all women with primary operable invasive breast cancer treated at the University of Michigan Breast Care Center over a 30-month period showed a total of 77 older patients aged > or = 65 years (median, 71; oldest patient, 92) for whom full information was available regarding comorbidity, tumor stage and histology, and details of surgery, radiation, and chemohormonal therapy and complications. Fifty-one similar younger patients aged 55-64 years (median, 59) were identified for comparison. Patients were classified as either having received standard treatment or non-standard treatment. Standard therapy was prospectively defined as follows: local/regional--lumpectomy and axillary lymph node dissection plus radiation therapy or modified radical mastectomy; systemic--chemotherapy and/or tamoxifen for stage II disease. A comorbidity score calculated for each patient assigned one point each for nursing home residence, nonambulatory status, recent surgery, and each medical problem requiring drug therapy. When overall treatment (local/regional plus systemic) was assessed, proportionately fewer older patients (55 of 77 versus 47 of 51; p < 0.01) received standard treatment. Fewer older than younger patients (62 of 77 versus 50 of 51; p < 0.01) received surgical therapy that included an axillary dissection. A smaller proportion of older patients received radiation therapy following lumpectomy and axillary lymph node dissection (26 of 29 versus 19 of 19; N.S.). Overall, only 59 of 77 older patients versus 50 of 51 younger patients (p < 0.001) received standard local/regional care. Similar proportions of younger and older patients (19 of 22 and 24 of 30, respectively) received standard systemic therapy for stage II breast cancer, but older patients were less likely to receive chemotherapy than younger patients (7% versus 50%; p < 0.001). Treatment-related complications were not age-related but were more frequent in patients receiving standard treatment than in patients receiving nonstandard treatment (45 of 102 versus two of 26; p < 0.001). Comorbidity score correlated with the use of nonstandard therapy but not with age. The scores for both older and younger patients receiving overall standard treatment were 0.8 versus 1.5 and 1.4, respectively, in patients receiving nonstandard treatment. Interestingly, explanations for decisions to deviate from standard treatment guidelines were often not identified. Comorbidity was explicitly noted in only one of four younger patients who received nonstandard treatment therapy. In 22 older patients who received nonstandard treatment, comorbidity was cited in eight cases, patient age was cited in six cases, and patient choice was cited in four cases. Follow-up (median, 34 months) did not show that disease-free or overall survival differences were related to age or to treatment (standard versus nonstandard). These data demonstrate age-related variations in breast cancer treatment in a multidisciplinary breast care unit. Lower complication rates and equivalent short-term outcomes in women who received nonstandard therapy suggest good clinical judgment may have played a role in these differences. Although age-related patient preferences and comorbidity are relevant, the age-related attitudes of caregivers must also be taken into account to fully explain these variations.