Determining the Factors Predicting the Response to Anti-HER2 Therapy in HER2-Positive Breast Cancer Patients.

PURPOSE: We aimed to identify the differently expressed genes or related pathways associated with good responses to anti-HER2 therapy and to suggest a model for predicting drug response in neoadjuvant systemic therapy with trastuzumab in HER2-positive breast cancer patients. METHODS: This study was retrospectively analyzed from consecutively collected patient data. We recruited 64 women with breast cancer and categorized them into 3 groups: complete response (CR), partial response (PR), and drug resistance (DR). The final number of patients in the study was 20. RNA from 20 core needle biopsy paraffin-embedded tissues and 4 cultured cell lines (SKBR3 and BT474 breast cancer parent cells and cultured resistant cells) was extracted, reverse transcribed, and subjected to GeneChip array analysis. The obtained data were analyzed using Gene Ontology, Kyoto Gene and Genome Encyclopedia, Database for Annotation, Visualization and Integrated Discovery. RESULTS: In total, 6,656 genes differentially expressed between trastuzumab-susceptible and trastuzumab-resistant cell lines were identified. Among these, 3,224 were upregulated and 3,432 were downregulated. Expression changes in 34 genes in several pathways were found to be related to the response to trastuzumab-containing treatment in HER2-type breast cancer, interfering with adhesion to other cells or tissues (focal adhesion) and regulating extracellular matrix interactions and phagosome action. Thus, decreased tumor invasiveness and enhanced drug effects might be the mechanisms explaining the better drug response in the CR group. CONCLUSIONS: This multigene assay-based study provides insights into breast cancer signaling and possible predictions of therapeutic response to targeted therapies such as trastuzumab.

The Sentinel Lymph Node Biopsy Using Indocyanine Green Fluorescence Plus Radioisotope Method Compared With the Radioisotope-Only Method for Breast Cancer Patients After Neoadjuvant Chemotherapy: A Prospective, Randomized, Open-Label, Single-Center Phase 2 Trial.

BACKGROUND: This study aimed to compare the sentinel lymph node (SLN) identification rates for breast cancer patients after neoadjuvant chemotherapy (NAC) between the dual method (DM) of indocyanine green fluorescence (ICG-F) plus a radioisotope (RI) and RI alone. METHODS: This randomized study enrolled 130 patients who received NAC for breast cancer and 122 patients who received SLN biopsy (SLNB) using either DM (n = 58) or RI only (n = 64). The study compared the identification rate, number of SLNs, and detection time of SLNB. RESULTS: Among the 122 patients, 113 (92.6%) were clinically node-positive before NAC. The SLN identification rate was 98.3% in the DM group and 93.8% in the RI group (p = 0.14). The DM group and the RI group were similar in the average number of SLNs (2.2 ± 1.13 vs. 1.9 ± 1.33; p = 0.26) and the time to detection of the first SLN (8.7 ± 4.98 vs. 8.3 ± 4.31 min; p = 0.30). In the DM group, transcutaneous lymphatic drainage was visualized by fluorescence imaging for 65.5% (38 of 58) of the patients. The SLN identification rate was 94.7% using ICG-F and 93% using RI (p = 0.79). During and after the operation, no complications, including allergic reactions or skin necrosis, occurred. CONCLUSIONS: This study is the first randomized trial to use ICG-F for SLNB in breast cancer patients after NAC. The DM including ICG-F could be a feasible and safe method for SLNB in initially node-positive breast cancer patients with NAC.

Use of adjuvant chemotherapy in hormone receptor-positive breast cancer patients with or without the 21-gene expression assay.

PURPOSE: We assessed the use of chemotherapy in breast cancer patients to investigate the factors that changed trends in chemotherapy following the adoption of the 21-gene expression assay in tumor genomic profiling. METHODS: Our study used 2033 patients from the National Cancer Center in Korea diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (tumor size of 0.5 cm or larger and 0-3 node metastases) from 2010 to 2015. We analyzed use of the 21-gene expression assay, changes in frequency of adjuvant chemotherapy use, and clinicopathological factors related to adjuvant chemotherapy to assess the impact of the 21-gene expression assay. RESULTS: Adjuvant chemotherapy use declined from 33.33% (2011) to 13.59% (2015) [relative risk (RR), 0.71; 95% CI 0.56-0.89; ptrend = 0.004] in patients with 21-gene expression assay data. Among patients without assay data, adjuvant chemotherapy use decreased from 76.79 to 40.17% between 2010 and 2015 (RR 0.87; 95% CI 0.84-0.91; ptrend < 0.001), especially for patients with node-negative/micrometastasis (RR 0.85; 95% CI 0.81-0.89; ptrend < 0.001). The frequency of adjuvant chemotherapy was significantly decreased after introduction of the 21-gene expression assay (p < 0.001). Tumor size (p < 0.001), progesterone receptor (PgR) status (p = 0.001), and proliferation index (Ki-67) levels (p < 0.001) were important factors for chemotherapy decision-making in node-negative/micrometastasis patients who did not undergo the assay. CONCLUSIONS: For HR-positive, HER2-negative breast cancer patients with 0-1 node metastases, chemotherapy use declined significantly after the adoption of the 21-gene assay. PgR status and Ki-67 were useful for chemotherapy decision-making in cases without the 21-gene assay.

Treatment factors affecting breast cancer-related lymphedema after systemic chemotherapy and radiotherapy in stage II/III breast cancer patients.

We evaluated whether the sequence or regimen of systemic chemotherapy could be a risk factor for breast cancer-related lymphedema (LE). We retrospectively analyzed 848 patients with stage II/III breast cancer who underwent curative surgery with adequate systemic therapy from 2004 to 2009. Adjuvant chemotherapy (ACT) was performed in 552 patients (65.1 %) and neoadjuvant chemotherapy (NAC) in 296 (34.9 %). We evaluated the incidence of LE based on clinicopathological factors and treatments. At a median follow-up of 5.1 years, 358 patients (42.2 %) had experienced LE and 243 (28.7 %) had retained (persistent LE) [120/552 (21.7 %) with ACT vs. 123/296 (41.6 %) with NAC; P < 0.001]. The incidence of LE in patients with taxane was greater than in those without taxane [233/704 (33.1 %) vs. 10/144 (6.9 %); P < 0.001]. Multivariate analysis showed that NAC [hazard ratio (HR), 1.63 in LE event; P < 0.001; HR, 1.39 in persistent LE; P = 0.02] and RT including supraclavicular area (SCRT) (HR 1.55; P = 0.02; HR 1.93; P = 0.006), number of dissected axillary lymph nodes (N-ALNs) >10 (HR, 1.37; P = 0.01; HR, 1.71; P = 0.001), advanced stage (HR, 1.31; P = 0.03; HR, 1.60; P = 0.002), and taxane (HR, 1.69; P = 0.03; HR, 2.07; P = 0.04) were independent risk factors for the LE occurrence. In addition to advanced stage, N-ALNs and SCRT, NAC, and taxane were shown to increase the risk of LE, which could help clinicians identify patients at risk for LE.

Comparison of sentinel lymph node biopsy guided by the multimodal method of indocyanine green fluorescence, radioisotope, and blue dye versus the radioisotope method in breast cancer: a randomized controlled trial.

PURPOSE: This study aimed to evaluate the identification rate and surgery time of sentinel lymph node biopsy (SLNB) by a multimodal method (MMM) using a mixture of indocyanine green (ICG), radioisotope (RI), and blue dye (BD) compared with the RI alone. METHODS: In this phase II randomized study, 86 patients with clinically node-negative breast cancer were enrolled and received SLNB with either MMM or RI. We compared the identification rate, number of sentinel lymph nodes (SLNs), and detection time of SLNB and evaluated the safety. RESULTS: The mean age of the MMM group and RI group was 48.2 and 51.0 years (p = 0.12), respectively. There were no differences in histopathologic factors, including tumor size, node positivity, and hormone receptor positivity between groups. SLNs were identified in all patients of both groups (100 % in the MMM group and 100 % in the RI group). The average number of SLNs in the MMM group was more than that in the RI group (3.4 ± 1.37 vs. 2.3 ± 1.04, respectively; p < 0.001). The time to detect the first sentinel lymph node was similar in each group (6.5 ± 5.16 vs. 8.0 ± 4.35 min; p = 0.13). In the MMM group, percutaneous lymphatic drainage was visualized by fluorescent imaging in 90.7 % (39 of 43 patients). During and after the operation, there were no complications, including allergic reactions, skin staining, or necrosis. CONCLUSIONS: This study is the first randomized trial that compared MMM using ICG, RI, and BD and the conventional RI method for SLNB. MMM is a feasible and safe method for SLNB.

Could axillary lymph node dissection be omitted in the mastectomy patient with tumor positive sentinel node?

Background: Recent data from the ACOSOG Z0011 trial suggest that axillary lymph node dissection (ALND) may not be necessary for patients with positive sentinel lymph node biopsy (SLNB) receiving breast-conserving surgery (BCS) with irradiation. However, consensus statements and guidelines have recommended that patients undergoing mastectomy with tumor-positive sentinel node undergo completion ALND. In this study, we compared the locoregional recurrence rate of patients with tumor-positive sentinel nodes among three groups: mastectomy with SLNB, mastectomy with ALND and BCS with SLNB. Method: We identified 6,163 women with invasive breast cancer who underwent surgical resection at our institution between January 2000 and December 2011. Clinicopathologic data obtained from the prospectively collected medical database were analyzed retrospectively. Among the patients with sentinel node positive, mastectomy with SLNB was performed in 39 cases, mastectomy with ALND in 181 cases, and BCS with SLNB in 165 cases. The primary end point was the loco-regional recurrence rate. Results: Clinicopathologic characteristics were similar among the groups. There were no cases of loco-regional recurrence in the sentinel groups. At a median follow-up of 61.0 months (last follow-up May 2013), the loco-regional recurrence rate of each group was 0% for BCS with SLNB and mastectomy with SLNB only, and 1.7% for mastectomy with ALND (p=0.182). Conclusion: In our study, there was no significant difference in loco-regional recurrence rates between groups. This result lends weight to the argument that SLNB without ALND may be a reasonable management for selected patients with appropriate surgery and adjuvant systemic therapy.

Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor-Positive and HER-2-Negative Breast Cancer with Neoadjuvant Chemotherapy.

PURPOSE: This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors. Materials and Methods: We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR. RESULTS: Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR-) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2-) subtype. The rate of pCR was 31.4% (196/624). AR- patients had a significantly higher rate of pCR than AR+ patients (AR- 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR- tumor showed higher pCR rate in HR+/HER2- subtype (AR- 28.6% vs. AR+ 7.3%, p=0.022). CONCLUSION: AR expression is predominant in the HR+/HER2- subtype. AR- is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2- subtype. When determining neoadjuvant chemotherapy for the HR+/HER2- subtype, AR expression can be considered as a pCR predictive marker.

Clinicopathological Factors Associated with Oncotype DX Risk Group in Patients with ER+/HER2- Breast Cancer.

Oncotype DX (ODX), a 21-gene assay, predicts the recurrence risk in early breast cancer; however, it has high costs and long testing times. We aimed to identify clinicopathological factors that can predict the ODX risk group and serve as alternatives to the ODX test. This retrospective study included 547 estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and lymph node-negative breast cancer patients who underwent ODX testing. Based on the recurrence scores, three ODX risk categories (low: 0-15, intermediate: 16-25, and high: 26-100) were established in patients aged ≤50 years (n = 379), whereas two ODX risk categories (low: 0-25 and high: 26-100) were established in patients aged >50 years (n = 168). Factors selected for analysis included body mass index, menopausal status, type of surgery, and pathological and immunohistochemical features. The ODX risk groups showed significant association with histologic grade (p = 0.0002), progesterone receptor expression (p < 0.0001), Ki-67 (p < 0.0001), and p53 expression (p = 0.023) in patients aged ≤50 years. In patients aged >50 years, tumor size (p = 0.022), Ki-67 (p = 0.001), and p53 expression (p = 0.001) were significantly associated with the risk group. Certain clinicopathological factors can predict the ODX risk group and enable decision-making on adjuvant chemotherapy; these factors differ according to age.

Phase II trial of preoperative paclitaxel, gemcitabine, and trastuzumab combination therapy in HER2 positive stage II/III breast cancer: the Korean Cancer Study Group BR 07-01.

An addition of trastuzumab preoperatively to chemotherapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer improved relapse-free survival (RFS). This study was designed to evaluate the efficacy and safety of preoperative paclitaxel, gemcitabine, and trastuzumab (PGH) combination for HER2-positive breast caner. Pathologically, proven node positive stage II/III breast cancer patients with adequate organ function and no history of anti-cancer therapy were eligible. Patients received weekly trastuzumab with paclitaxel 80 mg/m(2) and gemcitabine 1,200 mg/m(2) on days 1 and 8, every 3 weeks for 6 cycles. Postoperatively, patients completed trastuzumab for 1 year and hormone therapy for 5 years if indicated. All patients received postoperative radiation therapy. Of 53 enrolled patients with a median tumor of 5.3 (range, 2.0 to >12) cm; 43.4%, T3/T4; 75.4%, N2/N3; and 45.3%, positive hormone receptors. The pathologic complete response (pCR) rate was 58.5% in both tumor and lymph nodes. Grade 3/4 adverse events were neutropenia (32%), febrile neutropenia (0.6%), and transient elevation of AST/ALT (1.6%) during a total of 318 cycles. All patients maintained normal cardiac function. With a median follow-up of 40 months, 3-year RFS rate was 84% with 91.7% distant metastasis-free survival rates. Remarkable pCR rate was obtained with non-anthracycline-based PGH therapy for HER2-positive stage II/III breast cancer. Adverse events were mild with few incidences of febrile neutropenia.

A phase Ib study of preoperative lapatinib, paclitaxel, and gemcitabine combination therapy in women with HER2 positive early breast cancer.

We conducted a phase I trial to determine the feasible dose for lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor, with paclitaxel and gemcitabine as a neoadjuvant treatment in HER2 positive patients. In this phase I dose-escalation study, cohorts of 3-6 HER2-positive operable breast cancer patients received lapatinib (1,000 mg/day or 1,250 mg/day PO) with paclitaxel (80 mg/m(2)) and gemcitabine (1,000 or 1,200 mg/m(2)) on days 1 and 8 every 21 days to determine the tolerable dosages. Among 13 patients enrolled, 12 (stage III; n = 11: stage II; n = 1) completed treatment and one withdrew consent. The recommended doses were 1000-mg/day lapatinib, 80-mg/m(2) paclitaxel, and 1,000-mg/m(2) gemcitabine. One patient developed dose-limiting grade 3 hepatotoxicity; 3 experienced dose-limiting grade 4 neutropenia. No notable decline in left ventricle ejection fraction occurred. Eight patients achieved clinical partial response and four achieved clinical complete response (CR). Three patients (25%) achieved both tumor and nodal pathologic CR, 5 (42%) achieved tumor pathologic CR, and 6 (50%) underwent breast-conserving surgery. No relationship between lapatinib dose intensity and tumor response was apparent. Median follow-up was 16.2 (range, 6.5-20.7) months. Lapatinib plus paclitaxel and gemcitabine was tolerable with no overlapping toxicity.

Predictive factors of pathologic complete response and clinical tumor progression after preoperative chemotherapy in patients with stage II and III breast cancer.

BACKGROUND: This study aimed to define predictive factors of pathologic complete response (pCR) and disease progression in stage II and III breast cancer patients. PATIENTS AND METHODS: Three hundred thirty-eight patients were included in the study. Patients had received preoperative chemotherapy as follows: 101 had doxorubicin plus cyclophosphamide (AC); 91 had doxorubicin plus docetaxel; 103 had docetaxel plus capecitabine; and 43 had paclitaxel plus gemcitabine. A pCR was defined as the absence of residual invasive carcinoma in the breast. RESULTS: The majority of patients (73%) were premenopausal with a median age of 44 (range, 21-76) years. Fifty-four patients (16%) achieved pCR and were distributed among the 4 breast cancer subtypes as follows: 10% of patients with -ER or PR+/HER2-, 13% with ER or PR+/HER2+, 33% with ER-/PR-/HER2+, and 19% with ER-/PR-/HER2-(p = 0.001). Taxane-containing regimen (p = 0.042) and Breast cancer subtype (p = 0.005) were significant predictive variables for pCR. On the other hand, significantly more patients who received non-taxane-containing regimen (AC) experienced no response (p = 0.001) or progression (p = 0.006). CONCLUSIONS: Patients with ER-/PR-/HER2+ tumors and those who received taxane-containing regimen achieved a higher pCR rate, while significantly more patients developed tumor progression by preoperative non-taxane-containing regimen (AC) compared to those who received taxane-containing chemotherapy.

Adipokines, insulin resistance, metabolic syndrome, and breast cancer recurrence: a cohort study.

INTRODUCTION: Several in vitro studies have suggested the effects of adipokines and insulin resistance on breast cancer cell proliferation and survival. However, little is known about the clinical significance of these findings. METHODS: We examined associations between breast cancer recurrence and adiponectin, leptin, insulin resistance, and metabolic syndrome (MetS) in a cohort of 747 patients from 2001 to 2004. RESULTS: Adjusted hazard ratios showed an inverse trend across the quartiles for serum adiponectin concentration in estrogen receptor (ER)/progesterone receptor (PR) -negative patients (P for trend = 0.027) but not in ER/PR-positive patients. Compared to the highest quartile for adiponectin level, the lowest quartile showed a hazard ratio of 2.82 (1.03 to 7.68). Homeostasis model assessment for insulin resistance (HOMA-IR) showed a positive trend for recurrence in the ER/PR-negative group (P for trend = 0.087) and a negative trend in the ER/PR-positive group (P for trend = 0.081). Leptin did not show any associations (P for trend >0.05). A linear trend was observed with the number of components of MetS in ER/PR-negative patients (P for trend = 0.044). This association disappeared when adjusted for adiponectin and HOMA-IR. CONCLUSIONS: Adiponectin and HOMA-IR have prognostic significance in breast cancer recurrence and interventions related to these factors may protect against recurrence in ER/PR-negative patients. These findings were not observed in the case of ER/PR-positive patients. Further evaluation of these insignificant associations is needed because it might be biased by adjuvant chemotherapy or other confounders.

Peritoneal lymphomatosis confounded by prior history of colon cancer: a case report.

BACKGROUND: It is well known that carcinomas of the gastrointestinal tract are frequently associated with peritoneal carcinomatosis. In contrast to that entity extensive involvement of the peritoneal cavity with malignant lymphoma is rare. CASE PRESENTATION: This is the first case reporting coexistence of peritoneal lymphomatosis and a previous history of colon cancer, which is a highly challenging clinical situation. CONCLUSIONS: If not aware of this unusual condition medical history, radiologic finding and laboratory data alone can lead to wrong diagnosis as in this case.

Accumulation of p53 determined by immunohistochemistry as a prognostic marker in node negative breast cancer; analysis according to St Gallen consensus and intrinsic subtypes.

BACKGROUND: This study evaluated the prognostic impact of p53 accumulation by immunohistochemistry (IHC) in lymph node-negative breast cancer (LNN-BC), and in subgroups of St Gallen consensus and intrinsic subtypes. METHODS: A total 845 with a pathologic diagnosis of LNN-BC patients that underwent surgery at the National Cancer Center, Korea between 2001 and 2005 were retrospectively reviewed. RESULTS: The median age was 48 years (range: 25-85) and median follow-up period was 66.0 months (range: 9-101). Univariate analysis determined that tumor size, estrogen receptor (ER), progesterone receptor (PgR), p53, and Ki-67 were significant for disease free survival (DFS). Of these factors, PgR negativity (HR 3.57; 95% CI 1.26-10.09; P = 0.01) and p53 positivity (HR 3.17; 95% CI 1.51-6.65; P = 0.002) were independent prognostic factors in multivariate analysis. In the subanalysis for 4 intrinsic subtypes (luminal A, luminal B, HER2-overexpression, and triple-negative subtypes) and risk groups by St Gallen consensus, there were significant differences of DFS rates by p53 (5-year DFS rate, luminal A; 97.2% for p53 (-) vs 93.8% for p53 (+); P = 0.03, triple-negative subgroups; 94.1% vs 78.7%; P = 0.002, intermediate-risk group; 96.5% vs 90.7%; P = 0.003). CONCLUSIONS: P53 has prognostic power in LNN-BC, and gives the additional prognostic information for intrinsic subtypes and St Gallen consensus.

Systematic evaluation of scoring methods for Ki67 as a surrogate for 21-gene recurrence score.

Although Ki67 labeling index is a potential predictive marker for chemotherapy benefit, its clinical utility has been limited by the lack of a standard scoring method resulting in poor interobserver reproducibility. Especially, there is no consensus on the use of average versus hotspot score for reporting. In order to determine the best method for Ki67 scoring and validate manual scoring method proposed by the International Ki67 Working Group (IKWG), we systematically compared average versus hotspot score in 240 cases with a public domain image analysis program QuPath. We used OncotypeDx Recurrence Score (RS) as a benchmark to compare the potential clinical utility of each scoring methods. Both average and hotspot scores showed statistically significant but only modest correlation with OncotypeDx RS. Only hotspot score could meaningfully distinguish RS low-risk versus high-risk patients. However, hotspot score was less reproducible limiting its clinical utility. In summary, our data demonstrate that utility of the Ki67 labeling index is influenced by the choice of scoring method.

Programmed Death Ligand 1 Immunohistochemistry in Triple-Negative Breast Cancer: Evaluation of Inter-Pathologist Concordance and Inter-Assay Variability.

PURPOSE: The programmed death ligand 1 (PD-L1) SP142 assay with a 1% immune cell (IC) cutoff is approved for the selection of advanced triple-negative breast cancer (TNBC) patients for atezolizumab treatment. We aimed to evaluate the interobserver concordance of PD-L1 scoring and inter-assay variability of various PD-L1 assays in TNBC. METHODS: Thirty patients with primary TNBC were selected, and SP142, SP263, 22C3, and E1L3N assays were performed. PD-L1 staining in ICs and tumor cells (TCs) was scored by 10 pathologists who were blinded to the assay. The interobserver concordance among pathologists and the inter-assay variability of the four PD-L1 assays were analyzed. For SP142, the intraobserver concordance among the six pathologists was analyzed after training. RESULTS: The adjusted means of PD-L1 IC scoring ranged from 6.2% to 12.9% for the four assays; the intraclass correlations showed moderate (0.584-0.649) reader concordance. The PD-L1 IC scoring with a 1% cutoff resulted in identical scoring in 40.0%-66.7% of cases and a poor to moderate agreement (Fleiss κ statistic [FKS] = 0.345-0.534) for the four assays. The SP142 assay had the widest range of positive rate (56.5%-100.0%), lowest number of cases with identical scoring, and lowest FKS at 1% cutoff. Pairwise comparison of adjusted means showed significantly decreased PD-L1 staining in SP142 compared with the other assays in both ICs and TCs. As for the intraobserver concordance in the SP142 assay, the overall percent agreement was 87.8% with a 1% IC cutoff. After training, the proportion of cases with identical scoring at a 1% IC cutoff increased to 70.0%; the FKS also increased to 0.610. CONCLUSION: The concordance of PD-L1 IC scoring among pathologists was low, at the 1% cutoff for the SP142 assay without training. SP142 showed the lowest PD-L1 expression in both IC and TC.

Standardized pathology report for breast cancer.

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of 'standard data elements,' 'conditional data elements,' and a biomarker report form. The 'standard data elements' consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the 'conditional data elements.' In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

Standardized Pathology Report for Breast Cancer.

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of 'standard data elements,' 'conditional data elements,' and a biomarker report form. The 'standard data elements' consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the 'conditional data elements.' In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification.

BACKGROUND: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. METHODS: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). RESULTS: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. CONCLUSIONS: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Concordant HER2 status between metastatic breast cancer cells in CSF and primary breast cancer tissue.

It is not known whether the HER2 status of malignant CSF cells coincides with that of the original breast carcinoma cells. We investigated whether CSF cytology specimens were suitable to evaluate HER2 status by fluorescence in situ hybridization (FISH) in patient with leptomeningeal metastasis (LM). Both formalin-fixed paraffin-embedded (FFPE) breast cancer tissue and liquid based CSF cytology specimens were evaluated for HER2 status in 16 patients with LM. We evaluated HER2 gene amplification using FISH on destained CSF cytology slides containing a minimum of 20 malignant cells per slide, and compared these with the HER2 status by immunohistochemistry (IHC) or FISH in FFPE tissues. HER2 was considered positive when the HER2:CEP17 ratio was >or=2.0 or IHC 3+. Of 16 cases, four were HER2 positive and 12 were HER2 negative by FISH analysis in CSF cytology. All CSF-positive cases were HER2 positive by IHC in FFPE tissue. Of 12 HER2 FISH-negative cases in CSF cytology, 10 were HER2 negative (IHC 0 or 1+) and two were IHC 2+ in FFPE tissue. Two IHC 2+ cases had HER2:CEP17 ratios of 1.27 and 2.1, respectively, by FISH in FFPE tissue. As a result, the HER2 status concordance rate between metastatic breast cancer cells in CSF and FFPE primary tissue by IHC and FISH was very high. When CSF cytology specimens were appropriately prepared and had adequate cellularity without dry artifacts, the CSF cytology was suitable to evaluate HER2 status by FISH analysis in patients with LM.